TBD Meeting (3134-23)

This transcript has been edited for clarity.

This is my usual blog, except I am here from the absolutely beautiful city of Amsterdam, where the annual congress of the European Society of Cardiology has been going on.
 

SGLT2 inhibitors for HFpEF and HFrEF

I’m going to review very briefly the 2023 focused update to the ESC heart failure guidelines. Theresa McDonagh was the first author of this and of the previous ESC or European guidelines. These are a little bit different than the American guidelines, which were presented in 2022. We know that we need an update. The Europeans have gotten ahead of us, and now we have the European update, which I find incredibly well written and it really highlights the areas that I think the takeaways are for the clinicians.

First, we have been seeing now for several years – since 2018 – the benefits of the sodium-glucose cotransporter 2 (SGLT2) inhibitors. Every time we lift the veil on something, there they are in a positive light. We have learned about heart failure with reduced ejection fraction (HFrEF) for both empagliflozin and dapagliflozin. There are very similar results. One population may be enriched with a little of this and a little of that, but the basic messages are the same. In HFrEF, both of these drugs improve outcomes and it happens quickly. You don’t have to wait 1 or 2 years to see this. Within months, and actually within days, you start to see the curves split apart statistically.

The next logical ground was heart failure with preserved ejection fraction (HFpEF). The definition, when we started the HFpEF trials, was 45% or greater. I want the audience to realize that, in the midst of all these trials, we came out – we meaning the American Heart Association, the American College of Cardiology, and the Heart Failure Society – with the new definition of heart failure, which said that true HFpEF is 50% or greater. That in-between zone of 40%-50% or 41%-49% is mRF, or mid-range, what I call middle of the road. I think the Europeans have really emphasized that to us. I believe that those patients really behave much more like a HFrEF population.

Now that we have very positive findings with the SGLT2 inhibitors, both dapagliflozin and empagliflozin, in HFpEF – defined, as I said, as 40% or 45% or greater, not necessarily 50% – with excellent point estimates that just line up, one on top of the other. It doesn’t matter if patients have diabetes or not; the results are exactly the same.

This has been so promising that I am not surprised that the Europeans elevated the SGLT2 inhibitors to a class 1A indication. In the United States in 2022, we thought we were really way ahead by calling it a class 2A indication. Well, now it’s a class 1A indication in Europe, and I have a feeling that the AHA and the ACC are going to start talking about an update because the data are so strong.

Now, we even have data on initiating these drugs in the hospital. EMPULSE was a very large trial about the benefits of starting these drugs in the hospital. You do not have to wait until the patient is in the outpatient setting. You can start it in the hospital.

When? I have no specific day that I start it. I used to try to do a good diuresis first, get the patients somewhat decongested, and then start it. I don’t want to deprive the patients of the benefits of these drugs that happen very early by waiting until the patients are in the outpatient setting.

In the United States, we’ve had some issues with coverage of some of these drugs. In my institution, we now have both on the formulary, and I pick the drug depending upon the patient’s coverage. Medicare pretty much covers most of them. If the patient is older but not yet a Medicare patient, they may have a very large copay. I advise you to get your offices or your health system to look into this so that, when you give the prescription to the patient, whether they’re leaving the hospital or are now in your clinics, they can actually get the drug.
 

Finerenone and intravenous iron

There is an additional recommendation in these guidelines for finerenone, the mineralocorticoid receptor agonist that I’ve discussed before, that has some really promising data on type 2 diabetes with chronic kidney disease. They have called that a class 1A indication for finerenone. I think there is more to come.

One more: the iron deficiency. Giving intravenous iron actually does improve symptoms and quality of life. I have seen this in my own patients, so I have been very diligent at looking for iron deficiency.

It is a new era. We have more tools, obviously, for our patients. It means one more drug, and that’s always a challenge. We’ve already been doing the pillars of care. This is the fourth pillar of care, but now with a class 1A indication.

Take a look. They’re easy to read. Dr. McDonagh is the first author, and I think they’ve been extremely well done.

Dr. Piña is professor of medicine at Thomas Jefferson University Hospital in Philadelphia. She is a heart failure and cardiac transplantation expert. She disclosed serving as an adviser/consultant to the FDA’s Center for Devices and Radiological Health and has been a volunteer for the American Heart Association since 1982.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

This is my usual blog, except I am here from the absolutely beautiful city of Amsterdam, where the annual congress of the European Society of Cardiology has been going on.
 

SGLT2 inhibitors for HFpEF and HFrEF

I’m going to review very briefly the 2023 focused update to the ESC heart failure guidelines. Theresa McDonagh was the first author of this and of the previous ESC or European guidelines. These are a little bit different than the American guidelines, which were presented in 2022. We know that we need an update. The Europeans have gotten ahead of us, and now we have the European update, which I find incredibly well written and it really highlights the areas that I think the takeaways are for the clinicians.

First, we have been seeing now for several years – since 2018 – the benefits of the sodium-glucose cotransporter 2 (SGLT2) inhibitors. Every time we lift the veil on something, there they are in a positive light. We have learned about heart failure with reduced ejection fraction (HFrEF) for both empagliflozin and dapagliflozin. There are very similar results. One population may be enriched with a little of this and a little of that, but the basic messages are the same. In HFrEF, both of these drugs improve outcomes and it happens quickly. You don’t have to wait 1 or 2 years to see this. Within months, and actually within days, you start to see the curves split apart statistically.

The next logical ground was heart failure with preserved ejection fraction (HFpEF). The definition, when we started the HFpEF trials, was 45% or greater. I want the audience to realize that, in the midst of all these trials, we came out – we meaning the American Heart Association, the American College of Cardiology, and the Heart Failure Society – with the new definition of heart failure, which said that true HFpEF is 50% or greater. That in-between zone of 40%-50% or 41%-49% is mRF, or mid-range, what I call middle of the road. I think the Europeans have really emphasized that to us. I believe that those patients really behave much more like a HFrEF population.

Now that we have very positive findings with the SGLT2 inhibitors, both dapagliflozin and empagliflozin, in HFpEF – defined, as I said, as 40% or 45% or greater, not necessarily 50% – with excellent point estimates that just line up, one on top of the other. It doesn’t matter if patients have diabetes or not; the results are exactly the same.

This has been so promising that I am not surprised that the Europeans elevated the SGLT2 inhibitors to a class 1A indication. In the United States in 2022, we thought we were really way ahead by calling it a class 2A indication. Well, now it’s a class 1A indication in Europe, and I have a feeling that the AHA and the ACC are going to start talking about an update because the data are so strong.

Now, we even have data on initiating these drugs in the hospital. EMPULSE was a very large trial about the benefits of starting these drugs in the hospital. You do not have to wait until the patient is in the outpatient setting. You can start it in the hospital.

When? I have no specific day that I start it. I used to try to do a good diuresis first, get the patients somewhat decongested, and then start it. I don’t want to deprive the patients of the benefits of these drugs that happen very early by waiting until the patients are in the outpatient setting.

In the United States, we’ve had some issues with coverage of some of these drugs. In my institution, we now have both on the formulary, and I pick the drug depending upon the patient’s coverage. Medicare pretty much covers most of them. If the patient is older but not yet a Medicare patient, they may have a very large copay. I advise you to get your offices or your health system to look into this so that, when you give the prescription to the patient, whether they’re leaving the hospital or are now in your clinics, they can actually get the drug.
 

Finerenone and intravenous iron

There is an additional recommendation in these guidelines for finerenone, the mineralocorticoid receptor agonist that I’ve discussed before, that has some really promising data on type 2 diabetes with chronic kidney disease. They have called that a class 1A indication for finerenone. I think there is more to come.

One more: the iron deficiency. Giving intravenous iron actually does improve symptoms and quality of life. I have seen this in my own patients, so I have been very diligent at looking for iron deficiency.

It is a new era. We have more tools, obviously, for our patients. It means one more drug, and that’s always a challenge. We’ve already been doing the pillars of care. This is the fourth pillar of care, but now with a class 1A indication.

Take a look. They’re easy to read. Dr. McDonagh is the first author, and I think they’ve been extremely well done.

Dr. Piña is professor of medicine at Thomas Jefferson University Hospital in Philadelphia. She is a heart failure and cardiac transplantation expert. She disclosed serving as an adviser/consultant to the FDA’s Center for Devices and Radiological Health and has been a volunteer for the American Heart Association since 1982.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

This is my usual blog, except I am here from the absolutely beautiful city of Amsterdam, where the annual congress of the European Society of Cardiology has been going on.
 

SGLT2 inhibitors for HFpEF and HFrEF

I’m going to review very briefly the 2023 focused update to the ESC heart failure guidelines. Theresa McDonagh was the first author of this and of the previous ESC or European guidelines. These are a little bit different than the American guidelines, which were presented in 2022. We know that we need an update. The Europeans have gotten ahead of us, and now we have the European update, which I find incredibly well written and it really highlights the areas that I think the takeaways are for the clinicians.

First, we have been seeing now for several years – since 2018 – the benefits of the sodium-glucose cotransporter 2 (SGLT2) inhibitors. Every time we lift the veil on something, there they are in a positive light. We have learned about heart failure with reduced ejection fraction (HFrEF) for both empagliflozin and dapagliflozin. There are very similar results. One population may be enriched with a little of this and a little of that, but the basic messages are the same. In HFrEF, both of these drugs improve outcomes and it happens quickly. You don’t have to wait 1 or 2 years to see this. Within months, and actually within days, you start to see the curves split apart statistically.

The next logical ground was heart failure with preserved ejection fraction (HFpEF). The definition, when we started the HFpEF trials, was 45% or greater. I want the audience to realize that, in the midst of all these trials, we came out – we meaning the American Heart Association, the American College of Cardiology, and the Heart Failure Society – with the new definition of heart failure, which said that true HFpEF is 50% or greater. That in-between zone of 40%-50% or 41%-49% is mRF, or mid-range, what I call middle of the road. I think the Europeans have really emphasized that to us. I believe that those patients really behave much more like a HFrEF population.

Now that we have very positive findings with the SGLT2 inhibitors, both dapagliflozin and empagliflozin, in HFpEF – defined, as I said, as 40% or 45% or greater, not necessarily 50% – with excellent point estimates that just line up, one on top of the other. It doesn’t matter if patients have diabetes or not; the results are exactly the same.

This has been so promising that I am not surprised that the Europeans elevated the SGLT2 inhibitors to a class 1A indication. In the United States in 2022, we thought we were really way ahead by calling it a class 2A indication. Well, now it’s a class 1A indication in Europe, and I have a feeling that the AHA and the ACC are going to start talking about an update because the data are so strong.

Now, we even have data on initiating these drugs in the hospital. EMPULSE was a very large trial about the benefits of starting these drugs in the hospital. You do not have to wait until the patient is in the outpatient setting. You can start it in the hospital.

When? I have no specific day that I start it. I used to try to do a good diuresis first, get the patients somewhat decongested, and then start it. I don’t want to deprive the patients of the benefits of these drugs that happen very early by waiting until the patients are in the outpatient setting.

In the United States, we’ve had some issues with coverage of some of these drugs. In my institution, we now have both on the formulary, and I pick the drug depending upon the patient’s coverage. Medicare pretty much covers most of them. If the patient is older but not yet a Medicare patient, they may have a very large copay. I advise you to get your offices or your health system to look into this so that, when you give the prescription to the patient, whether they’re leaving the hospital or are now in your clinics, they can actually get the drug.
 

Finerenone and intravenous iron

There is an additional recommendation in these guidelines for finerenone, the mineralocorticoid receptor agonist that I’ve discussed before, that has some really promising data on type 2 diabetes with chronic kidney disease. They have called that a class 1A indication for finerenone. I think there is more to come.

One more: the iron deficiency. Giving intravenous iron actually does improve symptoms and quality of life. I have seen this in my own patients, so I have been very diligent at looking for iron deficiency.

It is a new era. We have more tools, obviously, for our patients. It means one more drug, and that’s always a challenge. We’ve already been doing the pillars of care. This is the fourth pillar of care, but now with a class 1A indication.

Take a look. They’re easy to read. Dr. McDonagh is the first author, and I think they’ve been extremely well done.

Dr. Piña is professor of medicine at Thomas Jefferson University Hospital in Philadelphia. She is a heart failure and cardiac transplantation expert. She disclosed serving as an adviser/consultant to the FDA’s Center for Devices and Radiological Health and has been a volunteer for the American Heart Association since 1982.

A version of this article appeared on Medscape.com.

AMSTERDAM – New European Society of Cardiology guidelines on the management of acute coronary syndromes (ACS) have for the first time combined ST-elevation MI (STEMI), non–ST-elevation MI (NSTEMI), and unstable angina into the same set of recommendations.

The new guideline was released at the annual congress of the European Society of Cardiology, and was published online in the European Heart Journal.

“We found that it was realized by the cardiology community that patients with STEMI, NSTEMI, or unstable angina represent a spectrum,” the chair of the guideline task force, Robert Byrne, MD, chair of cardiovascular research at the RCSI University of Medicine and Health Sciences, Dublin, explained to this news organization. “After the initial triage and management decisions, then most of the rest of the care follows a common pathway so it would make sense to consider everything in one guideline.”

Dr. Byrne noted that for all patients with a suspected ACS, the guideline recommendation is to administer an ECG within 10 minutes of presentation. The time is critical particularly for those with an occluded epicardial vessel. If there are features on the ECG that suggest an acutely occluded epicardial vessel, then the patient needs immediate angiography or primary angioplasty.

“The 10-minute guidance has been maintained from previous guidelines, but the nuance in the new guideline is that typically when we think of an occluded epicardial vessel we think of ST-elevation on the ECG,” Byrne said. “While this captures most occluded epicardial vessels, it doesn’t capture all of them. So, we have provided some guidance on alternative ECG patterns which might be indicative of an acute occlusion of the epicardial vessel and should be dealt with in the same way as an ST-elevation MI. This is a new concept.”

This situation could arise when a patient has an occluded circumflex artery and the regular ECG may not show ST elevation but the patient has ongoing pain, he noted. “There are additional ECG leads that can be looked at that might identify patients who need an immediate invasive strategy.

“This is one more reason why all ACS patients should be considered as part of one spectrum, and while the ECG gives us important information, it is not the only thing to consider. Dividing the conditions up as to whether a patient has ST elevation or not does not always make pathophysiological sense,” he added.

Dr. Byrne noted that the new guidelines have tried to reach a wider stakeholder group that includes emergency doctors, internal medicine physicians, general practitioners, and surgeons, as well as cardiologists. The document includes animations in an effort to increase the reach of the guidelines to noncardiology stakeholders, and for the first time, the task force included a patient representative.

“As part of this strategy, we have put more structure in to emphasize the importance that at first contact, we already want to be thinking of antithrombotic therapy and whether the patient needs urgent transfer to the nearest cath lab. We also want to be thinking straight away about preventing the next heart attack by implementing strong secondary prevention measures,” he commented.

Dr. Byrne highlighted a few changes to individual recommendations in the new guidelines.
 

Invasive management in NSTE-ACS

He pointed out that a small change has been made in the advice on invasive management for patients with non–ST-elevation ACS.

Dr. Byrne explained that patients with ST elevation should be sent immediately to a cath lab for PCI. If this is not possible within 120 minutes, then the patient should receive thrombolysis. This recommendation is the same as in previous guidelines.

He added, however, that there is some novelty in recommendations for patients who don’t have ST elevation but do have a positive troponin. For this group, previous guidelines gave a Class I recommendation that all such patients undergo an angiogram within the first 24 hours. However, an additional meta-analysis that was published in 2022 showed that the evidence for triaging all patients to the cath lab within 24 hours is somewhat limited, Dr. Byrne noted.

“At the end of the day, the task force felt that a Class I recommendation to get all patients to the cath lab within 24 hours was too strong and couldn’t be sustained, so it has been downgraded to a Class IIa recommendation, which we thought was more appropriate,” he said.

“So, while all patients should still have an angiogram during the hospital admission, if they are high-risk ACS, the imperative to get everyone to the cath lab within 24 hours – which many of our colleagues were finding difficult to achieve – does not seem to be backed up by the evidence,” he added.
 

Antithrombotic therapy

Addressing administration of antithrombotics, the guidelines emphasize that at the time of initial diagnosis, all patients should receive antithrombotic therapy, usually aspirin and a parenteral antithrombotic, such as heparin, enoxaparin, bivalirudin, or fondaparinux. Dr. Byrne noted that the guidelines have a new algorithm as to which of these antithrombotics to give, depending on the clinical presentation of the patient.

On the use of upfront P2Y12 inhibitors, Dr. Byrne said the new guidelines only give a weak recommendation for this.

“Giving a P2Y12 inhibitor up front does not have a strong evidence base, and it’s not unreasonable to wait, do the angiogram, see where you are, and then start the P2Y12 inhibitor. This is something that’s not widely done in clinical practice,” he commented.

“The last 2020 guideline gave a Class III recommendation for upfront P2Y12 inhibitor therapy for ACS patients who do not have STEMI. We’ve generally maintained that with the introduction of the exception that if you are in a health care system where there is a long wait to get to the cath lab – 5 ,6 or 7 days – then it’s reasonable to make an exception and give a P2Y12 inhibitor, but otherwise we’ve sustained the Class III recommendation,” he noted.

Also, for patients who have STEMI, there is a new Class IIb recommendation that upfront P2Y12 inhibitors may be considered.

“This is also rather a weak recommendation. There isn’t a strong rationale to give a P2Y12 inhibitor it in ST elevation either. It’s also reasonable to wait,” he added.
 

Don’t rush cardiac arrest patients to the cath lab

Another update in the guidelines involves the management of patients with cardiac arrest who have been resuscitated. Dr. Byrne explained that these patients would all receive an immediate ECG, and if it is found that they have ST elevation, they would be sent immediately to the cath lab. But a series of randomized trials has suggested that for patients who don’t have ST elevation, it is not necessary to rush these patients to the cath lab.

“We’ve given a Class III recommendation for this, saying it may be better to stabilize the patients first in the ICU. This is in recognition that a large proportion of these patients turn out not to have an MI. They have had a cardiac arrest for another reason,” Dr. Byrne noted. “Moving them to the cath lab when they are still unstable could be harming these patients rather than helping them.”
 

Revascularization for multivessel disease

Dr. Byrne notes that revascularization remains a critical element in the care for patients with STEMI, and there is a new recommendation in this area for patients with multivessel disease.

“Up to half of patients presenting with STEMI have multivessel disease, and we now have five randomized trials to say that these patients should have complete revascularization rather than just the culprit vessel. There is a new Class I recommendation for this,” he said.

However, the optimal timing of revascularization (immediate vs. staged) has still not been investigated in adequately sized randomized trials, and no recommendation has been made on this, the task force notes.

Dr. Byrne commented: “If you want to do everything in one go, that’s fine, but it’s also okay to do the culprit lesion first and then the other vessels at a later date within 45 days. This might depend on individual circumstances. For example, if there are complex lesions or the vessels are heavily calcified, then it may be best to get the culprit lesion fixed first and let the patient recover, then bring them back in for the rest.”

He pointed out that the results of the MULTISTARS trial, which were not available when the task force was formulating the guidelines, were reported at the ESC Congress and confirmed their recommendation.
 

DAPT after PCI

On the duration of dual antiplatelet therapy (DAPT) after PCI, the new guidelines have largely retained prior recommendations for a default strategy of 12 months for the combination of aspirin and a P2Y12 inhibitor.

“This was the subject of some discussion, as there have been several trials now looking at shorter durations of DAPT and deescalating after a few months to just one of these treatments. And while there is a rationale to do this, we think it’s best to be kept as an alternative strategy rather than the default strategy,” Dr. Byrne said.

He explained that the trials of DAPT deescalation tended to enroll lower-risk patients, which reduced the generalizability of the results.

Most of the trials only randomly assigned patients to shorter durations of DAPT when they were event-free for some period, she said.

