ESC Congress 2015

LONDON – Celecoxib was associated with very low cardiovascular event rates, and its use posed no more risk than other painkillers commonly used to treat elderly individuals with arthritic conditions but no heart disease in a large, pragmatic, family practice–based study.

Results of the Standard Care Versus Celecoxib Outcome Trial (SCOT) reported at the annual congress of the European Society of Cardiology also showed that celecoxib was no more likely than nonselective nonsteroidal anti-inflammatory drugs (nsNSAIDs) to cause ulcer-related upper gastrointestinal (GI) tract complications.

In fact, the rates of both cardiovascular and GI events were so low overall that it made the trial difficult to complete, said study investigator Dr. Tom MacDonald, professor of clinical pharmacology and pharmacoepidemiology at the University of Dundee (Scotland), which sponsored the study.

The on-treatment and intention-to-treat (ITT) cardiovascular event rates were 0.9% and 1.1% per 100 patient-years, he observed, adding that he would have expected the event rate to be around 2%-3% in the population studied. GI complication rates were even lower, with just 12 on-treatment and 15 ITT events reported during the entire follow-up period, which was a maximum of 6.3 years and mean of about 3 years.

“You may remember the brouhaha surrounding the use of rofecoxib and other [cyclo-oxygenase-2 inhibitors],” said Dr. MacDonald. Both coxibs and nsNSAIDs have been associated with adverse cardiovascular outcomes such as myocardial infarction (BMJ 2005;330:1366), and rofecoxib was voluntarily withdrawn in 2004 by its manufacturer from the U.S. market. A recent meta-analysis (Lancet 2013;382:769-79) has suggested that coxibs increase the risk of major cardiovascular events by about 37%.

The SCOT study (BMJ Open 2013;3:e002295) was designed to assess if celecoxib was better, worse, or the same as the other available NSAIDs in terms of its cardiovascular and gastrointestinal safety. It was originally set up because of a requirement by the European Medicines Agency, Dr. McDonald explained.

More than 9,400 patients aged 60 years or older with osteoarthritis or rheumatoid arthritis who were prescribed chronic NSAID therapy and had no existing cardiovascular disease were screened at 706 family practices in Scotland, England, Denmark, and the Netherlands. A total of 7,297 patients were included in the prospective study and were randomized to switch to treatment with celecoxib or to continue their current nsNSAID.

General practice records were linked to hospital and mortality databases to derive the primary composite endpoint of the first occurrence of hospitalization for nonfatal MI, nonfatal stroke, or cardiovascular death, as well as secondary endpoints such as time to first hospitalization or death from upper GI complications and all-cause mortality.

Randomized patients were about 68 years old, and about 40% of patients were male. Dr. MacDonald noted that, although there was no known existing cardiovascular disease at enrollment, the baseline characteristics showed that around 44% of patients had high blood pressure; a third of patients had high cholesterol; and 20%, 12%, and 38% were taking a statin, aspirin, or ulcer-healing treatments, respectively. The most common nsNSAIDs being used were diclofenac (38.7%) and ibuprofen (31%).

There was no significant difference between celecoxib or nsNSAIDs for any of the cardiovascular endpoints studied, with hazard ratios (HR) for the primary composite cardiovascular endpoints of 1.12 (95% confidence interval, 0.81-1.55; P = .5) while on celecoxib treatment and 1.04 (95% CI, 0.81-1.33; P = .75) in the ITT analysis. Similar results were obtained for all-cause mortality (HR, 1.2 and 0.92, respectively).

Dr. MacDonald reported that 50% of patients randomized to celecoxib and 30% randomized to continue nsNSAIDs withdrew from the study. The main reasons for stopping celecoxib were a lack of efficacy (11.2% vs. 2% for nsNSAIDs), adverse events (8.3% vs. 4.4%), patient request (6% vs. 2.3%), not tolerated (3.9% vs. 1.2%), or a serious adverse event (2.6% vs. 1.9%). There was, however, a lot of adverse publicity about the coxibs, he noted, and patients who had been happy on an nsNSAID might not have been happy with the switch.

The rates of serious cardiovascular adverse events (31.7% vs. 32.4%) or reactions (5.2% vs. 5.8%) were similar with celecoxib and nsNSAIDs, but there were significantly fewer serious GI adverse reactions with celecoxib than with nsNSAIDs (38 vs. 66; P = .007). Overall, the adverse reaction rate was 22% vs. 16.1%, respectively (P <.001).

“In the study population, nsNSAIDs and celecoxib both appeared acceptably safe,” Dr. MacDonald concluded. “In patients who get significant symptomatic relief from these medicines, the benefit/risk balance appears positive.”

Although the findings are perhaps reassuring, they are unlikely to change clinical practice, observed Dr. José López-Sendon, who was invited to comment on the study results after their presentation at the conference.

The study findings suggest that celecoxib may continue to be safe to use in patients without existing cardiac disease, noted Dr. López-Sendon of Hospital Universitario La Paz in Madrid, but he would not modify the guidelines that advise that the lowest effective dose be used for the shortest duration of time in low-risk patients.

The study was sponsored by the University of Dundee and funded by an investigator-initiated research grant from Pfizer. The university’s Medicines Monitoring Unit also holds research grants from Amgen, Menarini, and Novartis. Dr. MacDonald has consulted on the use of NSAIDs for AstraZeneca, NiCox, Novartis, and Pfizer. Dr. López-Sendon did not have any disclosures relevant to his comments.

LONDON – Celecoxib was associated with very low cardiovascular event rates, and its use posed no more risk than other painkillers commonly used to treat elderly individuals with arthritic conditions but no heart disease in a large, pragmatic, family practice–based study.

Results of the Standard Care Versus Celecoxib Outcome Trial (SCOT) reported at the annual congress of the European Society of Cardiology also showed that celecoxib was no more likely than nonselective nonsteroidal anti-inflammatory drugs (nsNSAIDs) to cause ulcer-related upper gastrointestinal (GI) tract complications.

In fact, the rates of both cardiovascular and GI events were so low overall that it made the trial difficult to complete, said study investigator Dr. Tom MacDonald, professor of clinical pharmacology and pharmacoepidemiology at the University of Dundee (Scotland), which sponsored the study.

The on-treatment and intention-to-treat (ITT) cardiovascular event rates were 0.9% and 1.1% per 100 patient-years, he observed, adding that he would have expected the event rate to be around 2%-3% in the population studied. GI complication rates were even lower, with just 12 on-treatment and 15 ITT events reported during the entire follow-up period, which was a maximum of 6.3 years and mean of about 3 years.

“You may remember the brouhaha surrounding the use of rofecoxib and other [cyclo-oxygenase-2 inhibitors],” said Dr. MacDonald. Both coxibs and nsNSAIDs have been associated with adverse cardiovascular outcomes such as myocardial infarction (BMJ 2005;330:1366), and rofecoxib was voluntarily withdrawn in 2004 by its manufacturer from the U.S. market. A recent meta-analysis (Lancet 2013;382:769-79) has suggested that coxibs increase the risk of major cardiovascular events by about 37%.

