In the JournalsPerspective

Societies update six guidelines with new recommendations on DAPT duration

The American College of Cardiology and the American Heart Association have released a focused update on duration of dual antiplatelet therapy for patients with CAD, generally recommending that dual antiplatelet therapy duration decisions be made on an individualized basis depending on thrombotic and bleeding risks.

The recommendations update six previously released guidelines, including the 2011 ACC/AHA/Society for Cardiovascular Angiography and Interventions guideline on PCI, the 2011 ACC/AHA guideline on CABG, the 2012 ACC/AHA/SCAI/American College of Physicians/American Association for Thoracic Surgery/Preventive Cardiovascular Nurses Association/Society of Thoracic Surgeons guideline on stable ischemic heart disease, the 2013 ACC/AHA guideline on STEMI, the 2014 AHA/ACC guideline on non-ST-elevation ACS and the 2014 ACC/AHA guideline on CV issues in patients undergoing noncardiac surgery.

“Treatment with more intensive antiplatelet therapy and treatment for a longer duration of time with antiplatelet medicines in general involves a fundamental tradeoff between a decreased risk of future [MI] and an increased risk of bleeding complications,” writing committee chair Glenn N. Levine, MD, FAHA, FACC, professor of medicine at Baylor College of Medicine and director of the cardiac care unit at the Michael E. DeBakey VA Medical Center in Houston, said in a press release.

Glenn N. Levine, MD, FACC, FAHA

Glenn N. Levine

General recommendations

According to the committee, “shorter-duration DAPT can be considered for patients at lower ischemic risk with high bleeding risk, whereas longer-duration DAPT may be reasonable for patients at higher ischemic risk with low bleeding risk.” The committee noted that, in general, a minimum duration of DAPT, usually 6 to 12 months, received a Class I recommendation, while duration of DAPT beyond 12 months received a Class IIb recommendation.

“Decisions about DAPT are best made on an individual basis and should integrate clinical judgment, assessment of the benefit/risk ratio and patient preference. Aspirin is almost always indefinitely continued in patients with CAD, and recommendations on duration of DAPT should be taken to mean the recommended duration of P2Y12 inhibitor therapy (in addition to aspirin therapy),” according to the document.

These recommendations do not apply to patients on oral anticoagulation, who were not included in most studies of DAPT duration.

Treatment algorithm

Levine and colleagues developed a master treatment algorithm for duration of P2Y12 inhibitor therapy in addition to aspirin therapy.

For patients with stable ischemic heart disease, those who have not had CABG or PCI should not have DAPT; those who had PCI with a bare-metal stent should have clopidogrel and aspirin for at least 1 month, though a longer duration may be reasonable in those not at high risk for bleeding and no significant overt bleeding on DAPT; those who had PCI with a drug-eluting stent should have clopidogrel and aspirin for at least 6 months, though a longer duration may be reasonable in those not at high risk for bleeding and no significant overt bleeding on DAPT; and it may be reasonable for those who had CABG to take clopidogrel and aspirin for 12 months, according to the document.

For patients with STEMI or NSTEACS, those treated with medical therapy should take clopidogrel or ticagrelor (Brilinta, AstraZeneca) and aspirin for at least 12 months; those with STEMI treated with lytic therapy should be treated with clopidogrel and aspirin for a minimum of 14 days and ideally at least 12 months; those treated with PCI (BMS or DES) should be treated with clopidogrel, prasugrel (Effient; Daiichi Sankyo/Eli Lilly) or ticagrelor plus aspirin for at least 12 months; and those treated with CABG should have DAPT for 12 months, according to the authors.

For patients with STEMI or NSTEACS treated with medical therapy, lytic therapy or PCI, continuing DAPT beyond 12 months may be reasonable if the patient does not have a high risk for bleeding and does not have significant overt bleeding in the first 12 months, Levine and colleagues wrote.

The document lists six risk factors associated with increased ischemic risk, which may favor longer-duration DAPT; 10 risk factors associated with increased risk for stent thrombosis, which may favor longer-duration DAPT; and nine risk factors associated with elevated risk for bleeding, which may favor shorter-duration DAPT.

DAPT Score

In related news, Robert W. Yeh, MD, MSc, MBA, from the Smith Center for Outcomes Research in Cardiology, Beth Israel Deaconess Medical Center, Boston, and colleagues published in JAMA the validation of a DAPT Score to predict benefit or harm from DAPT beyond 1 year after PCI. The findings were initially presented at the AHA Scientific Sessions in November 2015.

Robert Yeh

Robert W. Yeh

To calculate the score, a patient receives –2 points for age 75 years or older, –1 point for age 65 to 74 years, 1 point for current smoking, 1 point for diabetes, 1 point for MI at presentation, 1 point for prior MI or PCI, 1 point for stent diameter < 3 mm, 1 point for having a paclitaxel-eluting stent, 2 points for congestive HF or left ventricular ejection fraction < 30% and 2 points for a saphenous vein graft PCI. A score of 2 or more confers a favorable benefit/risk ratio for prolonged DAPT after PCI, while a score of less than 2 confers an unfavorable benefit/risk ratio.