“This is a dynamic decision-making process and reflects the real world to some extent. We think it is best to recommend the standard aspirin and a P2Y12 inhibitor for the 12-month duration, but at 3 months, if the patient is doing well but you may be worried about bleeding risk, then you could decide to deescalate to single antiplatelet therapy,” she noted. “So, there is Class IIa recommendation that this can be considered, but it is not recommended as the default position.”
 

Polypill for secondary prevention

Another innovation in the new guidelines is a new Class IIa recommendation for prescription of a polypill containing secondary prevention medications for patients on discharge from hospital.

This recommendation follows a trial that showed that the use of such a polypill helps patients be more adherent to the therapies prescribed.

Byrne explains that such a polypill may contain aspirin, an ACE inhibitor, and a statin. Several varieties are available in most European countries, but they are not widely used.

On secondary prevention, he stressed, “Prevention of the next heart attack starts before the patient leaves hospital. It is important to make sure the patient has the right medication on board, including a high-dose, high-intensity statin, and has been referred to a cardiac rehabilitation program. These are largely maintained recommendations from previous guidelines, but they are very important.”

A version of this article appeared on Medscape.com.

AMSTERDAM – New European Society of Cardiology guidelines on the management of acute coronary syndromes (ACS) have for the first time combined ST-elevation MI (STEMI), non–ST-elevation MI (NSTEMI), and unstable angina into the same set of recommendations.

The new guideline was released at the annual congress of the European Society of Cardiology, and was published online in the European Heart Journal.

“We found that it was realized by the cardiology community that patients with STEMI, NSTEMI, or unstable angina represent a spectrum,” the chair of the guideline task force, Robert Byrne, MD, chair of cardiovascular research at the RCSI University of Medicine and Health Sciences, Dublin, explained to this news organization. “After the initial triage and management decisions, then most of the rest of the care follows a common pathway so it would make sense to consider everything in one guideline.”

Dr. Byrne noted that for all patients with a suspected ACS, the guideline recommendation is to administer an ECG within 10 minutes of presentation. The time is critical particularly for those with an occluded epicardial vessel. If there are features on the ECG that suggest an acutely occluded epicardial vessel, then the patient needs immediate angiography or primary angioplasty.

“The 10-minute guidance has been maintained from previous guidelines, but the nuance in the new guideline is that typically when we think of an occluded epicardial vessel we think of ST-elevation on the ECG,” Byrne said. “While this captures most occluded epicardial vessels, it doesn’t capture all of them. So, we have provided some guidance on alternative ECG patterns which might be indicative of an acute occlusion of the epicardial vessel and should be dealt with in the same way as an ST-elevation MI. This is a new concept.”

This situation could arise when a patient has an occluded circumflex artery and the regular ECG may not show ST elevation but the patient has ongoing pain, he noted. “There are additional ECG leads that can be looked at that might identify patients who need an immediate invasive strategy.

“This is one more reason why all ACS patients should be considered as part of one spectrum, and while the ECG gives us important information, it is not the only thing to consider. Dividing the conditions up as to whether a patient has ST elevation or not does not always make pathophysiological sense,” he added.

Dr. Byrne noted that the new guidelines have tried to reach a wider stakeholder group that includes emergency doctors, internal medicine physicians, general practitioners, and surgeons, as well as cardiologists. The document includes animations in an effort to increase the reach of the guidelines to noncardiology stakeholders, and for the first time, the task force included a patient representative.

“As part of this strategy, we have put more structure in to emphasize the importance that at first contact, we already want to be thinking of antithrombotic therapy and whether the patient needs urgent transfer to the nearest cath lab. We also want to be thinking straight away about preventing the next heart attack by implementing strong secondary prevention measures,” he commented.

Dr. Byrne highlighted a few changes to individual recommendations in the new guidelines.
 

Invasive management in NSTE-ACS

He pointed out that a small change has been made in the advice on invasive management for patients with non–ST-elevation ACS.

Dr. Byrne explained that patients with ST elevation should be sent immediately to a cath lab for PCI. If this is not possible within 120 minutes, then the patient should receive thrombolysis. This recommendation is the same as in previous guidelines.

He added, however, that there is some novelty in recommendations for patients who don’t have ST elevation but do have a positive troponin. For this group, previous guidelines gave a Class I recommendation that all such patients undergo an angiogram within the first 24 hours. However, an additional meta-analysis that was published in 2022 showed that the evidence for triaging all patients to the cath lab within 24 hours is somewhat limited, Dr. Byrne noted.

“At the end of the day, the task force felt that a Class I recommendation to get all patients to the cath lab within 24 hours was too strong and couldn’t be sustained, so it has been downgraded to a Class IIa recommendation, which we thought was more appropriate,” he said.

“So, while all patients should still have an angiogram during the hospital admission, if they are high-risk ACS, the imperative to get everyone to the cath lab within 24 hours – which many of our colleagues were finding difficult to achieve – does not seem to be backed up by the evidence,” he added.
 

Antithrombotic therapy

Addressing administration of antithrombotics, the guidelines emphasize that at the time of initial diagnosis, all patients should receive antithrombotic therapy, usually aspirin and a parenteral antithrombotic, such as heparin, enoxaparin, bivalirudin, or fondaparinux. Dr. Byrne noted that the guidelines have a new algorithm as to which of these antithrombotics to give, depending on the clinical presentation of the patient.

On the use of upfront P2Y12 inhibitors, Dr. Byrne said the new guidelines only give a weak recommendation for this.

“Giving a P2Y12 inhibitor up front does not have a strong evidence base, and it’s not unreasonable to wait, do the angiogram, see where you are, and then start the P2Y12 inhibitor. This is something that’s not widely done in clinical practice,” he commented.

“The last 2020 guideline gave a Class III recommendation for upfront P2Y12 inhibitor therapy for ACS patients who do not have STEMI. We’ve generally maintained that with the introduction of the exception that if you are in a health care system where there is a long wait to get to the cath lab – 5 ,6 or 7 days – then it’s reasonable to make an exception and give a P2Y12 inhibitor, but otherwise we’ve sustained the Class III recommendation,” he noted.

Also, for patients who have STEMI, there is a new Class IIb recommendation that upfront P2Y12 inhibitors may be considered.

“This is also rather a weak recommendation. There isn’t a strong rationale to give a P2Y12 inhibitor it in ST elevation either. It’s also reasonable to wait,” he added.
 

Don’t rush cardiac arrest patients to the cath lab

Another update in the guidelines involves the management of patients with cardiac arrest who have been resuscitated. Dr. Byrne explained that these patients would all receive an immediate ECG, and if it is found that they have ST elevation, they would be sent immediately to the cath lab. But a series of randomized trials has suggested that for patients who don’t have ST elevation, it is not necessary to rush these patients to the cath lab.

“We’ve given a Class III recommendation for this, saying it may be better to stabilize the patients first in the ICU. This is in recognition that a large proportion of these patients turn out not to have an MI. They have had a cardiac arrest for another reason,” Dr. Byrne noted. “Moving them to the cath lab when they are still unstable could be harming these patients rather than helping them.”
 

Revascularization for multivessel disease

Dr. Byrne notes that revascularization remains a critical element in the care for patients with STEMI, and there is a new recommendation in this area for patients with multivessel disease.

“Up to half of patients presenting with STEMI have multivessel disease, and we now have five randomized trials to say that these patients should have complete revascularization rather than just the culprit vessel. There is a new Class I recommendation for this,” he said.

However, the optimal timing of revascularization (immediate vs. staged) has still not been investigated in adequately sized randomized trials, and no recommendation has been made on this, the task force notes.

Dr. Byrne commented: “If you want to do everything in one go, that’s fine, but it’s also okay to do the culprit lesion first and then the other vessels at a later date within 45 days. This might depend on individual circumstances. For example, if there are complex lesions or the vessels are heavily calcified, then it may be best to get the culprit lesion fixed first and let the patient recover, then bring them back in for the rest.”

He pointed out that the results of the MULTISTARS trial, which were not available when the task force was formulating the guidelines, were reported at the ESC Congress and confirmed their recommendation.
 

DAPT after PCI

On the duration of dual antiplatelet therapy (DAPT) after PCI, the new guidelines have largely retained prior recommendations for a default strategy of 12 months for the combination of aspirin and a P2Y12 inhibitor.

“This was the subject of some discussion, as there have been several trials now looking at shorter durations of DAPT and deescalating after a few months to just one of these treatments. And while there is a rationale to do this, we think it’s best to be kept as an alternative strategy rather than the default strategy,” Dr. Byrne said.

He explained that the trials of DAPT deescalation tended to enroll lower-risk patients, which reduced the generalizability of the results.

Most of the trials only randomly assigned patients to shorter durations of DAPT when they were event-free for some period, she said.

“This is a dynamic decision-making process and reflects the real world to some extent. We think it is best to recommend the standard aspirin and a P2Y12 inhibitor for the 12-month duration, but at 3 months, if the patient is doing well but you may be worried about bleeding risk, then you could decide to deescalate to single antiplatelet therapy,” she noted. “So, there is Class IIa recommendation that this can be considered, but it is not recommended as the default position.”
 

Polypill for secondary prevention

Another innovation in the new guidelines is a new Class IIa recommendation for prescription of a polypill containing secondary prevention medications for patients on discharge from hospital.

This recommendation follows a trial that showed that the use of such a polypill helps patients be more adherent to the therapies prescribed.

Byrne explains that such a polypill may contain aspirin, an ACE inhibitor, and a statin. Several varieties are available in most European countries, but they are not widely used.

On secondary prevention, he stressed, “Prevention of the next heart attack starts before the patient leaves hospital. It is important to make sure the patient has the right medication on board, including a high-dose, high-intensity statin, and has been referred to a cardiac rehabilitation program. These are largely maintained recommendations from previous guidelines, but they are very important.”

A version of this article appeared on Medscape.com.

AMSTERDAM – New European Society of Cardiology guidelines on the management of acute coronary syndromes (ACS) have for the first time combined ST-elevation MI (STEMI), non–ST-elevation MI (NSTEMI), and unstable angina into the same set of recommendations.

The new guideline was released at the annual congress of the European Society of Cardiology, and was published online in the European Heart Journal.

“We found that it was realized by the cardiology community that patients with STEMI, NSTEMI, or unstable angina represent a spectrum,” the chair of the guideline task force, Robert Byrne, MD, chair of cardiovascular research at the RCSI University of Medicine and Health Sciences, Dublin, explained to this news organization. “After the initial triage and management decisions, then most of the rest of the care follows a common pathway so it would make sense to consider everything in one guideline.”

Dr. Byrne noted that for all patients with a suspected ACS, the guideline recommendation is to administer an ECG within 10 minutes of presentation. The time is critical particularly for those with an occluded epicardial vessel. If there are features on the ECG that suggest an acutely occluded epicardial vessel, then the patient needs immediate angiography or primary angioplasty.

“The 10-minute guidance has been maintained from previous guidelines, but the nuance in the new guideline is that typically when we think of an occluded epicardial vessel we think of ST-elevation on the ECG,” Byrne said. “While this captures most occluded epicardial vessels, it doesn’t capture all of them. So, we have provided some guidance on alternative ECG patterns which might be indicative of an acute occlusion of the epicardial vessel and should be dealt with in the same way as an ST-elevation MI. This is a new concept.”

This situation could arise when a patient has an occluded circumflex artery and the regular ECG may not show ST elevation but the patient has ongoing pain, he noted. “There are additional ECG leads that can be looked at that might identify patients who need an immediate invasive strategy.

“This is one more reason why all ACS patients should be considered as part of one spectrum, and while the ECG gives us important information, it is not the only thing to consider. Dividing the conditions up as to whether a patient has ST elevation or not does not always make pathophysiological sense,” he added.

Dr. Byrne noted that the new guidelines have tried to reach a wider stakeholder group that includes emergency doctors, internal medicine physicians, general practitioners, and surgeons, as well as cardiologists. The document includes animations in an effort to increase the reach of the guidelines to noncardiology stakeholders, and for the first time, the task force included a patient representative.

“As part of this strategy, we have put more structure in to emphasize the importance that at first contact, we already want to be thinking of antithrombotic therapy and whether the patient needs urgent transfer to the nearest cath lab. We also want to be thinking straight away about preventing the next heart attack by implementing strong secondary prevention measures,” he commented.

Dr. Byrne highlighted a few changes to individual recommendations in the new guidelines.
 

Invasive management in NSTE-ACS

He pointed out that a small change has been made in the advice on invasive management for patients with non–ST-elevation ACS.

Dr. Byrne explained that patients with ST elevation should be sent immediately to a cath lab for PCI. If this is not possible within 120 minutes, then the patient should receive thrombolysis. This recommendation is the same as in previous guidelines.

He added, however, that there is some novelty in recommendations for patients who don’t have ST elevation but do have a positive troponin. For this group, previous guidelines gave a Class I recommendation that all such patients undergo an angiogram within the first 24 hours. However, an additional meta-analysis that was published in 2022 showed that the evidence for triaging all patients to the cath lab within 24 hours is somewhat limited, Dr. Byrne noted.

“At the end of the day, the task force felt that a Class I recommendation to get all patients to the cath lab within 24 hours was too strong and couldn’t be sustained, so it has been downgraded to a Class IIa recommendation, which we thought was more appropriate,” he said.

“So, while all patients should still have an angiogram during the hospital admission, if they are high-risk ACS, the imperative to get everyone to the cath lab within 24 hours – which many of our colleagues were finding difficult to achieve – does not seem to be backed up by the evidence,” he added.
 

Antithrombotic therapy

Addressing administration of antithrombotics, the guidelines emphasize that at the time of initial diagnosis, all patients should receive antithrombotic therapy, usually aspirin and a parenteral antithrombotic, such as heparin, enoxaparin, bivalirudin, or fondaparinux. Dr. Byrne noted that the guidelines have a new algorithm as to which of these antithrombotics to give, depending on the clinical presentation of the patient.

On the use of upfront P2Y12 inhibitors, Dr. Byrne said the new guidelines only give a weak recommendation for this.

“Giving a P2Y12 inhibitor up front does not have a strong evidence base, and it’s not unreasonable to wait, do the angiogram, see where you are, and then start the P2Y12 inhibitor. This is something that’s not widely done in clinical practice,” he commented.

“The last 2020 guideline gave a Class III recommendation for upfront P2Y12 inhibitor therapy for ACS patients who do not have STEMI. We’ve generally maintained that with the introduction of the exception that if you are in a health care system where there is a long wait to get to the cath lab – 5 ,6 or 7 days – then it’s reasonable to make an exception and give a P2Y12 inhibitor, but otherwise we’ve sustained the Class III recommendation,” he noted.

Also, for patients who have STEMI, there is a new Class IIb recommendation that upfront P2Y12 inhibitors may be considered.

“This is also rather a weak recommendation. There isn’t a strong rationale to give a P2Y12 inhibitor it in ST elevation either. It’s also reasonable to wait,” he added.
 

Don’t rush cardiac arrest patients to the cath lab

Another update in the guidelines involves the management of patients with cardiac arrest who have been resuscitated. Dr. Byrne explained that these patients would all receive an immediate ECG, and if it is found that they have ST elevation, they would be sent immediately to the cath lab. But a series of randomized trials has suggested that for patients who don’t have ST elevation, it is not necessary to rush these patients to the cath lab.

“We’ve given a Class III recommendation for this, saying it may be better to stabilize the patients first in the ICU. This is in recognition that a large proportion of these patients turn out not to have an MI. They have had a cardiac arrest for another reason,” Dr. Byrne noted. “Moving them to the cath lab when they are still unstable could be harming these patients rather than helping them.”
 

Revascularization for multivessel disease

Dr. Byrne notes that revascularization remains a critical element in the care for patients with STEMI, and there is a new recommendation in this area for patients with multivessel disease.

“Up to half of patients presenting with STEMI have multivessel disease, and we now have five randomized trials to say that these patients should have complete revascularization rather than just the culprit vessel. There is a new Class I recommendation for this,” he said.

However, the optimal timing of revascularization (immediate vs. staged) has still not been investigated in adequately sized randomized trials, and no recommendation has been made on this, the task force notes.

Dr. Byrne commented: “If you want to do everything in one go, that’s fine, but it’s also okay to do the culprit lesion first and then the other vessels at a later date within 45 days. This might depend on individual circumstances. For example, if there are complex lesions or the vessels are heavily calcified, then it may be best to get the culprit lesion fixed first and let the patient recover, then bring them back in for the rest.”

He pointed out that the results of the MULTISTARS trial, which were not available when the task force was formulating the guidelines, were reported at the ESC Congress and confirmed their recommendation.
 

DAPT after PCI

On the duration of dual antiplatelet therapy (DAPT) after PCI, the new guidelines have largely retained prior recommendations for a default strategy of 12 months for the combination of aspirin and a P2Y12 inhibitor.

“This was the subject of some discussion, as there have been several trials now looking at shorter durations of DAPT and deescalating after a few months to just one of these treatments. And while there is a rationale to do this, we think it’s best to be kept as an alternative strategy rather than the default strategy,” Dr. Byrne said.

He explained that the trials of DAPT deescalation tended to enroll lower-risk patients, which reduced the generalizability of the results.

Most of the trials only randomly assigned patients to shorter durations of DAPT when they were event-free for some period, she said.

“This is a dynamic decision-making process and reflects the real world to some extent. We think it is best to recommend the standard aspirin and a P2Y12 inhibitor for the 12-month duration, but at 3 months, if the patient is doing well but you may be worried about bleeding risk, then you could decide to deescalate to single antiplatelet therapy,” she noted. “So, there is Class IIa recommendation that this can be considered, but it is not recommended as the default position.”
 

Polypill for secondary prevention

Another innovation in the new guidelines is a new Class IIa recommendation for prescription of a polypill containing secondary prevention medications for patients on discharge from hospital.

This recommendation follows a trial that showed that the use of such a polypill helps patients be more adherent to the therapies prescribed.

Byrne explains that such a polypill may contain aspirin, an ACE inhibitor, and a statin. Several varieties are available in most European countries, but they are not widely used.

On secondary prevention, he stressed, “Prevention of the next heart attack starts before the patient leaves hospital. It is important to make sure the patient has the right medication on board, including a high-dose, high-intensity statin, and has been referred to a cardiac rehabilitation program. These are largely maintained recommendations from previous guidelines, but they are very important.”

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Michelle L. O’Donoghue, MD, MPH: Hi. This is Dr. Michelle O’Donoghue reporting for Medscape. Joining me today is Dr. Sahil Parikh, who’s a cardiologist and an interventionalist at Columbia University. He’s an associate professor of medicine.

We’ll be discussing two interesting trials that were presented at the ESC Congress here in Amsterdam. They do have the potential to be very practice-changing, so I think it’s worth talking about.
 

The FIRE trial

The first trial we’ll be talking about is the FIRE trial. Perhaps setting the stage, Sahil, I’d love to get your thoughts. We’ve had data in this space to suggest that, for patients with STEMI [ST-segment elevation myocardial infarction], a strategy of complete revascularization – and not only treating the culprit lesion but also treating additional lesions – may be of benefit. Where does that lead us in terms of what we didn’t know?

Sahil A. Parikh, MD: I think that the practice has moved, at least in the United States, over the past two decades, from staging percutaneous coronary interventions over 30 days from index to intervention to now trying to do patients in the same hospitalization whenever possible to achieve complete revascularization.

I think these data support not only that complete revascularization is compulsory now in these patients, but also doing it sooner rather than later, and that the benefit applies to most of the patients that we see in clinical practice. In the earlier data, the patients were relatively youthful – under Medicare age, less than 65 – and now this dataset has a median age of 80. This is more like the real-world clinical practice that most of us are encountering, and it extends the benefit, perhaps, greater than we’ve ever seen before.

O’Donoghue: The FIRE trial is interesting. As you say, it enrolled patients who were over the age of 75, where I think that some proceduralists are probably a little bit hesitant to think about complete revascularization due to concerns about any additional contrast load on their kidneys and other types of comorbidities. Of course, for any trial, there’s going to be some patient selection.