The SCOT study (BMJ Open 2013;3:e002295) was designed to assess if celecoxib was better, worse, or the same as the other available NSAIDs in terms of its cardiovascular and gastrointestinal safety. It was originally set up because of a requirement by the European Medicines Agency, Dr. McDonald explained.

More than 9,400 patients aged 60 years or older with osteoarthritis or rheumatoid arthritis who were prescribed chronic NSAID therapy and had no existing cardiovascular disease were screened at 706 family practices in Scotland, England, Denmark, and the Netherlands. A total of 7,297 patients were included in the prospective study and were randomized to switch to treatment with celecoxib or to continue their current nsNSAID.

General practice records were linked to hospital and mortality databases to derive the primary composite endpoint of the first occurrence of hospitalization for nonfatal MI, nonfatal stroke, or cardiovascular death, as well as secondary endpoints such as time to first hospitalization or death from upper GI complications and all-cause mortality.

Randomized patients were about 68 years old, and about 40% of patients were male. Dr. MacDonald noted that, although there was no known existing cardiovascular disease at enrollment, the baseline characteristics showed that around 44% of patients had high blood pressure; a third of patients had high cholesterol; and 20%, 12%, and 38% were taking a statin, aspirin, or ulcer-healing treatments, respectively. The most common nsNSAIDs being used were diclofenac (38.7%) and ibuprofen (31%).

There was no significant difference between celecoxib or nsNSAIDs for any of the cardiovascular endpoints studied, with hazard ratios (HR) for the primary composite cardiovascular endpoints of 1.12 (95% confidence interval, 0.81-1.55; P = .5) while on celecoxib treatment and 1.04 (95% CI, 0.81-1.33; P = .75) in the ITT analysis. Similar results were obtained for all-cause mortality (HR, 1.2 and 0.92, respectively).

Dr. MacDonald reported that 50% of patients randomized to celecoxib and 30% randomized to continue nsNSAIDs withdrew from the study. The main reasons for stopping celecoxib were a lack of efficacy (11.2% vs. 2% for nsNSAIDs), adverse events (8.3% vs. 4.4%), patient request (6% vs. 2.3%), not tolerated (3.9% vs. 1.2%), or a serious adverse event (2.6% vs. 1.9%). There was, however, a lot of adverse publicity about the coxibs, he noted, and patients who had been happy on an nsNSAID might not have been happy with the switch.

The rates of serious cardiovascular adverse events (31.7% vs. 32.4%) or reactions (5.2% vs. 5.8%) were similar with celecoxib and nsNSAIDs, but there were significantly fewer serious GI adverse reactions with celecoxib than with nsNSAIDs (38 vs. 66; P = .007). Overall, the adverse reaction rate was 22% vs. 16.1%, respectively (P <.001).

“In the study population, nsNSAIDs and celecoxib both appeared acceptably safe,” Dr. MacDonald concluded. “In patients who get significant symptomatic relief from these medicines, the benefit/risk balance appears positive.”

Although the findings are perhaps reassuring, they are unlikely to change clinical practice, observed Dr. José López-Sendon, who was invited to comment on the study results after their presentation at the conference.

The study findings suggest that celecoxib may continue to be safe to use in patients without existing cardiac disease, noted Dr. López-Sendon of Hospital Universitario La Paz in Madrid, but he would not modify the guidelines that advise that the lowest effective dose be used for the shortest duration of time in low-risk patients.

The study was sponsored by the University of Dundee and funded by an investigator-initiated research grant from Pfizer. The university’s Medicines Monitoring Unit also holds research grants from Amgen, Menarini, and Novartis. Dr. MacDonald has consulted on the use of NSAIDs for AstraZeneca, NiCox, Novartis, and Pfizer. Dr. López-Sendon did not have any disclosures relevant to his comments.

LONDON – Celecoxib was associated with very low cardiovascular event rates, and its use posed no more risk than other painkillers commonly used to treat elderly individuals with arthritic conditions but no heart disease in a large, pragmatic, family practice–based study.

Results of the Standard Care Versus Celecoxib Outcome Trial (SCOT) reported at the annual congress of the European Society of Cardiology also showed that celecoxib was no more likely than nonselective nonsteroidal anti-inflammatory drugs (nsNSAIDs) to cause ulcer-related upper gastrointestinal (GI) tract complications.

In fact, the rates of both cardiovascular and GI events were so low overall that it made the trial difficult to complete, said study investigator Dr. Tom MacDonald, professor of clinical pharmacology and pharmacoepidemiology at the University of Dundee (Scotland), which sponsored the study.

The on-treatment and intention-to-treat (ITT) cardiovascular event rates were 0.9% and 1.1% per 100 patient-years, he observed, adding that he would have expected the event rate to be around 2%-3% in the population studied. GI complication rates were even lower, with just 12 on-treatment and 15 ITT events reported during the entire follow-up period, which was a maximum of 6.3 years and mean of about 3 years.

“You may remember the brouhaha surrounding the use of rofecoxib and other [cyclo-oxygenase-2 inhibitors],” said Dr. MacDonald. Both coxibs and nsNSAIDs have been associated with adverse cardiovascular outcomes such as myocardial infarction (BMJ 2005;330:1366), and rofecoxib was voluntarily withdrawn in 2004 by its manufacturer from the U.S. market. A recent meta-analysis (Lancet 2013;382:769-79) has suggested that coxibs increase the risk of major cardiovascular events by about 37%.

The SCOT study (BMJ Open 2013;3:e002295) was designed to assess if celecoxib was better, worse, or the same as the other available NSAIDs in terms of its cardiovascular and gastrointestinal safety. It was originally set up because of a requirement by the European Medicines Agency, Dr. McDonald explained.

More than 9,400 patients aged 60 years or older with osteoarthritis or rheumatoid arthritis who were prescribed chronic NSAID therapy and had no existing cardiovascular disease were screened at 706 family practices in Scotland, England, Denmark, and the Netherlands. A total of 7,297 patients were included in the prospective study and were randomized to switch to treatment with celecoxib or to continue their current nsNSAID.

General practice records were linked to hospital and mortality databases to derive the primary composite endpoint of the first occurrence of hospitalization for nonfatal MI, nonfatal stroke, or cardiovascular death, as well as secondary endpoints such as time to first hospitalization or death from upper GI complications and all-cause mortality.

Randomized patients were about 68 years old, and about 40% of patients were male. Dr. MacDonald noted that, although there was no known existing cardiovascular disease at enrollment, the baseline characteristics showed that around 44% of patients had high blood pressure; a third of patients had high cholesterol; and 20%, 12%, and 38% were taking a statin, aspirin, or ulcer-healing treatments, respectively. The most common nsNSAIDs being used were diclofenac (38.7%) and ibuprofen (31%).

There was no significant difference between celecoxib or nsNSAIDs for any of the cardiovascular endpoints studied, with hazard ratios (HR) for the primary composite cardiovascular endpoints of 1.12 (95% confidence interval, 0.81-1.55; P = .5) while on celecoxib treatment and 1.04 (95% CI, 0.81-1.33; P = .75) in the ITT analysis. Similar results were obtained for all-cause mortality (HR, 1.2 and 0.92, respectively).