In their update of the guidelines, Levine and colleagues wrote that the DAPT Score “may be useful for decisions about whether to continue (prolong or extend) DAPT in patients treated with coronary stent implantation.”

The update was developed in conjunction with AATS, SCAI, STS, the American Society of Anesthesiologists and the Society of Cardiovascular Anesthesiologists, and endorsed by PCNA and the Society for Vascular Surgery. – by Erik Swain

References:

Levine GN, et al. Circulation. 2016; doi:10.1161/CIR.0000000000000404.
Levine GN, et al. J Am Coll Cardiol. 2016;doi:10.1016/j.jacc.2016.03.513.
Yeh RW, et al. JAMA. 2016;doi:10.1001/jama.2016.3775.

Disclosure: Levine reports no relevant financial disclosures. Please see the full document for a list of the other authors’ and reviewers’ financial disclosures. Yeh reports receiving personal fees from Abbott Vascular, Boston Scientific and Merck, a research salary from Harvard Clinical Research Institute and a pending patent for development and use of the DAPT Score. Please see the full study for a list of the other researchers’ relevant financial disclosures.

The American College of Cardiology and the American Heart Association have released a focused update on duration of dual antiplatelet therapy for patients with CAD, generally recommending that dual antiplatelet therapy duration decisions be made on an individualized basis depending on thrombotic and bleeding risks.

The recommendations update six previously released guidelines, including the 2011 ACC/AHA/Society for Cardiovascular Angiography and Interventions guideline on PCI, the 2011 ACC/AHA guideline on CABG, the 2012 ACC/AHA/SCAI/American College of Physicians/American Association for Thoracic Surgery/Preventive Cardiovascular Nurses Association/Society of Thoracic Surgeons guideline on stable ischemic heart disease, the 2013 ACC/AHA guideline on STEMI, the 2014 AHA/ACC guideline on non-ST-elevation ACS and the 2014 ACC/AHA guideline on CV issues in patients undergoing noncardiac surgery.

“Treatment with more intensive antiplatelet therapy and treatment for a longer duration of time with antiplatelet medicines in general involves a fundamental tradeoff between a decreased risk of future [MI] and an increased risk of bleeding complications,” writing committee chair Glenn N. Levine, MD, FAHA, FACC, professor of medicine at Baylor College of Medicine and director of the cardiac care unit at the Michael E. DeBakey VA Medical Center in Houston, said in a press release.

Glenn N. Levine, MD, FACC, FAHA

Glenn N. Levine

General recommendations

According to the committee, “shorter-duration DAPT can be considered for patients at lower ischemic risk with high bleeding risk, whereas longer-duration DAPT may be reasonable for patients at higher ischemic risk with low bleeding risk.” The committee noted that, in general, a minimum duration of DAPT, usually 6 to 12 months, received a Class I recommendation, while duration of DAPT beyond 12 months received a Class IIb recommendation.

“Decisions about DAPT are best made on an individual basis and should integrate clinical judgment, assessment of the benefit/risk ratio and patient preference. Aspirin is almost always indefinitely continued in patients with CAD, and recommendations on duration of DAPT should be taken to mean the recommended duration of P2Y12 inhibitor therapy (in addition to aspirin therapy),” according to the document.

These recommendations do not apply to patients on oral anticoagulation, who were not included in most studies of DAPT duration.

Treatment algorithm

Levine and colleagues developed a master treatment algorithm for duration of P2Y12 inhibitor therapy in addition to aspirin therapy.

For patients with stable ischemic heart disease, those who have not had CABG or PCI should not have DAPT; those who had PCI with a bare-metal stent should have clopidogrel and aspirin for at least 1 month, though a longer duration may be reasonable in those not at high risk for bleeding and no significant overt bleeding on DAPT; those who had PCI with a drug-eluting stent should have clopidogrel and aspirin for at least 6 months, though a longer duration may be reasonable in those not at high risk for bleeding and no significant overt bleeding on DAPT; and it may be reasonable for those who had CABG to take clopidogrel and aspirin for 12 months, according to the document.

For patients with STEMI or NSTEACS, those treated with medical therapy should take clopidogrel or ticagrelor (Brilinta, AstraZeneca) and aspirin for at least 12 months; those with STEMI treated with lytic therapy should be treated with clopidogrel and aspirin for a minimum of 14 days and ideally at least 12 months; those treated with PCI (BMS or DES) should be treated with clopidogrel, prasugrel (Effient; Daiichi Sankyo/Eli Lilly) or ticagrelor plus aspirin for at least 12 months; and those treated with CABG should have DAPT for 12 months, according to the authors.

For patients with STEMI or NSTEACS treated with medical therapy, lytic therapy or PCI, continuing DAPT beyond 12 months may be reasonable if the patient does not have a high risk for bleeding and does not have significant overt bleeding in the first 12 months, Levine and colleagues wrote.

The document lists six risk factors associated with increased ischemic risk, which may favor longer-duration DAPT; 10 risk factors associated with increased risk for stent thrombosis, which may favor longer-duration DAPT; and nine risk factors associated with elevated risk for bleeding, which may favor shorter-duration DAPT.

DAPT Score

In related news, Robert W. Yeh, MD, MSc, MBA, from the Smith Center for Outcomes Research in Cardiology, Beth Israel Deaconess Medical Center, Boston, and colleagues published in JAMA the validation of a DAPT Score to predict benefit or harm from DAPT beyond 1 year after PCI. The findings were initially presented at the AHA Scientific Sessions in November 2015.

Robert Yeh

Robert W. Yeh

To calculate the score, a patient receives –2 points for age 75 years or older, –1 point for age 65 to 74 years, 1 point for current smoking, 1 point for diabetes, 1 point for MI at presentation, 1 point for prior MI or PCI, 1 point for stent diameter < 3 mm, 1 point for having a paclitaxel-eluting stent, 2 points for congestive HF or left ventricular ejection fraction < 30% and 2 points for a saphenous vein graft PCI. A score of 2 or more confers a favorable benefit/risk ratio for prolonged DAPT after PCI, while a score of less than 2 confers an unfavorable benefit/risk ratio.

In their update of the guidelines, Levine and colleagues wrote that the DAPT Score “may be useful for decisions about whether to continue (prolong or extend) DAPT in patients treated with coronary stent implantation.”

The update was developed in conjunction with AATS, SCAI, STS, the American Society of Anesthesiologists and the Society of Cardiovascular Anesthesiologists, and endorsed by PCNA and the Society for Vascular Surgery. – by Erik Swain

References:

Levine GN, et al. Circulation. 2016; doi:10.1161/CIR.0000000000000404.
Levine GN, et al. J Am Coll Cardiol. 2016;doi:10.1016/j.jacc.2016.03.513.
Yeh RW, et al. JAMA. 2016;doi:10.1001/jama.2016.3775.

Disclosure: Levine reports no relevant financial disclosures. Please see the full document for a list of the other authors’ and reviewers’ financial disclosures. Yeh reports receiving personal fees from Abbott Vascular, Boston Scientific and Merck, a research salary from Harvard Clinical Research Institute and a pending patent for development and use of the DAPT Score. Please see the full study for a list of the other researchers’ relevant financial disclosures.

    Perspective
    Gregg W. Stone

    Gregg W. Stone

    For the most part, I believe the authors got it right. Overall, I am pleased with the direction of this focused update for DAPT after DES. There are a few items that I might quibble with, but in general it is an important advance forward that accurately incorporates most of a very large evidence base into practical guidelines that should improve patient outcomes.

    I don’t think it will have a major impact on clinical practice, because this is what most physicians have been doing already: taking an individualized approach to DAPT duration decisions. But it will give people assurance that they are doing the right thing, and it will also empower them to use shorter or longer durations of DAPT when appropriate.

    There are two issues that I believe the authors could have gone somewhat deeper into. No. 1, the committee discounted studies (the DAPT study itself, and some meta-analyses) showing increased mortality with routine use of prolonged DAPT, likely due to greater harm caused by the excessive risk for bleeding than the benefits of ischemia reduction. I believe the evidence is reasonably strong suggesting such a link. However, even if you do discount such a finding, it is important to note that perhaps surprisingly, there was not even a suggestion of a reduction in cardiac mortality with prolonged DAPT, even in the highest-risk patients such as post-MI or in those with a high DAPT Score. Thus at best, mortality from prolonged DAPT is neutral, whereas in patients at relatively higher risk for bleeding and lower risk for thrombosis, mortality is increased with prolonged DAPT. I believe this potential risk should have been more emphasized.

    No. 2, I would have made the preference of ticagrelor over clopidogrel in patients within 1 year of ACS a Class I recommendation. When you have an 18,600-patient, double blind, randomized trial showing a fairly profound reduction in mortality and cardiac mortality, that deserves a Class I recommendation. After the first year, a Class IIb recommendation is consistent with current studies.

    • Gregg W. Stone, MD
    • Cardiology Today’s Intervention Editorial Board member Professor of Medicine, Columbia University Director of Cardiovascular Research and Education, Columbia University Medical Center / New York-Presbyterian Hospital Co-Director, Medical Research and Education, Cardiovascular Research Foundation

    Disclosures: Stone reports no relevant financial disclosures.