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Coronary revascularization appropriate use criteria updated
For ST segment–elevation myocardial infarction (STEMI) patients presenting between 12 and 24 hours from symptom onset but with no signs of clinical instability, coronary revascularization “may be appropriate,” according to a new report. At the same time, for STEMI patients initially treated with fibrinolysis, revascularization was rated as “appropriate therapy” in the setting of suspected failed fibrinolytic therapy or in stable and asymptomatic patients from 3 to 24 hours after fibrinolysis.
Those are two conclusions contained in a revision of the appropriate use criteria (AUC) for coronary revascularization published on Dec. 21 (J Am Coll Cardiol. doi: 10.1016/j.jacc.2016.10.034).
“This update provides a reassessment of clinical scenarios that the writing group felt to be affected by significant changes in the medical literature or gaps from prior criteria,” Manesh R. Patel, MD, chief of the division of cardiology and codirector of the Duke Heart Center at Duke University, Durham, N.C., and chair of the seven-member writing committee for the document, said in a prepared statement. “The primary objective of the appropriate use criteria is to provide a framework for the assessment of practice patterns that will hopefully improve physician decision making and ultimately lead to better patient outcomes.”
The 22-page document contains 17 clinical scenarios that were scored by a separate committee of 17 experts to indicate whether revascularization in patients with acute coronary syndromes is appropriate, may be appropriate, or is rarely appropriate for the clinical scenario presented. Step-by-step flow charts are included to help use the criteria. “Since publication of the 2012 AUC document (J Am Coll Cardiol. 2012;59:857-81), new guidelines for [STEMI] and non–ST segment elevation myocardial infarction (NSTEMI)/unstable angina have been published with additional focused updates of the [stable ischemic heart disease] guideline and a combined focused update of the percutaneous coronary intervention (PCI) and STEMI guideline,” the writing committee noted. “New clinical trials have been published extending the knowledge and evidence around coronary revascularization, including trials that challenge earlier recommendations about the timing of nonculprit vessel PCI in the setting of STEMI. Additional studies related to coronary artery bypass graft surgery, medical therapy, and diagnostic technologies such as fractional flow reserve (FFR) have emerged as well as analyses from the National Cardiovascular Data Registry (NCDR) on the existing AUC that provide insights into practice patterns, clinical scenarios, and patient features not previously addressed.”
Conclusions in the document include those for nonculprit artery revascularization during the index hospitalization after primary PCI or fibrinolysis. This was rated as “appropriate and reasonable” for patients with one or more severe stenoses and spontaneous or easily provoked ischemia or for asymptomatic patients with ischemic findings on noninvasive testing. Meanwhile, in the presence of an intermediate-severity nonculprit artery stenosis, revascularization was rated as “appropriate therapy” in cases where the fractional flow reserve is at or below 0.80. For patients who are stable and asymptomatic after primary PCI, revascularization was rated as “may be appropriate” for one or more severe stenoses even in the absence of further testing.
The only “rarely appropriate” rating in patients with acute coronary syndromes occurred for asymptomatic patients with intermediate-severity nonculprit artery stenoses in the absence of any additional testing to demonstrate the functional significance of the stenosis.
“As in prior versions of the AUC, these revascularization ratings should be used to reinforce existing management strategies and identify patient populations that need more information to identify the most effective treatments,” the authors concluded. Dr. Patel reported having no financial disclosures.
For ST segment–elevation myocardial infarction (STEMI) patients presenting between 12 and 24 hours from symptom onset but with no signs of clinical instability, coronary revascularization “may be appropriate,” according to a new report. At the same time, for STEMI patients initially treated with fibrinolysis, revascularization was rated as “appropriate therapy” in the setting of suspected failed fibrinolytic therapy or in stable and asymptomatic patients from 3 to 24 hours after fibrinolysis.
Those are two conclusions contained in a revision of the appropriate use criteria (AUC) for coronary revascularization published on Dec. 21 (J Am Coll Cardiol. doi: 10.1016/j.jacc.2016.10.034).
“This update provides a reassessment of clinical scenarios that the writing group felt to be affected by significant changes in the medical literature or gaps from prior criteria,” Manesh R. Patel, MD, chief of the division of cardiology and codirector of the Duke Heart Center at Duke University, Durham, N.C., and chair of the seven-member writing committee for the document, said in a prepared statement. “The primary objective of the appropriate use criteria is to provide a framework for the assessment of practice patterns that will hopefully improve physician decision making and ultimately lead to better patient outcomes.”
The 22-page document contains 17 clinical scenarios that were scored by a separate committee of 17 experts to indicate whether revascularization in patients with acute coronary syndromes is appropriate, may be appropriate, or is rarely appropriate for the clinical scenario presented. Step-by-step flow charts are included to help use the criteria. “Since publication of the 2012 AUC document (J Am Coll Cardiol. 2012;59:857-81), new guidelines for [STEMI] and non–ST segment elevation myocardial infarction (NSTEMI)/unstable angina have been published with additional focused updates of the [stable ischemic heart disease] guideline and a combined focused update of the percutaneous coronary intervention (PCI) and STEMI guideline,” the writing committee noted. “New clinical trials have been published extending the knowledge and evidence around coronary revascularization, including trials that challenge earlier recommendations about the timing of nonculprit vessel PCI in the setting of STEMI. Additional studies related to coronary artery bypass graft surgery, medical therapy, and diagnostic technologies such as fractional flow reserve (FFR) have emerged as well as analyses from the National Cardiovascular Data Registry (NCDR) on the existing AUC that provide insights into practice patterns, clinical scenarios, and patient features not previously addressed.”
Conclusions in the document include those for nonculprit artery revascularization during the index hospitalization after primary PCI or fibrinolysis. This was rated as “appropriate and reasonable” for patients with one or more severe stenoses and spontaneous or easily provoked ischemia or for asymptomatic patients with ischemic findings on noninvasive testing. Meanwhile, in the presence of an intermediate-severity nonculprit artery stenosis, revascularization was rated as “appropriate therapy” in cases where the fractional flow reserve is at or below 0.80. For patients who are stable and asymptomatic after primary PCI, revascularization was rated as “may be appropriate” for one or more severe stenoses even in the absence of further testing.
The only “rarely appropriate” rating in patients with acute coronary syndromes occurred for asymptomatic patients with intermediate-severity nonculprit artery stenoses in the absence of any additional testing to demonstrate the functional significance of the stenosis.
“As in prior versions of the AUC, these revascularization ratings should be used to reinforce existing management strategies and identify patient populations that need more information to identify the most effective treatments,” the authors concluded. Dr. Patel reported having no financial disclosures.
For ST segment–elevation myocardial infarction (STEMI) patients presenting between 12 and 24 hours from symptom onset but with no signs of clinical instability, coronary revascularization “may be appropriate,” according to a new report. At the same time, for STEMI patients initially treated with fibrinolysis, revascularization was rated as “appropriate therapy” in the setting of suspected failed fibrinolytic therapy or in stable and asymptomatic patients from 3 to 24 hours after fibrinolysis.
Those are two conclusions contained in a revision of the appropriate use criteria (AUC) for coronary revascularization published on Dec. 21 (J Am Coll Cardiol. doi: 10.1016/j.jacc.2016.10.034).
“This update provides a reassessment of clinical scenarios that the writing group felt to be affected by significant changes in the medical literature or gaps from prior criteria,” Manesh R. Patel, MD, chief of the division of cardiology and codirector of the Duke Heart Center at Duke University, Durham, N.C., and chair of the seven-member writing committee for the document, said in a prepared statement. “The primary objective of the appropriate use criteria is to provide a framework for the assessment of practice patterns that will hopefully improve physician decision making and ultimately lead to better patient outcomes.”
The 22-page document contains 17 clinical scenarios that were scored by a separate committee of 17 experts to indicate whether revascularization in patients with acute coronary syndromes is appropriate, may be appropriate, or is rarely appropriate for the clinical scenario presented. Step-by-step flow charts are included to help use the criteria. “Since publication of the 2012 AUC document (J Am Coll Cardiol. 2012;59:857-81), new guidelines for [STEMI] and non–ST segment elevation myocardial infarction (NSTEMI)/unstable angina have been published with additional focused updates of the [stable ischemic heart disease] guideline and a combined focused update of the percutaneous coronary intervention (PCI) and STEMI guideline,” the writing committee noted. “New clinical trials have been published extending the knowledge and evidence around coronary revascularization, including trials that challenge earlier recommendations about the timing of nonculprit vessel PCI in the setting of STEMI. Additional studies related to coronary artery bypass graft surgery, medical therapy, and diagnostic technologies such as fractional flow reserve (FFR) have emerged as well as analyses from the National Cardiovascular Data Registry (NCDR) on the existing AUC that provide insights into practice patterns, clinical scenarios, and patient features not previously addressed.”
Conclusions in the document include those for nonculprit artery revascularization during the index hospitalization after primary PCI or fibrinolysis. This was rated as “appropriate and reasonable” for patients with one or more severe stenoses and spontaneous or easily provoked ischemia or for asymptomatic patients with ischemic findings on noninvasive testing. Meanwhile, in the presence of an intermediate-severity nonculprit artery stenosis, revascularization was rated as “appropriate therapy” in cases where the fractional flow reserve is at or below 0.80. For patients who are stable and asymptomatic after primary PCI, revascularization was rated as “may be appropriate” for one or more severe stenoses even in the absence of further testing.
The only “rarely appropriate” rating in patients with acute coronary syndromes occurred for asymptomatic patients with intermediate-severity nonculprit artery stenoses in the absence of any additional testing to demonstrate the functional significance of the stenosis.
“As in prior versions of the AUC, these revascularization ratings should be used to reinforce existing management strategies and identify patient populations that need more information to identify the most effective treatments,” the authors concluded. Dr. Patel reported having no financial disclosures.
FROM THE JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
CMS finalizes cardiac pay bundles, but their future is unclear
The Centers for Medicare & Medicaid Services has finalized three cardiac payment bundles that will qualify as advanced alternative payment models under MACRA’s Quality Payment Program, but questions linger as to whether the bundles will survive in the Trump administration.
The bundles include the Acute Myocardial Infarction (AMI) model, the Coronary Artery Bypass Graft (CABG) model, and the Cardiac Rehabilitation Incentive Payment model. The three programs were proposed in July 2016 and finalized in a rule posted Dec. 20, and scheduled for publication in the Federal Register on Jan. 3, 2017.
The bundled payment model will place accountability for patient outcomes 90 days after discharge on the hospital where treatment occurred. Beginning July 1, 2017, hospitals in 98 randomly selected metropolitan statistical areas will be placed under this model and monitored for 5 years to test whether the model leads to improved outcomes and lower costs.
Physician participation will be voluntary; those who do participate will eligible for bonus payments as part of a Quality Payment Program advanced Alternative Payment Model (APM) when savings are generated, and responsible for penalties when costs exceed targets. Physician participation would begin in 2018.
CMS also finalized a program to test whether an incentive payment will increase the use of cardiac rehabilitation services.
Participating hospitals will receive an initial payment of $25 per cardiac rehabilitation service for each of the first 11 services paid for by Medicare post-AMI or post-CABG, and $175 per service during the care period after 11 services. The care period runs parallel with the 90-day period for the AMI and CABG episode payment bundled.
“As we move from volume-based care to value-based care, this new path for cardiologists to participate in advanced alternative payment models under MACRA’s Quality Payment Program is a challenging step,” American College of Cardiology President Richard A. Chazal, MD, said in a statement. “It is our sincere hope that the end result will be opportunities for coordinated care and improvement in quality, while also decreasing costs for patients with heart attack or who undergo bypass surgery.”
The final rule also will test the Medicare ACO Track 1+ model, an accountable care organization that qualifies as an APM but has a lower risk of penalty than other ACOs, starting in 2018.
These new programs could be short-lived, depending on the direction taken by the Trump Administration. Rep. Tom Price, MD (R-Ga.), the incoming administration’s choice to lead the Health & Human Services department, was a lead cosigner to a Sept. 29 letter to Dr. Conway and CMS Acting Administrator Andy Slavitt that called on the agency to “cease all current and future planned mandatory initiatives” generating from the Centers for Medicare and Medicaid Innovation, which is where the bundles were developed. The letter said that the mandatory models “overhaul major payment systems, commandeer clinical decision-making, and dramatically alter the delivery of care.”
During the teleconference, Dr. Conway avoided answering questions about how the incoming administration might handle these models.
The final rule also offered a new bundle for patients requiring surgery after a hip fracture and provided updates to the Comprehensive Care for Joint Replacement (CJR) model.
The Centers for Medicare & Medicaid Services has finalized three cardiac payment bundles that will qualify as advanced alternative payment models under MACRA’s Quality Payment Program, but questions linger as to whether the bundles will survive in the Trump administration.
The bundles include the Acute Myocardial Infarction (AMI) model, the Coronary Artery Bypass Graft (CABG) model, and the Cardiac Rehabilitation Incentive Payment model. The three programs were proposed in July 2016 and finalized in a rule posted Dec. 20, and scheduled for publication in the Federal Register on Jan. 3, 2017.
The bundled payment model will place accountability for patient outcomes 90 days after discharge on the hospital where treatment occurred. Beginning July 1, 2017, hospitals in 98 randomly selected metropolitan statistical areas will be placed under this model and monitored for 5 years to test whether the model leads to improved outcomes and lower costs.
Physician participation will be voluntary; those who do participate will eligible for bonus payments as part of a Quality Payment Program advanced Alternative Payment Model (APM) when savings are generated, and responsible for penalties when costs exceed targets. Physician participation would begin in 2018.
CMS also finalized a program to test whether an incentive payment will increase the use of cardiac rehabilitation services.
Participating hospitals will receive an initial payment of $25 per cardiac rehabilitation service for each of the first 11 services paid for by Medicare post-AMI or post-CABG, and $175 per service during the care period after 11 services. The care period runs parallel with the 90-day period for the AMI and CABG episode payment bundled.
“As we move from volume-based care to value-based care, this new path for cardiologists to participate in advanced alternative payment models under MACRA’s Quality Payment Program is a challenging step,” American College of Cardiology President Richard A. Chazal, MD, said in a statement. “It is our sincere hope that the end result will be opportunities for coordinated care and improvement in quality, while also decreasing costs for patients with heart attack or who undergo bypass surgery.”
The final rule also will test the Medicare ACO Track 1+ model, an accountable care organization that qualifies as an APM but has a lower risk of penalty than other ACOs, starting in 2018.
These new programs could be short-lived, depending on the direction taken by the Trump Administration. Rep. Tom Price, MD (R-Ga.), the incoming administration’s choice to lead the Health & Human Services department, was a lead cosigner to a Sept. 29 letter to Dr. Conway and CMS Acting Administrator Andy Slavitt that called on the agency to “cease all current and future planned mandatory initiatives” generating from the Centers for Medicare and Medicaid Innovation, which is where the bundles were developed. The letter said that the mandatory models “overhaul major payment systems, commandeer clinical decision-making, and dramatically alter the delivery of care.”
During the teleconference, Dr. Conway avoided answering questions about how the incoming administration might handle these models.
The final rule also offered a new bundle for patients requiring surgery after a hip fracture and provided updates to the Comprehensive Care for Joint Replacement (CJR) model.
The Centers for Medicare & Medicaid Services has finalized three cardiac payment bundles that will qualify as advanced alternative payment models under MACRA’s Quality Payment Program, but questions linger as to whether the bundles will survive in the Trump administration.
The bundles include the Acute Myocardial Infarction (AMI) model, the Coronary Artery Bypass Graft (CABG) model, and the Cardiac Rehabilitation Incentive Payment model. The three programs were proposed in July 2016 and finalized in a rule posted Dec. 20, and scheduled for publication in the Federal Register on Jan. 3, 2017.
The bundled payment model will place accountability for patient outcomes 90 days after discharge on the hospital where treatment occurred. Beginning July 1, 2017, hospitals in 98 randomly selected metropolitan statistical areas will be placed under this model and monitored for 5 years to test whether the model leads to improved outcomes and lower costs.
Physician participation will be voluntary; those who do participate will eligible for bonus payments as part of a Quality Payment Program advanced Alternative Payment Model (APM) when savings are generated, and responsible for penalties when costs exceed targets. Physician participation would begin in 2018.
CMS also finalized a program to test whether an incentive payment will increase the use of cardiac rehabilitation services.
Participating hospitals will receive an initial payment of $25 per cardiac rehabilitation service for each of the first 11 services paid for by Medicare post-AMI or post-CABG, and $175 per service during the care period after 11 services. The care period runs parallel with the 90-day period for the AMI and CABG episode payment bundled.
“As we move from volume-based care to value-based care, this new path for cardiologists to participate in advanced alternative payment models under MACRA’s Quality Payment Program is a challenging step,” American College of Cardiology President Richard A. Chazal, MD, said in a statement. “It is our sincere hope that the end result will be opportunities for coordinated care and improvement in quality, while also decreasing costs for patients with heart attack or who undergo bypass surgery.”
The final rule also will test the Medicare ACO Track 1+ model, an accountable care organization that qualifies as an APM but has a lower risk of penalty than other ACOs, starting in 2018.
These new programs could be short-lived, depending on the direction taken by the Trump Administration. Rep. Tom Price, MD (R-Ga.), the incoming administration’s choice to lead the Health & Human Services department, was a lead cosigner to a Sept. 29 letter to Dr. Conway and CMS Acting Administrator Andy Slavitt that called on the agency to “cease all current and future planned mandatory initiatives” generating from the Centers for Medicare and Medicaid Innovation, which is where the bundles were developed. The letter said that the mandatory models “overhaul major payment systems, commandeer clinical decision-making, and dramatically alter the delivery of care.”