I think it’s very reassuring that even in this older patient group, a strategy of treating all the lesions – and not only in STEMI but also in non-STEMI patients – reduced cardiovascular events and mortality. I was really quite impressed by the mortality benefit.

Parikh: The mortality curve is almost surprising to me. On the other hand, it emboldens us now that we can treat these patients more completely and earlier in their clinical presentation. Certainly, we worried about contrast exposure and the duration of procedures in this older population, but it seems that the benefit that’s derived, which we saw in younger patients where we had a natural inclination to be more aggressive, extends also to this older population.
 

MULTISTARS AMI

O’Donoghue: To the question of timing, as you mentioned, prior to this, we had a study presented earlier this year, the BIOVASC trial, which also was suggestive that maybe earlier complete revascularization was better. But it wasn’t a significant difference, at least for the primary outcome. Now we have MULTISTARS AMI, which is very supportive of what we saw earlier this year, suggesting that complete revascularization really at the time that you’re treating the culprit may be the way to go.

Parikh: All of us, as interventionalists, are circumspect about what we might do in the middle of the night versus what we would do in the light of day. Certainly it seems clear, particularly if it’s straightforward anatomy, that taking care of it in the index procedure is not only saving contrast and fluoroscopy time, but it’s also providing a clinical benefit to the patients. That’s something that will also impact how clinicians interpret these data. Previously, there was always a question about whether we should just do it in the same hospitalization or do it at the same time. I think now, increasingly, we’re emboldened to do more in the index procedure.

O’Donoghue: When you’re thinking about nonculprit lesions and which ones to treat, do you always make that determination based on physiologic guidance of some kind? Are you using instantaneous wave-free ratio? What’s your practice?

Parikh: In the acute setting, imaging is superior for at least the assessment of which is a culprit. If you see a ruptured atherothrombotic situation on optical coherence tomography, for example, that’s fairly convincing and definitive. In the absence of that physiology, we are taught to avoid in the infarct-related artery because of potential spuriously false-negative findings.

In this situation, certainly, an imaging subgroup probably would be helpful because some of the benefit is almost certainly derived from identifying the infarct-related artery by accident – in other words, doing what you thought was the nonculprit artery, which is, in fact, the culprit. I think that probably is part of this. As somebody who uses imaging in the overwhelming number of my cases, I think that imaging would be an important surrogate to this.
 

Index procedure versus staged

O’Donoghue: For the operator who is coming in to do their STEMI case at 2:00 in the morning, would these data now push you toward doing complete revascularization at that time of night, or do you think that there is wiggle room in terms of interpreting these results regarding timing, where as long as you were doing it before hospital discharge and not, let’s say, 30 days out, that you may be able to derive the same benefit? What are some of the pros and cons?

Parikh: There’s definitely a fatigue factor in the middle of the night if it’s a particularly arduous intervention for the index infarct-related artery. I think there’s a human element where it may make sense just to stop and then bring the patient back in the same hospitalization. It’s clear, though, that doing complete revascularization is better and doing it sooner is better. How soon one actually does it is a judgment call, as ever.

In our practice, we’ve been pushing ourselves to get most of the patients done in their index hospitalization. If you have a left-sided culprit, the left anterior descending artery, for example, and there’s a high-grade stenosis in the circumflex, it may make sense to take care of that in the same index procedure. If, on the other hand, it’s in the right coronary artery where you have to put a new guide in and spend more time, that may be a patient whom you stage. I think those nuances will come up as interventionalists look at the subgroup analysis data more carefully.

O’Donoghue: Those are great points, and I think they also underscore that we always need to think about what type of patient was enrolled in these studies. Certainly, if you have somebody with renal dysfunction, there might be more concern about giving them a large contrast load all in one sitting, albeit hard to know whether they do or not. But spacing that out by just a couple of days would really have a big impact.

Parikh: Very often in the STEMI patient, you don’t have the benefit of knowing the creatinine. The patient will come in immediately, if not directly from the ambulance to the cath lab, and there are no laboratories at all to work with. If the patient has never been seen in the system before, you won’t know. Again, in those situations, one may have pause, particularly if it’s an older patient. I think what’s reassuring, though, is that the data are supportive of being more aggressive earlier, and certainly this is the dataset that we were looking for.

O’Donoghue: To summarize, the two key takeaways are that, one, we now have more data to support a complete revascularization strategy and even extending that now to non-STEMI patients. Two, sooner appears to be better, so ideally, all done at the time of the index procedure. I think this is very interesting science and we’ll see how it changes practice.

Thanks for joining me today. Signing off for Medscape, this is Dr. Michelle O’Donoghue.

Michelle O’Donoghue is a cardiologist at Brigham and Women’s Hospital and senior investigator with the TIMI Study Group.

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

Michelle L. O’Donoghue, MD, MPH: Hi. This is Dr. Michelle O’Donoghue reporting for Medscape. Joining me today is Dr. Sahil Parikh, who’s a cardiologist and an interventionalist at Columbia University. He’s an associate professor of medicine.

We’ll be discussing two interesting trials that were presented at the ESC Congress here in Amsterdam. They do have the potential to be very practice-changing, so I think it’s worth talking about.
 

The FIRE trial

The first trial we’ll be talking about is the FIRE trial. Perhaps setting the stage, Sahil, I’d love to get your thoughts. We’ve had data in this space to suggest that, for patients with STEMI [ST-segment elevation myocardial infarction], a strategy of complete revascularization – and not only treating the culprit lesion but also treating additional lesions – may be of benefit. Where does that lead us in terms of what we didn’t know?

Sahil A. Parikh, MD: I think that the practice has moved, at least in the United States, over the past two decades, from staging percutaneous coronary interventions over 30 days from index to intervention to now trying to do patients in the same hospitalization whenever possible to achieve complete revascularization.

I think these data support not only that complete revascularization is compulsory now in these patients, but also doing it sooner rather than later, and that the benefit applies to most of the patients that we see in clinical practice. In the earlier data, the patients were relatively youthful – under Medicare age, less than 65 – and now this dataset has a median age of 80. This is more like the real-world clinical practice that most of us are encountering, and it extends the benefit, perhaps, greater than we’ve ever seen before.

O’Donoghue: The FIRE trial is interesting. As you say, it enrolled patients who were over the age of 75, where I think that some proceduralists are probably a little bit hesitant to think about complete revascularization due to concerns about any additional contrast load on their kidneys and other types of comorbidities. Of course, for any trial, there’s going to be some patient selection.

I think it’s very reassuring that even in this older patient group, a strategy of treating all the lesions – and not only in STEMI but also in non-STEMI patients – reduced cardiovascular events and mortality. I was really quite impressed by the mortality benefit.

Parikh: The mortality curve is almost surprising to me. On the other hand, it emboldens us now that we can treat these patients more completely and earlier in their clinical presentation. Certainly, we worried about contrast exposure and the duration of procedures in this older population, but it seems that the benefit that’s derived, which we saw in younger patients where we had a natural inclination to be more aggressive, extends also to this older population.
 

MULTISTARS AMI

O’Donoghue: To the question of timing, as you mentioned, prior to this, we had a study presented earlier this year, the BIOVASC trial, which also was suggestive that maybe earlier complete revascularization was better. But it wasn’t a significant difference, at least for the primary outcome. Now we have MULTISTARS AMI, which is very supportive of what we saw earlier this year, suggesting that complete revascularization really at the time that you’re treating the culprit may be the way to go.

Parikh: All of us, as interventionalists, are circumspect about what we might do in the middle of the night versus what we would do in the light of day. Certainly it seems clear, particularly if it’s straightforward anatomy, that taking care of it in the index procedure is not only saving contrast and fluoroscopy time, but it’s also providing a clinical benefit to the patients. That’s something that will also impact how clinicians interpret these data. Previously, there was always a question about whether we should just do it in the same hospitalization or do it at the same time. I think now, increasingly, we’re emboldened to do more in the index procedure.

O’Donoghue: When you’re thinking about nonculprit lesions and which ones to treat, do you always make that determination based on physiologic guidance of some kind? Are you using instantaneous wave-free ratio? What’s your practice?

Parikh: In the acute setting, imaging is superior for at least the assessment of which is a culprit. If you see a ruptured atherothrombotic situation on optical coherence tomography, for example, that’s fairly convincing and definitive. In the absence of that physiology, we are taught to avoid in the infarct-related artery because of potential spuriously false-negative findings.

In this situation, certainly, an imaging subgroup probably would be helpful because some of the benefit is almost certainly derived from identifying the infarct-related artery by accident – in other words, doing what you thought was the nonculprit artery, which is, in fact, the culprit. I think that probably is part of this. As somebody who uses imaging in the overwhelming number of my cases, I think that imaging would be an important surrogate to this.
 

Index procedure versus staged

O’Donoghue: For the operator who is coming in to do their STEMI case at 2:00 in the morning, would these data now push you toward doing complete revascularization at that time of night, or do you think that there is wiggle room in terms of interpreting these results regarding timing, where as long as you were doing it before hospital discharge and not, let’s say, 30 days out, that you may be able to derive the same benefit? What are some of the pros and cons?

Parikh: There’s definitely a fatigue factor in the middle of the night if it’s a particularly arduous intervention for the index infarct-related artery. I think there’s a human element where it may make sense just to stop and then bring the patient back in the same hospitalization. It’s clear, though, that doing complete revascularization is better and doing it sooner is better. How soon one actually does it is a judgment call, as ever.

In our practice, we’ve been pushing ourselves to get most of the patients done in their index hospitalization. If you have a left-sided culprit, the left anterior descending artery, for example, and there’s a high-grade stenosis in the circumflex, it may make sense to take care of that in the same index procedure. If, on the other hand, it’s in the right coronary artery where you have to put a new guide in and spend more time, that may be a patient whom you stage. I think those nuances will come up as interventionalists look at the subgroup analysis data more carefully.

O’Donoghue: Those are great points, and I think they also underscore that we always need to think about what type of patient was enrolled in these studies. Certainly, if you have somebody with renal dysfunction, there might be more concern about giving them a large contrast load all in one sitting, albeit hard to know whether they do or not. But spacing that out by just a couple of days would really have a big impact.

Parikh: Very often in the STEMI patient, you don’t have the benefit of knowing the creatinine. The patient will come in immediately, if not directly from the ambulance to the cath lab, and there are no laboratories at all to work with. If the patient has never been seen in the system before, you won’t know. Again, in those situations, one may have pause, particularly if it’s an older patient. I think what’s reassuring, though, is that the data are supportive of being more aggressive earlier, and certainly this is the dataset that we were looking for.

O’Donoghue: To summarize, the two key takeaways are that, one, we now have more data to support a complete revascularization strategy and even extending that now to non-STEMI patients. Two, sooner appears to be better, so ideally, all done at the time of the index procedure. I think this is very interesting science and we’ll see how it changes practice.

Thanks for joining me today. Signing off for Medscape, this is Dr. Michelle O’Donoghue.

Michelle O’Donoghue is a cardiologist at Brigham and Women’s Hospital and senior investigator with the TIMI Study Group.

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

Michelle L. O’Donoghue, MD, MPH: Hi. This is Dr. Michelle O’Donoghue reporting for Medscape. Joining me today is Dr. Sahil Parikh, who’s a cardiologist and an interventionalist at Columbia University. He’s an associate professor of medicine.

We’ll be discussing two interesting trials that were presented at the ESC Congress here in Amsterdam. They do have the potential to be very practice-changing, so I think it’s worth talking about.
 

The FIRE trial

The first trial we’ll be talking about is the FIRE trial. Perhaps setting the stage, Sahil, I’d love to get your thoughts. We’ve had data in this space to suggest that, for patients with STEMI [ST-segment elevation myocardial infarction], a strategy of complete revascularization – and not only treating the culprit lesion but also treating additional lesions – may be of benefit. Where does that lead us in terms of what we didn’t know?

Sahil A. Parikh, MD: I think that the practice has moved, at least in the United States, over the past two decades, from staging percutaneous coronary interventions over 30 days from index to intervention to now trying to do patients in the same hospitalization whenever possible to achieve complete revascularization.

I think these data support not only that complete revascularization is compulsory now in these patients, but also doing it sooner rather than later, and that the benefit applies to most of the patients that we see in clinical practice. In the earlier data, the patients were relatively youthful – under Medicare age, less than 65 – and now this dataset has a median age of 80. This is more like the real-world clinical practice that most of us are encountering, and it extends the benefit, perhaps, greater than we’ve ever seen before.

O’Donoghue: The FIRE trial is interesting. As you say, it enrolled patients who were over the age of 75, where I think that some proceduralists are probably a little bit hesitant to think about complete revascularization due to concerns about any additional contrast load on their kidneys and other types of comorbidities. Of course, for any trial, there’s going to be some patient selection.

I think it’s very reassuring that even in this older patient group, a strategy of treating all the lesions – and not only in STEMI but also in non-STEMI patients – reduced cardiovascular events and mortality. I was really quite impressed by the mortality benefit.

Parikh: The mortality curve is almost surprising to me. On the other hand, it emboldens us now that we can treat these patients more completely and earlier in their clinical presentation. Certainly, we worried about contrast exposure and the duration of procedures in this older population, but it seems that the benefit that’s derived, which we saw in younger patients where we had a natural inclination to be more aggressive, extends also to this older population.
 

MULTISTARS AMI

O’Donoghue: To the question of timing, as you mentioned, prior to this, we had a study presented earlier this year, the BIOVASC trial, which also was suggestive that maybe earlier complete revascularization was better. But it wasn’t a significant difference, at least for the primary outcome. Now we have MULTISTARS AMI, which is very supportive of what we saw earlier this year, suggesting that complete revascularization really at the time that you’re treating the culprit may be the way to go.

Parikh: All of us, as interventionalists, are circumspect about what we might do in the middle of the night versus what we would do in the light of day. Certainly it seems clear, particularly if it’s straightforward anatomy, that taking care of it in the index procedure is not only saving contrast and fluoroscopy time, but it’s also providing a clinical benefit to the patients. That’s something that will also impact how clinicians interpret these data. Previously, there was always a question about whether we should just do it in the same hospitalization or do it at the same time. I think now, increasingly, we’re emboldened to do more in the index procedure.

O’Donoghue: When you’re thinking about nonculprit lesions and which ones to treat, do you always make that determination based on physiologic guidance of some kind? Are you using instantaneous wave-free ratio? What’s your practice?

Parikh: In the acute setting, imaging is superior for at least the assessment of which is a culprit. If you see a ruptured atherothrombotic situation on optical coherence tomography, for example, that’s fairly convincing and definitive. In the absence of that physiology, we are taught to avoid in the infarct-related artery because of potential spuriously false-negative findings.

In this situation, certainly, an imaging subgroup probably would be helpful because some of the benefit is almost certainly derived from identifying the infarct-related artery by accident – in other words, doing what you thought was the nonculprit artery, which is, in fact, the culprit. I think that probably is part of this. As somebody who uses imaging in the overwhelming number of my cases, I think that imaging would be an important surrogate to this.
 

Index procedure versus staged

O’Donoghue: For the operator who is coming in to do their STEMI case at 2:00 in the morning, would these data now push you toward doing complete revascularization at that time of night, or do you think that there is wiggle room in terms of interpreting these results regarding timing, where as long as you were doing it before hospital discharge and not, let’s say, 30 days out, that you may be able to derive the same benefit? What are some of the pros and cons?

Parikh: There’s definitely a fatigue factor in the middle of the night if it’s a particularly arduous intervention for the index infarct-related artery. I think there’s a human element where it may make sense just to stop and then bring the patient back in the same hospitalization. It’s clear, though, that doing complete revascularization is better and doing it sooner is better. How soon one actually does it is a judgment call, as ever.

In our practice, we’ve been pushing ourselves to get most of the patients done in their index hospitalization. If you have a left-sided culprit, the left anterior descending artery, for example, and there’s a high-grade stenosis in the circumflex, it may make sense to take care of that in the same index procedure. If, on the other hand, it’s in the right coronary artery where you have to put a new guide in and spend more time, that may be a patient whom you stage. I think those nuances will come up as interventionalists look at the subgroup analysis data more carefully.

O’Donoghue: Those are great points, and I think they also underscore that we always need to think about what type of patient was enrolled in these studies. Certainly, if you have somebody with renal dysfunction, there might be more concern about giving them a large contrast load all in one sitting, albeit hard to know whether they do or not. But spacing that out by just a couple of days would really have a big impact.

Parikh: Very often in the STEMI patient, you don’t have the benefit of knowing the creatinine. The patient will come in immediately, if not directly from the ambulance to the cath lab, and there are no laboratories at all to work with. If the patient has never been seen in the system before, you won’t know. Again, in those situations, one may have pause, particularly if it’s an older patient. I think what’s reassuring, though, is that the data are supportive of being more aggressive earlier, and certainly this is the dataset that we were looking for.

O’Donoghue: To summarize, the two key takeaways are that, one, we now have more data to support a complete revascularization strategy and even extending that now to non-STEMI patients. Two, sooner appears to be better, so ideally, all done at the time of the index procedure. I think this is very interesting science and we’ll see how it changes practice.

Thanks for joining me today. Signing off for Medscape, this is Dr. Michelle O’Donoghue.

Michelle O’Donoghue is a cardiologist at Brigham and Women’s Hospital and senior investigator with the TIMI Study Group.

A version of this article first appeared on Medscape.com.

AMSTERDAM – For patients hospitalized for acute heart failure, initiating treatment with the SGLT2 inhibitor dapagliflozin (Farxiga, AstraZeneca) before hospital discharge was safe, it appeared to improve diuresis and natriuresis while reducing the administered diuretic dose, and it meant quicker initiation of guideline-directed therapy in a controlled study of 238 patients.

Treatment with dapagliflozin was begun for people with heart failure on their first day of hospitalization for an acute episode. Such treatment “can be safely started to optimize a key medication,” Zachary Cox, PharmD, said at the annual congress of the European Society of Cardiology. It improved fluid removal, as evidenced in the “totality of diuretic measures,” it resulted in reduced doses of IV diuretics, and it shortened length of stay in the hospital.

In current U.S. practice, about 80% of people hospitalized with heart failure do not initially receive treatment with a sodium-glucose cotransporter 2 (SGLT2) inhibitor during their hospital stay when they are not already taking an agent from the class, noted Dr. Cox, professor of pharmacy at Lipscomb University College of Pharmacy in Nashville, Tenn.

Physicians are often uncomfortable changing a patient’s medications on the first day of a hospitalization, he noted. “Our results should embolden physicians” to begin treatment with an SGLT2 inhibitor early during hospitalization and to then continue it chronically, Dr. Cox said in a press briefing.

“Despite the messaging [from guidelines], we still see hesitancy. We hope more evidence of safety will improve uptake.” The study’s “key message is to start guideline-directed medical therapy early,” prior to hospital discharge, Dr. Cox concluded.
 

“Some support” for SGLT2 inhibitors

The study results “provide some support for SGLT2 inhibitors facilitating decongestion and hospital discharge without observed safety issues,” said Stephen D. Wiviott, MD, designated discussant for the report and a cardiologist and professor at Harvard Medical School in Boston.

While initiation of an SGLT2 inhibitor during an acute heart failure hospitalization received endorsement as a top management priority in both the 2023 heart failure guidelines of the European Society of Cardiology and in 2022 U.S. guidelines, evidence of the safety and efficacy of this approach has been scanty, Dr. Wiviott noted.

Two prior studies addressed the issue. The SOLOIST-WHF trial tested the combined SGLT1 and SGLT2 inhibitor sotagliflozin (Inpefa, Lexicon) for patients recently hospitalized for heart failure, but only 142 of the 596 participants who were randomly assigned to receive sotagliflozin began receiving it at least a day before hospital discharge; for the remaining 454, treatment with sotagliflozin began on their discharge day, noted Dr. Wiviott.