Dr. MacDonald reported that 50% of patients randomized to celecoxib and 30% randomized to continue nsNSAIDs withdrew from the study. The main reasons for stopping celecoxib were a lack of efficacy (11.2% vs. 2% for nsNSAIDs), adverse events (8.3% vs. 4.4%), patient request (6% vs. 2.3%), not tolerated (3.9% vs. 1.2%), or a serious adverse event (2.6% vs. 1.9%). There was, however, a lot of adverse publicity about the coxibs, he noted, and patients who had been happy on an nsNSAID might not have been happy with the switch.

The rates of serious cardiovascular adverse events (31.7% vs. 32.4%) or reactions (5.2% vs. 5.8%) were similar with celecoxib and nsNSAIDs, but there were significantly fewer serious GI adverse reactions with celecoxib than with nsNSAIDs (38 vs. 66; P = .007). Overall, the adverse reaction rate was 22% vs. 16.1%, respectively (P <.001).

“In the study population, nsNSAIDs and celecoxib both appeared acceptably safe,” Dr. MacDonald concluded. “In patients who get significant symptomatic relief from these medicines, the benefit/risk balance appears positive.”

Although the findings are perhaps reassuring, they are unlikely to change clinical practice, observed Dr. José López-Sendon, who was invited to comment on the study results after their presentation at the conference.

The study findings suggest that celecoxib may continue to be safe to use in patients without existing cardiac disease, noted Dr. López-Sendon of Hospital Universitario La Paz in Madrid, but he would not modify the guidelines that advise that the lowest effective dose be used for the shortest duration of time in low-risk patients.

The study was sponsored by the University of Dundee and funded by an investigator-initiated research grant from Pfizer. The university’s Medicines Monitoring Unit also holds research grants from Amgen, Menarini, and Novartis. Dr. MacDonald has consulted on the use of NSAIDs for AstraZeneca, NiCox, Novartis, and Pfizer. Dr. López-Sendon did not have any disclosures relevant to his comments.

Prescription medications

Photo courtesy of the CDC

LONDON—Patients with atrial fibrillation (AF) who receive the anticoagulant rivaroxaban as stroke prophylaxis have low rates of major bleeding and stroke, according to real-world data from the XANTUS trial.

Investigators said this finding is similar to clinical trial results with rivaroxaban and suggest the drug is safe and effective for stroke prevention in patients with AF who have a high or low risk of thromboembolic events.

The team reported results of the XANTUS trial in the European Heart Journal and at the ESC Congress 2015 (abstract 5072). The study was sponsored by Bayer, the company developing rivaroxaban in cooperation with Janssen Pharmaceuticals, Inc.

“The findings reaffirm the positive benefit-risk profile of rivaroxaban established in the phase 3 clinical trial ROCKET AF, in which rivaroxaban was shown to provide effective stroke prevention with a similar overall bleeding profile and significantly lower rates of the most feared intracranial and fatal bleeds compared with vitamin K antagonists,” said John A. Camm, MD, of St. George’s University of London in the UK.

“The patients included in ROCKET AF were at moderate to high risk of stroke, with a mean CHADS2 score of 3.5, and the incidence of major bleeding in those taking rivaroxaban was 3.6 per 100 person-years. In XANTUS, patients seen in daily clinical practice had a lower risk of stroke, with a mean CHADS2 score of 2.0, and the incidence rate of major bleeding was lower, at 2.1 per 100 person-years.”

Patients and treatment

For the XANTUS trial, Dr Camm and his colleagues evaluated the outcomes of rivaroxaban use in 6784 patients with non-valvular AF who were treated at 311 centers across Europe and Canada in routine clinical practice.

Patients had newly diagnosed AF (18.5%), paroxysmal AF (40.6%), persistent AF (13.6%), and permanent AF (27%). For 0.2% of patients, data on their exact diagnosis was missing.

Comorbidities included hypertension (74.7%), diabetes mellitus (19.6%), prior stroke/non-central nervous system systemic embolism/transient ischemic attack (19%), congestive heart failure (18.6%), and prior myocardial infarction (10.1%).

The patients’ mean age was 71.5, and 37.2% were older than 75. Their mean CHADS2 score was 2, and their mean CHA2DS2VASc score was 3.4. A little more than half (54.5%) of patients were vitamin K agonist-naïve.

All treatment and dosing decisions for rivaroxaban were at the discretion of the treating physicians. Patients received the drug at 15 mg (n=1410), 20 mg (n=5336), or other doses (n=35).

They were followed for 1 year or until 30 days after premature treatment discontinuation. Bleeding events and major thromboembolic events were centrally adjudicated by an independent committee.

Results

By the end of the observation period, most patients (96.1%) had not experienced treatment-emergent major bleeding, all-cause death, or stroke/systemic embolism. And the majority of patients (80%) continued taking rivaroxaban throughout the 1-year study period.

The rate of stroke was 0.7% per year, and the annual rate of stroke/systemic embolism was 0.8%.

Overall, 2.1% of patients per year experienced treatment-emergent major bleeding. Non-major bleeding events occurred in 15.4% of patients per year.

The yearly rate of fatal bleeding was 0.2%, critical organ bleeding was 0.7%, intracranial hemorrhage was 0.4%, mucosal bleeding was 1.0%, and gastrointestinal bleeding was 0.9%. In addition, 0.9% of patients required transfusions of 2 or more units of packed red blood cells or whole blood per year.

The rate of on-treatment, all-cause mortality was 1.9% per year. There were 118 deaths in all, and some patients had multiple reasons reported as the cause of death. Causes of death were cardiovascular events (n=49), cancer (n=23), bleeding (n=12), infectious disease (n=10), other (n=16), and unexplained (n=9).

“These real-world insights from XANTUS complement and expand on what we already know from clinical trials and provide physicians with reassurance to prescribe rivaroxaban as an effective and well-tolerated treatment option for the broad range of patients with AF seen in their everyday clinical practice,” Dr Camm concluded.

Prescription medications

Photo courtesy of the CDC

LONDON—Patients with atrial fibrillation (AF) who receive the anticoagulant rivaroxaban as stroke prophylaxis have low rates of major bleeding and stroke, according to real-world data from the XANTUS trial.

Investigators said this finding is similar to clinical trial results with rivaroxaban and suggest the drug is safe and effective for stroke prevention in patients with AF who have a high or low risk of thromboembolic events.

The team reported results of the XANTUS trial in the European Heart Journal and at the ESC Congress 2015 (abstract 5072). The study was sponsored by Bayer, the company developing rivaroxaban in cooperation with Janssen Pharmaceuticals, Inc.

“The findings reaffirm the positive benefit-risk profile of rivaroxaban established in the phase 3 clinical trial ROCKET AF, in which rivaroxaban was shown to provide effective stroke prevention with a similar overall bleeding profile and significantly lower rates of the most feared intracranial and fatal bleeds compared with vitamin K antagonists,” said John A. Camm, MD, of St. George’s University of London in the UK.