During the teleconference, Dr. Conway avoided answering questions about how the incoming administration might handle these models.
The final rule also offered a new bundle for patients requiring surgery after a hip fracture and provided updates to the Comprehensive Care for Joint Replacement (CJR) model.
Entresto cuts LV mass in hypertensive patients
NEW ORLEANS – Hypertensive patients without heart failure treated with the heart failure formulation sacubitril plus valsartan had a significantly greater drop in their left ventricular mass than did patients treated with olmesartan in a randomized trial with 114 patients.
Treatment with sacubitril plus valsartan for both 3 and 12 months led to roughly twice as much reduction in left ventricular (LV) mass as did treatment with olmesartan, and this difference persisted after adjustment for between-group differences in blood pressure reduction, Roland E. Schmieder, MD, reported at the American Heart Association Scientific Sessions.
During clinical development of sacubitril plus valsartan (Entresto), the company that owns this compound, Novartis, ran a few small studies using the formulation to treat hypertension, but eventually those studies stopped, he said in an interview. “I hope this pushes development of other neprilysin inhibitor formulations for their blood pressure effects. I think this finding helps us understand why sacubitril plus valsartan was so effective for treating heart failure.” (N Engl J Med. 2014 Sep 11;371[11]:933-1004.)
The study enrolled patients with mild or moderate hypertension; the average blood pressure of enrolled patients was 155/92 mm Hg. They averaged 60 years of age, two-thirds were men, and their average LV mass index at baseline was 72 g/m2. The study excluded patients with heart failure. Patients randomized to receive sacubitril plus valsartan began on a dose of 200 mg/day, and after 2 weeks this rose to 400 mg/day, the maximum recommended dosage in the labeling. Patients randomized to olmesartan began on 20 mg/day, and after 2 weeks their dosage increased to 40 mg/day. Patients in both arms were also eligible to receive amlodipine for additional blood pressure lowering if deemed necessary by the treating physician.
The sacubitril plus valsartan group patients had an average cut in systolic blood pressure of about 26 mm Hg, both 3 and 12 months after the start of treatment. Patients in the olmesartan arm had decreases of 23 mm Hg and 21 mm Hg, respectively, at the two follow-up times. These between-group differences were statistically significant, Dr. Schmieder said.
Measurement of LV mass index using MRI scans showed an average reduction of LV mass index, compared with baseline of 6.4 g/m2 and 6.8 g/m2 after 3 and 12 months of treatment with sacubitril plus valsartan, and average reductions from baseline of 2.3 g/m2 and 3.5 g/m2 at the two follow-up examinations for patients treated with olmesartan. These statistically significant differences remained after adjustment for degree of blood pressure reduction at 3 and 12 months.
Additional measurements showed no between-group differences in aortic distensibility, but central pulse pressure also showed a significantly greater reduction with sacubitril plus valsartan, compared with olmesartan.
The trial was investigator initiated and received funding from Novartis. Dr. Schmieder has received honoraria from Novartis and also from AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, and Servier.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
This study produced very interesting and convincing data. The results suggested that treating hypertension with sacubitril plus valsartan produced a significant, incremental improvement in left ventricular mass beyond the formulation’s blood pressure effect. This could potentially have importance when treating patients with hypertension and left ventricular hypertrophy.
Olmesartan was a fair comparator to use. It arguably is the most potent angiotensin receptor blocker for reducing blood pressure. However, in routine practice we generally combine an angiotensin receptor blocker with a diuretic to get maximum blood pressure lowering. In addition, it is not new to show that blood pressure lowering reduces left ventricular size. 
These data are too limited and the cost for prescribing sacubitril plus valsartan is so high, compared with most other antihypertensive drugs, that I would like to see additional study results documenting this effect before I’d be willing to prescribe sacubitril plus valsartan to patients with hypertension but no heart failure.
Dan J. Fintel, MD , a cardiologist and professor of medicine at Northwestern University in Chicago, made these comments in an interview. He has been a speaker on behalf of AstraZeneca, BMS, Daiichi Sankyo, Janssen, Merck, and Pfizer.
This study produced very interesting and convincing data. The results suggested that treating hypertension with sacubitril plus valsartan produced a significant, incremental improvement in left ventricular mass beyond the formulation’s blood pressure effect. This could potentially have importance when treating patients with hypertension and left ventricular hypertrophy.
Olmesartan was a fair comparator to use. It arguably is the most potent angiotensin receptor blocker for reducing blood pressure. However, in routine practice we generally combine an angiotensin receptor blocker with a diuretic to get maximum blood pressure lowering. In addition, it is not new to show that blood pressure lowering reduces left ventricular size.
These data are too limited and the cost for prescribing sacubitril plus valsartan is so high, compared with most other antihypertensive drugs, that I would like to see additional study results documenting this effect before I’d be willing to prescribe sacubitril plus valsartan to patients with hypertension but no heart failure.
Dan J. Fintel, MD , a cardiologist and professor of medicine at Northwestern University in Chicago, made these comments in an interview. He has been a speaker on behalf of AstraZeneca, BMS, Daiichi Sankyo, Janssen, Merck, and Pfizer.
This study produced very interesting and convincing data. The results suggested that treating hypertension with sacubitril plus valsartan produced a significant, incremental improvement in left ventricular mass beyond the formulation’s blood pressure effect. This could potentially have importance when treating patients with hypertension and left ventricular hypertrophy.
Olmesartan was a fair comparator to use. It arguably is the most potent angiotensin receptor blocker for reducing blood pressure. However, in routine practice we generally combine an angiotensin receptor blocker with a diuretic to get maximum blood pressure lowering. In addition, it is not new to show that blood pressure lowering reduces left ventricular size.
These data are too limited and the cost for prescribing sacubitril plus valsartan is so high, compared with most other antihypertensive drugs, that I would like to see additional study results documenting this effect before I’d be willing to prescribe sacubitril plus valsartan to patients with hypertension but no heart failure.
Dan J. Fintel, MD , a cardiologist and professor of medicine at Northwestern University in Chicago, made these comments in an interview. He has been a speaker on behalf of AstraZeneca, BMS, Daiichi Sankyo, Janssen, Merck, and Pfizer.
NEW ORLEANS – Hypertensive patients without heart failure treated with the heart failure formulation sacubitril plus valsartan had a significantly greater drop in their left ventricular mass than did patients treated with olmesartan in a randomized trial with 114 patients.
Treatment with sacubitril plus valsartan for both 3 and 12 months led to roughly twice as much reduction in left ventricular (LV) mass as did treatment with olmesartan, and this difference persisted after adjustment for between-group differences in blood pressure reduction, Roland E. Schmieder, MD, reported at the American Heart Association Scientific Sessions.
During clinical development of sacubitril plus valsartan (Entresto), the company that owns this compound, Novartis, ran a few small studies using the formulation to treat hypertension, but eventually those studies stopped, he said in an interview. “I hope this pushes development of other neprilysin inhibitor formulations for their blood pressure effects. I think this finding helps us understand why sacubitril plus valsartan was so effective for treating heart failure.” (N Engl J Med. 2014 Sep 11;371[11]:933-1004.)
The study enrolled patients with mild or moderate hypertension; the average blood pressure of enrolled patients was 155/92 mm Hg. They averaged 60 years of age, two-thirds were men, and their average LV mass index at baseline was 72 g/m2. The study excluded patients with heart failure. Patients randomized to receive sacubitril plus valsartan began on a dose of 200 mg/day, and after 2 weeks this rose to 400 mg/day, the maximum recommended dosage in the labeling. Patients randomized to olmesartan began on 20 mg/day, and after 2 weeks their dosage increased to 40 mg/day. Patients in both arms were also eligible to receive amlodipine for additional blood pressure lowering if deemed necessary by the treating physician.
The sacubitril plus valsartan group patients had an average cut in systolic blood pressure of about 26 mm Hg, both 3 and 12 months after the start of treatment. Patients in the olmesartan arm had decreases of 23 mm Hg and 21 mm Hg, respectively, at the two follow-up times. These between-group differences were statistically significant, Dr. Schmieder said.
Measurement of LV mass index using MRI scans showed an average reduction of LV mass index, compared with baseline of 6.4 g/m2 and 6.8 g/m2 after 3 and 12 months of treatment with sacubitril plus valsartan, and average reductions from baseline of 2.3 g/m2 and 3.5 g/m2 at the two follow-up examinations for patients treated with olmesartan. These statistically significant differences remained after adjustment for degree of blood pressure reduction at 3 and 12 months.
Additional measurements showed no between-group differences in aortic distensibility, but central pulse pressure also showed a significantly greater reduction with sacubitril plus valsartan, compared with olmesartan.
The trial was investigator initiated and received funding from Novartis. Dr. Schmieder has received honoraria from Novartis and also from AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, and Servier.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
NEW ORLEANS – Hypertensive patients without heart failure treated with the heart failure formulation sacubitril plus valsartan had a significantly greater drop in their left ventricular mass than did patients treated with olmesartan in a randomized trial with 114 patients.
Treatment with sacubitril plus valsartan for both 3 and 12 months led to roughly twice as much reduction in left ventricular (LV) mass as did treatment with olmesartan, and this difference persisted after adjustment for between-group differences in blood pressure reduction, Roland E. Schmieder, MD, reported at the American Heart Association Scientific Sessions.
During clinical development of sacubitril plus valsartan (Entresto), the company that owns this compound, Novartis, ran a few small studies using the formulation to treat hypertension, but eventually those studies stopped, he said in an interview. “I hope this pushes development of other neprilysin inhibitor formulations for their blood pressure effects. I think this finding helps us understand why sacubitril plus valsartan was so effective for treating heart failure.” (N Engl J Med. 2014 Sep 11;371[11]:933-1004.)
The study enrolled patients with mild or moderate hypertension; the average blood pressure of enrolled patients was 155/92 mm Hg. They averaged 60 years of age, two-thirds were men, and their average LV mass index at baseline was 72 g/m2. The study excluded patients with heart failure. Patients randomized to receive sacubitril plus valsartan began on a dose of 200 mg/day, and after 2 weeks this rose to 400 mg/day, the maximum recommended dosage in the labeling. Patients randomized to olmesartan began on 20 mg/day, and after 2 weeks their dosage increased to 40 mg/day. Patients in both arms were also eligible to receive amlodipine for additional blood pressure lowering if deemed necessary by the treating physician.
The sacubitril plus valsartan group patients had an average cut in systolic blood pressure of about 26 mm Hg, both 3 and 12 months after the start of treatment. Patients in the olmesartan arm had decreases of 23 mm Hg and 21 mm Hg, respectively, at the two follow-up times. These between-group differences were statistically significant, Dr. Schmieder said.
Measurement of LV mass index using MRI scans showed an average reduction of LV mass index, compared with baseline of 6.4 g/m2 and 6.8 g/m2 after 3 and 12 months of treatment with sacubitril plus valsartan, and average reductions from baseline of 2.3 g/m2 and 3.5 g/m2 at the two follow-up examinations for patients treated with olmesartan. These statistically significant differences remained after adjustment for degree of blood pressure reduction at 3 and 12 months.
Additional measurements showed no between-group differences in aortic distensibility, but central pulse pressure also showed a significantly greater reduction with sacubitril plus valsartan, compared with olmesartan.
The trial was investigator initiated and received funding from Novartis. Dr. Schmieder has received honoraria from Novartis and also from AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, and Servier.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
AT THE AHA SCIENTIFIC SESSIONS
Key clinical point: .
Major finding: After 1 year, average left ventricular mass index fell 6.8 g/m2 from baseline with sacubitril/valsartan and 3.5 g/m2 with olmesartan.
Data source: A multicenter, randomized trial with 114 patients with mild or moderate hypertension.
Disclosures: The trial was investigator initiated and received funding from Novartis, the company that markets sacubitril plus valsartan (Entresto). Dr. Schmieder has received honoraria from Novartis and also from AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, and Servier.
More tricuspid valve regurgitation should be fixed
CHICAGO – Fixing the tricuspid valve should be part of left-sided heart operations in many cases of functional tricuspid regurgitation, but study data and international guidelines supporting the practice are too frequently ignored, said Steven Bolling, MD.
Speaking during Heart Valve Summit 2016, Dr. Bolling said that of the approximately four million U.S. individuals with mitral regurgitation, about 1.6 million, or 40%, have concomitant tricuspid regurgitation (TR). Yet, he said, only about 7,000 concomitant tricuspid valve (TV) repairs are performed in the 60,000 patients receiving mitral valve (MV) repair surgery annually, for a TV repair rate of less than 12%. “Tricuspid regurgitation is ignored,” said Dr. Bolling, a conference organizer and professor of surgery at the University of Michigan, Ann Arbor.
A 2015 study followed 645 consecutive patients who underwent primary repair of degenerative mitral regurgitation. The patients who had concomitant TVR, he said, “had far less TR, better right ventricle function, and it’s safe. There was lower mortality and morbidity” (J Am Coll Cardiol. 2015 May 12;65[18]:1931-8).
Citing a study of 5,589 patients undergoing surgery for mitral valve regurgitation only, 16% of these had severe – grade 3-4+ – TR preoperatively. However, at discharge, 62% of those had severe residual TR. Despite a “good” mitral result, said Dr. Bolling, multiple studies dating back to the 1980s have demonstrated that surgical repair of just the mitral valve still results in functional tricuspid regurgitation (FTR) rates of up to 67%. “There’s no guarantee of FTR ‘getting better,’” said Dr. Bolling.
The problem lies fundamentally in the annular dilation and change of shape of the tricuspid annulus, and so these issues must be addressed for a good functional result, he said. This dilation and distortion has been shown to occur in up to 75% of all cases of MR (Circulation. 2006;114:1-492).
“Placing an ‘undersized’ tricuspid ring is actually restoring normal sizing to the annulus,” said Dr. Bolling. The normal tricuspid annular dimension is 2.8 cm, plus or minus 0.5 cm, he said. Patients fare better both in the immediate postoperative period and at follow-up with an “undersized” TV repair for FTR, he said.
And surgeons shouldn’t worry about stenosis with an “undersized” TV repair, he said. High school geometry shows that a 26-mm valve diameter yields an area of about 4 square cm, for a 2- to 3-mm gradient, said Dr. Bolling.
Detection of tricuspid regurgitation can itself be a tricky prospect, because tricuspid regurgitation is dynamic. “You should look for functional tricuspid regurgitation preoperatively,” said Dr. Bolling. “Under anesthesia, four-plus TR can become mild.” Accordingly, any significant intraoperative TR or a dilated annulus should be considered indications for tricuspid valve repair, he said.
Though adding TV repair to mitral surgery may add some complexity, it does not necessarily add risk, said Dr. Bolling, citing a study of 110 matched patients with FTR that found a trend toward lower 30-day mortality for combined repair, when compared to mitral repair only (2% versus 8.5%, P = .2).
However, the single-intervention group had a 40% rate of tricuspid progression compared to 5% when both valves were repaired, and the 5-year survival rate was higher for those who had the combined surgery (74% versus 45%; Ann Thorac Surg. 2009 Mar;87[3]:698-703).
According to American College of Cardiology/American Heart Association (ACC/AHA) guidelines for managing valvular heart disease, which were last updated in 2014, patients with severe TR who are undergoing left-sided valve surgery should have concomitant TV repair, a class I recommendation.
The European Society of Cardiology and the European Association for Cardio-Thoracic Surgery (ESC/EACTS) 2012 guidelines are in accord with the ACC/AHA for this population, also issuing a class I recommendation.
For patients with greater than mild TR who have tricuspid annular dilation or right-sided heart failure, TV repair is a class IIa recommendation, according to the ACC/AHA guidelines. For patients with FTR who also have either pulmonary hypertension or right ventricular dilation or dysfunction, TV repair is an ACC/AHA class IIb recommendation.
In the European guidelines, patients with moderate secondary TR with a tricuspid annulus over 40 mm in diameter who are undergoing left-sided valve surgery, or who have right ventricular dilation or dysfunction, should undergo TV repair. This is a class IIa recommendation in the ESC/EACTS schema.
Dr. Bolling reported financial relationships with the Sorin Group, Medtronic, and Edwards Lifesciences.
koakes@frontlinemedcom.com
On Twitter @karioakes
CHICAGO – Fixing the tricuspid valve should be part of left-sided heart operations in many cases of functional tricuspid regurgitation, but study data and international guidelines supporting the practice are too frequently ignored, said Steven Bolling, MD.
Speaking during Heart Valve Summit 2016, Dr. Bolling said that of the approximately four million U.S. individuals with mitral regurgitation, about 1.6 million, or 40%, have concomitant tricuspid regurgitation (TR). Yet, he said, only about 7,000 concomitant tricuspid valve (TV) repairs are performed in the 60,000 patients receiving mitral valve (MV) repair surgery annually, for a TV repair rate of less than 12%. “Tricuspid regurgitation is ignored,” said Dr. Bolling, a conference organizer and professor of surgery at the University of Michigan, Ann Arbor.
A 2015 study followed 645 consecutive patients who underwent primary repair of degenerative mitral regurgitation. The patients who had concomitant TVR, he said, “had far less TR, better right ventricle function, and it’s safe. There was lower mortality and morbidity” (J Am Coll Cardiol. 2015 May 12;65[18]:1931-8).