In the EMPULSE trial, 530 people hospitalized for acute heart failure were randomly assigned to initially receive empagliflozin (Jardiance, Boehringer Ingelheim and Lilly) or placebo during hospitalization. The primary endpoint was largely driven by an improvement in the patient-reported outcome, as assessed on the basis of the Kansas City Cardiomyopathy Questionnaire Total Symptom Score, Dr. Wiviott added.

The DICTATE-AHF study included 238 adults who were within 24 hours of first presenting to any of six participating U.S. hospitals with hypervolemic acute heart failure. All patients underwent a standard treatment protocol with IV loop diuretics, and half received additional, open-label treatment with a daily 10-mg dose of dapagliflozin.

The average age of the patients was 65 years, 71% had type 2 diabetes (the study excluded people with type 1 diabetes), and about half had a left ventricular ejection fraction of 40% or less.
 

Similar weight loss with lower diuretics dose

The study’s primary outcome was a measure of diuretic efficiency, calculated as a person’s cumulative weight change divided by the cumulative dose of loop diuretics.

Both treatment arms experienced nearly identical weight loss, but for the people who received dapagliflozin, this occurred with a lower cumulative dose of diuretics. The diuretic efficiency with dapagliflozin produced comparable weight loss with a 35% lower amount of loop diuretic dose, a difference that fell just short of significance (P = .06).

However, treatment with dapagliflozin also significantly boosted 24-hour natriuresis and 24-hour diuresis, and it significantly shortened the time to stopping treatment with IV diuretics and to hospital discharge, Dr. Cox reported. Dapagliflozin initiation and ongoing treatment was also safe and well tolerated compared with usual care.

The fact that the primary endpoint fell short of significance was “largely related” to the study’s relatively small size, Dr. Wiviott suggested. He noted that the DAPA ACT HF-TIMI 68 study, which is a much larger and potentially more definitive study of the safety and efficacy of dapagliflozin in comparison with usual care for patients with acute heart failure, is in progress. The study includes about 2,400 patients.

The primary outcome is the combined rate of cardiovascular death or worsening heart failure during the 2 months following randomization. Results are expected in 2024.

DICTATE-AHF was sponsored by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. Cox has received research funding from AstraZeneca and has been a consultant to Roche and Translational Catalyst. Dr. Wiviott has received research funding from AstraZeneca and from Merck and has been a consultant to Icon Clinical and Novo Nordisk.
 

A version of this article appeared on Medscape.com.

AMSTERDAM – For patients hospitalized for acute heart failure, initiating treatment with the SGLT2 inhibitor dapagliflozin (Farxiga, AstraZeneca) before hospital discharge was safe, it appeared to improve diuresis and natriuresis while reducing the administered diuretic dose, and it meant quicker initiation of guideline-directed therapy in a controlled study of 238 patients.

Treatment with dapagliflozin was begun for people with heart failure on their first day of hospitalization for an acute episode. Such treatment “can be safely started to optimize a key medication,” Zachary Cox, PharmD, said at the annual congress of the European Society of Cardiology. It improved fluid removal, as evidenced in the “totality of diuretic measures,” it resulted in reduced doses of IV diuretics, and it shortened length of stay in the hospital.

In current U.S. practice, about 80% of people hospitalized with heart failure do not initially receive treatment with a sodium-glucose cotransporter 2 (SGLT2) inhibitor during their hospital stay when they are not already taking an agent from the class, noted Dr. Cox, professor of pharmacy at Lipscomb University College of Pharmacy in Nashville, Tenn.

Physicians are often uncomfortable changing a patient’s medications on the first day of a hospitalization, he noted. “Our results should embolden physicians” to begin treatment with an SGLT2 inhibitor early during hospitalization and to then continue it chronically, Dr. Cox said in a press briefing.

“Despite the messaging [from guidelines], we still see hesitancy. We hope more evidence of safety will improve uptake.” The study’s “key message is to start guideline-directed medical therapy early,” prior to hospital discharge, Dr. Cox concluded.
 

“Some support” for SGLT2 inhibitors

The study results “provide some support for SGLT2 inhibitors facilitating decongestion and hospital discharge without observed safety issues,” said Stephen D. Wiviott, MD, designated discussant for the report and a cardiologist and professor at Harvard Medical School in Boston.

While initiation of an SGLT2 inhibitor during an acute heart failure hospitalization received endorsement as a top management priority in both the 2023 heart failure guidelines of the European Society of Cardiology and in 2022 U.S. guidelines, evidence of the safety and efficacy of this approach has been scanty, Dr. Wiviott noted.

Two prior studies addressed the issue. The SOLOIST-WHF trial tested the combined SGLT1 and SGLT2 inhibitor sotagliflozin (Inpefa, Lexicon) for patients recently hospitalized for heart failure, but only 142 of the 596 participants who were randomly assigned to receive sotagliflozin began receiving it at least a day before hospital discharge; for the remaining 454, treatment with sotagliflozin began on their discharge day, noted Dr. Wiviott.

In the EMPULSE trial, 530 people hospitalized for acute heart failure were randomly assigned to initially receive empagliflozin (Jardiance, Boehringer Ingelheim and Lilly) or placebo during hospitalization. The primary endpoint was largely driven by an improvement in the patient-reported outcome, as assessed on the basis of the Kansas City Cardiomyopathy Questionnaire Total Symptom Score, Dr. Wiviott added.

The DICTATE-AHF study included 238 adults who were within 24 hours of first presenting to any of six participating U.S. hospitals with hypervolemic acute heart failure. All patients underwent a standard treatment protocol with IV loop diuretics, and half received additional, open-label treatment with a daily 10-mg dose of dapagliflozin.

The average age of the patients was 65 years, 71% had type 2 diabetes (the study excluded people with type 1 diabetes), and about half had a left ventricular ejection fraction of 40% or less.
 

Similar weight loss with lower diuretics dose

The study’s primary outcome was a measure of diuretic efficiency, calculated as a person’s cumulative weight change divided by the cumulative dose of loop diuretics.

Both treatment arms experienced nearly identical weight loss, but for the people who received dapagliflozin, this occurred with a lower cumulative dose of diuretics. The diuretic efficiency with dapagliflozin produced comparable weight loss with a 35% lower amount of loop diuretic dose, a difference that fell just short of significance (P = .06).

However, treatment with dapagliflozin also significantly boosted 24-hour natriuresis and 24-hour diuresis, and it significantly shortened the time to stopping treatment with IV diuretics and to hospital discharge, Dr. Cox reported. Dapagliflozin initiation and ongoing treatment was also safe and well tolerated compared with usual care.

The fact that the primary endpoint fell short of significance was “largely related” to the study’s relatively small size, Dr. Wiviott suggested. He noted that the DAPA ACT HF-TIMI 68 study, which is a much larger and potentially more definitive study of the safety and efficacy of dapagliflozin in comparison with usual care for patients with acute heart failure, is in progress. The study includes about 2,400 patients.

The primary outcome is the combined rate of cardiovascular death or worsening heart failure during the 2 months following randomization. Results are expected in 2024.

DICTATE-AHF was sponsored by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. Cox has received research funding from AstraZeneca and has been a consultant to Roche and Translational Catalyst. Dr. Wiviott has received research funding from AstraZeneca and from Merck and has been a consultant to Icon Clinical and Novo Nordisk.
 

A version of this article appeared on Medscape.com.

AMSTERDAM – For patients hospitalized for acute heart failure, initiating treatment with the SGLT2 inhibitor dapagliflozin (Farxiga, AstraZeneca) before hospital discharge was safe, it appeared to improve diuresis and natriuresis while reducing the administered diuretic dose, and it meant quicker initiation of guideline-directed therapy in a controlled study of 238 patients.

Treatment with dapagliflozin was begun for people with heart failure on their first day of hospitalization for an acute episode. Such treatment “can be safely started to optimize a key medication,” Zachary Cox, PharmD, said at the annual congress of the European Society of Cardiology. It improved fluid removal, as evidenced in the “totality of diuretic measures,” it resulted in reduced doses of IV diuretics, and it shortened length of stay in the hospital.

In current U.S. practice, about 80% of people hospitalized with heart failure do not initially receive treatment with a sodium-glucose cotransporter 2 (SGLT2) inhibitor during their hospital stay when they are not already taking an agent from the class, noted Dr. Cox, professor of pharmacy at Lipscomb University College of Pharmacy in Nashville, Tenn.

Physicians are often uncomfortable changing a patient’s medications on the first day of a hospitalization, he noted. “Our results should embolden physicians” to begin treatment with an SGLT2 inhibitor early during hospitalization and to then continue it chronically, Dr. Cox said in a press briefing.

“Despite the messaging [from guidelines], we still see hesitancy. We hope more evidence of safety will improve uptake.” The study’s “key message is to start guideline-directed medical therapy early,” prior to hospital discharge, Dr. Cox concluded.
 

“Some support” for SGLT2 inhibitors

The study results “provide some support for SGLT2 inhibitors facilitating decongestion and hospital discharge without observed safety issues,” said Stephen D. Wiviott, MD, designated discussant for the report and a cardiologist and professor at Harvard Medical School in Boston.

While initiation of an SGLT2 inhibitor during an acute heart failure hospitalization received endorsement as a top management priority in both the 2023 heart failure guidelines of the European Society of Cardiology and in 2022 U.S. guidelines, evidence of the safety and efficacy of this approach has been scanty, Dr. Wiviott noted.

Two prior studies addressed the issue. The SOLOIST-WHF trial tested the combined SGLT1 and SGLT2 inhibitor sotagliflozin (Inpefa, Lexicon) for patients recently hospitalized for heart failure, but only 142 of the 596 participants who were randomly assigned to receive sotagliflozin began receiving it at least a day before hospital discharge; for the remaining 454, treatment with sotagliflozin began on their discharge day, noted Dr. Wiviott.

In the EMPULSE trial, 530 people hospitalized for acute heart failure were randomly assigned to initially receive empagliflozin (Jardiance, Boehringer Ingelheim and Lilly) or placebo during hospitalization. The primary endpoint was largely driven by an improvement in the patient-reported outcome, as assessed on the basis of the Kansas City Cardiomyopathy Questionnaire Total Symptom Score, Dr. Wiviott added.

The DICTATE-AHF study included 238 adults who were within 24 hours of first presenting to any of six participating U.S. hospitals with hypervolemic acute heart failure. All patients underwent a standard treatment protocol with IV loop diuretics, and half received additional, open-label treatment with a daily 10-mg dose of dapagliflozin.

The average age of the patients was 65 years, 71% had type 2 diabetes (the study excluded people with type 1 diabetes), and about half had a left ventricular ejection fraction of 40% or less.
 

Similar weight loss with lower diuretics dose

The study’s primary outcome was a measure of diuretic efficiency, calculated as a person’s cumulative weight change divided by the cumulative dose of loop diuretics.

Both treatment arms experienced nearly identical weight loss, but for the people who received dapagliflozin, this occurred with a lower cumulative dose of diuretics. The diuretic efficiency with dapagliflozin produced comparable weight loss with a 35% lower amount of loop diuretic dose, a difference that fell just short of significance (P = .06).

However, treatment with dapagliflozin also significantly boosted 24-hour natriuresis and 24-hour diuresis, and it significantly shortened the time to stopping treatment with IV diuretics and to hospital discharge, Dr. Cox reported. Dapagliflozin initiation and ongoing treatment was also safe and well tolerated compared with usual care.

The fact that the primary endpoint fell short of significance was “largely related” to the study’s relatively small size, Dr. Wiviott suggested. He noted that the DAPA ACT HF-TIMI 68 study, which is a much larger and potentially more definitive study of the safety and efficacy of dapagliflozin in comparison with usual care for patients with acute heart failure, is in progress. The study includes about 2,400 patients.

The primary outcome is the combined rate of cardiovascular death or worsening heart failure during the 2 months following randomization. Results are expected in 2024.

DICTATE-AHF was sponsored by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. Cox has received research funding from AstraZeneca and has been a consultant to Roche and Translational Catalyst. Dr. Wiviott has received research funding from AstraZeneca and from Merck and has been a consultant to Icon Clinical and Novo Nordisk.
 

A version of this article appeared on Medscape.com.

AMSTERDAM – At the Radical Health Festival Helsinki this past June, Gerhard Hindricks, MD, PhD, was challenged by a young man when he dared to look into the crystal ball. “In the middle of my presentation, a maybe 25-year-old man stood up and said, ‘Dr. Hindricks, in 10 years, we will no longer need you!’ ” Dr. Hindricks noted at the great debate event “Will Artificial Intelligence Replace Cardiologists?” held at the annual congress of the European Society of Cardiology. He subsequently had an interesting discussion with the man. In his opinion, the future role of the physician is “an unavoidable discussion for cardiovascular medicine.”

Dr. Hindricks, from the University of Leipzig (Germany), considered artificial intelligence in cardiology to be “potentially the most important topic of the congress” and suggested that “we have to be more open to introducing new technologies into our practice. I sometimes have the impression that we are neither quick nor open enough to introducing new technologies, to leaving the old and to letting the new, better technology be effective in our patients.”
 

Asset or threat?

AI is dramatically changing the field and the role of the physician – but it is not making cardiologists superfluous. In this respect, Dr. Hindricks; Folkert Asselbergs, MD, PhD, professor of cardiology at the Amsterdam Heart Center; and Harriette Van Spall, MD, associate professor of medicine at McMaster University in Hamilton, Ont., were unanimous: They agreed, although they assess the opportunities and risks posed by AI differently.

Dr. Asselbergs saw AI as less of a threat and more of an asset. In his opinion, a cardiology-specific speech model could be used to the advantage of both patient and physician. A medical chatbot could offer patients information and suggested readings, and it could create the patient’s self-reported medical history and medical summaries for laypersons.

For physicians, a medical chatbot could be beneficial in the creation of patient reports, the selection of relevant literature, the creation of automated laboratory orders, the review of clinical discharge reports, for consultations, and for processing the consultations, as well as for complying with guidelines.

Dr. Asselbergs considered AI’s primary advantage to be the time that it saves, which can then be used “for complex interventions, palliative care, and acute treatment.”

The advantages of AI, he said, include the following:

• Efficiency and scale of AI in data analysis
• Automation
• AI does not get tired and is not biased
• Proactive health care provision and early intervention
• Reduction in health care costs
• Remains up to date with the latest knowledge.

He sees the following disadvantages:

• Lack of human contact, empathy, and the physician-patient relationship
• Ethical implications and challenges
• The potential for AI to make incorrect diagnoses or to be influenced by bias in the training data.

Medical supervision needed

For Dr. Van Spall, AI is primarily a tool. A generative AI could create useful materials such as images, videos, text, sound, 3D models, virtual environments, notes for clinical visits, medical summaries, and answers to clinical queries. But “the use of AI can lead to misinformation and expose the patient to risk, and there are no laws regulating liability.”

Dr. Van Spall stressed that AI could greatly increase efficiency. For example, in echocardiography, chamber volumes and function can be quantified automatically. ECGs can be interpreted automatically. “Even the workload associated with reading off of screens can be reduced, compared with unsupported reading.” However, she maintained that the use of AI requires medical supervision. “AI cannot function without cardiologists,” since it has “enormous limitations.” Dr. Van Spall does not see “any way to close the gaps that cardiologists may leave in terms of knowledge, service, and communication.”

According to the American College of Cardiology, 26% of the 32,000 cardiologists in the United States are older than 61 years. “That is a net loss of 546 cardiologists per year. We must use AI to support cardiologists, not to replace them,” said Dr. Van Spall.
 

Cardiologists becoming supervisors?

Dr. Asselbergs saw AI as a means of creating more equality. “Nearly everyone now has a smartphone. Let’s take ultrasound via AI as an example. There are rural areas that have no access to health care. If nurses or dietitians there create an ultrasound based on AI and send pictures for medical analysis, it will really help people.”

Dr. Hindricks hypothesized that machine learning and AI will make a huge difference in the field of rare diseases. Rare diseases are massively underdiagnosed simply because they are so rare and it requires a lot of experience to recognize them. “Digital elements can significantly support this,” said Dr. Hindricks.

For Dr. Van Spall, AI could make care and treatment safer. There will be more digital tools and virtual models available during training too. “I believe that the cardiologist will continue to occupy an important role, in terms of communication and processes. I do not see this role disappearing,” she said. Efficiency and precision are so important. “To make good decisions, we also want to get in touch with the person we trust.”

For Dr. Asselbergs, the role of cardiologists will change to one of a supervisor. “More joint decision-making, more discussion with our patients: I think this is the direction we’re heading in.”

This article was translated from the Medscape German Edition.

A version of this article first appeared on Medscape.com.

AMSTERDAM – At the Radical Health Festival Helsinki this past June, Gerhard Hindricks, MD, PhD, was challenged by a young man when he dared to look into the crystal ball. “In the middle of my presentation, a maybe 25-year-old man stood up and said, ‘Dr. Hindricks, in 10 years, we will no longer need you!’ ” Dr. Hindricks noted at the great debate event “Will Artificial Intelligence Replace Cardiologists?” held at the annual congress of the European Society of Cardiology. He subsequently had an interesting discussion with the man. In his opinion, the future role of the physician is “an unavoidable discussion for cardiovascular medicine.”

Dr. Hindricks, from the University of Leipzig (Germany), considered artificial intelligence in cardiology to be “potentially the most important topic of the congress” and suggested that “we have to be more open to introducing new technologies into our practice. I sometimes have the impression that we are neither quick nor open enough to introducing new technologies, to leaving the old and to letting the new, better technology be effective in our patients.”
 

Asset or threat?

AI is dramatically changing the field and the role of the physician – but it is not making cardiologists superfluous. In this respect, Dr. Hindricks; Folkert Asselbergs, MD, PhD, professor of cardiology at the Amsterdam Heart Center; and Harriette Van Spall, MD, associate professor of medicine at McMaster University in Hamilton, Ont., were unanimous: They agreed, although they assess the opportunities and risks posed by AI differently.

Dr. Asselbergs saw AI as less of a threat and more of an asset. In his opinion, a cardiology-specific speech model could be used to the advantage of both patient and physician. A medical chatbot could offer patients information and suggested readings, and it could create the patient’s self-reported medical history and medical summaries for laypersons.

For physicians, a medical chatbot could be beneficial in the creation of patient reports, the selection of relevant literature, the creation of automated laboratory orders, the review of clinical discharge reports, for consultations, and for processing the consultations, as well as for complying with guidelines.

Dr. Asselbergs considered AI’s primary advantage to be the time that it saves, which can then be used “for complex interventions, palliative care, and acute treatment.”

The advantages of AI, he said, include the following:

• Efficiency and scale of AI in data analysis
• Automation
• AI does not get tired and is not biased
• Proactive health care provision and early intervention
• Reduction in health care costs
• Remains up to date with the latest knowledge.

He sees the following disadvantages:

• Lack of human contact, empathy, and the physician-patient relationship
• Ethical implications and challenges
• The potential for AI to make incorrect diagnoses or to be influenced by bias in the training data.

Medical supervision needed

For Dr. Van Spall, AI is primarily a tool. A generative AI could create useful materials such as images, videos, text, sound, 3D models, virtual environments, notes for clinical visits, medical summaries, and answers to clinical queries. But “the use of AI can lead to misinformation and expose the patient to risk, and there are no laws regulating liability.”

Dr. Van Spall stressed that AI could greatly increase efficiency. For example, in echocardiography, chamber volumes and function can be quantified automatically. ECGs can be interpreted automatically. “Even the workload associated with reading off of screens can be reduced, compared with unsupported reading.” However, she maintained that the use of AI requires medical supervision. “AI cannot function without cardiologists,” since it has “enormous limitations.” Dr. Van Spall does not see “any way to close the gaps that cardiologists may leave in terms of knowledge, service, and communication.”