“The patients included in ROCKET AF were at moderate to high risk of stroke, with a mean CHADS2 score of 3.5, and the incidence of major bleeding in those taking rivaroxaban was 3.6 per 100 person-years. In XANTUS, patients seen in daily clinical practice had a lower risk of stroke, with a mean CHADS2 score of 2.0, and the incidence rate of major bleeding was lower, at 2.1 per 100 person-years.”

Patients and treatment

For the XANTUS trial, Dr Camm and his colleagues evaluated the outcomes of rivaroxaban use in 6784 patients with non-valvular AF who were treated at 311 centers across Europe and Canada in routine clinical practice.

Patients had newly diagnosed AF (18.5%), paroxysmal AF (40.6%), persistent AF (13.6%), and permanent AF (27%). For 0.2% of patients, data on their exact diagnosis was missing.

Comorbidities included hypertension (74.7%), diabetes mellitus (19.6%), prior stroke/non-central nervous system systemic embolism/transient ischemic attack (19%), congestive heart failure (18.6%), and prior myocardial infarction (10.1%).

The patients’ mean age was 71.5, and 37.2% were older than 75. Their mean CHADS2 score was 2, and their mean CHA2DS2VASc score was 3.4. A little more than half (54.5%) of patients were vitamin K agonist-naïve.

All treatment and dosing decisions for rivaroxaban were at the discretion of the treating physicians. Patients received the drug at 15 mg (n=1410), 20 mg (n=5336), or other doses (n=35).

They were followed for 1 year or until 30 days after premature treatment discontinuation. Bleeding events and major thromboembolic events were centrally adjudicated by an independent committee.

Results

By the end of the observation period, most patients (96.1%) had not experienced treatment-emergent major bleeding, all-cause death, or stroke/systemic embolism. And the majority of patients (80%) continued taking rivaroxaban throughout the 1-year study period.

The rate of stroke was 0.7% per year, and the annual rate of stroke/systemic embolism was 0.8%.

Overall, 2.1% of patients per year experienced treatment-emergent major bleeding. Non-major bleeding events occurred in 15.4% of patients per year.

The yearly rate of fatal bleeding was 0.2%, critical organ bleeding was 0.7%, intracranial hemorrhage was 0.4%, mucosal bleeding was 1.0%, and gastrointestinal bleeding was 0.9%. In addition, 0.9% of patients required transfusions of 2 or more units of packed red blood cells or whole blood per year.

The rate of on-treatment, all-cause mortality was 1.9% per year. There were 118 deaths in all, and some patients had multiple reasons reported as the cause of death. Causes of death were cardiovascular events (n=49), cancer (n=23), bleeding (n=12), infectious disease (n=10), other (n=16), and unexplained (n=9).

“These real-world insights from XANTUS complement and expand on what we already know from clinical trials and provide physicians with reassurance to prescribe rivaroxaban as an effective and well-tolerated treatment option for the broad range of patients with AF seen in their everyday clinical practice,” Dr Camm concluded.

Prescription medications

Photo courtesy of the CDC

LONDON—Patients with atrial fibrillation (AF) who receive the anticoagulant rivaroxaban as stroke prophylaxis have low rates of major bleeding and stroke, according to real-world data from the XANTUS trial.

Investigators said this finding is similar to clinical trial results with rivaroxaban and suggest the drug is safe and effective for stroke prevention in patients with AF who have a high or low risk of thromboembolic events.

The team reported results of the XANTUS trial in the European Heart Journal and at the ESC Congress 2015 (abstract 5072). The study was sponsored by Bayer, the company developing rivaroxaban in cooperation with Janssen Pharmaceuticals, Inc.

“The findings reaffirm the positive benefit-risk profile of rivaroxaban established in the phase 3 clinical trial ROCKET AF, in which rivaroxaban was shown to provide effective stroke prevention with a similar overall bleeding profile and significantly lower rates of the most feared intracranial and fatal bleeds compared with vitamin K antagonists,” said John A. Camm, MD, of St. George’s University of London in the UK.

“The patients included in ROCKET AF were at moderate to high risk of stroke, with a mean CHADS2 score of 3.5, and the incidence of major bleeding in those taking rivaroxaban was 3.6 per 100 person-years. In XANTUS, patients seen in daily clinical practice had a lower risk of stroke, with a mean CHADS2 score of 2.0, and the incidence rate of major bleeding was lower, at 2.1 per 100 person-years.”

Patients and treatment

For the XANTUS trial, Dr Camm and his colleagues evaluated the outcomes of rivaroxaban use in 6784 patients with non-valvular AF who were treated at 311 centers across Europe and Canada in routine clinical practice.

Patients had newly diagnosed AF (18.5%), paroxysmal AF (40.6%), persistent AF (13.6%), and permanent AF (27%). For 0.2% of patients, data on their exact diagnosis was missing.

Comorbidities included hypertension (74.7%), diabetes mellitus (19.6%), prior stroke/non-central nervous system systemic embolism/transient ischemic attack (19%), congestive heart failure (18.6%), and prior myocardial infarction (10.1%).

The patients’ mean age was 71.5, and 37.2% were older than 75. Their mean CHADS2 score was 2, and their mean CHA2DS2VASc score was 3.4. A little more than half (54.5%) of patients were vitamin K agonist-naïve.

All treatment and dosing decisions for rivaroxaban were at the discretion of the treating physicians. Patients received the drug at 15 mg (n=1410), 20 mg (n=5336), or other doses (n=35).

They were followed for 1 year or until 30 days after premature treatment discontinuation. Bleeding events and major thromboembolic events were centrally adjudicated by an independent committee.

Results

By the end of the observation period, most patients (96.1%) had not experienced treatment-emergent major bleeding, all-cause death, or stroke/systemic embolism. And the majority of patients (80%) continued taking rivaroxaban throughout the 1-year study period.

The rate of stroke was 0.7% per year, and the annual rate of stroke/systemic embolism was 0.8%.

Overall, 2.1% of patients per year experienced treatment-emergent major bleeding. Non-major bleeding events occurred in 15.4% of patients per year.

The yearly rate of fatal bleeding was 0.2%, critical organ bleeding was 0.7%, intracranial hemorrhage was 0.4%, mucosal bleeding was 1.0%, and gastrointestinal bleeding was 0.9%. In addition, 0.9% of patients required transfusions of 2 or more units of packed red blood cells or whole blood per year.

The rate of on-treatment, all-cause mortality was 1.9% per year. There were 118 deaths in all, and some patients had multiple reasons reported as the cause of death. Causes of death were cardiovascular events (n=49), cancer (n=23), bleeding (n=12), infectious disease (n=10), other (n=16), and unexplained (n=9).

“These real-world insights from XANTUS complement and expand on what we already know from clinical trials and provide physicians with reassurance to prescribe rivaroxaban as an effective and well-tolerated treatment option for the broad range of patients with AF seen in their everyday clinical practice,” Dr Camm concluded.

Drug-eluting stent

LONDON—Extending dual antiplatelet therapy (DAPT) beyond the recommended 12 months after coronary stenting “should be considered” in patients with a drug-eluting stent (DES) who are at low risk for bleeding, according to investigators from the OPTIDUAL trial.