Citing a study of 5,589 patients undergoing surgery for mitral valve regurgitation only, 16% of these had severe – grade 3-4+ – TR preoperatively. However, at discharge, 62% of those had severe residual TR. Despite a “good” mitral result, said Dr. Bolling, multiple studies dating back to the 1980s have demonstrated that surgical repair of just the mitral valve still results in functional tricuspid regurgitation (FTR) rates of up to 67%. “There’s no guarantee of FTR ‘getting better,’” said Dr. Bolling.
The problem lies fundamentally in the annular dilation and change of shape of the tricuspid annulus, and so these issues must be addressed for a good functional result, he said. This dilation and distortion has been shown to occur in up to 75% of all cases of MR (Circulation. 2006;114:1-492).
“Placing an ‘undersized’ tricuspid ring is actually restoring normal sizing to the annulus,” said Dr. Bolling. The normal tricuspid annular dimension is 2.8 cm, plus or minus 0.5 cm, he said. Patients fare better both in the immediate postoperative period and at follow-up with an “undersized” TV repair for FTR, he said.
And surgeons shouldn’t worry about stenosis with an “undersized” TV repair, he said. High school geometry shows that a 26-mm valve diameter yields an area of about 4 square cm, for a 2- to 3-mm gradient, said Dr. Bolling.
Detection of tricuspid regurgitation can itself be a tricky prospect, because tricuspid regurgitation is dynamic. “You should look for functional tricuspid regurgitation preoperatively,” said Dr. Bolling. “Under anesthesia, four-plus TR can become mild.” Accordingly, any significant intraoperative TR or a dilated annulus should be considered indications for tricuspid valve repair, he said.
Though adding TV repair to mitral surgery may add some complexity, it does not necessarily add risk, said Dr. Bolling, citing a study of 110 matched patients with FTR that found a trend toward lower 30-day mortality for combined repair, when compared to mitral repair only (2% versus 8.5%, P = .2).
However, the single-intervention group had a 40% rate of tricuspid progression compared to 5% when both valves were repaired, and the 5-year survival rate was higher for those who had the combined surgery (74% versus 45%; Ann Thorac Surg. 2009 Mar;87[3]:698-703).
According to American College of Cardiology/American Heart Association (ACC/AHA) guidelines for managing valvular heart disease, which were last updated in 2014, patients with severe TR who are undergoing left-sided valve surgery should have concomitant TV repair, a class I recommendation.
The European Society of Cardiology and the European Association for Cardio-Thoracic Surgery (ESC/EACTS) 2012 guidelines are in accord with the ACC/AHA for this population, also issuing a class I recommendation.
For patients with greater than mild TR who have tricuspid annular dilation or right-sided heart failure, TV repair is a class IIa recommendation, according to the ACC/AHA guidelines. For patients with FTR who also have either pulmonary hypertension or right ventricular dilation or dysfunction, TV repair is an ACC/AHA class IIb recommendation.
In the European guidelines, patients with moderate secondary TR with a tricuspid annulus over 40 mm in diameter who are undergoing left-sided valve surgery, or who have right ventricular dilation or dysfunction, should undergo TV repair. This is a class IIa recommendation in the ESC/EACTS schema.
Dr. Bolling reported financial relationships with the Sorin Group, Medtronic, and Edwards Lifesciences.
koakes@frontlinemedcom.com
On Twitter @karioakes
CHICAGO – Fixing the tricuspid valve should be part of left-sided heart operations in many cases of functional tricuspid regurgitation, but study data and international guidelines supporting the practice are too frequently ignored, said Steven Bolling, MD.
Speaking during Heart Valve Summit 2016, Dr. Bolling said that of the approximately four million U.S. individuals with mitral regurgitation, about 1.6 million, or 40%, have concomitant tricuspid regurgitation (TR). Yet, he said, only about 7,000 concomitant tricuspid valve (TV) repairs are performed in the 60,000 patients receiving mitral valve (MV) repair surgery annually, for a TV repair rate of less than 12%. “Tricuspid regurgitation is ignored,” said Dr. Bolling, a conference organizer and professor of surgery at the University of Michigan, Ann Arbor.
A 2015 study followed 645 consecutive patients who underwent primary repair of degenerative mitral regurgitation. The patients who had concomitant TVR, he said, “had far less TR, better right ventricle function, and it’s safe. There was lower mortality and morbidity” (J Am Coll Cardiol. 2015 May 12;65[18]:1931-8).
Citing a study of 5,589 patients undergoing surgery for mitral valve regurgitation only, 16% of these had severe – grade 3-4+ – TR preoperatively. However, at discharge, 62% of those had severe residual TR. Despite a “good” mitral result, said Dr. Bolling, multiple studies dating back to the 1980s have demonstrated that surgical repair of just the mitral valve still results in functional tricuspid regurgitation (FTR) rates of up to 67%. “There’s no guarantee of FTR ‘getting better,’” said Dr. Bolling.
The problem lies fundamentally in the annular dilation and change of shape of the tricuspid annulus, and so these issues must be addressed for a good functional result, he said. This dilation and distortion has been shown to occur in up to 75% of all cases of MR (Circulation. 2006;114:1-492).
“Placing an ‘undersized’ tricuspid ring is actually restoring normal sizing to the annulus,” said Dr. Bolling. The normal tricuspid annular dimension is 2.8 cm, plus or minus 0.5 cm, he said. Patients fare better both in the immediate postoperative period and at follow-up with an “undersized” TV repair for FTR, he said.
And surgeons shouldn’t worry about stenosis with an “undersized” TV repair, he said. High school geometry shows that a 26-mm valve diameter yields an area of about 4 square cm, for a 2- to 3-mm gradient, said Dr. Bolling.
Detection of tricuspid regurgitation can itself be a tricky prospect, because tricuspid regurgitation is dynamic. “You should look for functional tricuspid regurgitation preoperatively,” said Dr. Bolling. “Under anesthesia, four-plus TR can become mild.” Accordingly, any significant intraoperative TR or a dilated annulus should be considered indications for tricuspid valve repair, he said.
Though adding TV repair to mitral surgery may add some complexity, it does not necessarily add risk, said Dr. Bolling, citing a study of 110 matched patients with FTR that found a trend toward lower 30-day mortality for combined repair, when compared to mitral repair only (2% versus 8.5%, P = .2).
However, the single-intervention group had a 40% rate of tricuspid progression compared to 5% when both valves were repaired, and the 5-year survival rate was higher for those who had the combined surgery (74% versus 45%; Ann Thorac Surg. 2009 Mar;87[3]:698-703).
According to American College of Cardiology/American Heart Association (ACC/AHA) guidelines for managing valvular heart disease, which were last updated in 2014, patients with severe TR who are undergoing left-sided valve surgery should have concomitant TV repair, a class I recommendation.
The European Society of Cardiology and the European Association for Cardio-Thoracic Surgery (ESC/EACTS) 2012 guidelines are in accord with the ACC/AHA for this population, also issuing a class I recommendation.
For patients with greater than mild TR who have tricuspid annular dilation or right-sided heart failure, TV repair is a class IIa recommendation, according to the ACC/AHA guidelines. For patients with FTR who also have either pulmonary hypertension or right ventricular dilation or dysfunction, TV repair is an ACC/AHA class IIb recommendation.
In the European guidelines, patients with moderate secondary TR with a tricuspid annulus over 40 mm in diameter who are undergoing left-sided valve surgery, or who have right ventricular dilation or dysfunction, should undergo TV repair. This is a class IIa recommendation in the ESC/EACTS schema.
Dr. Bolling reported financial relationships with the Sorin Group, Medtronic, and Edwards Lifesciences.
koakes@frontlinemedcom.com
On Twitter @karioakes
EXPERT ANALYSIS FROM HEART VALVE SUMMIT 2016
TAVR concerns hinder use in younger, lower-risk patients
NEW ORLEANS – Despite increasing use of transcatheter aortic valve replacement for patients with severe aortic stenosis at intermediate risk for surgery, the procedure is meeting selected resistance because of ongoing concerns about the procedure’s limitations.
As more data emerge from randomized trials and registries, cardiologists and cardiothoracic surgeons see the choice between transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR) for patients at intermediate surgical risk as something to individualize based on factors that include age, the type of TAVR access possible (transfemoral or an alternative route), and of course, patient preference. An added variable is the constant stream of new data that keeps TAVR in flux, with improved and smaller valves and delivery systems coming onto the market that eclipse the experience and lessons learned from older TAVR systems.
In intermediate-risk patients, usually defined as those with a Society of Thoracic Surgeons (STS) mortality risk score of 4%-8%, “I think you can go either way,” said Frank W. Sellke, MD, at the American Heart Association scientific sessions.
“If a patient is 90 years old and can’t expect to live more than a couple of years, you use TAVR; but if the patient is 55 years old and can expect to live 30 years, I would recommend SAVR,” said Dr. Sellke, professor and chief of cardiothoracic surgery at Brown University in Providence, R.I.
He rattled off four things about TAVR that keep it from being for everyone: periprocedural vascular complications, higher rates of paravalvular leak than with surgery, leaflet thrombosis (a phenomenon with unclear clinical consequences), and undocumented long-term durability.
Dr. Sellke made these comments while discussing the report at the meeting on registry data collected from nearly 6,000 intermediate-risk patients who underwent TAVR or SAVR in Germany during January 2011 through December 2013 and assembled in the German Aortic Valve Registry. During that 3-year period, German TAVR patients could receive either the SAPIEN XT valve or the CoreValve, two TAVR systems that now have been superseded in both Europe and the United States by next-generation systems, SAPIEN 3 and Evolut R.
Limitations of a transthoracic approach
Another factor limiting TAVR is the endovascular approach. The best TAVR results by far have come from using a transfemoral approach for endovascular valve placement, but experts estimate that today at least 10% of patients considered for TAVR have a vascular anatomy that makes the transfemoral TAVR impossible. In the past, when such patients underwent TAVR, it was via either a transapical or transaortic approach (collectively called transthoracic), although additional endovascular entry sites are now being tested.
The limitations of transthoracic TAVR were underscored by results from a prespecified quality-of-life analysis done as part of the PARTNER 2 trial that compared the SAPIEN XT system with SAVR in intermediate-risk patients (N Engl J Med. 2016 April 27;374[17]:1609-20).
In contrast, the patients in the study who had their TAVR done by a transthoracic route had a statistically nonsignificant incremental gain in their KCCQ score, compared with randomized SAVR patients, after 1 month, and their incremental rise in KCCQ score was not clinically meaningful.
The investigators measured KCCQ scores at both 1 and 2 years after treatment, and they were similar regardless of whether patients had undergone TAVR or SAVR in both the transfemoral and transthoracic subgroups. All the quality-of-life benefit from TAVR compared with SAVR occurred only during the first month (and possibly for a few additional months beyond that) and only in TAVR patients treated by the transfemoral route. Dr. Cohen stressed that the SAVR patients in both the transfemoral and transthoracic subgroups had very similar outcomes, showing that patient differences could not explain why the transfemoral patients received a much greater incremental benefit, compared with the SAVR patients, at 1 month than did the transthoracic patients.
“A transthoracic TAVR approach may not be preferable to SAVR, at least in the short to intermediate term,” said Dr. Cohen. “There is no benefit from TAVR, compared with SAVR, if you can’t do it transfemorally, although emerging evidence has suggested that other nontransfemoral approaches that stay out of the chest may provide benefit similar to transfemoral TAVR. The message is, stay out of the chest,” he concluded.
Concerns about durability
The durability of TAVR valves is another concern that has recently been influencing patients as they decide between TAVR and SAVR, said Dr. Smith. “A lot of patients don’t want TAVR because of their concerns about its durability.” These patients usually cite evidence reported in May 2016 at the annual congress of the European Association of Percutaneous Cardiovascular Interventions in Paris by Danny Dvir, MD, on longer-term follow-up of 378 patients who underwent TAVR at either of two pioneering centers. A retrospective review suggested a valve degeneration rate of about 50% after 8 years, Dr. Dvir reported.
This report “has gotten a lot of penetration over the Internet, and a lot of patients don’t like the uncertainty” about TAVR durability that this report produced. “A lot of the time now, patients come in with a fixed idea of whether they want TAVR or SAVR,” Dr. Smith said.
Dr. Smith essentially agreed with Dr. Sellke on the current role for TAVR relative to SAVR in lower-risk patients.
“If the patient is clearly intermediate risk, with an STS mortality risk of more than 6% and is at least 80 years old, then they’ll have TAVR 99% of the time. But if it’s a 75 year old with an STS score of 3.2% and otherwise healthy, the best choice is not as clear.”
Another cardiothoracic surgeon with lots of TAVR experience, Michael J. Reardon, MD, has much more enthusiasm for TAVR. “In my practice, I use TAVR exclusively in patients at least 80 years old. I don‘t care how healthy they look,” said Dr. Reardon, professor of cardiovascular surgery at Houston Methodist. He acknowledged that broader use of TAVR for intermediate-risk patients is getting push back from other cardiothoracic surgeons.
Dr. Sellke is one such surgeon, and he called uncertain TAVR valve durability the deciding factor. “We need longer-term data on [TAVR] valve longevity before we routinely put them into intermediate- or low-risk patients,” he said during a panel discussion at the meeting.
Dr. Reardon highlighted that newer TAVR systems have been reducing problems such as paravalvular leaks and the need for pacemakers following placement of self-expanding TAVR valves. Despite these technical improvements, the final frontier for TAVR for lower-risk patients is valve durability, Dr. Reardon said in an interview.
“I’m convinced the durability is there, and that any 80-year-old patient who is anatomically suited for transfemoral TAVR should get it no matter now healthy they look. If their likely survival is 15 years or less, then they are reasonable candidates for TAVR.”
Dr. Sellke had no relevant disclosures. PARTNER 2 was funded by Edwards, the company that markets Sapient TAVR systems. Dr. Cohen had no relevant disclosures. Dr. Smith has been an investigator in the PARTNER studies. Dr. Reardon has been a consultant to Medtronic, the company that markets the CoreValve and Evolut R TAVR systems.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
NEW ORLEANS – Despite increasing use of transcatheter aortic valve replacement for patients with severe aortic stenosis at intermediate risk for surgery, the procedure is meeting selected resistance because of ongoing concerns about the procedure’s limitations.
As more data emerge from randomized trials and registries, cardiologists and cardiothoracic surgeons see the choice between transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR) for patients at intermediate surgical risk as something to individualize based on factors that include age, the type of TAVR access possible (transfemoral or an alternative route), and of course, patient preference. An added variable is the constant stream of new data that keeps TAVR in flux, with improved and smaller valves and delivery systems coming onto the market that eclipse the experience and lessons learned from older TAVR systems.
In intermediate-risk patients, usually defined as those with a Society of Thoracic Surgeons (STS) mortality risk score of 4%-8%, “I think you can go either way,” said Frank W. Sellke, MD, at the American Heart Association scientific sessions.
“If a patient is 90 years old and can’t expect to live more than a couple of years, you use TAVR; but if the patient is 55 years old and can expect to live 30 years, I would recommend SAVR,” said Dr. Sellke, professor and chief of cardiothoracic surgery at Brown University in Providence, R.I.
He rattled off four things about TAVR that keep it from being for everyone: periprocedural vascular complications, higher rates of paravalvular leak than with surgery, leaflet thrombosis (a phenomenon with unclear clinical consequences), and undocumented long-term durability.
Dr. Sellke made these comments while discussing the report at the meeting on registry data collected from nearly 6,000 intermediate-risk patients who underwent TAVR or SAVR in Germany during January 2011 through December 2013 and assembled in the German Aortic Valve Registry. During that 3-year period, German TAVR patients could receive either the SAPIEN XT valve or the CoreValve, two TAVR systems that now have been superseded in both Europe and the United States by next-generation systems, SAPIEN 3 and Evolut R.
Limitations of a transthoracic approach
Another factor limiting TAVR is the endovascular approach. The best TAVR results by far have come from using a transfemoral approach for endovascular valve placement, but experts estimate that today at least 10% of patients considered for TAVR have a vascular anatomy that makes the transfemoral TAVR impossible. In the past, when such patients underwent TAVR, it was via either a transapical or transaortic approach (collectively called transthoracic), although additional endovascular entry sites are now being tested.
The limitations of transthoracic TAVR were underscored by results from a prespecified quality-of-life analysis done as part of the PARTNER 2 trial that compared the SAPIEN XT system with SAVR in intermediate-risk patients (N Engl J Med. 2016 April 27;374[17]:1609-20).
In contrast, the patients in the study who had their TAVR done by a transthoracic route had a statistically nonsignificant incremental gain in their KCCQ score, compared with randomized SAVR patients, after 1 month, and their incremental rise in KCCQ score was not clinically meaningful.
The investigators measured KCCQ scores at both 1 and 2 years after treatment, and they were similar regardless of whether patients had undergone TAVR or SAVR in both the transfemoral and transthoracic subgroups. All the quality-of-life benefit from TAVR compared with SAVR occurred only during the first month (and possibly for a few additional months beyond that) and only in TAVR patients treated by the transfemoral route. Dr. Cohen stressed that the SAVR patients in both the transfemoral and transthoracic subgroups had very similar outcomes, showing that patient differences could not explain why the transfemoral patients received a much greater incremental benefit, compared with the SAVR patients, at 1 month than did the transthoracic patients.
“A transthoracic TAVR approach may not be preferable to SAVR, at least in the short to intermediate term,” said Dr. Cohen. “There is no benefit from TAVR, compared with SAVR, if you can’t do it transfemorally, although emerging evidence has suggested that other nontransfemoral approaches that stay out of the chest may provide benefit similar to transfemoral TAVR. The message is, stay out of the chest,” he concluded.