According to the American College of Cardiology, 26% of the 32,000 cardiologists in the United States are older than 61 years. “That is a net loss of 546 cardiologists per year. We must use AI to support cardiologists, not to replace them,” said Dr. Van Spall.
 

Cardiologists becoming supervisors?

Dr. Asselbergs saw AI as a means of creating more equality. “Nearly everyone now has a smartphone. Let’s take ultrasound via AI as an example. There are rural areas that have no access to health care. If nurses or dietitians there create an ultrasound based on AI and send pictures for medical analysis, it will really help people.”

Dr. Hindricks hypothesized that machine learning and AI will make a huge difference in the field of rare diseases. Rare diseases are massively underdiagnosed simply because they are so rare and it requires a lot of experience to recognize them. “Digital elements can significantly support this,” said Dr. Hindricks.

For Dr. Van Spall, AI could make care and treatment safer. There will be more digital tools and virtual models available during training too. “I believe that the cardiologist will continue to occupy an important role, in terms of communication and processes. I do not see this role disappearing,” she said. Efficiency and precision are so important. “To make good decisions, we also want to get in touch with the person we trust.”

For Dr. Asselbergs, the role of cardiologists will change to one of a supervisor. “More joint decision-making, more discussion with our patients: I think this is the direction we’re heading in.”

This article was translated from the Medscape German Edition.

A version of this article first appeared on Medscape.com.

AMSTERDAM – At the Radical Health Festival Helsinki this past June, Gerhard Hindricks, MD, PhD, was challenged by a young man when he dared to look into the crystal ball. “In the middle of my presentation, a maybe 25-year-old man stood up and said, ‘Dr. Hindricks, in 10 years, we will no longer need you!’ ” Dr. Hindricks noted at the great debate event “Will Artificial Intelligence Replace Cardiologists?” held at the annual congress of the European Society of Cardiology. He subsequently had an interesting discussion with the man. In his opinion, the future role of the physician is “an unavoidable discussion for cardiovascular medicine.”

Dr. Hindricks, from the University of Leipzig (Germany), considered artificial intelligence in cardiology to be “potentially the most important topic of the congress” and suggested that “we have to be more open to introducing new technologies into our practice. I sometimes have the impression that we are neither quick nor open enough to introducing new technologies, to leaving the old and to letting the new, better technology be effective in our patients.”
 

Asset or threat?

AI is dramatically changing the field and the role of the physician – but it is not making cardiologists superfluous. In this respect, Dr. Hindricks; Folkert Asselbergs, MD, PhD, professor of cardiology at the Amsterdam Heart Center; and Harriette Van Spall, MD, associate professor of medicine at McMaster University in Hamilton, Ont., were unanimous: They agreed, although they assess the opportunities and risks posed by AI differently.

Dr. Asselbergs saw AI as less of a threat and more of an asset. In his opinion, a cardiology-specific speech model could be used to the advantage of both patient and physician. A medical chatbot could offer patients information and suggested readings, and it could create the patient’s self-reported medical history and medical summaries for laypersons.

For physicians, a medical chatbot could be beneficial in the creation of patient reports, the selection of relevant literature, the creation of automated laboratory orders, the review of clinical discharge reports, for consultations, and for processing the consultations, as well as for complying with guidelines.

Dr. Asselbergs considered AI’s primary advantage to be the time that it saves, which can then be used “for complex interventions, palliative care, and acute treatment.”

The advantages of AI, he said, include the following:

• Efficiency and scale of AI in data analysis
• Automation
• AI does not get tired and is not biased
• Proactive health care provision and early intervention
• Reduction in health care costs
• Remains up to date with the latest knowledge.

He sees the following disadvantages:

• Lack of human contact, empathy, and the physician-patient relationship
• Ethical implications and challenges
• The potential for AI to make incorrect diagnoses or to be influenced by bias in the training data.

Medical supervision needed

For Dr. Van Spall, AI is primarily a tool. A generative AI could create useful materials such as images, videos, text, sound, 3D models, virtual environments, notes for clinical visits, medical summaries, and answers to clinical queries. But “the use of AI can lead to misinformation and expose the patient to risk, and there are no laws regulating liability.”

Dr. Van Spall stressed that AI could greatly increase efficiency. For example, in echocardiography, chamber volumes and function can be quantified automatically. ECGs can be interpreted automatically. “Even the workload associated with reading off of screens can be reduced, compared with unsupported reading.” However, she maintained that the use of AI requires medical supervision. “AI cannot function without cardiologists,” since it has “enormous limitations.” Dr. Van Spall does not see “any way to close the gaps that cardiologists may leave in terms of knowledge, service, and communication.”

According to the American College of Cardiology, 26% of the 32,000 cardiologists in the United States are older than 61 years. “That is a net loss of 546 cardiologists per year. We must use AI to support cardiologists, not to replace them,” said Dr. Van Spall.
 

Cardiologists becoming supervisors?

Dr. Asselbergs saw AI as a means of creating more equality. “Nearly everyone now has a smartphone. Let’s take ultrasound via AI as an example. There are rural areas that have no access to health care. If nurses or dietitians there create an ultrasound based on AI and send pictures for medical analysis, it will really help people.”

Dr. Hindricks hypothesized that machine learning and AI will make a huge difference in the field of rare diseases. Rare diseases are massively underdiagnosed simply because they are so rare and it requires a lot of experience to recognize them. “Digital elements can significantly support this,” said Dr. Hindricks.

For Dr. Van Spall, AI could make care and treatment safer. There will be more digital tools and virtual models available during training too. “I believe that the cardiologist will continue to occupy an important role, in terms of communication and processes. I do not see this role disappearing,” she said. Efficiency and precision are so important. “To make good decisions, we also want to get in touch with the person we trust.”

For Dr. Asselbergs, the role of cardiologists will change to one of a supervisor. “More joint decision-making, more discussion with our patients: I think this is the direction we’re heading in.”

This article was translated from the Medscape German Edition.

A version of this article first appeared on Medscape.com.

AMSTERDAM – A short course of the interleukin-1 receptor antagonist, anakinra, appeared safe but did not reduce complications of acute myocarditis in the ARAMIS trial.

The trial was presented at the annual congress of the European Society of Cardiology.

Lead investigator, Mathieu Kerneis, MD, Pitie Salpetriere APHP University Hospital, Paris, said this was the largest randomized controlled trial of patients with acute myocarditis and probably the first ever study in the acute setting of myocarditis patients diagnosed with cardiac magnetic resonance (CMR) imaging, not on biopsy, who are mostly at low risk for events.

He suggested that one of the reasons for the neutral result could have been the low-risk population involved and the low complication rate. “We enrolled an all-comer acute myocarditis population diagnosed with CMR, who were mostly at a low risk of complications,” he noted.

“I don’t think the story of anti-inflammatory drugs in acute myocarditis is over. This is just the beginning. This was the first trial, and it was just a phase 2 trial. We need further randomized trials to explore the potential benefit of an anti-inflammatory strategy in acute myocarditis patients at higher risk of complications. In addition, larger studies are needed to evaluate prolonged anti-inflammatory strategies in acute myocarditis patients at low-to-moderate risk of complications,” Dr. Kerneis concluded.

“It is very challenging to do a trial in high-risk patients with myocarditis as these patients are quite rare,” he added.
 

Inflammation of the myocardium

Dr. Kerneis explained that acute myocarditis is an inflammation of the myocardium that can cause permanent damage to the heart muscle and lead to myocardial infarction, stroke, heart failure, arrhythmias, and death. The condition can occur in individuals of all ages but is most frequent in young people. There is no specific treatment, but patients are generally treated with beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, and sometimes steroids.

Anakinra is an interleukin-1 receptor antagonist that works by targeting the interleukin-1β innate immune pathway. Anakinra is used for the treatment of rheumatoid arthritis and has shown efficacy in pericarditis. Dr. Kerneis noted that there have been several case reports of successful treatment with anakinra in acute myocarditis.

The ARAMIS trial – conducted at six academic centers in France – was the first randomized study to evaluate inhibition of the interleukin-1β innate immune pathway in myocarditis patients. The trial enrolled 120 hospitalized, symptomatic patients with chest pain, increased cardiac troponin, and acute myocarditis diagnosed using CMR. More than half had had a recent bacterial or viral infection.

Patients were randomized within 72 hours of hospital admission to a daily subcutaneous dose of anakinra 100 mg or placebo until hospital discharge. Patients in both groups received standard-of-care treatments, including an ACE inhibitor, for at least 1 month. Consistent with prior data, the median age of participants was 28 years and 90% were men.

The primary endpoint was the number of days free of myocarditis complications (heart failure requiring hospitalization, chest pain requiring medication, left ventricular ejection fraction less than 50%, and ventricular arrhythmias) within 28 days postdischarge.

There was no significant difference in this endpoint between the two arms, with a median of 30 days for anakinra versus 31 days for placebo.

Overall, the rate of the composite endpoint of myocarditis complications occurred in 13.7% of patients, and there was a numerical reduction in the number of patients with these myocarditis complications with anakinra – 6 patients (10.5%) in the anakinra group versus 10 patients (16.5%) in the placebo group (odds ratio, 0.59; 95% confidence interval, 0.19-1.78). This was driven by fewer patients with chest pain requiring new medication (two patients versus six patients).

The safety endpoint was the number of serious adverse events within 28 days postdischarge. This endpoint occurred in seven patients (12.1%) in the anakinra arm and six patients (10.2%) in the placebo arm, with no significant difference between groups. Cases of severe infection within 28 days postdischarge were reported in both arms.
 

Low-risk population

Designated discussant of the study at the ESC Hotline session, Enrico Ammirati, MD, PhD, University of Milano-Bicocca, Monza, Italy, said that patients involved in ARAMIS fit the profile of acute myocarditis and that the CMR diagnosis was positive in all the patients enrolled.

Dr. Ammirati agreed with Dr. Kerneis that the neutral results of the study were probably caused by the low-risk population. “If we look at retrospective registries, at 30 days there are zero cardiac deaths or heart transplants at 30 days in patients with a low-risk presentation.

“The ARAMIS trial has shown the feasibility of conducting studies in the setting of acute myocarditis, and even if the primary endpoint was neutral, some important data are still missing, such as change in ejection fraction and troponin levels,” he noted.

“In terms of future perspective, we are moving to assessing efficacy of anakinra or other immunosuppressive drugs from acute low risk patients to higher risk patients with heart failure and severe dysfunction,” he said.  

Dr. Ammirati is the lead investigator of another ongoing study in such a higher-risk population; the MYTHS trial is investigating the use of intravenous steroids in patients with suspected acute myocarditis complicated by acute heart failure or cardiogenic shock, and an ejection fraction below 41%.

“So, we will have more results on the best treatment in this higher risk group of patients,” he concluded.

The ARAMIS trial was an academic study funded by the French Health Ministry and coordinated by the ACTION Group. Dr. Kerneis reports having received consulting fees from Kiniksa, Sanofi, and Bayer, and holds a patent for use of abatacept in immune checkpoint inhibitor (ICI)–induced myocarditis.

A version of this article first appeared on Medscape.com.

AMSTERDAM – A short course of the interleukin-1 receptor antagonist, anakinra, appeared safe but did not reduce complications of acute myocarditis in the ARAMIS trial.

The trial was presented at the annual congress of the European Society of Cardiology.

Lead investigator, Mathieu Kerneis, MD, Pitie Salpetriere APHP University Hospital, Paris, said this was the largest randomized controlled trial of patients with acute myocarditis and probably the first ever study in the acute setting of myocarditis patients diagnosed with cardiac magnetic resonance (CMR) imaging, not on biopsy, who are mostly at low risk for events.

He suggested that one of the reasons for the neutral result could have been the low-risk population involved and the low complication rate. “We enrolled an all-comer acute myocarditis population diagnosed with CMR, who were mostly at a low risk of complications,” he noted.

“I don’t think the story of anti-inflammatory drugs in acute myocarditis is over. This is just the beginning. This was the first trial, and it was just a phase 2 trial. We need further randomized trials to explore the potential benefit of an anti-inflammatory strategy in acute myocarditis patients at higher risk of complications. In addition, larger studies are needed to evaluate prolonged anti-inflammatory strategies in acute myocarditis patients at low-to-moderate risk of complications,” Dr. Kerneis concluded.

“It is very challenging to do a trial in high-risk patients with myocarditis as these patients are quite rare,” he added.
 

Inflammation of the myocardium

Dr. Kerneis explained that acute myocarditis is an inflammation of the myocardium that can cause permanent damage to the heart muscle and lead to myocardial infarction, stroke, heart failure, arrhythmias, and death. The condition can occur in individuals of all ages but is most frequent in young people. There is no specific treatment, but patients are generally treated with beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, and sometimes steroids.

Anakinra is an interleukin-1 receptor antagonist that works by targeting the interleukin-1β innate immune pathway. Anakinra is used for the treatment of rheumatoid arthritis and has shown efficacy in pericarditis. Dr. Kerneis noted that there have been several case reports of successful treatment with anakinra in acute myocarditis.

The ARAMIS trial – conducted at six academic centers in France – was the first randomized study to evaluate inhibition of the interleukin-1β innate immune pathway in myocarditis patients. The trial enrolled 120 hospitalized, symptomatic patients with chest pain, increased cardiac troponin, and acute myocarditis diagnosed using CMR. More than half had had a recent bacterial or viral infection.

Patients were randomized within 72 hours of hospital admission to a daily subcutaneous dose of anakinra 100 mg or placebo until hospital discharge. Patients in both groups received standard-of-care treatments, including an ACE inhibitor, for at least 1 month. Consistent with prior data, the median age of participants was 28 years and 90% were men.

The primary endpoint was the number of days free of myocarditis complications (heart failure requiring hospitalization, chest pain requiring medication, left ventricular ejection fraction less than 50%, and ventricular arrhythmias) within 28 days postdischarge.

There was no significant difference in this endpoint between the two arms, with a median of 30 days for anakinra versus 31 days for placebo.

Overall, the rate of the composite endpoint of myocarditis complications occurred in 13.7% of patients, and there was a numerical reduction in the number of patients with these myocarditis complications with anakinra – 6 patients (10.5%) in the anakinra group versus 10 patients (16.5%) in the placebo group (odds ratio, 0.59; 95% confidence interval, 0.19-1.78). This was driven by fewer patients with chest pain requiring new medication (two patients versus six patients).

The safety endpoint was the number of serious adverse events within 28 days postdischarge. This endpoint occurred in seven patients (12.1%) in the anakinra arm and six patients (10.2%) in the placebo arm, with no significant difference between groups. Cases of severe infection within 28 days postdischarge were reported in both arms.
 

Low-risk population

Designated discussant of the study at the ESC Hotline session, Enrico Ammirati, MD, PhD, University of Milano-Bicocca, Monza, Italy, said that patients involved in ARAMIS fit the profile of acute myocarditis and that the CMR diagnosis was positive in all the patients enrolled.

Dr. Ammirati agreed with Dr. Kerneis that the neutral results of the study were probably caused by the low-risk population. “If we look at retrospective registries, at 30 days there are zero cardiac deaths or heart transplants at 30 days in patients with a low-risk presentation.

“The ARAMIS trial has shown the feasibility of conducting studies in the setting of acute myocarditis, and even if the primary endpoint was neutral, some important data are still missing, such as change in ejection fraction and troponin levels,” he noted.

“In terms of future perspective, we are moving to assessing efficacy of anakinra or other immunosuppressive drugs from acute low risk patients to higher risk patients with heart failure and severe dysfunction,” he said.  

Dr. Ammirati is the lead investigator of another ongoing study in such a higher-risk population; the MYTHS trial is investigating the use of intravenous steroids in patients with suspected acute myocarditis complicated by acute heart failure or cardiogenic shock, and an ejection fraction below 41%.

“So, we will have more results on the best treatment in this higher risk group of patients,” he concluded.

The ARAMIS trial was an academic study funded by the French Health Ministry and coordinated by the ACTION Group. Dr. Kerneis reports having received consulting fees from Kiniksa, Sanofi, and Bayer, and holds a patent for use of abatacept in immune checkpoint inhibitor (ICI)–induced myocarditis.

A version of this article first appeared on Medscape.com.

AMSTERDAM – A short course of the interleukin-1 receptor antagonist, anakinra, appeared safe but did not reduce complications of acute myocarditis in the ARAMIS trial.

The trial was presented at the annual congress of the European Society of Cardiology.

Lead investigator, Mathieu Kerneis, MD, Pitie Salpetriere APHP University Hospital, Paris, said this was the largest randomized controlled trial of patients with acute myocarditis and probably the first ever study in the acute setting of myocarditis patients diagnosed with cardiac magnetic resonance (CMR) imaging, not on biopsy, who are mostly at low risk for events.

He suggested that one of the reasons for the neutral result could have been the low-risk population involved and the low complication rate. “We enrolled an all-comer acute myocarditis population diagnosed with CMR, who were mostly at a low risk of complications,” he noted.

“I don’t think the story of anti-inflammatory drugs in acute myocarditis is over. This is just the beginning. This was the first trial, and it was just a phase 2 trial. We need further randomized trials to explore the potential benefit of an anti-inflammatory strategy in acute myocarditis patients at higher risk of complications. In addition, larger studies are needed to evaluate prolonged anti-inflammatory strategies in acute myocarditis patients at low-to-moderate risk of complications,” Dr. Kerneis concluded.

“It is very challenging to do a trial in high-risk patients with myocarditis as these patients are quite rare,” he added.
 

Inflammation of the myocardium

Dr. Kerneis explained that acute myocarditis is an inflammation of the myocardium that can cause permanent damage to the heart muscle and lead to myocardial infarction, stroke, heart failure, arrhythmias, and death. The condition can occur in individuals of all ages but is most frequent in young people. There is no specific treatment, but patients are generally treated with beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, and sometimes steroids.

Anakinra is an interleukin-1 receptor antagonist that works by targeting the interleukin-1β innate immune pathway. Anakinra is used for the treatment of rheumatoid arthritis and has shown efficacy in pericarditis. Dr. Kerneis noted that there have been several case reports of successful treatment with anakinra in acute myocarditis.

The ARAMIS trial – conducted at six academic centers in France – was the first randomized study to evaluate inhibition of the interleukin-1β innate immune pathway in myocarditis patients. The trial enrolled 120 hospitalized, symptomatic patients with chest pain, increased cardiac troponin, and acute myocarditis diagnosed using CMR. More than half had had a recent bacterial or viral infection.

Patients were randomized within 72 hours of hospital admission to a daily subcutaneous dose of anakinra 100 mg or placebo until hospital discharge. Patients in both groups received standard-of-care treatments, including an ACE inhibitor, for at least 1 month. Consistent with prior data, the median age of participants was 28 years and 90% were men.

The primary endpoint was the number of days free of myocarditis complications (heart failure requiring hospitalization, chest pain requiring medication, left ventricular ejection fraction less than 50%, and ventricular arrhythmias) within 28 days postdischarge.

There was no significant difference in this endpoint between the two arms, with a median of 30 days for anakinra versus 31 days for placebo.

Overall, the rate of the composite endpoint of myocarditis complications occurred in 13.7% of patients, and there was a numerical reduction in the number of patients with these myocarditis complications with anakinra – 6 patients (10.5%) in the anakinra group versus 10 patients (16.5%) in the placebo group (odds ratio, 0.59; 95% confidence interval, 0.19-1.78). This was driven by fewer patients with chest pain requiring new medication (two patients versus six patients).

The safety endpoint was the number of serious adverse events within 28 days postdischarge. This endpoint occurred in seven patients (12.1%) in the anakinra arm and six patients (10.2%) in the placebo arm, with no significant difference between groups. Cases of severe infection within 28 days postdischarge were reported in both arms.
 

Low-risk population

Designated discussant of the study at the ESC Hotline session, Enrico Ammirati, MD, PhD, University of Milano-Bicocca, Monza, Italy, said that patients involved in ARAMIS fit the profile of acute myocarditis and that the CMR diagnosis was positive in all the patients enrolled.

