Catheterization and Cardiovascular Interventions 85:41–42 (2015)
Editorial Comment Optimal DAPT Duration: Each in Their Own Time William B. Hillegass,* MD, MPH, and Brigitta C. Brott, MD Heart South Cardiovascular Group, Alabaster, AL and University of Alabama at Birmingham, Birmingham, AL, USA.
Key Points
Meta-analysis of randomized trials shows no significant difference in major adverse cardiovascular events between shorter (3–6 months) and longer (12–24 months) durations of clopidogrel-based dual antiplatelet therapy (DAPT) after drug eluting stent (DES) implantation. Shorter durations (6 months) of DAPT should be considered in lower risk patients undergoing DES implantation in current practice. Further research should define the optimal agents and duration of DAPT after percutaneous coronary intervention based on patient specific factors.
In our practices, decisions on the duration of dual antiplatelet therapy (DAPT) after drug eluting stent (DES) implantation must be made almost daily. Pandit et al.’s meta-analysis of the four randomized trials of 6 months of DAPT after DES versus 12 months provides the most precise estimate of the populationaverage effect of the two strategies [1]. Short (3–6 months) versus long (12–24 months) of clopidogrel treatment in addition to aspirin after DES implantation yields no significant difference in mortality, myocardial infarction, or stent thrombosis (ST) in the randomized trials available. One extra major bleed occurs for every 225 patients exposed to long versus short duration of therapy (0.9% vs. 0.46%). This population-average estimate implies no significant difference between shorter and longer durations of clopidogrel-based DAPT after DES. Several caveats need consideration. First, the rates of death, myocardial infarction (MI), stroke, and ST observed in the underlying trials yielding the summary estimates are approximately half the rates observed in population-based C 2014 Wiley Periodicals, Inc. V
registries [2]. This implies this evidence is mainly applicable to patients at lower risk for bleeding and ischemic events. Second, the majority of the DES implanted was not third generation stents. At least for ST, third generation DES likely tip the balance in favor of shorter DAPT duration. Third, clopidogrel is the medication studied. In the Study of Platelet Inhibition and Patient Outcomes (PLATO), the ischemic event curves have increasing separation between clopidogrel and ticagrelor over time [3]. Two-thirds of the incremental lower mortality and myocardial infarction benefit of ticagrelor compared to optimally dosed clopidogrel occurred at a near constant rate throughout months 2–12 of follow-up in acute coronary syndrome patients. Hence, the specific agent may influence the time-dependent risks and benefits of DAPT. Most importantly, these are population-average estimates. Although an unproven hypothesis, informed clinical acumen applied to individual patients likely outperforms population-average guided DAPT treatment duration. The optimal agent and DAPT duration will be a function of many patient specific factors. Foremost will undoubtedly be the patient’s risk of recurrent atherothrombotic events. Index presentation, burden of disease, diabetes, renal function, platelet reactivity, and pharmacogenomics will all likely matter. Bleeding risk, frailty measures, and need for chronic oral anticoagulation will be important. Anatomic and procedural details such as stent number, diameter, length, complexity, and myocardium at risk should be evaluated. Cost effectiveness as a function of these patient specific factors and time should be examined [4]. REFERENCES 1. Pandit A, Giri S, Hakim FA, Fortuin FD. Shorter (6 months) versus longer (12 months) 1 duration dual anti-platelet therapy after drug eluting stents: A meta-analysis of randomized clinical trials. Catheter Cardiovasc Interv 2015;85:34–40.
Conflict of interest: Nothing to report. *Correspondence to: William B. Hillegass; HeartSouth Cardiovascular Group and the University of Alabama at Birmingham, Alabaster and Birmingham, AL. E-mail: [email protected] Received 10 November 2014; Revision accepted 12 November 2014 DOI: 10.1002/ccd.25737 Published online 18 December 2014 in Wiley Online Library (wileyonlinelibrary.com)
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2. Hillegass WB, Patel MR, Klein LW, Gurm HS, Brennan JM, Anstrom KA, Dai D, Eisenstein EL, Peterson ED, Messenger JC, Douglas PS. Long-term outcomes of older diabetic patients after percutaneous coronary stenting in the United States: A report from the National Cardiovascular Data Registry, 2004 to 2008. J Am Coll Cardiol 2012;60: 2280–2289. 3. Wallentin L, Becker RC, Budaj A, Cannon CP, Emanuelsson H, Held C, Horrow J, Husted S, James S, Katus H, Mahaffey KW,
Scirica BM, Skene A, Steg PG, Storey RF, Harrington RA. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009;361:1045–1057. 4. Hillegass WB, Brott BC, Zoghbi GJ, Chapman GC, Misra VK, Kilgore ML. Time-dependent cost-effectiveness of new oral antiplatelet agents for percutaneous coronary intervention in acute coronary syndrome patients. National Research Service Administration Meeting, Baltimore, MD, June 2013. http://www.ahrq.gov/ news/events/conference/index.html
Catheterization and Cardiovascular Interventions DOI 10.1002/ccd. Published on behalf of The Society for Cardiovascular Angiography and Interventions (SCAI).