Concerns about durability
The durability of TAVR valves is another concern that has recently been influencing patients as they decide between TAVR and SAVR, said Dr. Smith. “A lot of patients don’t want TAVR because of their concerns about its durability.” These patients usually cite evidence reported in May 2016 at the annual congress of the European Association of Percutaneous Cardiovascular Interventions in Paris by Danny Dvir, MD, on longer-term follow-up of 378 patients who underwent TAVR at either of two pioneering centers. A retrospective review suggested a valve degeneration rate of about 50% after 8 years, Dr. Dvir reported.
This report “has gotten a lot of penetration over the Internet, and a lot of patients don’t like the uncertainty” about TAVR durability that this report produced. “A lot of the time now, patients come in with a fixed idea of whether they want TAVR or SAVR,” Dr. Smith said.
Dr. Smith essentially agreed with Dr. Sellke on the current role for TAVR relative to SAVR in lower-risk patients.
“If the patient is clearly intermediate risk, with an STS mortality risk of more than 6% and is at least 80 years old, then they’ll have TAVR 99% of the time. But if it’s a 75 year old with an STS score of 3.2% and otherwise healthy, the best choice is not as clear.”
Another cardiothoracic surgeon with lots of TAVR experience, Michael J. Reardon, MD, has much more enthusiasm for TAVR. “In my practice, I use TAVR exclusively in patients at least 80 years old. I don‘t care how healthy they look,” said Dr. Reardon, professor of cardiovascular surgery at Houston Methodist. He acknowledged that broader use of TAVR for intermediate-risk patients is getting push back from other cardiothoracic surgeons.
Dr. Sellke is one such surgeon, and he called uncertain TAVR valve durability the deciding factor. “We need longer-term data on [TAVR] valve longevity before we routinely put them into intermediate- or low-risk patients,” he said during a panel discussion at the meeting.
Dr. Reardon highlighted that newer TAVR systems have been reducing problems such as paravalvular leaks and the need for pacemakers following placement of self-expanding TAVR valves. Despite these technical improvements, the final frontier for TAVR for lower-risk patients is valve durability, Dr. Reardon said in an interview.
“I’m convinced the durability is there, and that any 80-year-old patient who is anatomically suited for transfemoral TAVR should get it no matter now healthy they look. If their likely survival is 15 years or less, then they are reasonable candidates for TAVR.”
Dr. Sellke had no relevant disclosures. PARTNER 2 was funded by Edwards, the company that markets Sapient TAVR systems. Dr. Cohen had no relevant disclosures. Dr. Smith has been an investigator in the PARTNER studies. Dr. Reardon has been a consultant to Medtronic, the company that markets the CoreValve and Evolut R TAVR systems.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
NEW ORLEANS – Despite increasing use of transcatheter aortic valve replacement for patients with severe aortic stenosis at intermediate risk for surgery, the procedure is meeting selected resistance because of ongoing concerns about the procedure’s limitations.
As more data emerge from randomized trials and registries, cardiologists and cardiothoracic surgeons see the choice between transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR) for patients at intermediate surgical risk as something to individualize based on factors that include age, the type of TAVR access possible (transfemoral or an alternative route), and of course, patient preference. An added variable is the constant stream of new data that keeps TAVR in flux, with improved and smaller valves and delivery systems coming onto the market that eclipse the experience and lessons learned from older TAVR systems.
In intermediate-risk patients, usually defined as those with a Society of Thoracic Surgeons (STS) mortality risk score of 4%-8%, “I think you can go either way,” said Frank W. Sellke, MD, at the American Heart Association scientific sessions.
“If a patient is 90 years old and can’t expect to live more than a couple of years, you use TAVR; but if the patient is 55 years old and can expect to live 30 years, I would recommend SAVR,” said Dr. Sellke, professor and chief of cardiothoracic surgery at Brown University in Providence, R.I.
He rattled off four things about TAVR that keep it from being for everyone: periprocedural vascular complications, higher rates of paravalvular leak than with surgery, leaflet thrombosis (a phenomenon with unclear clinical consequences), and undocumented long-term durability.
Dr. Sellke made these comments while discussing the report at the meeting on registry data collected from nearly 6,000 intermediate-risk patients who underwent TAVR or SAVR in Germany during January 2011 through December 2013 and assembled in the German Aortic Valve Registry. During that 3-year period, German TAVR patients could receive either the SAPIEN XT valve or the CoreValve, two TAVR systems that now have been superseded in both Europe and the United States by next-generation systems, SAPIEN 3 and Evolut R.
Limitations of a transthoracic approach
Another factor limiting TAVR is the endovascular approach. The best TAVR results by far have come from using a transfemoral approach for endovascular valve placement, but experts estimate that today at least 10% of patients considered for TAVR have a vascular anatomy that makes the transfemoral TAVR impossible. In the past, when such patients underwent TAVR, it was via either a transapical or transaortic approach (collectively called transthoracic), although additional endovascular entry sites are now being tested.
The limitations of transthoracic TAVR were underscored by results from a prespecified quality-of-life analysis done as part of the PARTNER 2 trial that compared the SAPIEN XT system with SAVR in intermediate-risk patients (N Engl J Med. 2016 April 27;374[17]:1609-20).
In contrast, the patients in the study who had their TAVR done by a transthoracic route had a statistically nonsignificant incremental gain in their KCCQ score, compared with randomized SAVR patients, after 1 month, and their incremental rise in KCCQ score was not clinically meaningful.
The investigators measured KCCQ scores at both 1 and 2 years after treatment, and they were similar regardless of whether patients had undergone TAVR or SAVR in both the transfemoral and transthoracic subgroups. All the quality-of-life benefit from TAVR compared with SAVR occurred only during the first month (and possibly for a few additional months beyond that) and only in TAVR patients treated by the transfemoral route. Dr. Cohen stressed that the SAVR patients in both the transfemoral and transthoracic subgroups had very similar outcomes, showing that patient differences could not explain why the transfemoral patients received a much greater incremental benefit, compared with the SAVR patients, at 1 month than did the transthoracic patients.
“A transthoracic TAVR approach may not be preferable to SAVR, at least in the short to intermediate term,” said Dr. Cohen. “There is no benefit from TAVR, compared with SAVR, if you can’t do it transfemorally, although emerging evidence has suggested that other nontransfemoral approaches that stay out of the chest may provide benefit similar to transfemoral TAVR. The message is, stay out of the chest,” he concluded.
Concerns about durability
The durability of TAVR valves is another concern that has recently been influencing patients as they decide between TAVR and SAVR, said Dr. Smith. “A lot of patients don’t want TAVR because of their concerns about its durability.” These patients usually cite evidence reported in May 2016 at the annual congress of the European Association of Percutaneous Cardiovascular Interventions in Paris by Danny Dvir, MD, on longer-term follow-up of 378 patients who underwent TAVR at either of two pioneering centers. A retrospective review suggested a valve degeneration rate of about 50% after 8 years, Dr. Dvir reported.
This report “has gotten a lot of penetration over the Internet, and a lot of patients don’t like the uncertainty” about TAVR durability that this report produced. “A lot of the time now, patients come in with a fixed idea of whether they want TAVR or SAVR,” Dr. Smith said.
Dr. Smith essentially agreed with Dr. Sellke on the current role for TAVR relative to SAVR in lower-risk patients.
“If the patient is clearly intermediate risk, with an STS mortality risk of more than 6% and is at least 80 years old, then they’ll have TAVR 99% of the time. But if it’s a 75 year old with an STS score of 3.2% and otherwise healthy, the best choice is not as clear.”
Another cardiothoracic surgeon with lots of TAVR experience, Michael J. Reardon, MD, has much more enthusiasm for TAVR. “In my practice, I use TAVR exclusively in patients at least 80 years old. I don‘t care how healthy they look,” said Dr. Reardon, professor of cardiovascular surgery at Houston Methodist. He acknowledged that broader use of TAVR for intermediate-risk patients is getting push back from other cardiothoracic surgeons.
Dr. Sellke is one such surgeon, and he called uncertain TAVR valve durability the deciding factor. “We need longer-term data on [TAVR] valve longevity before we routinely put them into intermediate- or low-risk patients,” he said during a panel discussion at the meeting.
Dr. Reardon highlighted that newer TAVR systems have been reducing problems such as paravalvular leaks and the need for pacemakers following placement of self-expanding TAVR valves. Despite these technical improvements, the final frontier for TAVR for lower-risk patients is valve durability, Dr. Reardon said in an interview.
“I’m convinced the durability is there, and that any 80-year-old patient who is anatomically suited for transfemoral TAVR should get it no matter now healthy they look. If their likely survival is 15 years or less, then they are reasonable candidates for TAVR.”
Dr. Sellke had no relevant disclosures. PARTNER 2 was funded by Edwards, the company that markets Sapient TAVR systems. Dr. Cohen had no relevant disclosures. Dr. Smith has been an investigator in the PARTNER studies. Dr. Reardon has been a consultant to Medtronic, the company that markets the CoreValve and Evolut R TAVR systems.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
EXPERT ANALYSIS FROM THE AHA SCIENTIFIC SESSIONS
Sutureless aortic valve replacement: Is ease worth the cost?
CHICAGO – Rapid deployment sutureless valves can be a good option for some patients, providing a highly functional and nearly leakproof valve with less cardiopulmonary bypass and aortic cross-clamp times than those of conventional procedures.
“Why use a sutureless valve?” asked Vinod H. Thourani, MD, speaking at Heart Valve Summit 2016. He said that for many patients, there are abundant good reasons for the choice. The rapidity of the implantation procedure is a huge plus, he said. Cardiopulmonary bypass times are reduced when sutureless valve replacement is a stand-alone procedure, added Dr. Thourani, chief of cardiovascular surgery at Emory Hospital Midtown and codirector of the Structural Heart and Valve Center at Emory University, Atlanta. 
Rapid deployment is also of benefit in combined cases, or when patients have multiple comorbidities or poor left ventricular function. Sutureless valves, he said, are “optimal for multiple valve or concomitant procedures.”
Hemodynamics also are favorable, said Dr. Thourani; sutureless valves produce lower gradients than do their sutured alternatives, and work well in patients with a small aortic root.
Both sutureless valves that are currently available use bovine tissue; one, Sorin’s Perceval, uses a nitinol stent, while the Edwards’ Intuity uses stainless steel. The Perceval stent requires no sutures, while the Intuity requires just three. Also, the Perceval is collapsible, while the Intuity is not.
Removal of the pathologic valve in the sutureless procedure, he said, may contribute to the lower paravalvular leak and stroke rates than are seen in transcatheter aortic valve replacement (TAVR).
Expanded indications for sutureless valves include a calcified aortic root or a homograft; sutureless valves also can be used as an aortic valve redo, with patent grafts. Dr. Thourani said that he favors a transverse incision with a high aortotomy, about 2 cm above the sinotubular junction (STJ). In addition, off-label indications have included bicuspid aortic valve, pure aortic insufficiency, a prior mitral prosthesis or a degenerated aortic bioprosthesis, and a rescue procedure for a failed TAVR.
Dr. Thourani cited results of a trial conducted by Theodor Fischlein, MD, of Paracelsus Medical University in Nuremberg, Germany, and coauthors. These 1-year follow-up data from 628 patients participating in CAVALIER (Perceval S Valve Clinical Trial for Extended CE Mark), an international multicenter prospective trial, were presented at AATS 2016 (J Thorac Cardiovasc Surg. 2016 Jun;51[6]:1617-26.e4).
Of the 658 patients who met enrollment criteria and had a Perceval valve placement attempted, 30 wound up with a different prosthesis, most often because the correct valve size was not available. The remaining 628 patients who received the Perceval valve were included in the study. At 1 year, 549 patients remained; 50 had died, 12 had undergone valve explantation, and the remainder withdrew or were lost to follow-up.
Of the original Perceval recipients, 219 had received their valve via minimally invasive access. At 1 year, effective orifice area remained stable at the same mean 1.5 cm2 that was seen at discharge, an improvement from the mean 0.7 cm2 effective orifice area seen preoperatively. The mean pressure gradient, which was 45 mm Hg preoperatively, dropped precipitously to 10.3 mm Hg at discharge, and dropped a bit more at 1 year, to 9.2 mm Hg.
“This is a rapid and reproducible procedure: Over 20,000 implants have been performed worldwide,” said Dr. Thourani. The procedure looks good for low- to medium-risk patients, and may be the first procedure to consider for patients with a small aortic root, who have had prior coronary artery bypass surgery with patent grafts, or those with a calcified aortic root and homografts.
Questions still to be answered, he said, include whether “the cost will justify the decrease in cross-clamp times.” Also, though midrange results are good, longitudinal follow-up to track long-term valve hemodynamics is still ongoing.
Although patient demand seems to be high for a minimally invasive approach, sutureless valves still have low adoption rates, he said.
Dr. Thourani reported multiple financial relationships with medical device companies.
koakes@frontlinemedcom.com
On Twitter @karioakes
CHICAGO – Rapid deployment sutureless valves can be a good option for some patients, providing a highly functional and nearly leakproof valve with less cardiopulmonary bypass and aortic cross-clamp times than those of conventional procedures.
“Why use a sutureless valve?” asked Vinod H. Thourani, MD, speaking at Heart Valve Summit 2016. He said that for many patients, there are abundant good reasons for the choice. The rapidity of the implantation procedure is a huge plus, he said. Cardiopulmonary bypass times are reduced when sutureless valve replacement is a stand-alone procedure, added Dr. Thourani, chief of cardiovascular surgery at Emory Hospital Midtown and codirector of the Structural Heart and Valve Center at Emory University, Atlanta.
Rapid deployment is also of benefit in combined cases, or when patients have multiple comorbidities or poor left ventricular function. Sutureless valves, he said, are “optimal for multiple valve or concomitant procedures.”
Hemodynamics also are favorable, said Dr. Thourani; sutureless valves produce lower gradients than do their sutured alternatives, and work well in patients with a small aortic root.
Both sutureless valves that are currently available use bovine tissue; one, Sorin’s Perceval, uses a nitinol stent, while the Edwards’ Intuity uses stainless steel. The Perceval stent requires no sutures, while the Intuity requires just three. Also, the Perceval is collapsible, while the Intuity is not.
Removal of the pathologic valve in the sutureless procedure, he said, may contribute to the lower paravalvular leak and stroke rates than are seen in transcatheter aortic valve replacement (TAVR).
Expanded indications for sutureless valves include a calcified aortic root or a homograft; sutureless valves also can be used as an aortic valve redo, with patent grafts. Dr. Thourani said that he favors a transverse incision with a high aortotomy, about 2 cm above the sinotubular junction (STJ). In addition, off-label indications have included bicuspid aortic valve, pure aortic insufficiency, a prior mitral prosthesis or a degenerated aortic bioprosthesis, and a rescue procedure for a failed TAVR.
Dr. Thourani cited results of a trial conducted by Theodor Fischlein, MD, of Paracelsus Medical University in Nuremberg, Germany, and coauthors. These 1-year follow-up data from 628 patients participating in CAVALIER (Perceval S Valve Clinical Trial for Extended CE Mark), an international multicenter prospective trial, were presented at AATS 2016 (J Thorac Cardiovasc Surg. 2016 Jun;51[6]:1617-26.e4).
Of the 658 patients who met enrollment criteria and had a Perceval valve placement attempted, 30 wound up with a different prosthesis, most often because the correct valve size was not available. The remaining 628 patients who received the Perceval valve were included in the study. At 1 year, 549 patients remained; 50 had died, 12 had undergone valve explantation, and the remainder withdrew or were lost to follow-up.
Of the original Perceval recipients, 219 had received their valve via minimally invasive access. At 1 year, effective orifice area remained stable at the same mean 1.5 cm2 that was seen at discharge, an improvement from the mean 0.7 cm2 effective orifice area seen preoperatively. The mean pressure gradient, which was 45 mm Hg preoperatively, dropped precipitously to 10.3 mm Hg at discharge, and dropped a bit more at 1 year, to 9.2 mm Hg.
“This is a rapid and reproducible procedure: Over 20,000 implants have been performed worldwide,” said Dr. Thourani. The procedure looks good for low- to medium-risk patients, and may be the first procedure to consider for patients with a small aortic root, who have had prior coronary artery bypass surgery with patent grafts, or those with a calcified aortic root and homografts.
Questions still to be answered, he said, include whether “the cost will justify the decrease in cross-clamp times.” Also, though midrange results are good, longitudinal follow-up to track long-term valve hemodynamics is still ongoing.
Although patient demand seems to be high for a minimally invasive approach, sutureless valves still have low adoption rates, he said.
Dr. Thourani reported multiple financial relationships with medical device companies.
koakes@frontlinemedcom.com
On Twitter @karioakes
CHICAGO – Rapid deployment sutureless valves can be a good option for some patients, providing a highly functional and nearly leakproof valve with less cardiopulmonary bypass and aortic cross-clamp times than those of conventional procedures.
“Why use a sutureless valve?” asked Vinod H. Thourani, MD, speaking at Heart Valve Summit 2016. He said that for many patients, there are abundant good reasons for the choice. The rapidity of the implantation procedure is a huge plus, he said. Cardiopulmonary bypass times are reduced when sutureless valve replacement is a stand-alone procedure, added Dr. Thourani, chief of cardiovascular surgery at Emory Hospital Midtown and codirector of the Structural Heart and Valve Center at Emory University, Atlanta.
Rapid deployment is also of benefit in combined cases, or when patients have multiple comorbidities or poor left ventricular function. Sutureless valves, he said, are “optimal for multiple valve or concomitant procedures.”