Dr. Ammirati agreed with Dr. Kerneis that the neutral results of the study were probably caused by the low-risk population. “If we look at retrospective registries, at 30 days there are zero cardiac deaths or heart transplants at 30 days in patients with a low-risk presentation.

“The ARAMIS trial has shown the feasibility of conducting studies in the setting of acute myocarditis, and even if the primary endpoint was neutral, some important data are still missing, such as change in ejection fraction and troponin levels,” he noted.

“In terms of future perspective, we are moving to assessing efficacy of anakinra or other immunosuppressive drugs from acute low risk patients to higher risk patients with heart failure and severe dysfunction,” he said.  

Dr. Ammirati is the lead investigator of another ongoing study in such a higher-risk population; the MYTHS trial is investigating the use of intravenous steroids in patients with suspected acute myocarditis complicated by acute heart failure or cardiogenic shock, and an ejection fraction below 41%.

“So, we will have more results on the best treatment in this higher risk group of patients,” he concluded.

The ARAMIS trial was an academic study funded by the French Health Ministry and coordinated by the ACTION Group. Dr. Kerneis reports having received consulting fees from Kiniksa, Sanofi, and Bayer, and holds a patent for use of abatacept in immune checkpoint inhibitor (ICI)–induced myocarditis.

A version of this article first appeared on Medscape.com.

AMSTERDAM – Dropping aspirin and using low-dose prasugrel (Effient) alone in the initial month of treatment after percutaneous coronary intervention (PCI) failed to lower bleeding risk, compared with dual antiplatelet therapy (DAPT), and there was a signal of possible harm in terms of increased subacute stent thrombosis, in the STOPDAPT-3 trial.

“Therefore, dual antiplatelet therapy with aspirin and a P2Y12 inhibitor should still remain the standard strategy at least for 1 month after PCI,” said the trial’s lead investigator Masahiro Natsuaki, MD, Saga (Japan) University.

The STOPDAPT-3 trial was presented at the recent annual congress of the European Society of Cardiology.

Designated discussant Marco Valgimigli, MD, Cardiocentro Ticino Foundation, Lugano, Switzerland, explained that the current wisdom before this study was that aspirin withdrawal in the postacute phase after PCI (after 1 month of DAPT onwards) is associated with lower bleeding risk without affecting ischemic risk, but this STOPDAPT-3 trial is the first to look at the idea of not giving aspirin at all.

“This study is a well-designed, well-conducted trial, and the results are very clear: there is no benefit of dropping aspirin in this early period with respect to major bleeding, and at the same time there was some signal for possible harm,” Dr. Valgimigli said.

He pointed out that the possible harm was not related to the coprimary cardiovascular composite endpoint, which did fulfill noninferiority, although he acknowledged the “generous” noninferiority margin.

Rather, the possible harm was related to an increase in subacute stent thrombosis, which was three times higher in the nonaspirin group (0.58% vs. 0.17%). 

“While these absolute event rates are extremely low, they are unquestionably higher in the nonaspirin group,” he added.

In his presentation, Dr. Natsuaki explained that very short durations (1-3 months) of DAPT followed by P2Y12 inhibitor monotherapy has been shown to reduce bleeding events without increasing cardiovascular events, compared with longer durations of DAPT after PCI using drug-eluting stents.

However, the incidence of major bleeding events within the 1-month mandatory DAPT period after PCI remains high in clinical practice, particularly in patients with ACS or high bleeding risk.

In single-arm studies, use of prasugrel or ticagrelor (Brilinta) alone following new-generation drug-eluting stent implantation was not associated with any stent thrombosis in selected low-risk patients with or without ACS, and it is thought that removing aspirin from the DAPT regimen might reduce bleeding events early after PCI without compromising the risk of cardiovascular events. However, the efficacy and safety of this strategy has not been proven in randomized trials.
 

STOPDAPT-3 trial

STOPDAPT-3 investigated the efficacy and safety of prasugrel monotherapy compared with 1-month DAPT with aspirin and prasugrel in Japanese patients with ACS or high bleeding risk undergoing PCI with cobalt-chromium everolimus-eluting stents.

The study enrolled 6,002 patients with ACS or high bleeding risk who were randomly assigned to prasugrel monotherapy (3.75 mg/day; the licensed dose in Japan) or to DAPT with aspirin (81-100 mg/day) and prasugrel after a loading dose of prasugrel 20 mg in both groups.

There were two primary endpoints: major bleeding events (defined as BARC type 3 or 5) at 1 month for superiority and cardiovascular events (a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or stroke) at 1 month for noninferiority.

The major secondary endpoint was a composite of the coprimary bleeding and cardiovascular endpoints (cardiovascular death, myocardial infarction, definite stent thrombosis, stroke, or major bleeding) at 1 month representing net clinical benefit.

Results showed that, at 1 month, the no-aspirin strategy was not superior to DAPT for the coprimary bleeding endpoint, with major bleeding events occurring in 4.47% of the prasugrel monotherapy group versus 4.71% of those on DAPT (hazard ratio, 0.95; 95% confidence interval, 0.75-1.20).

The prasugrel monotherapy strategy was noninferior to DAPT, although there was a relative 50% margin for the coprimary cardiovascular endpoint. Cardiovascular endpoints occurred in 4.12% of prasugrel monotherapy group versus 3.69% of the DAPT patients (HR, 1.12; 95% CI, 0.87-1.45; P for noninferiority = .01).

The major secondary net clinical benefit endpoint occurred in 7.14% patients in the prasugrel monotherapy group and 7.38% patients in the DAPT group, with no between-group difference, indicating a similar effect on net clinical benefit for both groups.

However, there was an excess of any coronary revascularization (1.15% vs. 0.57%) and definite or probable stent thrombosis (0.71% vs. 0.44%) in the prasugrel monotherapy group compared with the DAPT group, while definite stent thrombosis was not different between the two groups (0.47% vs. 0.37%).

In a subgroup analysis stratified by ACS and non-ACS, the excess risk for cardiovascular events in the no-aspirin group, compared with the DAPT group, was seen in patients with ACS, but not in those without ACS.
 

Future: Focus on dose and timing

In his discussion, Dr. Valgimigli said the implications of this trial for clinical practice were very clear: “Aspirin remains a cornerstone treatment in the periprocedural and acute phase of PCI in patients without indications for oral anticoagulation.” 

However, he added that the study opens several important points for subsequent discussion.

These include the role of type and dose of P2Y12 inhibitor therapy used; specifically, he questioned whether the 3.75-mg dose of prasugrel was enough.

Dr. Valgimigli also pointed out that this study did not include a purely high bleeding risk population, and he said there was still potential to investigate periprocedure versus postprocedure aspirin administration.

The STOPDAPT-3 trial was funded by Abbott Medical Japan. Dr. Natsuaki reported receiving honoraria from Abbott Medical Japan, Daiichi Sankyo, and Bayer.

A version of this article first appeared on Medscape.com.

AMSTERDAM – Dropping aspirin and using low-dose prasugrel (Effient) alone in the initial month of treatment after percutaneous coronary intervention (PCI) failed to lower bleeding risk, compared with dual antiplatelet therapy (DAPT), and there was a signal of possible harm in terms of increased subacute stent thrombosis, in the STOPDAPT-3 trial.

“Therefore, dual antiplatelet therapy with aspirin and a P2Y12 inhibitor should still remain the standard strategy at least for 1 month after PCI,” said the trial’s lead investigator Masahiro Natsuaki, MD, Saga (Japan) University.

The STOPDAPT-3 trial was presented at the recent annual congress of the European Society of Cardiology.

Designated discussant Marco Valgimigli, MD, Cardiocentro Ticino Foundation, Lugano, Switzerland, explained that the current wisdom before this study was that aspirin withdrawal in the postacute phase after PCI (after 1 month of DAPT onwards) is associated with lower bleeding risk without affecting ischemic risk, but this STOPDAPT-3 trial is the first to look at the idea of not giving aspirin at all.

“This study is a well-designed, well-conducted trial, and the results are very clear: there is no benefit of dropping aspirin in this early period with respect to major bleeding, and at the same time there was some signal for possible harm,” Dr. Valgimigli said.

He pointed out that the possible harm was not related to the coprimary cardiovascular composite endpoint, which did fulfill noninferiority, although he acknowledged the “generous” noninferiority margin.

Rather, the possible harm was related to an increase in subacute stent thrombosis, which was three times higher in the nonaspirin group (0.58% vs. 0.17%). 

“While these absolute event rates are extremely low, they are unquestionably higher in the nonaspirin group,” he added.

In his presentation, Dr. Natsuaki explained that very short durations (1-3 months) of DAPT followed by P2Y12 inhibitor monotherapy has been shown to reduce bleeding events without increasing cardiovascular events, compared with longer durations of DAPT after PCI using drug-eluting stents.

However, the incidence of major bleeding events within the 1-month mandatory DAPT period after PCI remains high in clinical practice, particularly in patients with ACS or high bleeding risk.

In single-arm studies, use of prasugrel or ticagrelor (Brilinta) alone following new-generation drug-eluting stent implantation was not associated with any stent thrombosis in selected low-risk patients with or without ACS, and it is thought that removing aspirin from the DAPT regimen might reduce bleeding events early after PCI without compromising the risk of cardiovascular events. However, the efficacy and safety of this strategy has not been proven in randomized trials.
 

STOPDAPT-3 trial

STOPDAPT-3 investigated the efficacy and safety of prasugrel monotherapy compared with 1-month DAPT with aspirin and prasugrel in Japanese patients with ACS or high bleeding risk undergoing PCI with cobalt-chromium everolimus-eluting stents.

The study enrolled 6,002 patients with ACS or high bleeding risk who were randomly assigned to prasugrel monotherapy (3.75 mg/day; the licensed dose in Japan) or to DAPT with aspirin (81-100 mg/day) and prasugrel after a loading dose of prasugrel 20 mg in both groups.

There were two primary endpoints: major bleeding events (defined as BARC type 3 or 5) at 1 month for superiority and cardiovascular events (a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or stroke) at 1 month for noninferiority.

The major secondary endpoint was a composite of the coprimary bleeding and cardiovascular endpoints (cardiovascular death, myocardial infarction, definite stent thrombosis, stroke, or major bleeding) at 1 month representing net clinical benefit.

Results showed that, at 1 month, the no-aspirin strategy was not superior to DAPT for the coprimary bleeding endpoint, with major bleeding events occurring in 4.47% of the prasugrel monotherapy group versus 4.71% of those on DAPT (hazard ratio, 0.95; 95% confidence interval, 0.75-1.20).

The prasugrel monotherapy strategy was noninferior to DAPT, although there was a relative 50% margin for the coprimary cardiovascular endpoint. Cardiovascular endpoints occurred in 4.12% of prasugrel monotherapy group versus 3.69% of the DAPT patients (HR, 1.12; 95% CI, 0.87-1.45; P for noninferiority = .01).

The major secondary net clinical benefit endpoint occurred in 7.14% patients in the prasugrel monotherapy group and 7.38% patients in the DAPT group, with no between-group difference, indicating a similar effect on net clinical benefit for both groups.

However, there was an excess of any coronary revascularization (1.15% vs. 0.57%) and definite or probable stent thrombosis (0.71% vs. 0.44%) in the prasugrel monotherapy group compared with the DAPT group, while definite stent thrombosis was not different between the two groups (0.47% vs. 0.37%).

In a subgroup analysis stratified by ACS and non-ACS, the excess risk for cardiovascular events in the no-aspirin group, compared with the DAPT group, was seen in patients with ACS, but not in those without ACS.
 

Future: Focus on dose and timing

In his discussion, Dr. Valgimigli said the implications of this trial for clinical practice were very clear: “Aspirin remains a cornerstone treatment in the periprocedural and acute phase of PCI in patients without indications for oral anticoagulation.” 

However, he added that the study opens several important points for subsequent discussion.

These include the role of type and dose of P2Y12 inhibitor therapy used; specifically, he questioned whether the 3.75-mg dose of prasugrel was enough.

Dr. Valgimigli also pointed out that this study did not include a purely high bleeding risk population, and he said there was still potential to investigate periprocedure versus postprocedure aspirin administration.

The STOPDAPT-3 trial was funded by Abbott Medical Japan. Dr. Natsuaki reported receiving honoraria from Abbott Medical Japan, Daiichi Sankyo, and Bayer.

A version of this article first appeared on Medscape.com.

AMSTERDAM – Dropping aspirin and using low-dose prasugrel (Effient) alone in the initial month of treatment after percutaneous coronary intervention (PCI) failed to lower bleeding risk, compared with dual antiplatelet therapy (DAPT), and there was a signal of possible harm in terms of increased subacute stent thrombosis, in the STOPDAPT-3 trial.

“Therefore, dual antiplatelet therapy with aspirin and a P2Y12 inhibitor should still remain the standard strategy at least for 1 month after PCI,” said the trial’s lead investigator Masahiro Natsuaki, MD, Saga (Japan) University.

The STOPDAPT-3 trial was presented at the recent annual congress of the European Society of Cardiology.

Designated discussant Marco Valgimigli, MD, Cardiocentro Ticino Foundation, Lugano, Switzerland, explained that the current wisdom before this study was that aspirin withdrawal in the postacute phase after PCI (after 1 month of DAPT onwards) is associated with lower bleeding risk without affecting ischemic risk, but this STOPDAPT-3 trial is the first to look at the idea of not giving aspirin at all.

“This study is a well-designed, well-conducted trial, and the results are very clear: there is no benefit of dropping aspirin in this early period with respect to major bleeding, and at the same time there was some signal for possible harm,” Dr. Valgimigli said.

He pointed out that the possible harm was not related to the coprimary cardiovascular composite endpoint, which did fulfill noninferiority, although he acknowledged the “generous” noninferiority margin.

Rather, the possible harm was related to an increase in subacute stent thrombosis, which was three times higher in the nonaspirin group (0.58% vs. 0.17%). 

“While these absolute event rates are extremely low, they are unquestionably higher in the nonaspirin group,” he added.

In his presentation, Dr. Natsuaki explained that very short durations (1-3 months) of DAPT followed by P2Y12 inhibitor monotherapy has been shown to reduce bleeding events without increasing cardiovascular events, compared with longer durations of DAPT after PCI using drug-eluting stents.

However, the incidence of major bleeding events within the 1-month mandatory DAPT period after PCI remains high in clinical practice, particularly in patients with ACS or high bleeding risk.

In single-arm studies, use of prasugrel or ticagrelor (Brilinta) alone following new-generation drug-eluting stent implantation was not associated with any stent thrombosis in selected low-risk patients with or without ACS, and it is thought that removing aspirin from the DAPT regimen might reduce bleeding events early after PCI without compromising the risk of cardiovascular events. However, the efficacy and safety of this strategy has not been proven in randomized trials.
 

STOPDAPT-3 trial

STOPDAPT-3 investigated the efficacy and safety of prasugrel monotherapy compared with 1-month DAPT with aspirin and prasugrel in Japanese patients with ACS or high bleeding risk undergoing PCI with cobalt-chromium everolimus-eluting stents.

The study enrolled 6,002 patients with ACS or high bleeding risk who were randomly assigned to prasugrel monotherapy (3.75 mg/day; the licensed dose in Japan) or to DAPT with aspirin (81-100 mg/day) and prasugrel after a loading dose of prasugrel 20 mg in both groups.

There were two primary endpoints: major bleeding events (defined as BARC type 3 or 5) at 1 month for superiority and cardiovascular events (a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or stroke) at 1 month for noninferiority.

The major secondary endpoint was a composite of the coprimary bleeding and cardiovascular endpoints (cardiovascular death, myocardial infarction, definite stent thrombosis, stroke, or major bleeding) at 1 month representing net clinical benefit.

Results showed that, at 1 month, the no-aspirin strategy was not superior to DAPT for the coprimary bleeding endpoint, with major bleeding events occurring in 4.47% of the prasugrel monotherapy group versus 4.71% of those on DAPT (hazard ratio, 0.95; 95% confidence interval, 0.75-1.20).

The prasugrel monotherapy strategy was noninferior to DAPT, although there was a relative 50% margin for the coprimary cardiovascular endpoint. Cardiovascular endpoints occurred in 4.12% of prasugrel monotherapy group versus 3.69% of the DAPT patients (HR, 1.12; 95% CI, 0.87-1.45; P for noninferiority = .01).

The major secondary net clinical benefit endpoint occurred in 7.14% patients in the prasugrel monotherapy group and 7.38% patients in the DAPT group, with no between-group difference, indicating a similar effect on net clinical benefit for both groups.

However, there was an excess of any coronary revascularization (1.15% vs. 0.57%) and definite or probable stent thrombosis (0.71% vs. 0.44%) in the prasugrel monotherapy group compared with the DAPT group, while definite stent thrombosis was not different between the two groups (0.47% vs. 0.37%).

In a subgroup analysis stratified by ACS and non-ACS, the excess risk for cardiovascular events in the no-aspirin group, compared with the DAPT group, was seen in patients with ACS, but not in those without ACS.
 

Future: Focus on dose and timing

In his discussion, Dr. Valgimigli said the implications of this trial for clinical practice were very clear: “Aspirin remains a cornerstone treatment in the periprocedural and acute phase of PCI in patients without indications for oral anticoagulation.” 

However, he added that the study opens several important points for subsequent discussion.

These include the role of type and dose of P2Y12 inhibitor therapy used; specifically, he questioned whether the 3.75-mg dose of prasugrel was enough.

Dr. Valgimigli also pointed out that this study did not include a purely high bleeding risk population, and he said there was still potential to investigate periprocedure versus postprocedure aspirin administration.

The STOPDAPT-3 trial was funded by Abbott Medical Japan. Dr. Natsuaki reported receiving honoraria from Abbott Medical Japan, Daiichi Sankyo, and Bayer.

A version of this article first appeared on Medscape.com.

The European Society of Cardiology has released new guidelines for cardiomyopathies, their first major comprehensive international guidelines to address diagnosis and treatment of the broad causes of heart muscle dysfunction.

The document was released in conjunction with the annual congress of the European Society of Cardiology and is also available online in the European Heart Journal.

“We have considered cardiomyopathies across the life course from pediatric to adult,” explained Elena Arbelo, MD, PhD, coordinator of the cardiac genetic diseases and sudden arrhythmic death unit, Hospital Clinic de Barcelona. Dr. Arbelo is first author and one of two chairpersons of the ESC task force that brought the guidelines forward.

Not an update, the ESC guidelines are the first to “include all cardiomyopathy subtypes, and the first time that specific recommendations are made for cardiomyopathies other than hypertrophic cardiomyopathy” (HCM), Dr. Arbelo said.
 

Guidelines organize cardiomyopathy phenotypes

Cardiomyopathy can present at any age. It can have multiple complex etiologies, including genetic predisposition, heart muscle injury caused by disease, or a mix of participating factors. The ESC task force employed several strategies in taking a comprehensive approach to the condition, said Juan Kaski, MD, PhD, professor of pediatric inherited cardiovascular medicine at the University College of London.

“From my point of view, the key innovations include a diagnostic workup that starts with a detailed phenotypic description, including the new phenotype of nondilated left ventricular cardiomyopathy, that then triggers a multiparametric, systematic evaluation,” said Dr. Kaski, cochair of the task force.

As explained in the introduction to the guideline and reiterated by both Dr. Arbelo and Dr. Kaski, the guidelines have been organized around the patient pathway, meaning that focus should be placed on recognizing the presenting phenotype as a critical first step in discerning the underlying etiology and its treatments.

“Central to this approach is not only the individual patient but also the family as a whole,” Dr. Arbelo said. “Clinical findings in relatives are essential for understanding what happens to the patient and vice versa.”
 

Genetic testing in children described

The new guidelines include specific recommendations about genetic testing of children. They also emphasize the value of cardiovascular magnetic resonance (CMR) imaging in the “diagnosis, screening, monitoring, and prognostication” for patients of all ages, according to Dr. Kaski.

