Impact of Bleeding on Myocardial Infarction, Stroke, and Death During 12 Months Dual Antiplatelet Therapy After Acute Coronary Syndrome



      Bleeding remains a complication during dual antiplatelet therapy (DAPT) for acute coronary syndrome (ACS). Some data suggest a link between bleeding and worsened vascular outcomes. However, this association is unclear, due to omitting of minor bleedings when applying conservative scales. In contrast, the Platelet Inhibition and Outcomes (PLATO) trial classification used broad realistic capturing of all bleedings.


      Access was gained to the Food and Drug Administration-issued adjudication data set on which post hoc analyses of bleeding, myocardial infarction (MI), stroke, and death were conducted. Bleeding was defined as minimal, minor, major, and life-threatening or fatal (LTOF) as per the original PLATO scale.


      Among 18,624 enrollees, 10,705 adjudicated events occurred across 7171 patients. There were 618 minimal, 1412 minor, 1216 major, and 536 LTOF bleedings for the total of 3782 events reported in 3387 patients. There were 938 deaths, 2751 MIs and 359 strokes. The overall bleeding was 20.3%, exhibited in 19.2% patients. Total bleeds were associated with less deaths (odds ratio [OR]: 0.55, 95% confidence interval [CI]: 0.47-0.63) and MI (OR: 0.47, 95% CI: 0.41-0.54; P < .001 for both). There were no differences in deaths (OR: 1.11, 95% CI: 0.93-1.34; P = .24), but less MIs (OR: 0.72. 95% CI: 0.59-0.86; P < .001), and more strokes (OR: 2.17, 95% CI: 1.64-2.88; P < .001) after LTOF. Major, minor, and minimal bleeds were associated with less deaths and MI but not strokes.


      These large uniformly adjudicated data reveal that within 12 months of dual antiplatelet therapy, 1 out of 5 patients experiences bleeding. Overall, bleeding was associated with diminished incidence of death and MI but not strokes.


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        • Giustino G
        • Baber U
        • Sartori S
        • et al.
        Duration of dual antiplatelet therapy after drug-eluting stent implantation: a systematic review and meta-analysis of randomized controlled trials.
        J Am Coll Cardiol. 2015; 65: 1298-1310
        • Watanabe H
        • Domei T
        • Morimoto T
        • et al.
        Effect of 1-month dual antiplatelet therapy followed by clopidogrel vs 12-month dual antiplatelet therapy on cardiovascular and bleeding events in patients receiving PCI: The STOPDAPT-2 randomized clinical trial.
        JAMA. 2019; 321: 2414-2427
        • Valgimigli M
        • Frigoli E
        • Dik Heg D
        • et al.
        Dual antiplatelet therapy after PCI in patients at high bleeding risk.
        N Engl J Med. 2021; 385: 1643-1655
        • Mauri L
        • Kereiakes DJ
        • Yeh RW
        • et al.
        Twelve or 30 months of dual antiplatelet therapy after drug-eluting stents.
        N Engl J Med. 2014; 371: 2155-2166
        • Kamran H
        • Jneid H
        • Kayani WT
        • et al.
        Oral antiplatelet therapy after acute coronary syndrome: a review.
        JAMA. 2021; 325: 1545-1555
        • Trifan G
        • Gorelick PB
        • Testai FD.
        Efficacy and Safety of using dual versus monotherapy antiplatelet agents in secondary stroke prevention: systematic review and meta-analysis of randomized controlled clinical trials.
        Circulation. 2021; 143: 2441-2453
        • Simonsson M
        • Wallentin L
        • Alfredsson J
        • et al.
        Temporal trends in bleeding events in acute myocardial infarction: insights from the SWEDEHEART registry.
        Eur Heart J. 2020; 41: 833-843
        • Alexander D
        • Ou FS
        • Roe MT
        • et al.
        Use of and in-hospital outcomes after early clopidogrel therapy in patients not undergoing an early invasive strategy for treatment of non-ST-segment elevation myocardial infarction: results from Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the American College of Cardiology/American Heart Association guidelines (CRUSADE).
        Am Heart J. 2008; 156: 606-612
        • Serebruany V
        • Rao SV
        • Silva MA
        • et al.
        Correlation of inhibition of platelet aggregation after clopidogrel with post discharge bleeding events: assessment by different bleeding classifications.
        Eur Heart J. 2010; 31: 227-235
        • Chew DP
        • Bhatt DL
        • Sapp S
        • Topol EJ.
        Increased mortality with oral platelet glycoprotein IIb/IIIa antagonists: a meta-analysis of phase III multicenter randomized trials.
        Circulation. 2001; 103: 201-206
        • Bhatt DL
        • Topol EJ.
        Current role of platelet glycoprotein IIb/IIIa inhibitors in acute coronary syndromes.
        JAMA. 2000; 284: 1549-1558
        • Wallentin L
        • Becker RC
        • Budaj A
        • et al.
        Ticagrelor versus clopidogrel in patients with acute coronary syndromes.
        N Engl J Med. 2009; 61: 1045-1057
      1. US Food and Drug Administration. The FDA ticagrelor review of complete response. Available at: Accessed February 4, 2022.

      2. US Food and Drug Administration. Brilinta Prescription Information. Available at: Accessed February 4, 2022.

      3. US Food and Drug Administration. Plavix Prescription Information. Available at: Accessed February 4, 2022.

        • Rao AK
        • Pratt C
        • Berke A
        • et al.
        Thrombolysis in myocardial infarction (TIMI) trial—phase I: hemorrhagic manifestations and changes in plasma fibrinogen and the fibrinolytic system in patients treated with recombinant tissue plasminogen activator and streptokinase.
        J Am Coll Cardiol. 1988; 11: 1-11
        • The GUSTO investigators
        An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction.
        N Engl J Med. 1993; 329: 673-682
        • Serebruany VL
        • Atar D.
        Assessment of bleeding events in clinical trials – proposal of a new classification.
        Am J Cardiol. 2007; 99: 288-290
        • Mehran R
        • Rao SV
        • Bhatt DL
        • et al.
        Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the Bleeding Academic Research Consortium.
        Circulation. 2011; 123: 2736-2747
        • Marciniak TA
        • Cherepanov V
        • Golukhova E
        • Kim MH
        • Serebruany V.
        Drug discontinuation and follow-up rates in oral antithrombotic trials.
        JAMA Intern Med. 2016; 176: 257-259
        • Eikelboom JW
        • Mehta SR
        • Anand SS
        • Xie C
        • Fox KA
        • Yusuf S.
        Adverse impact of bleeding on prognosis in patients with acute coronary syndromes.
        Circulation. 2006; 114: 774-782