Hemodynamics also are favorable, said Dr. Thourani; sutureless valves produce lower gradients than do their sutured alternatives, and work well in patients with a small aortic root.
Both sutureless valves that are currently available use bovine tissue; one, Sorin’s Perceval, uses a nitinol stent, while the Edwards’ Intuity uses stainless steel. The Perceval stent requires no sutures, while the Intuity requires just three. Also, the Perceval is collapsible, while the Intuity is not.
Removal of the pathologic valve in the sutureless procedure, he said, may contribute to the lower paravalvular leak and stroke rates than are seen in transcatheter aortic valve replacement (TAVR).
Expanded indications for sutureless valves include a calcified aortic root or a homograft; sutureless valves also can be used as an aortic valve redo, with patent grafts. Dr. Thourani said that he favors a transverse incision with a high aortotomy, about 2 cm above the sinotubular junction (STJ). In addition, off-label indications have included bicuspid aortic valve, pure aortic insufficiency, a prior mitral prosthesis or a degenerated aortic bioprosthesis, and a rescue procedure for a failed TAVR.
Dr. Thourani cited results of a trial conducted by Theodor Fischlein, MD, of Paracelsus Medical University in Nuremberg, Germany, and coauthors. These 1-year follow-up data from 628 patients participating in CAVALIER (Perceval S Valve Clinical Trial for Extended CE Mark), an international multicenter prospective trial, were presented at AATS 2016 (J Thorac Cardiovasc Surg. 2016 Jun;51[6]:1617-26.e4).
Of the 658 patients who met enrollment criteria and had a Perceval valve placement attempted, 30 wound up with a different prosthesis, most often because the correct valve size was not available. The remaining 628 patients who received the Perceval valve were included in the study. At 1 year, 549 patients remained; 50 had died, 12 had undergone valve explantation, and the remainder withdrew or were lost to follow-up.
Of the original Perceval recipients, 219 had received their valve via minimally invasive access. At 1 year, effective orifice area remained stable at the same mean 1.5 cm2 that was seen at discharge, an improvement from the mean 0.7 cm2 effective orifice area seen preoperatively. The mean pressure gradient, which was 45 mm Hg preoperatively, dropped precipitously to 10.3 mm Hg at discharge, and dropped a bit more at 1 year, to 9.2 mm Hg.
“This is a rapid and reproducible procedure: Over 20,000 implants have been performed worldwide,” said Dr. Thourani. The procedure looks good for low- to medium-risk patients, and may be the first procedure to consider for patients with a small aortic root, who have had prior coronary artery bypass surgery with patent grafts, or those with a calcified aortic root and homografts.
Questions still to be answered, he said, include whether “the cost will justify the decrease in cross-clamp times.” Also, though midrange results are good, longitudinal follow-up to track long-term valve hemodynamics is still ongoing.
Although patient demand seems to be high for a minimally invasive approach, sutureless valves still have low adoption rates, he said.
Dr. Thourani reported multiple financial relationships with medical device companies.
koakes@frontlinemedcom.com
On Twitter @karioakes
EXPERT ANALYSIS FROM THE HEART VALVE SUMMIT 2016
TAVR valve durability supported in large follow-up
WASHINGTON – First-generation, balloon-expandable transcatheter aortic valves had a less than 1% rate of valve failure in planned echocardiography examinations during follow-up that extended as long as 5 years after valve placement in more than 2,400 patients, a demonstration of durability that experts uniformly called “reassuring.”
This finding from patients who underwent transcatheter aortic valve replacement (TAVR) in the first U.S. pivotal trial for these devices, PARTNER 1 parts A and B, and during the subsequent continued-access program at PARTNER 1 study sites, represents the largest and longest systematic ultrasound follow-up of TAVR patients, Pamela S. Douglas, MD, said at the Transcatheter Cardiovascular Therapeutics annual meeting.
This evaluation of 2,404 TAVR patients in the PARTNER 1 trial examined by echocardiography and encompassing 6,493 patient-years of follow-up is the “largest core-lab based study of transcatheter heart valves to date. These data demonstrate excellent durability of transcatheter heart valves, suggesting that the low 5-year survival observed in this cohort is not related to adverse hemodynamics or transcatheter heart valve deterioration,” said Dr. Douglas, professor of medicine at Duke University, Durham, N.C.
Her findings showed that out of the 2,482 patients treated with TAVR (and including those without echo follow-up) either in the trial or during the continued access program and followed for a median of 2.9 years and an average of 2.6 years, 20 patients (0.8%) required a reintervention. Four of these 20 patients (0.2% of the total cohort) showed a “classic pattern” of aortic valve deterioration marked by an increased valve pressure gradient and a reduced valve area, she reported.
“Reintervention was rare, became less frequent over time, and was usually not due to structural deterioration of the transcatheter heart valve,” she said. But Dr. Douglas also cautioned that among the patients who received the first-generation, balloon expandable Sapien valve in this cohort, just 39% survived to 5 years, and a mere 282 patients (11%) actually underwent echocardiographic examination at 5 years.
“This is one of several steps we need to take to figure out the durability of transcatheter valves,” said Jeffrey J. Popma, MD, professor of medicine and an interventional cardiologist at Beth Israel Deaconess Medical Center, Boston. He noted that data are needed from follow-up periods of 8 or 10 years, but these data will not be available until intermediate- or low-risk patients undergo TAVR in controlled circumstances and have long-term follow-up. 
“Ten-year follow-up data will essentially be impossible” for the high-risk or inoperable patients treated with TAVR in the PARTNER 1 trial, which focused on the sickest patients with aortic stenosis, said Dr. Popma, lead investigator for several studies of TAVR using self-expanding aortic valves and marketed as CoreValve devices.
“We obviously need to follow patients longer. The 5-year results look terrific, and so very reassuring, but we need to keep an eye on this as we move TAVR into less sick and younger patients,” said Dr. Robert O. Bonow, professor of cardiology at Northwestern University, Chicago. “Durability is the remaining frontier in terms of moving TAVR into younger patients,” Dr. Bonow said at the meeting, which was sponsored by the Cardiovascular Research Foundation.
These data continue to show that “transcatheter valves have looked hemodynamically superior to surgically-placed valves with respect to the VARC (Valve Academic Research Consortium)–2 criteria” for prosthetic valve function, Dr. Popma noted. “I think the benefits of surgical valves have been overstated and the benefits of transcatheter valves understated,” he said.
“Surgical valves have not been held to the same [very demanding] standard as transcatheter valves,” Dr. Douglas agreed.
The data Dr. Douglas reported contrast with longer-term follow-up reported in May 2016 for 378 patients who underwent TAVR at either of two pioneering centers in a retrospective review. Those data suggested a valve degeneration rate of about 50% after 8 years, Danny Dvir, MD, reported at the annual congress of the European Association of Percutaneous Cardiovascular Interventions. Speaking recently in an interview, Dr. Dvir acknowledged some of the challenges in trying to derive valve durability information from a relatively small number of very-high-risk patients who underwent TAVR very early during development of the procedure.
Some TAVR experts have also questioned the criteria that Dr. Dvir used to identify valve structural valve degeneration for this analysis. “The criteria he used were much more stringent that the criteria we have used to assess surgically-placed valves,” said Michael J. Reardon, MD, professor of cardiovascular surgery at Houston Methodist Hospital. “If surgically-placed aortic valves were subjected to the same criteria Dr. Dvir applied then they would perform even worse,” Dr. Reardon said in an interview.
PARTNER 1 was sponsored by Edwards Lifesciences, the company that had marketed the Sapien first-generation, balloon expandable TAVR system. Dr. Douglas has received research support from Edwards. Dr. Bonow had no disclosures. Dr. Popma has been the lead investigator for several studies of a self-expanding TAVR system sponsored by Medtronic, and he has also received research funding from several other companies, has been a consultant to Boston Scientific and Direct Flow, and owns equity in Direct Flow. Dr. Dvir has been a consultant to and received research support from Edwards, Medtronic, and St. Jude. Dr. Reardon has been a consultant to Medtronic.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
The data reported by Dr. Douglas are very important and very reassuring. It isn’t easy to evaluate long-term results in patients who underwent TAVR in the early days because that population of patients was old and at very high risk. Even when patients had successful procedures their longevity wasn’t long. Only about 10% of the starting population of 2,482 patients in Dr. Douglas’ study actually had echocardiography done after 5 years. To assess durability you need longer-term echo follow-up, but it will be very challenging to have enough patients to have statistical power to do that.
I am not nervous about long-term durability of TAVR in octogenarian patients, the most typical age for TAVR patients today and since we began using it. Durability is more of an issue for patients who are 75 or younger, and we will need data from 7- to 10-year follow-up of younger patients to have a reasonable answer. Younger patients who undergo TAVR may face more of a threat from valve deterioration simply because of their longer life expectancy. In addition, with surgical valves we know that younger age is one of the strongest predictors of valve degeneration.
Danny Dvir, MD , is an interventional cardiologist at the University of Washington in Seattle. He has been a consultant to and received research support from Edwards, Medtronic, and St. Jude. He made these comments in an interview.
The data reported by Dr. Douglas are very important and very reassuring. It isn’t easy to evaluate long-term results in patients who underwent TAVR in the early days because that population of patients was old and at very high risk. Even when patients had successful procedures their longevity wasn’t long. Only about 10% of the starting population of 2,482 patients in Dr. Douglas’ study actually had echocardiography done after 5 years. To assess durability you need longer-term echo follow-up, but it will be very challenging to have enough patients to have statistical power to do that.
I am not nervous about long-term durability of TAVR in octogenarian patients, the most typical age for TAVR patients today and since we began using it. Durability is more of an issue for patients who are 75 or younger, and we will need data from 7- to 10-year follow-up of younger patients to have a reasonable answer. Younger patients who undergo TAVR may face more of a threat from valve deterioration simply because of their longer life expectancy. In addition, with surgical valves we know that younger age is one of the strongest predictors of valve degeneration.
Danny Dvir, MD , is an interventional cardiologist at the University of Washington in Seattle. He has been a consultant to and received research support from Edwards, Medtronic, and St. Jude. He made these comments in an interview.
The data reported by Dr. Douglas are very important and very reassuring. It isn’t easy to evaluate long-term results in patients who underwent TAVR in the early days because that population of patients was old and at very high risk. Even when patients had successful procedures their longevity wasn’t long. Only about 10% of the starting population of 2,482 patients in Dr. Douglas’ study actually had echocardiography done after 5 years. To assess durability you need longer-term echo follow-up, but it will be very challenging to have enough patients to have statistical power to do that.
I am not nervous about long-term durability of TAVR in octogenarian patients, the most typical age for TAVR patients today and since we began using it. Durability is more of an issue for patients who are 75 or younger, and we will need data from 7- to 10-year follow-up of younger patients to have a reasonable answer. Younger patients who undergo TAVR may face more of a threat from valve deterioration simply because of their longer life expectancy. In addition, with surgical valves we know that younger age is one of the strongest predictors of valve degeneration.
Danny Dvir, MD , is an interventional cardiologist at the University of Washington in Seattle. He has been a consultant to and received research support from Edwards, Medtronic, and St. Jude. He made these comments in an interview.
WASHINGTON – First-generation, balloon-expandable transcatheter aortic valves had a less than 1% rate of valve failure in planned echocardiography examinations during follow-up that extended as long as 5 years after valve placement in more than 2,400 patients, a demonstration of durability that experts uniformly called “reassuring.”
This finding from patients who underwent transcatheter aortic valve replacement (TAVR) in the first U.S. pivotal trial for these devices, PARTNER 1 parts A and B, and during the subsequent continued-access program at PARTNER 1 study sites, represents the largest and longest systematic ultrasound follow-up of TAVR patients, Pamela S. Douglas, MD, said at the Transcatheter Cardiovascular Therapeutics annual meeting.
This evaluation of 2,404 TAVR patients in the PARTNER 1 trial examined by echocardiography and encompassing 6,493 patient-years of follow-up is the “largest core-lab based study of transcatheter heart valves to date. These data demonstrate excellent durability of transcatheter heart valves, suggesting that the low 5-year survival observed in this cohort is not related to adverse hemodynamics or transcatheter heart valve deterioration,” said Dr. Douglas, professor of medicine at Duke University, Durham, N.C.
Her findings showed that out of the 2,482 patients treated with TAVR (and including those without echo follow-up) either in the trial or during the continued access program and followed for a median of 2.9 years and an average of 2.6 years, 20 patients (0.8%) required a reintervention. Four of these 20 patients (0.2% of the total cohort) showed a “classic pattern” of aortic valve deterioration marked by an increased valve pressure gradient and a reduced valve area, she reported.
“Reintervention was rare, became less frequent over time, and was usually not due to structural deterioration of the transcatheter heart valve,” she said. But Dr. Douglas also cautioned that among the patients who received the first-generation, balloon expandable Sapien valve in this cohort, just 39% survived to 5 years, and a mere 282 patients (11%) actually underwent echocardiographic examination at 5 years.
“This is one of several steps we need to take to figure out the durability of transcatheter valves,” said Jeffrey J. Popma, MD, professor of medicine and an interventional cardiologist at Beth Israel Deaconess Medical Center, Boston. He noted that data are needed from follow-up periods of 8 or 10 years, but these data will not be available until intermediate- or low-risk patients undergo TAVR in controlled circumstances and have long-term follow-up.
“Ten-year follow-up data will essentially be impossible” for the high-risk or inoperable patients treated with TAVR in the PARTNER 1 trial, which focused on the sickest patients with aortic stenosis, said Dr. Popma, lead investigator for several studies of TAVR using self-expanding aortic valves and marketed as CoreValve devices.
“We obviously need to follow patients longer. The 5-year results look terrific, and so very reassuring, but we need to keep an eye on this as we move TAVR into less sick and younger patients,” said Dr. Robert O. Bonow, professor of cardiology at Northwestern University, Chicago. “Durability is the remaining frontier in terms of moving TAVR into younger patients,” Dr. Bonow said at the meeting, which was sponsored by the Cardiovascular Research Foundation.
These data continue to show that “transcatheter valves have looked hemodynamically superior to surgically-placed valves with respect to the VARC (Valve Academic Research Consortium)–2 criteria” for prosthetic valve function, Dr. Popma noted. “I think the benefits of surgical valves have been overstated and the benefits of transcatheter valves understated,” he said.
“Surgical valves have not been held to the same [very demanding] standard as transcatheter valves,” Dr. Douglas agreed.
The data Dr. Douglas reported contrast with longer-term follow-up reported in May 2016 for 378 patients who underwent TAVR at either of two pioneering centers in a retrospective review. Those data suggested a valve degeneration rate of about 50% after 8 years, Danny Dvir, MD, reported at the annual congress of the European Association of Percutaneous Cardiovascular Interventions. Speaking recently in an interview, Dr. Dvir acknowledged some of the challenges in trying to derive valve durability information from a relatively small number of very-high-risk patients who underwent TAVR very early during development of the procedure.
Some TAVR experts have also questioned the criteria that Dr. Dvir used to identify valve structural valve degeneration for this analysis. “The criteria he used were much more stringent that the criteria we have used to assess surgically-placed valves,” said Michael J. Reardon, MD, professor of cardiovascular surgery at Houston Methodist Hospital. “If surgically-placed aortic valves were subjected to the same criteria Dr. Dvir applied then they would perform even worse,” Dr. Reardon said in an interview.
PARTNER 1 was sponsored by Edwards Lifesciences, the company that had marketed the Sapien first-generation, balloon expandable TAVR system. Dr. Douglas has received research support from Edwards. Dr. Bonow had no disclosures. Dr. Popma has been the lead investigator for several studies of a self-expanding TAVR system sponsored by Medtronic, and he has also received research funding from several other companies, has been a consultant to Boston Scientific and Direct Flow, and owns equity in Direct Flow. Dr. Dvir has been a consultant to and received research support from Edwards, Medtronic, and St. Jude. Dr. Reardon has been a consultant to Medtronic.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
WASHINGTON – First-generation, balloon-expandable transcatheter aortic valves had a less than 1% rate of valve failure in planned echocardiography examinations during follow-up that extended as long as 5 years after valve placement in more than 2,400 patients, a demonstration of durability that experts uniformly called “reassuring.”
This finding from patients who underwent transcatheter aortic valve replacement (TAVR) in the first U.S. pivotal trial for these devices, PARTNER 1 parts A and B, and during the subsequent continued-access program at PARTNER 1 study sites, represents the largest and longest systematic ultrasound follow-up of TAVR patients, Pamela S. Douglas, MD, said at the Transcatheter Cardiovascular Therapeutics annual meeting.
This evaluation of 2,404 TAVR patients in the PARTNER 1 trial examined by echocardiography and encompassing 6,493 patient-years of follow-up is the “largest core-lab based study of transcatheter heart valves to date. These data demonstrate excellent durability of transcatheter heart valves, suggesting that the low 5-year survival observed in this cohort is not related to adverse hemodynamics or transcatheter heart valve deterioration,” said Dr. Douglas, professor of medicine at Duke University, Durham, N.C.
Her findings showed that out of the 2,482 patients treated with TAVR (and including those without echo follow-up) either in the trial or during the continued access program and followed for a median of 2.9 years and an average of 2.6 years, 20 patients (0.8%) required a reintervention. Four of these 20 patients (0.2% of the total cohort) showed a “classic pattern” of aortic valve deterioration marked by an increased valve pressure gradient and a reduced valve area, she reported.