“CMR is recommended at the initial evaluation for every patient with cardiomyopathy,” Dr. Arbelo said. It should be “considered” during follow-up and for many other applications, including the evaluation of “genotype-positive but phenotype-negative relatives.”

Etiologic prediction models have been incorporated into the guidelines, including genotyping for dilated cardiomyopathies and nondilated left ventricular cardiomyopathy, said both Dr. Arbelo and Dr. Kaski, interviewed separately. They both indicated that the task force did their best to make the guidelines user friendly.

Each of the recommendations in the guidelines is provided with an evidence-based classification. In order, these are class I (recommended), class IIa (should be considered), class IIb (may be considered), and class III (not recommended).
 

Many symptoms are cardiomyopathy related

Dr. Kaski and Dr. Arbelo both emphasized that the guidelines draw attention to the relationship of cardiomyopathy to common cardiovascular conditions, such as heart failure, arrhythmia, and chest pain. Dr. Kaski pointed out that these are the types of problems commonly encountered by general cardiologists and well as primary care physicians.

In 2014, the ESC published guidelines specific to HCM. The new broader guidelines do not overlook this subtype. According to Dr. Kaski, there have been several innovations in HCM since the previous guidelines, such as when to consider cardiac myosin inhibitors for symptomatic left ventricular outflow tract obstruction.

The ESC guidelines place an emphasis on a “coordinated, systematic, and individualized” care pathway based on a multidisciplinary approach, according to Dr. Arbelo. Although the composition of the interdisciplinary team depends on the individual case, the guidelines recognize a key role for general cardiologists in managing the majority of patients. Suggestions of when to refer challenging cases to expert centers are outlined.
 

32 key messages derived from guidelines

The guidelines include almost 90 pages of recommendations. The task force isolated 32 key messages from 13 sections ranging from descriptions of how the patient pathway is defined to what types of physical activity should be considered for different forms of cardiomyopathy. There is also a section devoted to important gaps in evidence and areas in which there is the most need for further studies.

The guidelines end with a comprehensive list of “what to do” and “what not to do” in the diagnosis and care of cardiomyopathy. These include most of the class I recommendations and summarize some important class III cautions.

“Most of the recommendations in the guideline are new,” the authors wrote in the introduction. Although they acknowledged that they did not attempt to provide detailed recommendations for every cardiomyopathy phenotype, they endeavored to cover general evaluation and management issues supported by relevant evidence.

Dr. Arbelo and Dr. Kaski disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The European Society of Cardiology has released new guidelines for cardiomyopathies, their first major comprehensive international guidelines to address diagnosis and treatment of the broad causes of heart muscle dysfunction.

The document was released in conjunction with the annual congress of the European Society of Cardiology and is also available online in the European Heart Journal.

“We have considered cardiomyopathies across the life course from pediatric to adult,” explained Elena Arbelo, MD, PhD, coordinator of the cardiac genetic diseases and sudden arrhythmic death unit, Hospital Clinic de Barcelona. Dr. Arbelo is first author and one of two chairpersons of the ESC task force that brought the guidelines forward.

Not an update, the ESC guidelines are the first to “include all cardiomyopathy subtypes, and the first time that specific recommendations are made for cardiomyopathies other than hypertrophic cardiomyopathy” (HCM), Dr. Arbelo said.
 

Guidelines organize cardiomyopathy phenotypes

Cardiomyopathy can present at any age. It can have multiple complex etiologies, including genetic predisposition, heart muscle injury caused by disease, or a mix of participating factors. The ESC task force employed several strategies in taking a comprehensive approach to the condition, said Juan Kaski, MD, PhD, professor of pediatric inherited cardiovascular medicine at the University College of London.

“From my point of view, the key innovations include a diagnostic workup that starts with a detailed phenotypic description, including the new phenotype of nondilated left ventricular cardiomyopathy, that then triggers a multiparametric, systematic evaluation,” said Dr. Kaski, cochair of the task force.

As explained in the introduction to the guideline and reiterated by both Dr. Arbelo and Dr. Kaski, the guidelines have been organized around the patient pathway, meaning that focus should be placed on recognizing the presenting phenotype as a critical first step in discerning the underlying etiology and its treatments.

“Central to this approach is not only the individual patient but also the family as a whole,” Dr. Arbelo said. “Clinical findings in relatives are essential for understanding what happens to the patient and vice versa.”
 

Genetic testing in children described

The new guidelines include specific recommendations about genetic testing of children. They also emphasize the value of cardiovascular magnetic resonance (CMR) imaging in the “diagnosis, screening, monitoring, and prognostication” for patients of all ages, according to Dr. Kaski.

“CMR is recommended at the initial evaluation for every patient with cardiomyopathy,” Dr. Arbelo said. It should be “considered” during follow-up and for many other applications, including the evaluation of “genotype-positive but phenotype-negative relatives.”

Etiologic prediction models have been incorporated into the guidelines, including genotyping for dilated cardiomyopathies and nondilated left ventricular cardiomyopathy, said both Dr. Arbelo and Dr. Kaski, interviewed separately. They both indicated that the task force did their best to make the guidelines user friendly.

Each of the recommendations in the guidelines is provided with an evidence-based classification. In order, these are class I (recommended), class IIa (should be considered), class IIb (may be considered), and class III (not recommended).
 

Many symptoms are cardiomyopathy related

Dr. Kaski and Dr. Arbelo both emphasized that the guidelines draw attention to the relationship of cardiomyopathy to common cardiovascular conditions, such as heart failure, arrhythmia, and chest pain. Dr. Kaski pointed out that these are the types of problems commonly encountered by general cardiologists and well as primary care physicians.

In 2014, the ESC published guidelines specific to HCM. The new broader guidelines do not overlook this subtype. According to Dr. Kaski, there have been several innovations in HCM since the previous guidelines, such as when to consider cardiac myosin inhibitors for symptomatic left ventricular outflow tract obstruction.

The ESC guidelines place an emphasis on a “coordinated, systematic, and individualized” care pathway based on a multidisciplinary approach, according to Dr. Arbelo. Although the composition of the interdisciplinary team depends on the individual case, the guidelines recognize a key role for general cardiologists in managing the majority of patients. Suggestions of when to refer challenging cases to expert centers are outlined.
 

32 key messages derived from guidelines

The guidelines include almost 90 pages of recommendations. The task force isolated 32 key messages from 13 sections ranging from descriptions of how the patient pathway is defined to what types of physical activity should be considered for different forms of cardiomyopathy. There is also a section devoted to important gaps in evidence and areas in which there is the most need for further studies.

The guidelines end with a comprehensive list of “what to do” and “what not to do” in the diagnosis and care of cardiomyopathy. These include most of the class I recommendations and summarize some important class III cautions.

“Most of the recommendations in the guideline are new,” the authors wrote in the introduction. Although they acknowledged that they did not attempt to provide detailed recommendations for every cardiomyopathy phenotype, they endeavored to cover general evaluation and management issues supported by relevant evidence.

Dr. Arbelo and Dr. Kaski disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The European Society of Cardiology has released new guidelines for cardiomyopathies, their first major comprehensive international guidelines to address diagnosis and treatment of the broad causes of heart muscle dysfunction.

The document was released in conjunction with the annual congress of the European Society of Cardiology and is also available online in the European Heart Journal.

“We have considered cardiomyopathies across the life course from pediatric to adult,” explained Elena Arbelo, MD, PhD, coordinator of the cardiac genetic diseases and sudden arrhythmic death unit, Hospital Clinic de Barcelona. Dr. Arbelo is first author and one of two chairpersons of the ESC task force that brought the guidelines forward.

Not an update, the ESC guidelines are the first to “include all cardiomyopathy subtypes, and the first time that specific recommendations are made for cardiomyopathies other than hypertrophic cardiomyopathy” (HCM), Dr. Arbelo said.
 

Guidelines organize cardiomyopathy phenotypes

Cardiomyopathy can present at any age. It can have multiple complex etiologies, including genetic predisposition, heart muscle injury caused by disease, or a mix of participating factors. The ESC task force employed several strategies in taking a comprehensive approach to the condition, said Juan Kaski, MD, PhD, professor of pediatric inherited cardiovascular medicine at the University College of London.

“From my point of view, the key innovations include a diagnostic workup that starts with a detailed phenotypic description, including the new phenotype of nondilated left ventricular cardiomyopathy, that then triggers a multiparametric, systematic evaluation,” said Dr. Kaski, cochair of the task force.

As explained in the introduction to the guideline and reiterated by both Dr. Arbelo and Dr. Kaski, the guidelines have been organized around the patient pathway, meaning that focus should be placed on recognizing the presenting phenotype as a critical first step in discerning the underlying etiology and its treatments.

“Central to this approach is not only the individual patient but also the family as a whole,” Dr. Arbelo said. “Clinical findings in relatives are essential for understanding what happens to the patient and vice versa.”
 

Genetic testing in children described

The new guidelines include specific recommendations about genetic testing of children. They also emphasize the value of cardiovascular magnetic resonance (CMR) imaging in the “diagnosis, screening, monitoring, and prognostication” for patients of all ages, according to Dr. Kaski.

“CMR is recommended at the initial evaluation for every patient with cardiomyopathy,” Dr. Arbelo said. It should be “considered” during follow-up and for many other applications, including the evaluation of “genotype-positive but phenotype-negative relatives.”

Etiologic prediction models have been incorporated into the guidelines, including genotyping for dilated cardiomyopathies and nondilated left ventricular cardiomyopathy, said both Dr. Arbelo and Dr. Kaski, interviewed separately. They both indicated that the task force did their best to make the guidelines user friendly.

Each of the recommendations in the guidelines is provided with an evidence-based classification. In order, these are class I (recommended), class IIa (should be considered), class IIb (may be considered), and class III (not recommended).
 

Many symptoms are cardiomyopathy related

Dr. Kaski and Dr. Arbelo both emphasized that the guidelines draw attention to the relationship of cardiomyopathy to common cardiovascular conditions, such as heart failure, arrhythmia, and chest pain. Dr. Kaski pointed out that these are the types of problems commonly encountered by general cardiologists and well as primary care physicians.

In 2014, the ESC published guidelines specific to HCM. The new broader guidelines do not overlook this subtype. According to Dr. Kaski, there have been several innovations in HCM since the previous guidelines, such as when to consider cardiac myosin inhibitors for symptomatic left ventricular outflow tract obstruction.

The ESC guidelines place an emphasis on a “coordinated, systematic, and individualized” care pathway based on a multidisciplinary approach, according to Dr. Arbelo. Although the composition of the interdisciplinary team depends on the individual case, the guidelines recognize a key role for general cardiologists in managing the majority of patients. Suggestions of when to refer challenging cases to expert centers are outlined.
 

32 key messages derived from guidelines

The guidelines include almost 90 pages of recommendations. The task force isolated 32 key messages from 13 sections ranging from descriptions of how the patient pathway is defined to what types of physical activity should be considered for different forms of cardiomyopathy. There is also a section devoted to important gaps in evidence and areas in which there is the most need for further studies.

The guidelines end with a comprehensive list of “what to do” and “what not to do” in the diagnosis and care of cardiomyopathy. These include most of the class I recommendations and summarize some important class III cautions.

“Most of the recommendations in the guideline are new,” the authors wrote in the introduction. Although they acknowledged that they did not attempt to provide detailed recommendations for every cardiomyopathy phenotype, they endeavored to cover general evaluation and management issues supported by relevant evidence.

Dr. Arbelo and Dr. Kaski disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Minimizing atrial pacing does not alter the risk of atrial fibrillation (AF) associated with sinus node dysfunction (SND), suggest results of a trial that randomly assigned patients with SND who had received their first pacemaker implant to one of two pacing programs.

Over 2 years of follow-up with remote monitoring, there was no difference in the primary endpoint of time to first device-detected episode of AF lasting more than 6 minutes, reported Max Brix Kronborg, MD, PhD, department of cardiology, Aarhus University Hospital, Denmark.

The study, DANPACE II, excluded patients with permanent or persistent AF or persistent bradycardia prior to or at the time of enrollment.

The findings were presented at annual congress of the European Society of Cardiology and were published online simultaneously in the European Heart Journal.

The 539 participants in the trial were randomly assigned in a 1:1 ratio to a pacing program of 60 beats/minute with rate-adaptive pacing (DDR-60) or 40 beats/minute without rate-adaptive pacing (DDD-40). All patients were equipped with remote monitoring and were followed for 2 years. Tracings were adjudicated for atrial high-rate episodes by experienced device specialists, Dr. Kronborg said.
 

No difference seen in primary outcome

When graphed, curves for the primary outcome in the two groups were essentially superimposable. For the secondary outcomes of AF lasting more than 6 hours and AF lasting more than 24 hours, there was a modest but progressive separation in the lines favoring the DDR-60 group for both. However, the P value did not approach significance in the first of these endpoints (P = .35) and remained only a trend (P = .08) in the second.

There were no substantial differences in results when patients were stratified by age (> 73 years vs. younger), gender (women represented 50% of patients), PR interval (> 150 milliseconds vs. less), or history of AF prior to study entry; the latter group represented approximately 40% of the trial participants.

There was a between-group difference in the primary composite safety endpoint of syncope and presyncope. By 2 years, 13% of those in the DDR-60 group had experienced one of these safety events, vs. 22% (P = .01) of the DDD-40 group.

The study was not designed to determine a cause for these episodes, but Dr. Kronborg reported that bradycardia was suspected in the majority of cases.
 

Crossovers more common on minimal pacing

Crossovers were permitted, and 26% of patients did so at some point in the trial. Of these, about one-third were switched to the opposite arm in response to syncope. Almost all of the others crossed over because of chronotropic incompetence. The greater crossover rate in the DDD-40 group (23% vs. 3%; P < .001) was highly significant.

Quality of life was measured with the SF36 tool, and physical function was evaluated with the 6-minute walk distance test (6MWD). Results on these measures did not differ significantly between groups. For 6MWD, the mean gain from baseline was 8 m in both groups.

The results of this study are important because they challenge what has been a widely held perception among electrophysiologists, according to Cecilia Linde, MD, PhD, a professor of cardiology at the Karolinska Institute, Stockholm.

“I think many of us involved in pacing thought for many years that minimizing pacing would be beneficial, and this clearly shows it is not,” said Dr. Linde, who was the moderator of the scientific session in which these results were presented.
 

Results appear definitive

The ESC-invited discussant, Jose L. Merino, MD, PhD, director of arrhythmia and electrophysiology research, La Paz University Hospital, Madrid, concurred. He said these results are convincing.

On the basis of these findings, which not only failed to show a benefit but showed in the experimental arm a higher incidence of syncope and chronotropic incompetence, Dr. Merino concluded, “Programming intended to minimize atrial pacing should not be used as routine in unselected patients with SND.”

A trend for protection from DDR-60 over DDD-40 from the longest episodes of AF caught Dr. Merino’s attention, leading him to question whether the optimal rate of pacing might be even higher than 60 beats/minute in SND, but he said that is a separate issue. DANPACE was not powered to examine the effect in long duration episodes.

Ultimately, while Dr. Merino characterized the increased risk of syncope with minimized pacing as “an important finding” in regard to dissuading clinicians to pursue this strategy, he said that the underlying question of the DANPACE trial remains unanswered.

Pacing remains “a treatment of choice” in SND, but further investigation is needed “about the optimal pacing rate to minimize AF and syncope” in this population, he said.

Dr. Kronborg reports a financial relationship with Abbott. Dr. Linde reports financial relationships with Cardio 3, Medtronic, St. Jude, and Vifor. Dr. Merino reports financial relationships with Abbott, Medtronic, and Microport.

A version of this article first appeared on Medscape.com.

Minimizing atrial pacing does not alter the risk of atrial fibrillation (AF) associated with sinus node dysfunction (SND), suggest results of a trial that randomly assigned patients with SND who had received their first pacemaker implant to one of two pacing programs.

Over 2 years of follow-up with remote monitoring, there was no difference in the primary endpoint of time to first device-detected episode of AF lasting more than 6 minutes, reported Max Brix Kronborg, MD, PhD, department of cardiology, Aarhus University Hospital, Denmark.

The study, DANPACE II, excluded patients with permanent or persistent AF or persistent bradycardia prior to or at the time of enrollment.

The findings were presented at annual congress of the European Society of Cardiology and were published online simultaneously in the European Heart Journal.

The 539 participants in the trial were randomly assigned in a 1:1 ratio to a pacing program of 60 beats/minute with rate-adaptive pacing (DDR-60) or 40 beats/minute without rate-adaptive pacing (DDD-40). All patients were equipped with remote monitoring and were followed for 2 years. Tracings were adjudicated for atrial high-rate episodes by experienced device specialists, Dr. Kronborg said.
 

No difference seen in primary outcome

When graphed, curves for the primary outcome in the two groups were essentially superimposable. For the secondary outcomes of AF lasting more than 6 hours and AF lasting more than 24 hours, there was a modest but progressive separation in the lines favoring the DDR-60 group for both. However, the P value did not approach significance in the first of these endpoints (P = .35) and remained only a trend (P = .08) in the second.

There were no substantial differences in results when patients were stratified by age (> 73 years vs. younger), gender (women represented 50% of patients), PR interval (> 150 milliseconds vs. less), or history of AF prior to study entry; the latter group represented approximately 40% of the trial participants.

There was a between-group difference in the primary composite safety endpoint of syncope and presyncope. By 2 years, 13% of those in the DDR-60 group had experienced one of these safety events, vs. 22% (P = .01) of the DDD-40 group.

The study was not designed to determine a cause for these episodes, but Dr. Kronborg reported that bradycardia was suspected in the majority of cases.
 

Crossovers more common on minimal pacing

Crossovers were permitted, and 26% of patients did so at some point in the trial. Of these, about one-third were switched to the opposite arm in response to syncope. Almost all of the others crossed over because of chronotropic incompetence. The greater crossover rate in the DDD-40 group (23% vs. 3%; P < .001) was highly significant.

Quality of life was measured with the SF36 tool, and physical function was evaluated with the 6-minute walk distance test (6MWD). Results on these measures did not differ significantly between groups. For 6MWD, the mean gain from baseline was 8 m in both groups.

The results of this study are important because they challenge what has been a widely held perception among electrophysiologists, according to Cecilia Linde, MD, PhD, a professor of cardiology at the Karolinska Institute, Stockholm.

“I think many of us involved in pacing thought for many years that minimizing pacing would be beneficial, and this clearly shows it is not,” said Dr. Linde, who was the moderator of the scientific session in which these results were presented.
 

Results appear definitive

The ESC-invited discussant, Jose L. Merino, MD, PhD, director of arrhythmia and electrophysiology research, La Paz University Hospital, Madrid, concurred. He said these results are convincing.

On the basis of these findings, which not only failed to show a benefit but showed in the experimental arm a higher incidence of syncope and chronotropic incompetence, Dr. Merino concluded, “Programming intended to minimize atrial pacing should not be used as routine in unselected patients with SND.”

A trend for protection from DDR-60 over DDD-40 from the longest episodes of AF caught Dr. Merino’s attention, leading him to question whether the optimal rate of pacing might be even higher than 60 beats/minute in SND, but he said that is a separate issue. DANPACE was not powered to examine the effect in long duration episodes.

Ultimately, while Dr. Merino characterized the increased risk of syncope with minimized pacing as “an important finding” in regard to dissuading clinicians to pursue this strategy, he said that the underlying question of the DANPACE trial remains unanswered.

Pacing remains “a treatment of choice” in SND, but further investigation is needed “about the optimal pacing rate to minimize AF and syncope” in this population, he said.

Dr. Kronborg reports a financial relationship with Abbott. Dr. Linde reports financial relationships with Cardio 3, Medtronic, St. Jude, and Vifor. Dr. Merino reports financial relationships with Abbott, Medtronic, and Microport.

A version of this article first appeared on Medscape.com.