The study showed that receiving DAPT—aspirin and clopidogrel—for an additional 36 months did not decrease the rate of major adverse cardiovascular and cerebrovascular events (MACCE).

However, there was a suggestion that it might reduce ischemic outcomes without excess bleeding.

“Given the lack of harm and the signal for benefit of prolonged DAPT in the OPTIDUAL trial, and the results from prior randomized trials testing long durations of DAPT, prolongation of DAPT beyond 12 months should be considered in patients without high-risk bleeding who have received a drug-eluting coronary stent and are event-free at 12 months,” said study investigator Gérard Helft, MD, PhD, of Hôpital Universitaire Pitié-Salpétrière in Paris, France.

He presented results of the trial at the ESC Congress 2015 (abstract 3159).

The study included 1385 patients from 58 French sites who had undergone percutaneous coronary intervention with placement of at least 1 DES for either stable coronary artery disease or acute coronary syndrome.

All patients had been on DAPT for 1 year and were randomly assigned to continue or to remain on aspirin alone for an additional 36 months.

There was no significant difference between the groups with regard to MACCE, a composite of all-cause death, myocardial infarction, stroke, and major bleeding. These events occurred in 5.8% of patients in the extended-DAPT group and 7.5% in the aspirin-only group (hazard ratio (HR=0.75, P=0.17).

Likewise, there was no significant difference between the treatment groups for any of the components of MACCE—stroke (HR=0.69, P=0.53), myocardial infarction (HR=0.67, P=0.31), major bleeding (HR=0.98, P=0.95), or death (HR=0.65, P=0.18).

There was a non-significant (but borderline) reduction in ischemic outcomes—a post-hoc outcome composite rate of death, myocardial infarction, or stroke—with extended DAPT. These events occurred in 4.2% of patients in the extended-DAPT group and 6.4% in the aspirin-only group (HR=0.64, P=0.06).

“The results are consistent with the recent findings on ischemic outcomes from the DAPT trial regarding the value of prolonging DAPT after DES placement,” Dr Helft said.

“There was no apparent harm, and the post-hoc efficacy signal on MACCE is consistent with the benefit seen in the DAPT trial. Thus, OPTIDUAL adds to the evidence suggesting benefit to extended DAPT after DES in patients who are event-free at 12 months.”

This study was funded by Assistance Publique - Hôpitaux de Paris and the Fédération Française de Cardiologie, with unrestricted grants from Cordis, Boston, Medtronic, Terumo, and Biotronik.

Drug-eluting stent

LONDON—Extending dual antiplatelet therapy (DAPT) beyond the recommended 12 months after coronary stenting “should be considered” in patients with a drug-eluting stent (DES) who are at low risk for bleeding, according to investigators from the OPTIDUAL trial.

The study showed that receiving DAPT—aspirin and clopidogrel—for an additional 36 months did not decrease the rate of major adverse cardiovascular and cerebrovascular events (MACCE).

However, there was a suggestion that it might reduce ischemic outcomes without excess bleeding.

“Given the lack of harm and the signal for benefit of prolonged DAPT in the OPTIDUAL trial, and the results from prior randomized trials testing long durations of DAPT, prolongation of DAPT beyond 12 months should be considered in patients without high-risk bleeding who have received a drug-eluting coronary stent and are event-free at 12 months,” said study investigator Gérard Helft, MD, PhD, of Hôpital Universitaire Pitié-Salpétrière in Paris, France.

He presented results of the trial at the ESC Congress 2015 (abstract 3159).

The study included 1385 patients from 58 French sites who had undergone percutaneous coronary intervention with placement of at least 1 DES for either stable coronary artery disease or acute coronary syndrome.

All patients had been on DAPT for 1 year and were randomly assigned to continue or to remain on aspirin alone for an additional 36 months.

There was no significant difference between the groups with regard to MACCE, a composite of all-cause death, myocardial infarction, stroke, and major bleeding. These events occurred in 5.8% of patients in the extended-DAPT group and 7.5% in the aspirin-only group (hazard ratio (HR=0.75, P=0.17).

Likewise, there was no significant difference between the treatment groups for any of the components of MACCE—stroke (HR=0.69, P=0.53), myocardial infarction (HR=0.67, P=0.31), major bleeding (HR=0.98, P=0.95), or death (HR=0.65, P=0.18).

There was a non-significant (but borderline) reduction in ischemic outcomes—a post-hoc outcome composite rate of death, myocardial infarction, or stroke—with extended DAPT. These events occurred in 4.2% of patients in the extended-DAPT group and 6.4% in the aspirin-only group (HR=0.64, P=0.06).

“The results are consistent with the recent findings on ischemic outcomes from the DAPT trial regarding the value of prolonging DAPT after DES placement,” Dr Helft said.

“There was no apparent harm, and the post-hoc efficacy signal on MACCE is consistent with the benefit seen in the DAPT trial. Thus, OPTIDUAL adds to the evidence suggesting benefit to extended DAPT after DES in patients who are event-free at 12 months.”

This study was funded by Assistance Publique - Hôpitaux de Paris and the Fédération Française de Cardiologie, with unrestricted grants from Cordis, Boston, Medtronic, Terumo, and Biotronik.

Drug-eluting stent

LONDON—Extending dual antiplatelet therapy (DAPT) beyond the recommended 12 months after coronary stenting “should be considered” in patients with a drug-eluting stent (DES) who are at low risk for bleeding, according to investigators from the OPTIDUAL trial.

The study showed that receiving DAPT—aspirin and clopidogrel—for an additional 36 months did not decrease the rate of major adverse cardiovascular and cerebrovascular events (MACCE).

However, there was a suggestion that it might reduce ischemic outcomes without excess bleeding.

“Given the lack of harm and the signal for benefit of prolonged DAPT in the OPTIDUAL trial, and the results from prior randomized trials testing long durations of DAPT, prolongation of DAPT beyond 12 months should be considered in patients without high-risk bleeding who have received a drug-eluting coronary stent and are event-free at 12 months,” said study investigator Gérard Helft, MD, PhD, of Hôpital Universitaire Pitié-Salpétrière in Paris, France.

He presented results of the trial at the ESC Congress 2015 (abstract 3159).

The study included 1385 patients from 58 French sites who had undergone percutaneous coronary intervention with placement of at least 1 DES for either stable coronary artery disease or acute coronary syndrome.

All patients had been on DAPT for 1 year and were randomly assigned to continue or to remain on aspirin alone for an additional 36 months.

There was no significant difference between the groups with regard to MACCE, a composite of all-cause death, myocardial infarction, stroke, and major bleeding. These events occurred in 5.8% of patients in the extended-DAPT group and 7.5% in the aspirin-only group (hazard ratio (HR=0.75, P=0.17).

Likewise, there was no significant difference between the treatment groups for any of the components of MACCE—stroke (HR=0.69, P=0.53), myocardial infarction (HR=0.67, P=0.31), major bleeding (HR=0.98, P=0.95), or death (HR=0.65, P=0.18).