“Reintervention was rare, became less frequent over time, and was usually not due to structural deterioration of the transcatheter heart valve,” she said. But Dr. Douglas also cautioned that among the patients who received the first-generation, balloon expandable Sapien valve in this cohort, just 39% survived to 5 years, and a mere 282 patients (11%) actually underwent echocardiographic examination at 5 years.
“This is one of several steps we need to take to figure out the durability of transcatheter valves,” said Jeffrey J. Popma, MD, professor of medicine and an interventional cardiologist at Beth Israel Deaconess Medical Center, Boston. He noted that data are needed from follow-up periods of 8 or 10 years, but these data will not be available until intermediate- or low-risk patients undergo TAVR in controlled circumstances and have long-term follow-up.
“Ten-year follow-up data will essentially be impossible” for the high-risk or inoperable patients treated with TAVR in the PARTNER 1 trial, which focused on the sickest patients with aortic stenosis, said Dr. Popma, lead investigator for several studies of TAVR using self-expanding aortic valves and marketed as CoreValve devices.
“We obviously need to follow patients longer. The 5-year results look terrific, and so very reassuring, but we need to keep an eye on this as we move TAVR into less sick and younger patients,” said Dr. Robert O. Bonow, professor of cardiology at Northwestern University, Chicago. “Durability is the remaining frontier in terms of moving TAVR into younger patients,” Dr. Bonow said at the meeting, which was sponsored by the Cardiovascular Research Foundation.
These data continue to show that “transcatheter valves have looked hemodynamically superior to surgically-placed valves with respect to the VARC (Valve Academic Research Consortium)–2 criteria” for prosthetic valve function, Dr. Popma noted. “I think the benefits of surgical valves have been overstated and the benefits of transcatheter valves understated,” he said.
“Surgical valves have not been held to the same [very demanding] standard as transcatheter valves,” Dr. Douglas agreed.
The data Dr. Douglas reported contrast with longer-term follow-up reported in May 2016 for 378 patients who underwent TAVR at either of two pioneering centers in a retrospective review. Those data suggested a valve degeneration rate of about 50% after 8 years, Danny Dvir, MD, reported at the annual congress of the European Association of Percutaneous Cardiovascular Interventions. Speaking recently in an interview, Dr. Dvir acknowledged some of the challenges in trying to derive valve durability information from a relatively small number of very-high-risk patients who underwent TAVR very early during development of the procedure.
Some TAVR experts have also questioned the criteria that Dr. Dvir used to identify valve structural valve degeneration for this analysis. “The criteria he used were much more stringent that the criteria we have used to assess surgically-placed valves,” said Michael J. Reardon, MD, professor of cardiovascular surgery at Houston Methodist Hospital. “If surgically-placed aortic valves were subjected to the same criteria Dr. Dvir applied then they would perform even worse,” Dr. Reardon said in an interview.
PARTNER 1 was sponsored by Edwards Lifesciences, the company that had marketed the Sapien first-generation, balloon expandable TAVR system. Dr. Douglas has received research support from Edwards. Dr. Bonow had no disclosures. Dr. Popma has been the lead investigator for several studies of a self-expanding TAVR system sponsored by Medtronic, and he has also received research funding from several other companies, has been a consultant to Boston Scientific and Direct Flow, and owns equity in Direct Flow. Dr. Dvir has been a consultant to and received research support from Edwards, Medtronic, and St. Jude. Dr. Reardon has been a consultant to Medtronic.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
AT TCT 2016
Key clinical point:
Major finding: During median follow-up of 2.9 years, 0.2% of patients had valves with classic hemodynamic signs of valve deterioration.
Data source: A total of 2,482 TAVR patients either enrolled in the PARTNER 1 trial or who underwent TAVR during a continued access program.
Disclosures: PARTNER 1 was sponsored by Edwards Lifesciences, the company that had marketed the Sapien first-generation, balloon expandable TAVR system. Dr. Douglas has received research support from Edwards. Dr. Bonow had no disclosures. Dr. Popma has been the lead investigator for several studies of a self-expanding TAVR system sponsored by Medtronic, and he has also received research funding from several other companies, has been a consultant to Boston Scientific and Direct Flow, and owns equity in Direct Flow. Dr. Dvir has been a consultant to and received research support from Edwards, Medtronic, and St. Jude. Dr. Reardon has been a consultant to Medtronic.
SYNTAX analysis: Making the case for CABG over PCI
Whenever seminal clinical trials report results that challenge conventional thinking, physicians face the challenge of actually applying those findings in the clinic. A team of cardiac surgeons from Baylor University in Plano, Tex., has offered its take on the clinical implications of recent findings from the cause-of-death analysis of the SYNTAX trial that compared coronary artery bypass grafting with stenting: When counseling higher-risk patients with coronary artery disease about revascularization procedures, cardiologists and cardiac surgeons should clearly elucidate the dramatic advantage of coronary artery bypass grafting over stenting that SYNTAX had demonstrated.
Michael Mack, MD, and coauthors made their case in a featured expert opinion in the Journal of Thoracic and Cardiovascular Surgery (2016;152:1237-40).
“In fact, there was a significant survival advantage for CABG in the patients with intermediate and high SYNTAX scores, with the death rate of CABG versus PCI being 9.6% versus 16.3% (P less than .047) and 8.8% versus 17.8% (P less than .02), respectively,” they wrote.
The advantages of surgery “have been most striking for patients with intermediate or high SYNTAX scores, but seem to exist for patients with low scores as well, although requiring more follow-up,” Dr. Mack and colleagues said. But the situation is less clear in other subgroups, particularly in patients with less diffuse distal disease and lower SYNTAX scores, they added.
Complete revascularization after the procedure may explain the better outcomes with CABG, as 43.3% of those in the PCI arm had incomplete revascularization vs. 36.8% in the CABG arm. “Incomplete revascularization was associated with increased risk for major adverse cardiac or cerebrovascular events three years after PCI, but incomplete revascularization in the CABG group could not be identified as a predictor for worse outcomes,” Dr. Mack and colleagues noted.
The expert opinion authors debunk one of the recent criticisms of SYNTAX: that its reliance on first-generation drug-eluting stents is dated and not relevant today. They noted the more recent Bypass Surgery Vs. Everolimus-Eluting Stent Implantation for Multivessel Coronary Artery Disease trial found a similarly higher rate of death, heart attack, and target vessel revascularization occurred more frequently in the PCI group (15.3% vs. 10.6% in the CABG group) (N Engl J Med. 2015;372:1204-12).
Nonetheless, Dr. Mack and coauthors found room for improvement for CABG through increased use of atrial revascularization and appropriate measures to minimize stroke.
The latest SYNTAX findings can inform the approach surgeons take with high-risk patients, they said. This should include “a discussion of these data, particularly in regard to survival.” And physicians should base their therapeutic recommendations on these data. “At present, there are data seeming to indicate that the majority of patients with three-vessel disease receiving invasive treatment in the United States are being treated with PCI, an outcome that is not congruent with these outcome findings,” they said.
Taking into consideration other SYNTAX analyses that have shown that completeness of revascularization is a determining factor in post-PCI outcomes, Dr. Mack and coauthors said that physicians should calculate the degree of coronary artery disease (CAD) left untreated after intervention, “and those patients who are likely to have a high residual SYNTAX score should be strongly considered for CABG.” Doctors should also focus “intensive efforts” on adherence to optimal medical therapy after both CABG and PCI.
“Finally, although there is a strong patient preference for a less-invasive treatment of their CAD, patients with advanced disease should be made aware that the choice of PCI puts them at an increased risk of death relative to CABG, and a full and transparent discussion should occur regarding the implications of their decision,” Dr. Mack and coauthors concluded.
They had no relevant financial relationships to disclose.
In their invited editorial commentary, Saswata Deb, MD, and Stephen E. Fremes, MD, of the Schulich Heart Center at the University of Toronto, concurred with the conclusions of Dr. Mack and colleagues (J Thorac Cardiovasc Surg. 2016;152:1241-2). And Joseph F. Sabik III, MD, of the Cleveland Clinic arrived at a similar conclusion in an accompanying editorial (J. Thorac Cardiovasc Surg. 2016;152:1227-8).
Dr. Deb and Dr. Fremes found noteworthy the point Dr. Mack and coauthors raised about cardiologists and internists continuing to recommend PCI to patients with complex multivessel CAD despite evidence from SYNTAX and other trials. “This raises the importance of having a multidisciplinary heart team,” Dr. Deb and Dr. Fremes said.
But they also raised an important question about the difference in outcomes between CABG and PCI in complex multivessel disease. CABG should be the preferred intervention if the high rates of late fatal myocardial infarction after PCI are due to incomplete revascularization; however, if late stent thrombosis was the cause of this disparity in outcomes, then improvements in PCI could close that gap.
In his editorial, Dr. Sabik attributed the difference in outcomes between PCI and CABG to the ability of the former to both treat existing and prevent future stenosis. PCI can be “difficult, dangerous, and even impossible” when the target vessel is totally occluded or the stenosis is complex, hence leading to incomplete revascularization and residual ischemia. “Performing CABG to these vessels is no more difficult than for an isolated, noncomplex stenosis,” Dr. Sabik said.
Dr. Sabik disclosed he is the principal investigator for an Abbott Laboratories–sponsored trial of left main coronary disease, and is on the scientific advisory board of Medtronic.
Dr. Deb and Dr. Fremes had no relationships to disclose.
In their invited editorial commentary, Saswata Deb, MD, and Stephen E. Fremes, MD, of the Schulich Heart Center at the University of Toronto, concurred with the conclusions of Dr. Mack and colleagues (J Thorac Cardiovasc Surg. 2016;152:1241-2). And Joseph F. Sabik III, MD, of the Cleveland Clinic arrived at a similar conclusion in an accompanying editorial (J. Thorac Cardiovasc Surg. 2016;152:1227-8).
Dr. Deb and Dr. Fremes found noteworthy the point Dr. Mack and coauthors raised about cardiologists and internists continuing to recommend PCI to patients with complex multivessel CAD despite evidence from SYNTAX and other trials. “This raises the importance of having a multidisciplinary heart team,” Dr. Deb and Dr. Fremes said.
But they also raised an important question about the difference in outcomes between CABG and PCI in complex multivessel disease. CABG should be the preferred intervention if the high rates of late fatal myocardial infarction after PCI are due to incomplete revascularization; however, if late stent thrombosis was the cause of this disparity in outcomes, then improvements in PCI could close that gap.
In his editorial, Dr. Sabik attributed the difference in outcomes between PCI and CABG to the ability of the former to both treat existing and prevent future stenosis. PCI can be “difficult, dangerous, and even impossible” when the target vessel is totally occluded or the stenosis is complex, hence leading to incomplete revascularization and residual ischemia. “Performing CABG to these vessels is no more difficult than for an isolated, noncomplex stenosis,” Dr. Sabik said.
Dr. Sabik disclosed he is the principal investigator for an Abbott Laboratories–sponsored trial of left main coronary disease, and is on the scientific advisory board of Medtronic.
Dr. Deb and Dr. Fremes had no relationships to disclose.
In their invited editorial commentary, Saswata Deb, MD, and Stephen E. Fremes, MD, of the Schulich Heart Center at the University of Toronto, concurred with the conclusions of Dr. Mack and colleagues (J Thorac Cardiovasc Surg. 2016;152:1241-2). And Joseph F. Sabik III, MD, of the Cleveland Clinic arrived at a similar conclusion in an accompanying editorial (J. Thorac Cardiovasc Surg. 2016;152:1227-8).
Dr. Deb and Dr. Fremes found noteworthy the point Dr. Mack and coauthors raised about cardiologists and internists continuing to recommend PCI to patients with complex multivessel CAD despite evidence from SYNTAX and other trials. “This raises the importance of having a multidisciplinary heart team,” Dr. Deb and Dr. Fremes said.
But they also raised an important question about the difference in outcomes between CABG and PCI in complex multivessel disease. CABG should be the preferred intervention if the high rates of late fatal myocardial infarction after PCI are due to incomplete revascularization; however, if late stent thrombosis was the cause of this disparity in outcomes, then improvements in PCI could close that gap.
In his editorial, Dr. Sabik attributed the difference in outcomes between PCI and CABG to the ability of the former to both treat existing and prevent future stenosis. PCI can be “difficult, dangerous, and even impossible” when the target vessel is totally occluded or the stenosis is complex, hence leading to incomplete revascularization and residual ischemia. “Performing CABG to these vessels is no more difficult than for an isolated, noncomplex stenosis,” Dr. Sabik said.
Dr. Sabik disclosed he is the principal investigator for an Abbott Laboratories–sponsored trial of left main coronary disease, and is on the scientific advisory board of Medtronic.
Dr. Deb and Dr. Fremes had no relationships to disclose.
Whenever seminal clinical trials report results that challenge conventional thinking, physicians face the challenge of actually applying those findings in the clinic. A team of cardiac surgeons from Baylor University in Plano, Tex., has offered its take on the clinical implications of recent findings from the cause-of-death analysis of the SYNTAX trial that compared coronary artery bypass grafting with stenting: When counseling higher-risk patients with coronary artery disease about revascularization procedures, cardiologists and cardiac surgeons should clearly elucidate the dramatic advantage of coronary artery bypass grafting over stenting that SYNTAX had demonstrated.
Michael Mack, MD, and coauthors made their case in a featured expert opinion in the Journal of Thoracic and Cardiovascular Surgery (2016;152:1237-40).
“In fact, there was a significant survival advantage for CABG in the patients with intermediate and high SYNTAX scores, with the death rate of CABG versus PCI being 9.6% versus 16.3% (P less than .047) and 8.8% versus 17.8% (P less than .02), respectively,” they wrote.
The advantages of surgery “have been most striking for patients with intermediate or high SYNTAX scores, but seem to exist for patients with low scores as well, although requiring more follow-up,” Dr. Mack and colleagues said. But the situation is less clear in other subgroups, particularly in patients with less diffuse distal disease and lower SYNTAX scores, they added.
Complete revascularization after the procedure may explain the better outcomes with CABG, as 43.3% of those in the PCI arm had incomplete revascularization vs. 36.8% in the CABG arm. “Incomplete revascularization was associated with increased risk for major adverse cardiac or cerebrovascular events three years after PCI, but incomplete revascularization in the CABG group could not be identified as a predictor for worse outcomes,” Dr. Mack and colleagues noted.
The expert opinion authors debunk one of the recent criticisms of SYNTAX: that its reliance on first-generation drug-eluting stents is dated and not relevant today. They noted the more recent Bypass Surgery Vs. Everolimus-Eluting Stent Implantation for Multivessel Coronary Artery Disease trial found a similarly higher rate of death, heart attack, and target vessel revascularization occurred more frequently in the PCI group (15.3% vs. 10.6% in the CABG group) (N Engl J Med. 2015;372:1204-12).
Nonetheless, Dr. Mack and coauthors found room for improvement for CABG through increased use of atrial revascularization and appropriate measures to minimize stroke.
The latest SYNTAX findings can inform the approach surgeons take with high-risk patients, they said. This should include “a discussion of these data, particularly in regard to survival.” And physicians should base their therapeutic recommendations on these data. “At present, there are data seeming to indicate that the majority of patients with three-vessel disease receiving invasive treatment in the United States are being treated with PCI, an outcome that is not congruent with these outcome findings,” they said.
Taking into consideration other SYNTAX analyses that have shown that completeness of revascularization is a determining factor in post-PCI outcomes, Dr. Mack and coauthors said that physicians should calculate the degree of coronary artery disease (CAD) left untreated after intervention, “and those patients who are likely to have a high residual SYNTAX score should be strongly considered for CABG.” Doctors should also focus “intensive efforts” on adherence to optimal medical therapy after both CABG and PCI.
“Finally, although there is a strong patient preference for a less-invasive treatment of their CAD, patients with advanced disease should be made aware that the choice of PCI puts them at an increased risk of death relative to CABG, and a full and transparent discussion should occur regarding the implications of their decision,” Dr. Mack and coauthors concluded.
They had no relevant financial relationships to disclose.
Whenever seminal clinical trials report results that challenge conventional thinking, physicians face the challenge of actually applying those findings in the clinic. A team of cardiac surgeons from Baylor University in Plano, Tex., has offered its take on the clinical implications of recent findings from the cause-of-death analysis of the SYNTAX trial that compared coronary artery bypass grafting with stenting: When counseling higher-risk patients with coronary artery disease about revascularization procedures, cardiologists and cardiac surgeons should clearly elucidate the dramatic advantage of coronary artery bypass grafting over stenting that SYNTAX had demonstrated.
Michael Mack, MD, and coauthors made their case in a featured expert opinion in the Journal of Thoracic and Cardiovascular Surgery (2016;152:1237-40).
“In fact, there was a significant survival advantage for CABG in the patients with intermediate and high SYNTAX scores, with the death rate of CABG versus PCI being 9.6% versus 16.3% (P less than .047) and 8.8% versus 17.8% (P less than .02), respectively,” they wrote.
The advantages of surgery “have been most striking for patients with intermediate or high SYNTAX scores, but seem to exist for patients with low scores as well, although requiring more follow-up,” Dr. Mack and colleagues said. But the situation is less clear in other subgroups, particularly in patients with less diffuse distal disease and lower SYNTAX scores, they added.
Complete revascularization after the procedure may explain the better outcomes with CABG, as 43.3% of those in the PCI arm had incomplete revascularization vs. 36.8% in the CABG arm. “Incomplete revascularization was associated with increased risk for major adverse cardiac or cerebrovascular events three years after PCI, but incomplete revascularization in the CABG group could not be identified as a predictor for worse outcomes,” Dr. Mack and colleagues noted.