Minimizing atrial pacing does not alter the risk of atrial fibrillation (AF) associated with sinus node dysfunction (SND), suggest results of a trial that randomly assigned patients with SND who had received their first pacemaker implant to one of two pacing programs.

Over 2 years of follow-up with remote monitoring, there was no difference in the primary endpoint of time to first device-detected episode of AF lasting more than 6 minutes, reported Max Brix Kronborg, MD, PhD, department of cardiology, Aarhus University Hospital, Denmark.

The study, DANPACE II, excluded patients with permanent or persistent AF or persistent bradycardia prior to or at the time of enrollment.

The findings were presented at annual congress of the European Society of Cardiology and were published online simultaneously in the European Heart Journal.

The 539 participants in the trial were randomly assigned in a 1:1 ratio to a pacing program of 60 beats/minute with rate-adaptive pacing (DDR-60) or 40 beats/minute without rate-adaptive pacing (DDD-40). All patients were equipped with remote monitoring and were followed for 2 years. Tracings were adjudicated for atrial high-rate episodes by experienced device specialists, Dr. Kronborg said.
 

No difference seen in primary outcome

When graphed, curves for the primary outcome in the two groups were essentially superimposable. For the secondary outcomes of AF lasting more than 6 hours and AF lasting more than 24 hours, there was a modest but progressive separation in the lines favoring the DDR-60 group for both. However, the P value did not approach significance in the first of these endpoints (P = .35) and remained only a trend (P = .08) in the second.

There were no substantial differences in results when patients were stratified by age (> 73 years vs. younger), gender (women represented 50% of patients), PR interval (> 150 milliseconds vs. less), or history of AF prior to study entry; the latter group represented approximately 40% of the trial participants.

There was a between-group difference in the primary composite safety endpoint of syncope and presyncope. By 2 years, 13% of those in the DDR-60 group had experienced one of these safety events, vs. 22% (P = .01) of the DDD-40 group.

The study was not designed to determine a cause for these episodes, but Dr. Kronborg reported that bradycardia was suspected in the majority of cases.
 

Crossovers more common on minimal pacing

Crossovers were permitted, and 26% of patients did so at some point in the trial. Of these, about one-third were switched to the opposite arm in response to syncope. Almost all of the others crossed over because of chronotropic incompetence. The greater crossover rate in the DDD-40 group (23% vs. 3%; P < .001) was highly significant.

Quality of life was measured with the SF36 tool, and physical function was evaluated with the 6-minute walk distance test (6MWD). Results on these measures did not differ significantly between groups. For 6MWD, the mean gain from baseline was 8 m in both groups.

The results of this study are important because they challenge what has been a widely held perception among electrophysiologists, according to Cecilia Linde, MD, PhD, a professor of cardiology at the Karolinska Institute, Stockholm.

“I think many of us involved in pacing thought for many years that minimizing pacing would be beneficial, and this clearly shows it is not,” said Dr. Linde, who was the moderator of the scientific session in which these results were presented.
 

Results appear definitive

The ESC-invited discussant, Jose L. Merino, MD, PhD, director of arrhythmia and electrophysiology research, La Paz University Hospital, Madrid, concurred. He said these results are convincing.

On the basis of these findings, which not only failed to show a benefit but showed in the experimental arm a higher incidence of syncope and chronotropic incompetence, Dr. Merino concluded, “Programming intended to minimize atrial pacing should not be used as routine in unselected patients with SND.”

A trend for protection from DDR-60 over DDD-40 from the longest episodes of AF caught Dr. Merino’s attention, leading him to question whether the optimal rate of pacing might be even higher than 60 beats/minute in SND, but he said that is a separate issue. DANPACE was not powered to examine the effect in long duration episodes.

Ultimately, while Dr. Merino characterized the increased risk of syncope with minimized pacing as “an important finding” in regard to dissuading clinicians to pursue this strategy, he said that the underlying question of the DANPACE trial remains unanswered.

Pacing remains “a treatment of choice” in SND, but further investigation is needed “about the optimal pacing rate to minimize AF and syncope” in this population, he said.

Dr. Kronborg reports a financial relationship with Abbott. Dr. Linde reports financial relationships with Cardio 3, Medtronic, St. Jude, and Vifor. Dr. Merino reports financial relationships with Abbott, Medtronic, and Microport.

A version of this article first appeared on Medscape.com.

One of the hardest tasks of a clinician is applying evidence from trials to the person in your office. At the annual congress of the European Society of Cardiology, the surprising and unexpected results of the FRAIL-AF trial confirm the massive challenge of evidence translation.

FRAIL-AF investigators set out to study the question of whether frail, elderly patients with atrial fibrillation who were doing well with vitamin K antagonists (VKA) should be switched to direct-acting oral anticoagulants (DOAC).

Senior author Geert-Jan Geersing, MD, PhD, from the University Medical Center Utrecht (the Netherlands), told me that frustration led him to design this study. He was frustrated that colleagues assumed that evidence in nonfrail patients can always be translated to frail patients. 

Dr. Geersing offered two reasons why common wisdom may be wrong. First was that the large DOAC versus warfarin trials included few elderly patients with frailty. Second, first author Linda Joosten, MD, made it clear in her presentation that frailty is a lot more than aging. It is a clinical syndrome, which entails a “high burden of comorbidities, dependency on others, and a reduced ability to resist stressors.”
 

The FRAIL-AF trial

The investigators recruited elderly, frail patients with fibrillation who were treated with VKAs and had stable international normalized ratios from outpatient clinics throughout the Netherlands. They screened about 2,600 patients and enrolled nearly 1,400. Most were excluded for not being frail.

Half the group was randomized to switching to a DOAC – drug choice was left to the treating clinician – and the other half remained on VKAs. Patients were 83 years of age on average with a mean CHA2DS2-VASc score of 4. All four classes of DOAC were used in the switching arm.

The primary endpoint was major or clinically relevant nonmajor bleeding, whichever came first, accounting for death as a competing risk. Follow-up was 1 year.
 

The results for switching to DOAC vs. VKA

Dr. Joosten started her presentation with this: “The results turned out to be different than we expected.” The authors designed the trial with the idea that switching to DOACs would be superior in safety to remaining on VKAs.

But the trial was halted after an interim analysis found a rate of major bleeding in the switching arm of 15.3% versus 9.4% in the arm staying on VKA (hazard ratio, 1.69; 95% confidence interval, 1.23-2.32; P = .0012).

The Kaplan-Meier event curves reveal that the excess risk of bleeding occurred after 100 days and increased with time. This argued against an early effect from transitioning the drugs.

An analysis looking at specific DOAC drugs revealed similar hazards for the two most common ones used – apixaban and rivaroxaban.

Thrombotic events were a secondary endpoint and were low in absolute numbers, 2.4% versus 2.0%, for remaining on VKA and switching to DOAC, respectively (HR, 1.26; 95% CI, 0.60-2.61).

The time in therapeutic range in FRAIL-AF was similar to that in the seminal DOAC trials.
 

Comments

Three reasons lead me to choose FRAIL-AF as the most important study from the 2023 ESC congress.

First is the specific lesson about switching drugs. Note that FRAIL-AF did not address the question of starting anticoagulation. The trial results show that if you have a frail older patient who is doing well on VKA, don’t change to a DOAC. That is important to know, but it is not what gives this study its heft.

The second reason centers on the investigators choice to do this trial. Dr. Geersing had a feeling that common wisdom was wrong. He did not try to persuade colleagues with anecdote or plausibility or meta-analyses of observational studies. He set out to answer a question in the correct way – with a randomized trial.

This is the path forward in medicine. I’ve often heard proponents of observational research declare that many topics in medicine cannot be studied with trials. I could hear people arguing that it’s not feasible to study mostly home-bound, elderly frail patients. And the fact that there exist so few trials in this space would support that argument.

But the FRAIL-AF authors showed that it is possible. This is the kind of science that medicine should celebrate. There were no soft endpoints, financial conflicts, or spin. If medical science had science as its incentive, rather than attention, FRAIL-AF easily wins top honors.

The third reason FRAIL-AF is so important is that it teaches us the humility required in translating evidence in our clinics. I like to say evidence is what separates doctors from palm readers. But using this evidence requires thinking hard about how average effects in trial environments apply to our patient.

Yes, of course, there is clear evidence from tens of thousands of patients in the DOAC versus warfarin trials, that, for those patients, on average, DOACs compare favorably with VKA. The average age of patients in these trials was 70-73 years; the average age in FRAIL-AF was 83 years. And that is just age. A substudy of the ENGAGE AF-TIMI 48 trial found that only 360 of more than 20,000 patients in the trial had severe frailty.

FRAIL-AF clearly shows how cautious we should be in applying evidence gathered in younger, healthier patients to older, more vulnerable patients. That lesson extends to nearly every common therapy in medicine today. It also casts great doubt on the soft-thinking idea of using evidence from trials to derive quality metrics. As if the nuance of evidence translation can be captured in an electronic health record.

The skillful use of evidence will be one of the main challenges of the next generation of clinicians. Thanks to advances in medical science, more patients will live long enough to become frail. And the so-called “guideline-directed” therapies may not apply to them.

Dr. Joosten, Dr. Geersing, and the FRAIL-AF team have taught us specific lessons about anticoagulation, but their greatest contribution has been to demonstrate the value of humility in science and the practice of evidence-based medicine.

If you treat patients, no trial at this meeting is more important.

Dr. Mandrola is a clinical electrophysiologist at Baptist Medical Associates, Louisville, Ky. He reported no relevant conflicts of interest.
 

A version of this article first appeared on Medscape.com.

One of the hardest tasks of a clinician is applying evidence from trials to the person in your office. At the annual congress of the European Society of Cardiology, the surprising and unexpected results of the FRAIL-AF trial confirm the massive challenge of evidence translation.

FRAIL-AF investigators set out to study the question of whether frail, elderly patients with atrial fibrillation who were doing well with vitamin K antagonists (VKA) should be switched to direct-acting oral anticoagulants (DOAC).

Senior author Geert-Jan Geersing, MD, PhD, from the University Medical Center Utrecht (the Netherlands), told me that frustration led him to design this study. He was frustrated that colleagues assumed that evidence in nonfrail patients can always be translated to frail patients. 

Dr. Geersing offered two reasons why common wisdom may be wrong. First was that the large DOAC versus warfarin trials included few elderly patients with frailty. Second, first author Linda Joosten, MD, made it clear in her presentation that frailty is a lot more than aging. It is a clinical syndrome, which entails a “high burden of comorbidities, dependency on others, and a reduced ability to resist stressors.”
 

The FRAIL-AF trial

The investigators recruited elderly, frail patients with fibrillation who were treated with VKAs and had stable international normalized ratios from outpatient clinics throughout the Netherlands. They screened about 2,600 patients and enrolled nearly 1,400. Most were excluded for not being frail.

Half the group was randomized to switching to a DOAC – drug choice was left to the treating clinician – and the other half remained on VKAs. Patients were 83 years of age on average with a mean CHA2DS2-VASc score of 4. All four classes of DOAC were used in the switching arm.

The primary endpoint was major or clinically relevant nonmajor bleeding, whichever came first, accounting for death as a competing risk. Follow-up was 1 year.
 

The results for switching to DOAC vs. VKA

Dr. Joosten started her presentation with this: “The results turned out to be different than we expected.” The authors designed the trial with the idea that switching to DOACs would be superior in safety to remaining on VKAs.

But the trial was halted after an interim analysis found a rate of major bleeding in the switching arm of 15.3% versus 9.4% in the arm staying on VKA (hazard ratio, 1.69; 95% confidence interval, 1.23-2.32; P = .0012).

The Kaplan-Meier event curves reveal that the excess risk of bleeding occurred after 100 days and increased with time. This argued against an early effect from transitioning the drugs.

An analysis looking at specific DOAC drugs revealed similar hazards for the two most common ones used – apixaban and rivaroxaban.

Thrombotic events were a secondary endpoint and were low in absolute numbers, 2.4% versus 2.0%, for remaining on VKA and switching to DOAC, respectively (HR, 1.26; 95% CI, 0.60-2.61).

The time in therapeutic range in FRAIL-AF was similar to that in the seminal DOAC trials.
 

Comments

Three reasons lead me to choose FRAIL-AF as the most important study from the 2023 ESC congress.

First is the specific lesson about switching drugs. Note that FRAIL-AF did not address the question of starting anticoagulation. The trial results show that if you have a frail older patient who is doing well on VKA, don’t change to a DOAC. That is important to know, but it is not what gives this study its heft.

The second reason centers on the investigators choice to do this trial. Dr. Geersing had a feeling that common wisdom was wrong. He did not try to persuade colleagues with anecdote or plausibility or meta-analyses of observational studies. He set out to answer a question in the correct way – with a randomized trial.

This is the path forward in medicine. I’ve often heard proponents of observational research declare that many topics in medicine cannot be studied with trials. I could hear people arguing that it’s not feasible to study mostly home-bound, elderly frail patients. And the fact that there exist so few trials in this space would support that argument.

But the FRAIL-AF authors showed that it is possible. This is the kind of science that medicine should celebrate. There were no soft endpoints, financial conflicts, or spin. If medical science had science as its incentive, rather than attention, FRAIL-AF easily wins top honors.

The third reason FRAIL-AF is so important is that it teaches us the humility required in translating evidence in our clinics. I like to say evidence is what separates doctors from palm readers. But using this evidence requires thinking hard about how average effects in trial environments apply to our patient.

Yes, of course, there is clear evidence from tens of thousands of patients in the DOAC versus warfarin trials, that, for those patients, on average, DOACs compare favorably with VKA. The average age of patients in these trials was 70-73 years; the average age in FRAIL-AF was 83 years. And that is just age. A substudy of the ENGAGE AF-TIMI 48 trial found that only 360 of more than 20,000 patients in the trial had severe frailty.

FRAIL-AF clearly shows how cautious we should be in applying evidence gathered in younger, healthier patients to older, more vulnerable patients. That lesson extends to nearly every common therapy in medicine today. It also casts great doubt on the soft-thinking idea of using evidence from trials to derive quality metrics. As if the nuance of evidence translation can be captured in an electronic health record.

The skillful use of evidence will be one of the main challenges of the next generation of clinicians. Thanks to advances in medical science, more patients will live long enough to become frail. And the so-called “guideline-directed” therapies may not apply to them.

Dr. Joosten, Dr. Geersing, and the FRAIL-AF team have taught us specific lessons about anticoagulation, but their greatest contribution has been to demonstrate the value of humility in science and the practice of evidence-based medicine.

If you treat patients, no trial at this meeting is more important.

Dr. Mandrola is a clinical electrophysiologist at Baptist Medical Associates, Louisville, Ky. He reported no relevant conflicts of interest.
 

A version of this article first appeared on Medscape.com.

One of the hardest tasks of a clinician is applying evidence from trials to the person in your office. At the annual congress of the European Society of Cardiology, the surprising and unexpected results of the FRAIL-AF trial confirm the massive challenge of evidence translation.

FRAIL-AF investigators set out to study the question of whether frail, elderly patients with atrial fibrillation who were doing well with vitamin K antagonists (VKA) should be switched to direct-acting oral anticoagulants (DOAC).

Senior author Geert-Jan Geersing, MD, PhD, from the University Medical Center Utrecht (the Netherlands), told me that frustration led him to design this study. He was frustrated that colleagues assumed that evidence in nonfrail patients can always be translated to frail patients. 

Dr. Geersing offered two reasons why common wisdom may be wrong. First was that the large DOAC versus warfarin trials included few elderly patients with frailty. Second, first author Linda Joosten, MD, made it clear in her presentation that frailty is a lot more than aging. It is a clinical syndrome, which entails a “high burden of comorbidities, dependency on others, and a reduced ability to resist stressors.”
 

The FRAIL-AF trial

The investigators recruited elderly, frail patients with fibrillation who were treated with VKAs and had stable international normalized ratios from outpatient clinics throughout the Netherlands. They screened about 2,600 patients and enrolled nearly 1,400. Most were excluded for not being frail.

Half the group was randomized to switching to a DOAC – drug choice was left to the treating clinician – and the other half remained on VKAs. Patients were 83 years of age on average with a mean CHA2DS2-VASc score of 4. All four classes of DOAC were used in the switching arm.

The primary endpoint was major or clinically relevant nonmajor bleeding, whichever came first, accounting for death as a competing risk. Follow-up was 1 year.
 

The results for switching to DOAC vs. VKA

Dr. Joosten started her presentation with this: “The results turned out to be different than we expected.” The authors designed the trial with the idea that switching to DOACs would be superior in safety to remaining on VKAs.

But the trial was halted after an interim analysis found a rate of major bleeding in the switching arm of 15.3% versus 9.4% in the arm staying on VKA (hazard ratio, 1.69; 95% confidence interval, 1.23-2.32; P = .0012).

The Kaplan-Meier event curves reveal that the excess risk of bleeding occurred after 100 days and increased with time. This argued against an early effect from transitioning the drugs.

An analysis looking at specific DOAC drugs revealed similar hazards for the two most common ones used – apixaban and rivaroxaban.

Thrombotic events were a secondary endpoint and were low in absolute numbers, 2.4% versus 2.0%, for remaining on VKA and switching to DOAC, respectively (HR, 1.26; 95% CI, 0.60-2.61).

The time in therapeutic range in FRAIL-AF was similar to that in the seminal DOAC trials.
 

Comments

Three reasons lead me to choose FRAIL-AF as the most important study from the 2023 ESC congress.

First is the specific lesson about switching drugs. Note that FRAIL-AF did not address the question of starting anticoagulation. The trial results show that if you have a frail older patient who is doing well on VKA, don’t change to a DOAC. That is important to know, but it is not what gives this study its heft.

The second reason centers on the investigators choice to do this trial. Dr. Geersing had a feeling that common wisdom was wrong. He did not try to persuade colleagues with anecdote or plausibility or meta-analyses of observational studies. He set out to answer a question in the correct way – with a randomized trial.

This is the path forward in medicine. I’ve often heard proponents of observational research declare that many topics in medicine cannot be studied with trials. I could hear people arguing that it’s not feasible to study mostly home-bound, elderly frail patients. And the fact that there exist so few trials in this space would support that argument.

But the FRAIL-AF authors showed that it is possible. This is the kind of science that medicine should celebrate. There were no soft endpoints, financial conflicts, or spin. If medical science had science as its incentive, rather than attention, FRAIL-AF easily wins top honors.

The third reason FRAIL-AF is so important is that it teaches us the humility required in translating evidence in our clinics. I like to say evidence is what separates doctors from palm readers. But using this evidence requires thinking hard about how average effects in trial environments apply to our patient.

Yes, of course, there is clear evidence from tens of thousands of patients in the DOAC versus warfarin trials, that, for those patients, on average, DOACs compare favorably with VKA. The average age of patients in these trials was 70-73 years; the average age in FRAIL-AF was 83 years. And that is just age. A substudy of the ENGAGE AF-TIMI 48 trial found that only 360 of more than 20,000 patients in the trial had severe frailty.

FRAIL-AF clearly shows how cautious we should be in applying evidence gathered in younger, healthier patients to older, more vulnerable patients. That lesson extends to nearly every common therapy in medicine today. It also casts great doubt on the soft-thinking idea of using evidence from trials to derive quality metrics. As if the nuance of evidence translation can be captured in an electronic health record.

The skillful use of evidence will be one of the main challenges of the next generation of clinicians. Thanks to advances in medical science, more patients will live long enough to become frail. And the so-called “guideline-directed” therapies may not apply to them.

Dr. Joosten, Dr. Geersing, and the FRAIL-AF team have taught us specific lessons about anticoagulation, but their greatest contribution has been to demonstrate the value of humility in science and the practice of evidence-based medicine.

If you treat patients, no trial at this meeting is more important.

Dr. Mandrola is a clinical electrophysiologist at Baptist Medical Associates, Louisville, Ky. He reported no relevant conflicts of interest.
 

A version of this article first appeared on Medscape.com.