There was a non-significant (but borderline) reduction in ischemic outcomes—a post-hoc outcome composite rate of death, myocardial infarction, or stroke—with extended DAPT. These events occurred in 4.2% of patients in the extended-DAPT group and 6.4% in the aspirin-only group (HR=0.64, P=0.06).

“The results are consistent with the recent findings on ischemic outcomes from the DAPT trial regarding the value of prolonging DAPT after DES placement,” Dr Helft said.

“There was no apparent harm, and the post-hoc efficacy signal on MACCE is consistent with the benefit seen in the DAPT trial. Thus, OPTIDUAL adds to the evidence suggesting benefit to extended DAPT after DES in patients who are event-free at 12 months.”

This study was funded by Assistance Publique - Hôpitaux de Paris and the Fédération Française de Cardiologie, with unrestricted grants from Cordis, Boston, Medtronic, Terumo, and Biotronik.

LONDON – Bivalirudin did not prove superior to unfractionated heparin in reducing the rate of major adverse cardiovascular events in two nested, open-label, randomized clinical trials involving patients presenting with acute coronary syndrome who were expected to undergo percutaneous coronary intervention, Dr. Marco Valgimigli reported.

In addition, post-PCI infusions of bivalirudin for 4 hours or longer did not reduce the rate of adverse bleeding events, compared with no infusion.

These findings add important data to the understanding of antithrombotic therapy in ACS patients undergoing invasive treatment, but they do not resolve the persistent question of which method is best for preventing thrombotic complications while limiting the risk of bleeding during and after such procedures, said Dr. Valgimigli of Erasmus University in Rotterdam.

Previous studies comparing bivalirudin, a direct thrombin inhibitor, against unfractionated heparin, an indirect thrombin inhibitor, have yielded conflicting results regarding ischemic and bleeding outcomes, so Dr. Valgimigli and his fellow investigators in the MATRIX (Minimizing Adverse Hemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox) trial conducted two industry-sponsored superiority trials to try to settle the question.

The findings of one of these trials were reported by Dr. Valgimigli at the annual congress of the European Society of Cardiology on Sept. 1, when the results of both were simultaneously published online (N Engl J Med. 2015 Sept 1. doi: 10.1056/NEJMoa1507854).

The MATRIX studies were conducted at 78 medical centers in Italy, the Netherlands, Spain, and Sweden. They involved 7,213 patients who presented with either ST-elevation MI or non-STEMI ACS and were expected to undergo PCI. The first trial, MATRIX Antithrombin, assessed outcomes in 3,610 of these participants who were randomly assigned to receive bivalirudin and 3,603 assigned to receive unfractionated heparin. In the second trial, MATRIX Treatment Duration, the bivalirudin group was further randomized to receive either a post-PCI bivalirudin infusion (1,799 patients) or no post-PCI infusion (1,811 patients).

MATRIX Antithrombin

At 1-month follow-up, the rate of major adverse cardiovascular events (MACEs) – a composite of death from any cause, myocardial infarction, or stroke – was no lower in the bivalirudin group (10.3%) than in the heparin group (10.9%), for a rate ratio of 0.94. Similarly, the rate of net adverse clinical events was not significantly lower with bivalirudin (11.2%) than with heparin (12.4%), for a rate ratio of 0.89.

MATRIX Treatment Duration

The primary outcome in the MATRIX Treatment Duration study – a composite of urgent target-vessel revascularization, definite stent thrombosis, or net adverse clinical events at 30 days – occurred in 11.0% of patients who received post-PCI bivalirudin infusions and 11.9% of those who did not, a nonsignificant difference (rate ratio, 0.91). However, the rate of subacute definite stent thrombosis was significantly higher in the post-PCI infusion group, at 0.7%, compared with 0.2% in the group that didn’t receive post-PCI infusions (RR, 4.37).

“I believe the option to prolong or stop bivalirudin infusion after PCI remains open for clinicians, who will have to decide based on the ischemic and bleeding risk of individual patients as well as, perhaps, based on type of acute coronary syndrome, timing of loading dose, and type of oral P2Y12 inhibitors,” Dr. Valgimigli said, noting that this is in keeping with the current labeling of the drug in Europe and the United States.

The MATRIX study was sponsored by the nonprofit Italian Society of Invasive Cardiology and financially supported by the Medicines Company and Terumo Medical. Dr. Valgimigli reported ties to AstraZeneca, the Medicines Company, Terumo Medical, St. Jude Vascular, Alvimedica, Abbott Vascular, and Correvio; his associates reported ties to numerous industry sources.

Mary Ann Moon contributed to this report.

LONDON – Bivalirudin did not prove superior to unfractionated heparin in reducing the rate of major adverse cardiovascular events in two nested, open-label, randomized clinical trials involving patients presenting with acute coronary syndrome who were expected to undergo percutaneous coronary intervention, Dr. Marco Valgimigli reported.

In addition, post-PCI infusions of bivalirudin for 4 hours or longer did not reduce the rate of adverse bleeding events, compared with no infusion.

These findings add important data to the understanding of antithrombotic therapy in ACS patients undergoing invasive treatment, but they do not resolve the persistent question of which method is best for preventing thrombotic complications while limiting the risk of bleeding during and after such procedures, said Dr. Valgimigli of Erasmus University in Rotterdam.

Previous studies comparing bivalirudin, a direct thrombin inhibitor, against unfractionated heparin, an indirect thrombin inhibitor, have yielded conflicting results regarding ischemic and bleeding outcomes, so Dr. Valgimigli and his fellow investigators in the MATRIX (Minimizing Adverse Hemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox) trial conducted two industry-sponsored superiority trials to try to settle the question.

The findings of one of these trials were reported by Dr. Valgimigli at the annual congress of the European Society of Cardiology on Sept. 1, when the results of both were simultaneously published online (N Engl J Med. 2015 Sept 1. doi: 10.1056/NEJMoa1507854).

The MATRIX studies were conducted at 78 medical centers in Italy, the Netherlands, Spain, and Sweden. They involved 7,213 patients who presented with either ST-elevation MI or non-STEMI ACS and were expected to undergo PCI. The first trial, MATRIX Antithrombin, assessed outcomes in 3,610 of these participants who were randomly assigned to receive bivalirudin and 3,603 assigned to receive unfractionated heparin. In the second trial, MATRIX Treatment Duration, the bivalirudin group was further randomized to receive either a post-PCI bivalirudin infusion (1,799 patients) or no post-PCI infusion (1,811 patients).

MATRIX Antithrombin

At 1-month follow-up, the rate of major adverse cardiovascular events (MACEs) – a composite of death from any cause, myocardial infarction, or stroke – was no lower in the bivalirudin group (10.3%) than in the heparin group (10.9%), for a rate ratio of 0.94. Similarly, the rate of net adverse clinical events was not significantly lower with bivalirudin (11.2%) than with heparin (12.4%), for a rate ratio of 0.89.