The expert opinion authors debunk one of the recent criticisms of SYNTAX: that its reliance on first-generation drug-eluting stents is dated and not relevant today. They noted the more recent Bypass Surgery Vs. Everolimus-Eluting Stent Implantation for Multivessel Coronary Artery Disease trial found a similarly higher rate of death, heart attack, and target vessel revascularization occurred more frequently in the PCI group (15.3% vs. 10.6% in the CABG group) (N Engl J Med. 2015;372:1204-12).
Nonetheless, Dr. Mack and coauthors found room for improvement for CABG through increased use of atrial revascularization and appropriate measures to minimize stroke.
The latest SYNTAX findings can inform the approach surgeons take with high-risk patients, they said. This should include “a discussion of these data, particularly in regard to survival.” And physicians should base their therapeutic recommendations on these data. “At present, there are data seeming to indicate that the majority of patients with three-vessel disease receiving invasive treatment in the United States are being treated with PCI, an outcome that is not congruent with these outcome findings,” they said.
Taking into consideration other SYNTAX analyses that have shown that completeness of revascularization is a determining factor in post-PCI outcomes, Dr. Mack and coauthors said that physicians should calculate the degree of coronary artery disease (CAD) left untreated after intervention, “and those patients who are likely to have a high residual SYNTAX score should be strongly considered for CABG.” Doctors should also focus “intensive efforts” on adherence to optimal medical therapy after both CABG and PCI.
“Finally, although there is a strong patient preference for a less-invasive treatment of their CAD, patients with advanced disease should be made aware that the choice of PCI puts them at an increased risk of death relative to CABG, and a full and transparent discussion should occur regarding the implications of their decision,” Dr. Mack and coauthors concluded.
They had no relevant financial relationships to disclose.
FROM THE JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
Key clinical point: Physicians should clearly communicate to patients with complex multivessel artery disease the key findings of the SYNTAX trial.
Major finding: The SYNTAX trials showed the risk of cardiac death from myocardial infarction after percutaneous coronary intervention (PCI) is 10 times greater than that after coronary artery bypass grafting in higher-risk patients.
Data source: A post hoc analysis of causes of death in all 3,075 trial and registry patients in the Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery (SYNTAX) trial.
Disclosures: Dr. Mack and coauthors reported having no financial disclosures.
VIDEO: HeartMate 3 LVAD solves pump thrombosis
NEW ORLEANS – HeartMate 3, the latest left ventricular assist device in the HeartMate line, appears to have solved the problem of pump thrombosis, a complication that has dogged ventricular pumps since the issue leapt into medical awareness about 3 years ago (New Engl J Med. 2014 Jan 2;370:33-40).
During 6 months of follow-up, none of 152 heart failure patients assigned to receive a HeartMate 3 left ventricular assist device (LVAD) developed suspected or confirmed pump thrombosis, compared with 14 patients (10%) having pump thrombosis out of 138 recipients of the prior-generation HeartMate II LVAD who served as the control group for the study.
“Three years ago, when the issue of pump thrombosis was first revealed, there was a lot of consternation and some drop in LVAD use, especially as destination therapy. We think that seeing no pump thrombosis whatsoever will give people renewed confidence in this technology,” said Dr. Mehra, professor of medicine at Harvard Medical School and medical director of the Heart and Vascular Center of Brigham and Women’s Hospital, both in Boston.
Pump thrombosis has also been a problem for the patients who have received a competitor LVAD, the HeartWare HVAD device (Circulation. 2015 Nov 10;132[suppl 3]:A19675), approved for U.S. use as bridge to transplant. HeartMate II is approved for both bridge to transplant and for destination therapy.
In addition to apparently eliminating pump thrombosis, HeartMate 3’s size and potential implantation approach should make its placement during routine use as quick and minimally invasive as the HeartWare device, features that should further help broader use of HeartMate 3, commented Mark Slaughter, MD, professor and chairman of cardiovascular and thoracic surgery at the University of Louisville (Ky.). But Dr. Slaughter and others were also quick to highlight the shortcomings that remain with both devices that will continue to hamper a broader role for LVAD treatment of patients with advanced heart failure.
“We thought that if there was less pump thrombosis we’d see less stroke, but that is not what the data suggest. It’s the big puzzle we need to figure out before we see widespread acceptance of this treatment,” Dr. Sweitzer said.
“This will not shift LVAD use substantially,” commented Christopher B. Granger, MD, a professor of medicine and a heart failure specialist at Duke University, Durham, N.C. “Reducing the need for reoperation is good for the field, and is an incremental advance, but it is not transformational,” he said in an interview.
The MOMENTUM 3 (Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy with HeartMate 3) trial randomized 294 patients at 69 U.S. centers. The study’s primary endpoint of 6-month survival free from disabling stroke or reoperation to repair or replace the LVAD occurred in 86% of 152 patients who received a HeartMate 3 and 77% of 142 patients randomized to HeartMate II, a statistical difference that met the prespecified criteria for both noninferiority and superiority. Concurrently with Dr. Mehra’s report at the meeting, a journal article appeared online (New Engl J Med. 2016 Nov 16. doi: 10.1056/NEJMoa1610426). He stated that as far as he understood, St. Jude would submit the 6-month data he reported to the Food and Drug Administration in an application for marketing approval for HeartMate 3.
“I agree that there are still morbid evens [with HeartMate 3] that need to be surmounted, but this is a confidence-building step in the right direction,” Dr. Mehra said.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
By eliminating all episodes of pump thrombosis during 6-month follow-up, the HeartMate 3 appeared to resolve one of the major issues that has stood in the way of patients and physicians feeling comfortable with left ventricular assist devices. The smaller size of the HeartMate 3 pump and its ability to be placed with minimally invasive and fairly rapid surgery is another big advance, putting this device on par with the rival pump, the HeartWare HVAD.
But the performance of the HeartMate 3 left ventricular assist device (LVAD) in MOMENTUM 3 also highlighted the shortcomings that still remain for these devices: the unchanged rates of stroke, gastrointestinal bleeds, and infections with HeartMate 3, compared with HeartMate II in this trial, and similar 6-month survival rates in the two arms of the study.
The HeartMate 3 can be implanted without sternotomy, using an 8 cm incision on the lateral chest wall, resulting in a shorter postoperative stay and fewer perisurgical adverse events. Despite the less invasive surgery and absence of pump thrombosis, some patients and physicians will remain hesitant to use an LVAD unless it is unavoidable because of concern about strokes. Until further design and procedural refinements change the rate of serious strokes and other adverse events, LVADs will not be fully competitive with heart transplantation.
The competition between HeartMate and the HeartWare devices will help drive this field forward, leading to further improvements in outcomes and expanded LVAD use.
Mark Slaughter, MD, is professor of surgery and chairman of cardiovascular and thoracic surgery at the University of Louisville (Ky.). He was an investigator in MOMENTUM 3, he has been a consultant to EvaHeart and Oregon Heart, and he has received research support from Carmat and HeartWare. He made these comments as designated discussant for the report and in a video interview.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
By eliminating all episodes of pump thrombosis during 6-month follow-up, the HeartMate 3 appeared to resolve one of the major issues that has stood in the way of patients and physicians feeling comfortable with left ventricular assist devices. The smaller size of the HeartMate 3 pump and its ability to be placed with minimally invasive and fairly rapid surgery is another big advance, putting this device on par with the rival pump, the HeartWare HVAD.
But the performance of the HeartMate 3 left ventricular assist device (LVAD) in MOMENTUM 3 also highlighted the shortcomings that still remain for these devices: the unchanged rates of stroke, gastrointestinal bleeds, and infections with HeartMate 3, compared with HeartMate II in this trial, and similar 6-month survival rates in the two arms of the study.
The HeartMate 3 can be implanted without sternotomy, using an 8 cm incision on the lateral chest wall, resulting in a shorter postoperative stay and fewer perisurgical adverse events. Despite the less invasive surgery and absence of pump thrombosis, some patients and physicians will remain hesitant to use an LVAD unless it is unavoidable because of concern about strokes. Until further design and procedural refinements change the rate of serious strokes and other adverse events, LVADs will not be fully competitive with heart transplantation.
The competition between HeartMate and the HeartWare devices will help drive this field forward, leading to further improvements in outcomes and expanded LVAD use.
Mark Slaughter, MD, is professor of surgery and chairman of cardiovascular and thoracic surgery at the University of Louisville (Ky.). He was an investigator in MOMENTUM 3, he has been a consultant to EvaHeart and Oregon Heart, and he has received research support from Carmat and HeartWare. He made these comments as designated discussant for the report and in a video interview.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
By eliminating all episodes of pump thrombosis during 6-month follow-up, the HeartMate 3 appeared to resolve one of the major issues that has stood in the way of patients and physicians feeling comfortable with left ventricular assist devices. The smaller size of the HeartMate 3 pump and its ability to be placed with minimally invasive and fairly rapid surgery is another big advance, putting this device on par with the rival pump, the HeartWare HVAD.
But the performance of the HeartMate 3 left ventricular assist device (LVAD) in MOMENTUM 3 also highlighted the shortcomings that still remain for these devices: the unchanged rates of stroke, gastrointestinal bleeds, and infections with HeartMate 3, compared with HeartMate II in this trial, and similar 6-month survival rates in the two arms of the study.
The HeartMate 3 can be implanted without sternotomy, using an 8 cm incision on the lateral chest wall, resulting in a shorter postoperative stay and fewer perisurgical adverse events. Despite the less invasive surgery and absence of pump thrombosis, some patients and physicians will remain hesitant to use an LVAD unless it is unavoidable because of concern about strokes. Until further design and procedural refinements change the rate of serious strokes and other adverse events, LVADs will not be fully competitive with heart transplantation.
The competition between HeartMate and the HeartWare devices will help drive this field forward, leading to further improvements in outcomes and expanded LVAD use.
Mark Slaughter, MD, is professor of surgery and chairman of cardiovascular and thoracic surgery at the University of Louisville (Ky.). He was an investigator in MOMENTUM 3, he has been a consultant to EvaHeart and Oregon Heart, and he has received research support from Carmat and HeartWare. He made these comments as designated discussant for the report and in a video interview.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
NEW ORLEANS – HeartMate 3, the latest left ventricular assist device in the HeartMate line, appears to have solved the problem of pump thrombosis, a complication that has dogged ventricular pumps since the issue leapt into medical awareness about 3 years ago (New Engl J Med. 2014 Jan 2;370:33-40).
During 6 months of follow-up, none of 152 heart failure patients assigned to receive a HeartMate 3 left ventricular assist device (LVAD) developed suspected or confirmed pump thrombosis, compared with 14 patients (10%) having pump thrombosis out of 138 recipients of the prior-generation HeartMate II LVAD who served as the control group for the study.
“Three years ago, when the issue of pump thrombosis was first revealed, there was a lot of consternation and some drop in LVAD use, especially as destination therapy. We think that seeing no pump thrombosis whatsoever will give people renewed confidence in this technology,” said Dr. Mehra, professor of medicine at Harvard Medical School and medical director of the Heart and Vascular Center of Brigham and Women’s Hospital, both in Boston.
Pump thrombosis has also been a problem for the patients who have received a competitor LVAD, the HeartWare HVAD device (Circulation. 2015 Nov 10;132[suppl 3]:A19675), approved for U.S. use as bridge to transplant. HeartMate II is approved for both bridge to transplant and for destination therapy.
In addition to apparently eliminating pump thrombosis, HeartMate 3’s size and potential implantation approach should make its placement during routine use as quick and minimally invasive as the HeartWare device, features that should further help broader use of HeartMate 3, commented Mark Slaughter, MD, professor and chairman of cardiovascular and thoracic surgery at the University of Louisville (Ky.). But Dr. Slaughter and others were also quick to highlight the shortcomings that remain with both devices that will continue to hamper a broader role for LVAD treatment of patients with advanced heart failure.
“We thought that if there was less pump thrombosis we’d see less stroke, but that is not what the data suggest. It’s the big puzzle we need to figure out before we see widespread acceptance of this treatment,” Dr. Sweitzer said.
“This will not shift LVAD use substantially,” commented Christopher B. Granger, MD, a professor of medicine and a heart failure specialist at Duke University, Durham, N.C. “Reducing the need for reoperation is good for the field, and is an incremental advance, but it is not transformational,” he said in an interview.
The MOMENTUM 3 (Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy with HeartMate 3) trial randomized 294 patients at 69 U.S. centers. The study’s primary endpoint of 6-month survival free from disabling stroke or reoperation to repair or replace the LVAD occurred in 86% of 152 patients who received a HeartMate 3 and 77% of 142 patients randomized to HeartMate II, a statistical difference that met the prespecified criteria for both noninferiority and superiority. Concurrently with Dr. Mehra’s report at the meeting, a journal article appeared online (New Engl J Med. 2016 Nov 16. doi: 10.1056/NEJMoa1610426). He stated that as far as he understood, St. Jude would submit the 6-month data he reported to the Food and Drug Administration in an application for marketing approval for HeartMate 3.
“I agree that there are still morbid evens [with HeartMate 3] that need to be surmounted, but this is a confidence-building step in the right direction,” Dr. Mehra said.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
NEW ORLEANS – HeartMate 3, the latest left ventricular assist device in the HeartMate line, appears to have solved the problem of pump thrombosis, a complication that has dogged ventricular pumps since the issue leapt into medical awareness about 3 years ago (New Engl J Med. 2014 Jan 2;370:33-40).
During 6 months of follow-up, none of 152 heart failure patients assigned to receive a HeartMate 3 left ventricular assist device (LVAD) developed suspected or confirmed pump thrombosis, compared with 14 patients (10%) having pump thrombosis out of 138 recipients of the prior-generation HeartMate II LVAD who served as the control group for the study.
“Three years ago, when the issue of pump thrombosis was first revealed, there was a lot of consternation and some drop in LVAD use, especially as destination therapy. We think that seeing no pump thrombosis whatsoever will give people renewed confidence in this technology,” said Dr. Mehra, professor of medicine at Harvard Medical School and medical director of the Heart and Vascular Center of Brigham and Women’s Hospital, both in Boston.
Pump thrombosis has also been a problem for the patients who have received a competitor LVAD, the HeartWare HVAD device (Circulation. 2015 Nov 10;132[suppl 3]:A19675), approved for U.S. use as bridge to transplant. HeartMate II is approved for both bridge to transplant and for destination therapy.
In addition to apparently eliminating pump thrombosis, HeartMate 3’s size and potential implantation approach should make its placement during routine use as quick and minimally invasive as the HeartWare device, features that should further help broader use of HeartMate 3, commented Mark Slaughter, MD, professor and chairman of cardiovascular and thoracic surgery at the University of Louisville (Ky.). But Dr. Slaughter and others were also quick to highlight the shortcomings that remain with both devices that will continue to hamper a broader role for LVAD treatment of patients with advanced heart failure.
“We thought that if there was less pump thrombosis we’d see less stroke, but that is not what the data suggest. It’s the big puzzle we need to figure out before we see widespread acceptance of this treatment,” Dr. Sweitzer said.
“This will not shift LVAD use substantially,” commented Christopher B. Granger, MD, a professor of medicine and a heart failure specialist at Duke University, Durham, N.C. “Reducing the need for reoperation is good for the field, and is an incremental advance, but it is not transformational,” he said in an interview.
The MOMENTUM 3 (Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy with HeartMate 3) trial randomized 294 patients at 69 U.S. centers. The study’s primary endpoint of 6-month survival free from disabling stroke or reoperation to repair or replace the LVAD occurred in 86% of 152 patients who received a HeartMate 3 and 77% of 142 patients randomized to HeartMate II, a statistical difference that met the prespecified criteria for both noninferiority and superiority. Concurrently with Dr. Mehra’s report at the meeting, a journal article appeared online (New Engl J Med. 2016 Nov 16. doi: 10.1056/NEJMoa1610426). He stated that as far as he understood, St. Jude would submit the 6-month data he reported to the Food and Drug Administration in an application for marketing approval for HeartMate 3.
“I agree that there are still morbid evens [with HeartMate 3] that need to be surmounted, but this is a confidence-building step in the right direction,” Dr. Mehra said.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
AT THE AHA SCIENTIFIC SESSIONS
Key clinical point:
Major finding: During 6 months, suspected or confirmed pump thrombosis occurred in no HeartMate 3 patients and in 10% of HeartMate II recipients.
Data source: The MOMENTUM 3 trial, which randomized 294 patients at 69 U.S. centers.
Disclosures: MOMENTUM 3 was sponsored by St. Jude, the company developing the HeartMate 3 LVAD. Dr. Mehra has received travel reimbursements from St. Jude and has been a consultant to Medtronic, Stealth, and Teva. Dr. Sweitzer was an investigator in MOMENTUM 3 and has been a consultant to Acorda and Medtronic and received research support from Bayer, Corvia, and Novartis. Dr. Granger has been a consultant to Boehringer Ingelheim, and received research support from Medtronic and several other drug and device companies. Dr. Slaughter was an investigator in MOMENTUM 3, has been a consultant to EvaHeart and Oregon Heart, and has received research support from Carmat and HeartWare.
PPIs may boost ischemic stroke risk
NEW ORLEANS – The use of proton pump inhibitors (PPIs) was associated with significantly increased risk of having a first ischemic stroke in a large nationwide Danish cohort study, Thomas S. Sehested, MD, reported at the American Heart Association scientific sessions.
The relationship was dose dependent. At the lowest available dose of each of the four PPIs studied there was no significantly increased risk. At the intermediate doses of three of the four PPIs studied, the increased risk of ischemic stroke became statistically significant. And the highest dose of each drug was associated with the greatest ischemic stroke risk.
In Denmark, for instance, where most PPIs are prescription only and use is easily trackable, it’s estimated that, at any given time, 7% of the adult population is taking a PPI, often not as directed in the labeling.
The impetus for this study, Dr. Sehested explained, was the mounting evidence that PPIs may constitute an independent risk factor for acute MI and other cardiovascular events. For example, a recent meta-analysis of 17 randomized controlled trials totaling 7,540 participants published through mid-2015 concluded that the use of PPIs was associated with a 70% increase in cardiovascular risk (Neurogastroenterol Motil. 2016 Aug 30. doi: 10.1111/nmo.12926).
He reported on 245,676 Danes above age 30 who were free of prior MI or stroke when they underwent elective GI endoscopy during 1997-2012. After a 30-day postendoscopy grace period during which 1,476 patients had a first MI, stroke, or died of any cause, the final study population was 244,200, of whom 43.7% were PPI users during the grace period and beyond.
During a median 5.8 years of follow-up, 9,489 subjects (3.9%) had a first ischemic stroke. Because of the comprehensive nature of Denmark’s interlocking birth to death registries, there was virtually no loss to follow-up in this study.
The unadjusted incidence of ischemic stroke in PPI nonusers was 55.7 per 10,000 person-years, compared with 88.9 per 10,000 in PPI users.
The PPI users were slightly older than nonusers by roughly 3 years. They were also an absolute 5% more likely to be hypertensive and an absolute 1.7% more likely to be regular users of NSAIDs. All of these differences, while modest, were statistically significant because of the large patient numbers involved.
In a multivariate analysis adjusted for age, sex, calendar year, comorbid diabetes, hypertension, alcohol use disorder, heart failure, peptic ulcer, peripheral artery disease, kidney disease, aspirin, oral anticoagulants and other medications, and socioeconomic status, current users of PPIs were 19% more likely to have a first ischemic stroke than nonusers. That difference is statistically significant and clinically meaningful, Dr. Sehested said.
In contrast, when the same sort of nationwide analysis was repeated, comparing current users of histamine-2 receptor antagonists to nonusers of those drugs or PPIs, there was no difference in ischemic stroke risk between the two groups.
The message, according to Dr. Sehested, is that physicians should encourage more cautious use of PPIs. And especially in the United States, where most PPIs are available over the counter, it’s prudent during office visits to ask what nonprescription drugs a patient is taking.
Dr. Sehested presented his study findings in a session devoted to original research in cardiovascular epidemiology. Many top American epidemiologists were present in the audience, and several rose to congratulate him on his presentation of the latest elegant epidemiologic study to come out of Denmark, the only place in the world where this sort of nationwide comprehensive research is possible.
“Wow! I just love the work you do in Denmark. It’s really inspiring,” commented David Siscovick, MD, senior vice president for research at the New York Academy of Medicine and professor emeritus of medicine and epidemiology at the University of Washington in Seattle.
He had a question: “Did you deal with PPI starters and stoppers and compliance in any way?”
Dr. Sehested replied that he and his coinvestigators were able to see who was on a PPI at any given point in the study, and they accounted for that. One issue the researchers plan to examine but haven’t yet had a chance to, however, is the relationship between duration of PPI therapy and ischemic stroke risk. It’s likely that some patients had already been on a PPI for a lengthy time at elective endoscopy, which is when the study in its current form began.
“I think that would strengthen the study,” he said.
Comoderator Jorge Kizer, MD, of Albert Einstein College of Medicine in New York, commented, “Confounding by indication is clearly the elephant in the room. The guidelines actually recommend adding a PPI if a patient is on dual-antiplatelet therapy and has an NSAID added. Did you adjust for that? It would boost confidence that the results are actually due to the PPI.”
Dr. Sehested answered that the great majority of individuals with cardiovascular disease at baseline were excluded from the analysis.
“I don’t think we had that many on dual-antiplatelet therapy,” he added.
Preclinical studies suggest a possible mechanism by which PPIs may harm cardiovascular health. The drugs reduce nitric oxide synthase levels, with resultant endothelial dysfunction, he said.
Dr. Sehested is employed at the Danish Heart Foundation, which funded the study.
A growing number of retrospective studies have associated proton pump inhibitors with a host of serious adverse effects. These include chronic kidney disease, dementia, osteoporosis, cardiovascular events, pneumonia, enteric infections, and others. The authors of this large, retrospective Danish study have now added ischemic stroke to the list.
Nonetheless, this study should serve as wake-up call to closely examine the risks and benefits of ongoing PPI use for each individual patient. For example, guidelines clearly advocate the use of PPIs in patients at high risk for peptic ulcer disease (for example, use of aspirin and warfarin together), and these patients should continue PPIs unless more convincing evidence of serious side effects emerge. On the other hand, several studies have shown that many patients with uncomplicated gastroesophageal reflux disease symptoms can achieve symptom control with substitution of histamine2 blockers, p.r.n. dosing of PPIs, or without acid-reducing medications entirely. Still, many patients with confirmed pathologic acid reflux are likely to require ongoing PPIs. For patients who continue PPIs, they should use the lowest effective dose.
Surely, physicians will be discussing PPI adverse effects with increasing numbers of patients. Until higher-quality evidence in the form of a randomized controlled trial emerges, physicians should get used to explaining the principles of epidemiology.
Jacob Kurlander, MD, is a clinical lecturer in the division of gastroenterology, University of Michigan, Ann Arbor. He has received research funding from Ironwood Pharmaceuticals.
A growing number of retrospective studies have associated proton pump inhibitors with a host of serious adverse effects. These include chronic kidney disease, dementia, osteoporosis, cardiovascular events, pneumonia, enteric infections, and others. The authors of this large, retrospective Danish study have now added ischemic stroke to the list.
Nonetheless, this study should serve as wake-up call to closely examine the risks and benefits of ongoing PPI use for each individual patient. For example, guidelines clearly advocate the use of PPIs in patients at high risk for peptic ulcer disease (for example, use of aspirin and warfarin together), and these patients should continue PPIs unless more convincing evidence of serious side effects emerge. On the other hand, several studies have shown that many patients with uncomplicated gastroesophageal reflux disease symptoms can achieve symptom control with substitution of histamine2 blockers, p.r.n. dosing of PPIs, or without acid-reducing medications entirely. Still, many patients with confirmed pathologic acid reflux are likely to require ongoing PPIs. For patients who continue PPIs, they should use the lowest effective dose.
Surely, physicians will be discussing PPI adverse effects with increasing numbers of patients. Until higher-quality evidence in the form of a randomized controlled trial emerges, physicians should get used to explaining the principles of epidemiology.
Jacob Kurlander, MD, is a clinical lecturer in the division of gastroenterology, University of Michigan, Ann Arbor. He has received research funding from Ironwood Pharmaceuticals.
A growing number of retrospective studies have associated proton pump inhibitors with a host of serious adverse effects. These include chronic kidney disease, dementia, osteoporosis, cardiovascular events, pneumonia, enteric infections, and others. The authors of this large, retrospective Danish study have now added ischemic stroke to the list.
Nonetheless, this study should serve as wake-up call to closely examine the risks and benefits of ongoing PPI use for each individual patient. For example, guidelines clearly advocate the use of PPIs in patients at high risk for peptic ulcer disease (for example, use of aspirin and warfarin together), and these patients should continue PPIs unless more convincing evidence of serious side effects emerge. On the other hand, several studies have shown that many patients with uncomplicated gastroesophageal reflux disease symptoms can achieve symptom control with substitution of histamine2 blockers, p.r.n. dosing of PPIs, or without acid-reducing medications entirely. Still, many patients with confirmed pathologic acid reflux are likely to require ongoing PPIs. For patients who continue PPIs, they should use the lowest effective dose.
Surely, physicians will be discussing PPI adverse effects with increasing numbers of patients. Until higher-quality evidence in the form of a randomized controlled trial emerges, physicians should get used to explaining the principles of epidemiology.
Jacob Kurlander, MD, is a clinical lecturer in the division of gastroenterology, University of Michigan, Ann Arbor. He has received research funding from Ironwood Pharmaceuticals.
NEW ORLEANS – The use of proton pump inhibitors (PPIs) was associated with significantly increased risk of having a first ischemic stroke in a large nationwide Danish cohort study, Thomas S. Sehested, MD, reported at the American Heart Association scientific sessions.
The relationship was dose dependent. At the lowest available dose of each of the four PPIs studied there was no significantly increased risk. At the intermediate doses of three of the four PPIs studied, the increased risk of ischemic stroke became statistically significant. And the highest dose of each drug was associated with the greatest ischemic stroke risk.
In Denmark, for instance, where most PPIs are prescription only and use is easily trackable, it’s estimated that, at any given time, 7% of the adult population is taking a PPI, often not as directed in the labeling.
The impetus for this study, Dr. Sehested explained, was the mounting evidence that PPIs may constitute an independent risk factor for acute MI and other cardiovascular events. For example, a recent meta-analysis of 17 randomized controlled trials totaling 7,540 participants published through mid-2015 concluded that the use of PPIs was associated with a 70% increase in cardiovascular risk (Neurogastroenterol Motil. 2016 Aug 30. doi: 10.1111/nmo.12926).
He reported on 245,676 Danes above age 30 who were free of prior MI or stroke when they underwent elective GI endoscopy during 1997-2012. After a 30-day postendoscopy grace period during which 1,476 patients had a first MI, stroke, or died of any cause, the final study population was 244,200, of whom 43.7% were PPI users during the grace period and beyond.
During a median 5.8 years of follow-up, 9,489 subjects (3.9%) had a first ischemic stroke. Because of the comprehensive nature of Denmark’s interlocking birth to death registries, there was virtually no loss to follow-up in this study.
The unadjusted incidence of ischemic stroke in PPI nonusers was 55.7 per 10,000 person-years, compared with 88.9 per 10,000 in PPI users.
The PPI users were slightly older than nonusers by roughly 3 years. They were also an absolute 5% more likely to be hypertensive and an absolute 1.7% more likely to be regular users of NSAIDs. All of these differences, while modest, were statistically significant because of the large patient numbers involved.
In a multivariate analysis adjusted for age, sex, calendar year, comorbid diabetes, hypertension, alcohol use disorder, heart failure, peptic ulcer, peripheral artery disease, kidney disease, aspirin, oral anticoagulants and other medications, and socioeconomic status, current users of PPIs were 19% more likely to have a first ischemic stroke than nonusers. That difference is statistically significant and clinically meaningful, Dr. Sehested said.
In contrast, when the same sort of nationwide analysis was repeated, comparing current users of histamine-2 receptor antagonists to nonusers of those drugs or PPIs, there was no difference in ischemic stroke risk between the two groups.
The message, according to Dr. Sehested, is that physicians should encourage more cautious use of PPIs. And especially in the United States, where most PPIs are available over the counter, it’s prudent during office visits to ask what nonprescription drugs a patient is taking.
Dr. Sehested presented his study findings in a session devoted to original research in cardiovascular epidemiology. Many top American epidemiologists were present in the audience, and several rose to congratulate him on his presentation of the latest elegant epidemiologic study to come out of Denmark, the only place in the world where this sort of nationwide comprehensive research is possible.
“Wow! I just love the work you do in Denmark. It’s really inspiring,” commented David Siscovick, MD, senior vice president for research at the New York Academy of Medicine and professor emeritus of medicine and epidemiology at the University of Washington in Seattle.
He had a question: “Did you deal with PPI starters and stoppers and compliance in any way?”
Dr. Sehested replied that he and his coinvestigators were able to see who was on a PPI at any given point in the study, and they accounted for that. One issue the researchers plan to examine but haven’t yet had a chance to, however, is the relationship between duration of PPI therapy and ischemic stroke risk. It’s likely that some patients had already been on a PPI for a lengthy time at elective endoscopy, which is when the study in its current form began.
“I think that would strengthen the study,” he said.
Comoderator Jorge Kizer, MD, of Albert Einstein College of Medicine in New York, commented, “Confounding by indication is clearly the elephant in the room. The guidelines actually recommend adding a PPI if a patient is on dual-antiplatelet therapy and has an NSAID added. Did you adjust for that? It would boost confidence that the results are actually due to the PPI.”
Dr. Sehested answered that the great majority of individuals with cardiovascular disease at baseline were excluded from the analysis.
“I don’t think we had that many on dual-antiplatelet therapy,” he added.
Preclinical studies suggest a possible mechanism by which PPIs may harm cardiovascular health. The drugs reduce nitric oxide synthase levels, with resultant endothelial dysfunction, he said.
Dr. Sehested is employed at the Danish Heart Foundation, which funded the study.
NEW ORLEANS – The use of proton pump inhibitors (PPIs) was associated with significantly increased risk of having a first ischemic stroke in a large nationwide Danish cohort study, Thomas S. Sehested, MD, reported at the American Heart Association scientific sessions.
The relationship was dose dependent. At the lowest available dose of each of the four PPIs studied there was no significantly increased risk. At the intermediate doses of three of the four PPIs studied, the increased risk of ischemic stroke became statistically significant. And the highest dose of each drug was associated with the greatest ischemic stroke risk.
In Denmark, for instance, where most PPIs are prescription only and use is easily trackable, it’s estimated that, at any given time, 7% of the adult population is taking a PPI, often not as directed in the labeling.
The impetus for this study, Dr. Sehested explained, was the mounting evidence that PPIs may constitute an independent risk factor for acute MI and other cardiovascular events. For example, a recent meta-analysis of 17 randomized controlled trials totaling 7,540 participants published through mid-2015 concluded that the use of PPIs was associated with a 70% increase in cardiovascular risk (Neurogastroenterol Motil. 2016 Aug 30. doi: 10.1111/nmo.12926).
He reported on 245,676 Danes above age 30 who were free of prior MI or stroke when they underwent elective GI endoscopy during 1997-2012. After a 30-day postendoscopy grace period during which 1,476 patients had a first MI, stroke, or died of any cause, the final study population was 244,200, of whom 43.7% were PPI users during the grace period and beyond.
During a median 5.8 years of follow-up, 9,489 subjects (3.9%) had a first ischemic stroke. Because of the comprehensive nature of Denmark’s interlocking birth to death registries, there was virtually no loss to follow-up in this study.
The unadjusted incidence of ischemic stroke in PPI nonusers was 55.7 per 10,000 person-years, compared with 88.9 per 10,000 in PPI users.
The PPI users were slightly older than nonusers by roughly 3 years. They were also an absolute 5% more likely to be hypertensive and an absolute 1.7% more likely to be regular users of NSAIDs. All of these differences, while modest, were statistically significant because of the large patient numbers involved.
In a multivariate analysis adjusted for age, sex, calendar year, comorbid diabetes, hypertension, alcohol use disorder, heart failure, peptic ulcer, peripheral artery disease, kidney disease, aspirin, oral anticoagulants and other medications, and socioeconomic status, current users of PPIs were 19% more likely to have a first ischemic stroke than nonusers. That difference is statistically significant and clinically meaningful, Dr. Sehested said.
In contrast, when the same sort of nationwide analysis was repeated, comparing current users of histamine-2 receptor antagonists to nonusers of those drugs or PPIs, there was no difference in ischemic stroke risk between the two groups.
The message, according to Dr. Sehested, is that physicians should encourage more cautious use of PPIs. And especially in the United States, where most PPIs are available over the counter, it’s prudent during office visits to ask what nonprescription drugs a patient is taking.
Dr. Sehested presented his study findings in a session devoted to original research in cardiovascular epidemiology. Many top American epidemiologists were present in the audience, and several rose to congratulate him on his presentation of the latest elegant epidemiologic study to come out of Denmark, the only place in the world where this sort of nationwide comprehensive research is possible.
“Wow! I just love the work you do in Denmark. It’s really inspiring,” commented David Siscovick, MD, senior vice president for research at the New York Academy of Medicine and professor emeritus of medicine and epidemiology at the University of Washington in Seattle.
He had a question: “Did you deal with PPI starters and stoppers and compliance in any way?”
Dr. Sehested replied that he and his coinvestigators were able to see who was on a PPI at any given point in the study, and they accounted for that. One issue the researchers plan to examine but haven’t yet had a chance to, however, is the relationship between duration of PPI therapy and ischemic stroke risk. It’s likely that some patients had already been on a PPI for a lengthy time at elective endoscopy, which is when the study in its current form began.
“I think that would strengthen the study,” he said.
Comoderator Jorge Kizer, MD, of Albert Einstein College of Medicine in New York, commented, “Confounding by indication is clearly the elephant in the room. The guidelines actually recommend adding a PPI if a patient is on dual-antiplatelet therapy and has an NSAID added. Did you adjust for that? It would boost confidence that the results are actually due to the PPI.”
Dr. Sehested answered that the great majority of individuals with cardiovascular disease at baseline were excluded from the analysis.
“I don’t think we had that many on dual-antiplatelet therapy,” he added.
Preclinical studies suggest a possible mechanism by which PPIs may harm cardiovascular health. The drugs reduce nitric oxide synthase levels, with resultant endothelial dysfunction, he said.
Dr. Sehested is employed at the Danish Heart Foundation, which funded the study.
AT THE AHA SCIENTIFIC SESSIONS
Key clinical point:
Major finding: Current use of a proton pump inhibitor was independently associated with a 19% increased risk of a first ischemic stroke, and the risk was greater at the top approved doses.
Data source: This retrospective nationwide Danish study involved 244,200 adults age 30 or older followed for a median of nearly 6 years following elective GI endoscopy.
Disclosures: The presenter is employed at the Danish Heart Foundation, which funded the study.