Editorial Comment Optimal DAPT Duration: Each in Their Own Time William B. Hillegass,* MD, MPH, and Brigitta C. Brott, MD Heart South Cardiovascular Group, Alabaster, AL and University of Alabama at Birmingham, Birmingham, AL, USA.
Key Points
Meta-analysis of randomized trials shows no significant difference in major adverse cardiovascular events between shorter (3–6 months) and longer (12–24 months) durations of clopidogrel-based dual antiplatelet therapy (DAPT) after drug eluting stent (DES) implantation. Shorter durations (6 months) of DAPT should be considered in lower risk patients undergoing DES implantation in current practice. Further research should define the optimal agents and duration of DAPT after percutaneous coronary intervention based on patient specific factors.
In our practices, decisions on the duration of dual antiplatelet therapy (DAPT) after drug eluting stent (DES) implantation must be made almost daily. Pandit et al.’s meta-analysis of the four randomized trials of 6 months of DAPT after DES versus 12 months provides the most precise estimate of the populationaverage effect of the two strategies [1]. Short (3–6 months) versus long (12–24 months) of clopidogrel treatment in addition to aspirin after DES implantation yields no significant difference in mortality, myocardial infarction, or stent thrombosis (ST) in the randomized trials available. One extra major bleed occurs for every 225 patients exposed to long versus short duration of therapy (0.9% vs. 0.46%). This population-average estimate implies no significant difference between shorter and longer durations of clopidogrel-based DAPT after DES. Several caveats need consideration. First, the rates of death, myocardial infarction (MI), stroke, and ST observed in the underlying trials yielding the summary estimates are approximately half the rates observed in population-based C 2014 Wiley Periodicals, Inc. V
registries [2]. This implies this evidence is mainly applicable to patients at lower risk for bleeding and ischemic events. Second, the majority of the DES implanted was not third generation stents. At least for ST, third generation DES likely tip the balance in favor of shorter DAPT duration. Third, clopidogrel is the medication studied. In the Study of Platelet Inhibition and Patient Outcomes (PLATO), the ischemic event curves have increasing separation between clopidogrel and ticagrelor over time [3]. Two-thirds of the incremental lower mortality and myocardial infarction benefit of ticagrelor compared to optimally dosed clopidogrel occurred at a near constant rate throughout months 2–12 of follow-up in acute coronary syndrome patients. Hence, the specific agent may influence the time-dependent risks and benefits of DAPT. Most importantly, these are population-average estimates. Although an unproven hypothesis, informed clinical acumen applied to individual patients likely outperforms population-average guided DAPT treatment duration. The optimal agent and DAPT duration will be a function of many patient specific factors. Foremost will undoubtedly be the patient’s risk of recurrent atherothrombotic events. Index presentation, burden of disease, diabetes, renal function, platelet reactivity, and pharmacogenomics will all likely matter. Bleeding risk, frailty measures, and need for chronic oral anticoagulation will be important. Anatomic and procedural details such as stent number, diameter, length, complexity, and myocardium at risk should be evaluated. Cost effectiveness as a function of these patient specific factors and time should be examined [4]. REFERENCES 1. Pandit A, Giri S, Hakim FA, Fortuin FD. Shorter (6 months) versus longer (12 months) 1 duration dual anti-platelet therapy after drug eluting stents: A meta-analysis of randomized clinical trials. Catheter Cardiovasc Interv 2015;85:34–40.
Conflict of interest: Nothing to report. *Correspondence to: William B. Hillegass; HeartSouth Cardiovascular Group and the University of Alabama at Birmingham, Alabaster and Birmingham, AL. E-mail: [email protected] Received 10 November 2014; Revision accepted 12 November 2014 DOI: 10.1002/ccd.25737 Published online 18 December 2014 in Wiley Online Library (wileyonlinelibrary.com)
42
Hillegass and Brott
2. Hillegass WB, Patel MR, Klein LW, Gurm HS, Brennan JM, Anstrom KA, Dai D, Eisenstein EL, Peterson ED, Messenger JC, Douglas PS. Long-term outcomes of older diabetic patients after percutaneous coronary stenting in the United States: A report from the National Cardiovascular Data Registry, 2004 to 2008. J Am Coll Cardiol 2012;60: 2280–2289. 3. Wallentin L, Becker RC, Budaj A, Cannon CP, Emanuelsson H, Held C, Horrow J, Husted S, James S, Katus H, Mahaffey KW,
Scirica BM, Skene A, Steg PG, Storey RF, Harrington RA. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009;361:1045–1057. 4. Hillegass WB, Brott BC, Zoghbi GJ, Chapman GC, Misra VK, Kilgore ML. Time-dependent cost-effectiveness of new oral antiplatelet agents for percutaneous coronary intervention in acute coronary syndrome patients. National Research Service Administration Meeting, Baltimore, MD, June 2013. http://www.ahrq.gov/ news/events/conference/index.html
Catheterization and Cardiovascular Interventions DOI 10.1002/ccd. Published on behalf of The Society for Cardiovascular Angiography and Interventions (SCAI).