MATRIX Treatment Duration

The primary outcome in the MATRIX Treatment Duration study – a composite of urgent target-vessel revascularization, definite stent thrombosis, or net adverse clinical events at 30 days – occurred in 11.0% of patients who received post-PCI bivalirudin infusions and 11.9% of those who did not, a nonsignificant difference (rate ratio, 0.91). However, the rate of subacute definite stent thrombosis was significantly higher in the post-PCI infusion group, at 0.7%, compared with 0.2% in the group that didn’t receive post-PCI infusions (RR, 4.37).

“I believe the option to prolong or stop bivalirudin infusion after PCI remains open for clinicians, who will have to decide based on the ischemic and bleeding risk of individual patients as well as, perhaps, based on type of acute coronary syndrome, timing of loading dose, and type of oral P2Y12 inhibitors,” Dr. Valgimigli said, noting that this is in keeping with the current labeling of the drug in Europe and the United States.

The MATRIX study was sponsored by the nonprofit Italian Society of Invasive Cardiology and financially supported by the Medicines Company and Terumo Medical. Dr. Valgimigli reported ties to AstraZeneca, the Medicines Company, Terumo Medical, St. Jude Vascular, Alvimedica, Abbott Vascular, and Correvio; his associates reported ties to numerous industry sources.

Mary Ann Moon contributed to this report.

LONDON – Bivalirudin did not prove superior to unfractionated heparin in reducing the rate of major adverse cardiovascular events in two nested, open-label, randomized clinical trials involving patients presenting with acute coronary syndrome who were expected to undergo percutaneous coronary intervention, Dr. Marco Valgimigli reported.

In addition, post-PCI infusions of bivalirudin for 4 hours or longer did not reduce the rate of adverse bleeding events, compared with no infusion.

These findings add important data to the understanding of antithrombotic therapy in ACS patients undergoing invasive treatment, but they do not resolve the persistent question of which method is best for preventing thrombotic complications while limiting the risk of bleeding during and after such procedures, said Dr. Valgimigli of Erasmus University in Rotterdam.

Previous studies comparing bivalirudin, a direct thrombin inhibitor, against unfractionated heparin, an indirect thrombin inhibitor, have yielded conflicting results regarding ischemic and bleeding outcomes, so Dr. Valgimigli and his fellow investigators in the MATRIX (Minimizing Adverse Hemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox) trial conducted two industry-sponsored superiority trials to try to settle the question.

The findings of one of these trials were reported by Dr. Valgimigli at the annual congress of the European Society of Cardiology on Sept. 1, when the results of both were simultaneously published online (N Engl J Med. 2015 Sept 1. doi: 10.1056/NEJMoa1507854).

The MATRIX studies were conducted at 78 medical centers in Italy, the Netherlands, Spain, and Sweden. They involved 7,213 patients who presented with either ST-elevation MI or non-STEMI ACS and were expected to undergo PCI. The first trial, MATRIX Antithrombin, assessed outcomes in 3,610 of these participants who were randomly assigned to receive bivalirudin and 3,603 assigned to receive unfractionated heparin. In the second trial, MATRIX Treatment Duration, the bivalirudin group was further randomized to receive either a post-PCI bivalirudin infusion (1,799 patients) or no post-PCI infusion (1,811 patients).

MATRIX Antithrombin

At 1-month follow-up, the rate of major adverse cardiovascular events (MACEs) – a composite of death from any cause, myocardial infarction, or stroke – was no lower in the bivalirudin group (10.3%) than in the heparin group (10.9%), for a rate ratio of 0.94. Similarly, the rate of net adverse clinical events was not significantly lower with bivalirudin (11.2%) than with heparin (12.4%), for a rate ratio of 0.89.

MATRIX Treatment Duration

The primary outcome in the MATRIX Treatment Duration study – a composite of urgent target-vessel revascularization, definite stent thrombosis, or net adverse clinical events at 30 days – occurred in 11.0% of patients who received post-PCI bivalirudin infusions and 11.9% of those who did not, a nonsignificant difference (rate ratio, 0.91). However, the rate of subacute definite stent thrombosis was significantly higher in the post-PCI infusion group, at 0.7%, compared with 0.2% in the group that didn’t receive post-PCI infusions (RR, 4.37).

“I believe the option to prolong or stop bivalirudin infusion after PCI remains open for clinicians, who will have to decide based on the ischemic and bleeding risk of individual patients as well as, perhaps, based on type of acute coronary syndrome, timing of loading dose, and type of oral P2Y12 inhibitors,” Dr. Valgimigli said, noting that this is in keeping with the current labeling of the drug in Europe and the United States.

The MATRIX study was sponsored by the nonprofit Italian Society of Invasive Cardiology and financially supported by the Medicines Company and Terumo Medical. Dr. Valgimigli reported ties to AstraZeneca, the Medicines Company, Terumo Medical, St. Jude Vascular, Alvimedica, Abbott Vascular, and Correvio; his associates reported ties to numerous industry sources.

Mary Ann Moon contributed to this report.

LONDON – Routine catheter ablation that electrically isolates the left atrial appendage safely boosted the success rate of treatment for long-standing, persistent atrial fibrillation in a randomized trial with 173 patients.

This finding from the first prospective randomized trial to test adding routine left atrial appendage (LAA) electrical isolation to the established catheter-ablation protocol of pulmonary-vein isolation should encourage electrophysiologists to make LAA isolation a more standard part of their approach to treating long-standing, persistent atrial fibrillation (Afib), Dr. Jagmeet P. Singh commented in an interview at the annual congress of the European Society of Cardiology.

“A lot of us have, in the past, been hesitant to ablate the LAA” out of concern that it could render the LAA inert and more likely to become a source of blood clots, noted Dr. Singh, professor of medicine at Harvard Medical School and director of the cardiac resynchronization therapy program at Massachusetts General Hospital in Boston. “This study result provides, for the first time in a randomized fashion, direction on this area of ablation.” Based on the results, Dr. Singh said that in his practice now he would “look for LAA activity” when assessing an Afib patient in the electrophysiology laboratory, “and if the LAA was active I would ablate it,” he said.

The BELIEF (Effect of Empirical Left Atrial Appendage Isolation on Long-Term Procedure Outcome in Patients With Persistent or Long-Standing Persistent Atrial Fibrillation Undergoing Catheter Ablation) trial enrolled 173 patients with long-standing persistent Afib that was refractory to treatment with antiarrhythmic drugs at two U.S. centers and randomized them to receive either conventional pulmonary vein isolation alone, or pulmonary vein isolation and additional point ablations to also produce LAA isolation. The study’s primary endpoint was freedom from Afib episodes at 12 months after treatment.

At 12 months after treatment, freedom from Afib recurrence occurred in 48 of the 85 patients (56%) assigned to LAA isolation and in 25 of the 88 patients (25%) treated with pulmonary vein isolation only, a statistically significant difference, reported Dr. Luigi Di Biasi at the congress. In an analysis that adjusted for patient age, sex, and left atrial diameter the addition of LAA ablation linked with a statistically significant 55% reduction in Afib recurrence, said Dr. Di Biasi, director of the arrhythmia service at Montefiore Medical Center in New York.

Adding LAA isolation to the standard ablation procedure did not result in additional complications, said Dr. Di Biasi, although it did increase procedure time by about 15 minutes. The patients who underwent LAA isolation had no strokes during 2 years of follow-up, and no statistically significant change in the incidence of Afib-related hospitalizations or hospitalizations for heart failure, compared with control patients. One pericardial effusion occurred in each of the study arms during follow-up, and there were no deaths during follow-up in either group. LAA isolation resulted in impaired LAA function in about half of the patients who had the isolation procedure, detected by transesophageal echocardiography after the procedure, but the clinical outcomes indicated that this did not appear to affect patients’ stroke risk.

Dr. Singh has been a consultant to Boston Scientific, St. Jude, Medtronic, Sorin, and Biotronik. Dr. Di Biasi has been a consultant to Biosense Webster, Stereotaxis, and St. Jude, and a speaker for Biotronik, Medtronic, Boston Scientific, and Epi EP.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

LONDON – Routine catheter ablation that electrically isolates the left atrial appendage safely boosted the success rate of treatment for long-standing, persistent atrial fibrillation in a randomized trial with 173 patients.

This finding from the first prospective randomized trial to test adding routine left atrial appendage (LAA) electrical isolation to the established catheter-ablation protocol of pulmonary-vein isolation should encourage electrophysiologists to make LAA isolation a more standard part of their approach to treating long-standing, persistent atrial fibrillation (Afib), Dr. Jagmeet P. Singh commented in an interview at the annual congress of the European Society of Cardiology.

“A lot of us have, in the past, been hesitant to ablate the LAA” out of concern that it could render the LAA inert and more likely to become a source of blood clots, noted Dr. Singh, professor of medicine at Harvard Medical School and director of the cardiac resynchronization therapy program at Massachusetts General Hospital in Boston. “This study result provides, for the first time in a randomized fashion, direction on this area of ablation.” Based on the results, Dr. Singh said that in his practice now he would “look for LAA activity” when assessing an Afib patient in the electrophysiology laboratory, “and if the LAA was active I would ablate it,” he said.

The BELIEF (Effect of Empirical Left Atrial Appendage Isolation on Long-Term Procedure Outcome in Patients With Persistent or Long-Standing Persistent Atrial Fibrillation Undergoing Catheter Ablation) trial enrolled 173 patients with long-standing persistent Afib that was refractory to treatment with antiarrhythmic drugs at two U.S. centers and randomized them to receive either conventional pulmonary vein isolation alone, or pulmonary vein isolation and additional point ablations to also produce LAA isolation. The study’s primary endpoint was freedom from Afib episodes at 12 months after treatment.

At 12 months after treatment, freedom from Afib recurrence occurred in 48 of the 85 patients (56%) assigned to LAA isolation and in 25 of the 88 patients (25%) treated with pulmonary vein isolation only, a statistically significant difference, reported Dr. Luigi Di Biasi at the congress. In an analysis that adjusted for patient age, sex, and left atrial diameter the addition of LAA ablation linked with a statistically significant 55% reduction in Afib recurrence, said Dr. Di Biasi, director of the arrhythmia service at Montefiore Medical Center in New York.

Adding LAA isolation to the standard ablation procedure did not result in additional complications, said Dr. Di Biasi, although it did increase procedure time by about 15 minutes. The patients who underwent LAA isolation had no strokes during 2 years of follow-up, and no statistically significant change in the incidence of Afib-related hospitalizations or hospitalizations for heart failure, compared with control patients. One pericardial effusion occurred in each of the study arms during follow-up, and there were no deaths during follow-up in either group. LAA isolation resulted in impaired LAA function in about half of the patients who had the isolation procedure, detected by transesophageal echocardiography after the procedure, but the clinical outcomes indicated that this did not appear to affect patients’ stroke risk.

Dr. Singh has been a consultant to Boston Scientific, St. Jude, Medtronic, Sorin, and Biotronik. Dr. Di Biasi has been a consultant to Biosense Webster, Stereotaxis, and St. Jude, and a speaker for Biotronik, Medtronic, Boston Scientific, and Epi EP.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

LONDON – Routine catheter ablation that electrically isolates the left atrial appendage safely boosted the success rate of treatment for long-standing, persistent atrial fibrillation in a randomized trial with 173 patients.

This finding from the first prospective randomized trial to test adding routine left atrial appendage (LAA) electrical isolation to the established catheter-ablation protocol of pulmonary-vein isolation should encourage electrophysiologists to make LAA isolation a more standard part of their approach to treating long-standing, persistent atrial fibrillation (Afib), Dr. Jagmeet P. Singh commented in an interview at the annual congress of the European Society of Cardiology.

“A lot of us have, in the past, been hesitant to ablate the LAA” out of concern that it could render the LAA inert and more likely to become a source of blood clots, noted Dr. Singh, professor of medicine at Harvard Medical School and director of the cardiac resynchronization therapy program at Massachusetts General Hospital in Boston. “This study result provides, for the first time in a randomized fashion, direction on this area of ablation.” Based on the results, Dr. Singh said that in his practice now he would “look for LAA activity” when assessing an Afib patient in the electrophysiology laboratory, “and if the LAA was active I would ablate it,” he said.

The BELIEF (Effect of Empirical Left Atrial Appendage Isolation on Long-Term Procedure Outcome in Patients With Persistent or Long-Standing Persistent Atrial Fibrillation Undergoing Catheter Ablation) trial enrolled 173 patients with long-standing persistent Afib that was refractory to treatment with antiarrhythmic drugs at two U.S. centers and randomized them to receive either conventional pulmonary vein isolation alone, or pulmonary vein isolation and additional point ablations to also produce LAA isolation. The study’s primary endpoint was freedom from Afib episodes at 12 months after treatment.

At 12 months after treatment, freedom from Afib recurrence occurred in 48 of the 85 patients (56%) assigned to LAA isolation and in 25 of the 88 patients (25%) treated with pulmonary vein isolation only, a statistically significant difference, reported Dr. Luigi Di Biasi at the congress. In an analysis that adjusted for patient age, sex, and left atrial diameter the addition of LAA ablation linked with a statistically significant 55% reduction in Afib recurrence, said Dr. Di Biasi, director of the arrhythmia service at Montefiore Medical Center in New York.

Adding LAA isolation to the standard ablation procedure did not result in additional complications, said Dr. Di Biasi, although it did increase procedure time by about 15 minutes. The patients who underwent LAA isolation had no strokes during 2 years of follow-up, and no statistically significant change in the incidence of Afib-related hospitalizations or hospitalizations for heart failure, compared with control patients. One pericardial effusion occurred in each of the study arms during follow-up, and there were no deaths during follow-up in either group. LAA isolation resulted in impaired LAA function in about half of the patients who had the isolation procedure, detected by transesophageal echocardiography after the procedure, but the clinical outcomes indicated that this did not appear to affect patients’ stroke risk.

Dr. Singh has been a consultant to Boston Scientific, St. Jude, Medtronic, Sorin, and Biotronik. Dr. Di Biasi has been a consultant to Biosense Webster, Stereotaxis, and St. Jude, and a speaker for Biotronik, Medtronic, Boston Scientific, and Epi EP.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler