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Review

Bleeding after antiplatelet therapy for the treatment of acute coronary syndromes: a review of the evidence and evolving paradigms

, , &
Pages 1171-1189 | Received 17 Aug 2019, Accepted 10 Oct 2019, Published online: 25 Oct 2019

References

  • Bentzon JF, Otsuka F, Virmani R, et al. Mechanisms of plaque formation and rupture. Circ Res. 2014;114:1852–1866.
  • Crea F, Libby P. Acute coronary syndromes: the way forward from mechanisms to precision treatment. Circulation. 2017;136:1155–1166.
  • Angiolillo DJ, Ueno M, Goto S. Basic principles of platelet biology and clinical implications. Circ J. 2010;74:597–607.
  • Wallentin L, Becker RC, Budaj A, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009;361:1045–1057.
  • Wiviott SD, Braunwald E, McCabe CH, et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2007;357:2001–2015.
  • Franchi F, Angiolillo DJ. Novel antiplatelet agents in acute coronary syndrome. Nat Rev Cardiol. 2015;12:30–47.
  • Franchi F, Rollini F, Angiolillo DJ. Antithrombotic therapy for patients with STEMI undergoing primary PCI. Nat Rev Cardiol. 2017;14:361–379.
  • Capodanno D, Alfonso F, Levine GN, et al. ACC/AHA versus ESC guidelines on dual antiplatelet therapy: JACC guideline comparison. J Am Coll Cardiol. 2018;72:2915–2931.
  • Howell SJ, Hoeks SE, West RM, et al. Prospective observational cohort study of the association between antiplatelet therapy, bleeding and thrombosis in patients with coronary stents undergoing noncardiac surgery. Br J Anaesth. 2019;122:17079.
  • van Den Brand CL, Tolido T, Rambach AH, et al. Systematic review and meta-analysis: is pre-injury antiplatelet therapy associated with traumatic intracranial hemorrhage? J Neurotrauma. 2016;34:1–7.
  • Eikelboom JW, Mehta SR, Anand SS, et al. Adverse impact of bleeding on prognosis in patients with acute coronary syndromes. Circulation. 2006;114:77482.
  • Vranckx P, White HD, Huang Z, et al. Validation of BARC bleeding criteria in patients with acute coronary syndromes the TRACER trial. J Am Coll Cardiol. 2016;67:2135–2144.
  • Manoukian SV, Feit F, Mehran R, et al. Impact of major bleeding on 30-day mortality and clinical outcomes in patients with acute coronary syndromes analysis from the ACUITY trial. J Am Coll Cardiol. 2007;49:1362–1368.
  • Hochholzer W, Wiviott SD, Antman EM, et al. Predictors of bleeding and time dependence of association of bleeding with mortality. Circulation. 2011;123:2681–2689.
  • Palmerini T, Stone GW. Optimal duration of dual antiplatelet therapy after drug-eluting stent implantation: conceptual evolution based on emerging evidence. Eur Heart J. 2016;37:353–364.
  • Costa F, van Klaveren D, James S, et al. Derivation and validation of the predicting bleeding complications in patients undergoing stent implantation and subsequent dual antiplatelet therapy (PRECISE-DAPT) score: a pooled analysis of individual-patient datasets from clinical trials. Lancet. 2017;389:1025–1034.
  • Mehran R, Pocock SJ, Nikolsky E, et al. A risk score to predict bleeding in patients with acute coronary syndromes. J Am Coll Cardiol. 2010;55:2556–2566.
  • Subherwal S, Bach RG, Chen AY, et al. Baseline risk of major bleeding in non-ST-segment-elevation myocardial infarction the CRUSADE (can rapid risk stratification of unstable angina patients suppress ADverse outcomes with early implementation of the ACC/AHA guidelines) bleeding score. Circulation. 2009;119:1873–1882.
  • Urban P, Mehran R, Colleran R, et al. Defining high bleeding risk in patients undergoing percutaneous coronary intervention: a consensus document from the academic research consortium for high bleeding risk. Circulation. 2019;140:240–261.
  • Wiviott SD, Antman EM, Gibson CM, et al. Evaluation of prasugrel compared with clopidogrel in patients with acute coronary syndromes: design and rationale for the trial to assess improvement in therapeutic outcomes by optimizing platelet inhibition with prasugrel thrombolysis in myocardial infar. Am Heart J. 2006;152:627–635.
  • Stone GW, McLaurin BT, Cox DA, et al. Bivalirudin for patients with acute coronary syndromes. N Engl J Med. 2006;355:2203–2216.
  • Yusuf S, Zhao F, Mehta SR, et al., Clopidogrel in Unstable Angina to Prevent Recurrent Events Trial Investigators. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med. 2001;345:494–502.
  • GUSTO investigators. An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. N Engl J Med. 1993;329:673–682.
  • James S, Åkerblom A, Cannon CP, et al. Comparison of ticagrelor, the first reversible oral P2Y12 receptor antagonist, with clopidogrel in patients with acute coronary syndromes: rationale, design, and baseline characteristics of the PLATelet inhibition and patient Outcomes (PLATO) trial. Am Heart J. 2009;157:599–605.
  • Mehran R, Rao SV, Bhatt DL, et al. Standardized bleeding definitions for cardiovascular clinical trials. Circulation. 2011;123:2736–2747.
  • Vranckx P, Leonardi S, Tebaldi M, et al. Prospective validation of the bleeding academic research consortium classification in the all-comer PRODIGY trial. Eur Heart J. 2014;35:2524–2529.
  • Valgimigli M, Costa F, Lokhnygina Y, et al. Trade-off of myocardial infarction vs. bleeding types on mortality after acute coronary syndrome: lessons from the Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER) randomized trial. Eur Heart J. 2017;38:804–810.
  • Mehran R, Pocock SJ, Stone GW, et al. Associations of major bleeding and myocardial infarction with the incidence and timing of mortality in patients presenting with non-ST-elevation acute coronary syndromes: A risk model from the ACUITY trial. Eur Heart J. 2009;30:1457–1466.
  • Rao SV. The conundrum of reducing ischemic and bleeding events after PCI. J Am Coll Cardiol. 2015;65:1421–1423.
  • Kwok CS, Sherwood MW, Watson SM, et al. Blood transfusion after percutaneous coronary intervention and risk of subsequent adverse outcomes: A systematic review and meta-analysis. JACC Cardiovasc Interv. 2015;8:436–446.
  • Mehran R, Baber U, Steg PG, et al. Cessation of dual antiplatelet treatment and cardiac events after percutaneous coronary intervention (PARIS): 2 year results from a prospective observational study. Lancet. 2013;382:1714–1722.
  • Reidenberg MM. Drug discontinuation effects are part of the pharmacology of a drug. J Pharmacol Exp Ther. 2011;339:324–328.
  • Valgimigli M, Bueno H, Byrne RA, et al. 2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS. Eur Heart J. 2018;39:213–260.
  • Angiolillo DJ. The evolution of antiplatelet therapy in the treatment of acute coronary syndromes: from aspirin to the present day. Drugs. 2012;72:2087–2116.
  • Capodanno D, Ferreiro JL, Angiolillo DJ. Antiplatelet therapy: new pharmacological agents and changing paradigms. J Thromb Haemost. 2013;11:316–329.
  • Bhatt DL. Aspirin—still the GLOBAL LEADER in antiplatelet therapy. Lancet. 2018;392:896–897.
  • Amsterdam EA, Wenger NK, Brindis RG, et al. AHA/ACC guideline for the management of patients with non–st-elevation acute coronary syndromes: executive summary. Circulation. 2014;2014(130):2354–2394.
  • O’Gara PT, Kushner FG, Ascheim DD, et al. ACCF/AHA guideline for the management of ST-elevation myocardial infarction: executive summary. Circulation. 2013;2012(127):529–555.
  • Antithrombotic Trialists’ Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ. 2002;324:71–86.
  • Collins R, Peto R, Hennekens C, et al. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet. 2009;373:1849–1860.
  • Huang ES, Strate LL, Ho WW, et al. Long-term use of aspirin and the risk of gastrointestinal bleeding. Am J Med. 2011;124:426–433.
  • Capodanno D, Angiolillo DJ. Aspirin for primary cardiovascular risk prevention and beyond in diabetes mellitus. Circulation. 2016;134:1579–1594.
  • Sostres C, Lanas A. Gastrointestinal effects of aspirin. Nat Rev Gastroenterol Hepatol. 2011;8:385–394.
  • Bhatt DL, Cryer BL, Contant CF, et al. Clopidogrel with or without omeprazole in coronary artery disease. N Engl J Med. 2010;363:1909–1917.
  • Sehested TSG, Carlson N, Hansen PW, et al. Reduced risk of gastrointestinal bleeding associated with proton pump inhibitor therapy in patients treated with dual antiplatelet therapy after myocardial infarction. Eur Heart J. 2019;40:1963–1970.
  • Serebruany VL, Steinhubl SR, Berger PB, et al. Analysis of risk of bleeding complications after different doses of aspirin in 192,036 patients enrolled in 31 randomized controlled trials. Am J Cardiol. 2005;95:1218–1222.
  • Capodanno D. Quo vadis, aspirin? EuroIntervention. 2018;14:e1153–e1157.
  • Capodanno D, Angiolillo DJ. Aspirin for primary prevention of cardiovascular disease. Lancet. 2018;392:988–990.
  • Mehta SR, Tanguay JF, Eikelboom JW, et al. Double-dose versus standard-dose clopidogrel and high-dose versus low-dose aspirin in individuals undergoing percutaneous coronary intervention for acute coronary syndromes (CURRENT-OASIS 7): A randomised factorial trial. Lancet. 2010;376:1233–1243.
  • Cox D, Maree AO, Dooley M, et al. Effect of enteric coating on antiplatelet activity of low-dose aspirin in healthy volunteers. Stroke. 2006;37:2153–2158.
  • Grosser T, Fries S, Lawson JA, et al. Drug resistance and pseudoresistance: an unintended consequence of enteric coating aspirin. Circulation. 2013;127:377–385.
  • Kelly JP, Kaufman DW, Jurgelon JM, et al. Risk of aspirin-associated major upper-gastrointestinal bleeding with enteric-coated or buffered product. Lancet. 1996;348:1413–1416.
  • Mollace V, Rosano G, Malara N, et al. Aspirin wears smart. Eur Hear J Cardiovasc Pharmacother. 2017;3:185–188.
  • Bhatt DL, Grosser T, Dong JF, et al. enteric coating and aspirin nonresponsiveness in patients with type 2 diabetes mellitus. J Am Coll Cardiol. 2017;69:603–612.
  • Cryer B, Bhatt DL, Lanza FL, et al. Low-dose aspirin-induced ulceration is attenuated by aspirin- phosphatidylcholine: A randomized clinical trial. Am J Gastroenterol. 2011;106:272–277.
  • Angiolillo DJ, Bhatt DL, Lanza F, et al. Pharmacokinetic/pharmacodynamic assessment of a novel, pharmaceutical lipid-aspirin complex: results of a randomized, crossover, bioequivalence study. J Thromb Thrombolysis. 2019; Epub ahead of print.
  • Mehta SR, Yusuf S, Peters RJ, et al. Effects of pretreatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary intervention: the PCI-CURE study. Lancet. 2001;358:527–533.
  • Peters RJ, Mehta SR, Fox KA, et al. Effects of aspirin dose when used alone or in combination with clopidogrel in patients with acute coronary syndromes. Circulation. 2003;108:1682–1687.
  • Chen ZM, Jiang LX, Chen YP, et al., COMMIT (ClOpidogrel and Metoprolol in Myocardial Infarction Trial) collaborative group. Addition of clopidogrel to aspirin in 45 852 patients with acute myocardial infarction: randomised placebo-controlled trial. Lancet. 2005;366:1607–1621.
  • Sabatine MS, Cannon CP, Gibson CM, et al. Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial infarction with ST-segment elevation. N Engl J Med. 2005;352:1179–1189.
  • Angiolillo DJ, Suryadevara S, Capranzano P, et al. Prasugrel: a novel platelet ADP P2Y12 receptor antagonist. A review on its mechanism of action and clinical development. Expert Opin Pharmacother. 2008;9:2893–2900.
  • Kohli P, Udell JA, Murphy SA, et al. Discharge aspirin dose and clinical outcomes in patients with acute coronary syndromes treated with prasugrel versus clopidogrel: an analysis from the TRITON-TIMI 38 study (trial to assess improvement in therapeutic outcomes by optimizing platelet inhibit. J Am Coll Cardiol. 2014;63:225–232.
  • Erlinge D, Ten BJ, Foley D, et al. Reduction in platelet reactivity with prasugrel 5 mg in low-body-weight patients is noninferior to prasugrel 10 mg in higher-body-weight patients. J Am Coll Cardiol. 2012;60:2032–2040.
  • Erlinge D, Gurbel PA, James S, et al. Prasugrel 5 mg in the very elderly attenuates platelet inhibition but maintains noninferiority to prasugrel 10 mg in nonelderly patients: the GENERATIONS trial, a pharmacodynamic and pharmacokinetic study in stable coronary artery disease patients. J Am Coll Cardiol. 2013;62:577–583.
  • Roe MT, Armstrong PW, Fox KA, et al. Prasugrel versus clopidogrel for acute coronary syndromes without revascularization. N Engl J Med. 2012;367:1297–1309.
  • Montalescot G, Bolognese L, Dudek D, et al. Pretreatment with prasugrel in non–st-segment elevation acute coronary syndromes. N Engl J Med. 2013;369:999–1010.
  • Gurbel PA, Bliden KP, Butler K, et al. Randomized double-blind assessment of the ONSET and OFFSET of the antiplatelet effects of ticagrelor versus clopidogrel in patients with stable coronary artery disease: the ONSET/OFFSET study. Circulation. 2009;120:2577–2585.
  • Mahaffey KW, Wojdyla DM, Carroll K, et al. Ticagrelor compared with clopidogrel by geographic region in the Platelet Inhibition and Patient Outcomes (PLATO) Trial. Circulation. 2011;124:544–554.
  • Bonaca MP, Bhatt DL, Cohen M, et al. Long-term use of ticagrelor in patients with prior myocardial infarction. N Engl J Med. 2015;372:1791–1800.
  • Keaney JF. Balancing the risks and benefits of dual platelet inhibition. N Engl J Med. 2015;372:1854–1856.
  • Kruger P, Chan N, Eikelboom JW. Platelet transfusion for ticagrelor reversal. Circ Cardiovasc Interv. 2017;10:e005579.
  • Bhatt DL, Pollack CV, Weitz JI, et al. Antibody-based ticagrelor reversal agent in healthy volunteers. N Engl J Med. 2019;380:1825–1833.
  • Schüpke S, Neumann FJ, Menichelli M, et al. Ticagrelor or prasugrel in patients with acute coronary syndromes. N Engl J Med. 2019;381:1524–1534.
  • Angiolillo DJ, Capodanno D, Goto S. Platelet thrombin receptor antagonism and atherothrombosis. Eur Heart J. 2010;31:17–28.
  • Moon JY, Franchi F, Rollini F, et al. Role for thrombin receptor antagonism with vorapaxar in secondary prevention of atherothrombotic events: from bench to bedside. J Cardiovasc Pharmacol Ther. 2018;23:23–37.
  • Tricoci P, Huang Z, Held C, et al. Thrombin-receptor antagonist vorapaxar in acute coronary syndromes. N Engl J Med. 2012;366:20–33.
  • Morrow DA, Braunwald E, Bonaca MP, et al. Vorapaxar in the secondary prevention of atherothrombotic events. N Engl J Med. 2012;366:1404–1413.
  • Angiolillo DJ, Rollini F, Storey RF, et al. International expert consensus on switching platelet P2Y12 receptor-inhibiting therapies. Circulation. 2017;136:1955–1975.
  • Muñiz Lozano A, Rollini F, Franchi F, et al. Update on platelet glycoprotein IIb/IIIa inhibitors: recommendations for clinical practice. Ther Adv Cardiovasc Dis. 2013;7:197–213.
  • Gurk-Turner C. Glycoprotein IIb/IIIa receptor antagonists: a review of the pivotal trials. Baylor Univ Med Cent Proc. 2017;13:179–182.
  • Tricoci P, Newby LK, Hasselblad V, et al. Upstream use of small-molecule glycoprotein IIb/IIIa inhibitors in patients with non-ST-segment elevation acute coronary syndromes a systematic overview of randomized clinical trials. Circ Cardiovasc Qual Outcomes. 2011;4:448–458.
  • Di Mario C. Rise and fall of glycoprotein IIb–iIIa inhibitors in ST-segment elevation myocardial infarction. Heart. 2014;100:823–824.
  • Gargiulo G, Carrara G, Frigoli E, et al. Bivalirudin or heparin in patients undergoing invasive management of acute coronary syndromes. J Am Coll Cardiol. 2018;71:1231–1242.
  • Alexander KP, Chen AY, Roe MT, et al. Excess dosing of antiplatelet and antithrombin agents in the treatment of non-ST-segment elevation acute coronary syndromes. J Am Med Assoc. 2005;294:3108–3116.
  • Alexander KP, Chen AY, Newby LK, et al. Sex differences in major bleeding with glycoprotein IIb/IIIa Inhibitors. Circulation. 2006;114:1380–1387.
  • Mudrick DW, Chen AY, Roe MT, et al. Changes in glycoprotein IIb/IIIa inhibitor excess dosing with site-specific safety feedback in the can rapid risk stratification of Unstable angina patients suppress adverse outcomes with early implementation of the ACC/AHA guidelines (CRUSADE) initiative. Am Heart J. 2010;160:1072–1078.
  • Franchi F, Rollini F, Park Y, et al. A safety evaluation of cangrelor in patients undergoing PCI. Expert Opin Drug Saf. 2015;15:275–285.
  • Angiolillo DJ, Schneider DJ, Bhatt DL, et al. Pharmacodynamic effects of cangrelor and clopidogrel: the platelet function substudy from the cangrelor versus standard therapy to achieve optimal management of platelet inhibition (CHAMPION) trials. J Thromb Thrombolysis. 2012;34:44–55.
  • Angiolillo DJ, Firstenberg MS, Price MJ, et al. Bridging antiplatelet therapy with cangrelor in patients undergoing cardiac surgery: a randomized controlled trial. JAMA. 2012;307:265–274.
  • Angiolillo DJ, Bhatt DL, Steg PG, et al. Impact of cangrelor overdosing on bleeding complications in patients undergoing percutaneous coronary intervention: insights from the CHAMPION trials. J Thromb Thrombolysis. 2015;40:317–322.
  • Bhatt DL, Stone GW, Mahaffey KW, et al. Effect of platelet inhibition with cangrelor during PCI on ischemic events. N Engl J Med. 2013;368:1303–1313.
  • Steg PG, Bhatt DL, Hamm CW, et al. Effect of cangrelor on periprocedural outcomes in percutaneous coronary interventions: A pooled analysis of patient-level data. Lancet. 2013;382:1981–1992.
  • Moon JY, Franchi F, Rollini F, et al. The quest for safer antithrombotic treatment regimens in patients with coronary artery disease: new strategies and paradigm shifts. Expert Rev Hematol. 2018;11:5–12.
  • 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.
  • Buccheri S, Sarno G, Lagerqvist B, et al. Bioabsorbable polymer everolimus-eluting stents in patients with acute myocardial infarction: A report from the swedish coronary angiography and angioplasty registry. EuroIntervention. 2018;14:e562–e569.
  • Moon JY, Franchi F, Rollini F, et al. Evolution of coronary stent technology and implications for duration of dual antiplatelet therapy. Prog Cardiovasc Dis. 2018;60:478–490.
  • Palmerini T, Della Riva D, Benedetto U, et al. Three, six, or twelve months of dual antiplatelet therapy after des implantation in patients with or without acute coronary syndromes: an individual patient data pairwise and network meta-analysis of six randomized trials and 11 473 patients. Eur Heart J. 2017;38:1034–1043.
  • Jang JY, Shin DH, Kim JS, et al. Optimal duration of DAPT after second-generation drug-eluting stent in acute coronary syndrome. PLoS One. 2018;13:e0207386.
  • Kedhi E, Fabris E, Van Der Ent M, et al. Six months versus 12 months dual antiplatelet therapy after drug-eluting stent implantation in ST-elevation myocardial infarction (DAPT-STEMI): randomised, multicentre, non-inferiority trial. BMJ. 2018;363:k3793.
  • Hahn JY, Bin SY, Oh JH, et al. 6-month versus 12-month or longer dual antiplatelet therapy after percutaneous coronary intervention in patients with acute coronary syndrome (SMART-DATE): a randomised, open-label, non-inferiority trial. Lancet. 2018;391:1274–1284.
  • Frigoli E, Smits P, Vranckx P, et al. Design and rationale of the management of high bleeding risk patients post bioresorbable polymer coated stent implantation with an abbreviated versus standard DAPT regimen (MASTER DAPT) study. Am Heart J. 2019;209:97–105.
  • Mauri L, Kirtane AJ, Windecker S, et al. Rationale and design of the EVOLVE short DAPT study to assess 3-month dual antiplatelet therapy in subjects at high risk for bleeding undergoing percutaneous coronary intervention. Am Heart J. 2018;205:110–117.
  • Angiolillo DJ, Patti G, Chan KT, et al. De-escalation from ticagrelor to clopidogrel in acute coronary syndrome patients: a systematic review and meta-analysis. J Thromb Thrombolysis. 2019;48:1–10.
  • Rollini F, Franchi F, Angiolillo DJ. Switching P2Y12-receptor inhibitors in patients with coronary artery disease. Nat Rev Cardiol. 2016;13:11–27.
  • Angiolillo DJ. Dual antiplatelet therapy guided by platelet function testing. Lancet. 2017;390:1718–1720.
  • De Luca L, D’Ascenzo F, Musumeci G, et al. Incidence and outcome of switching of oral platelet P2Y12 receptor inhibitors in patients with acute coronary syndromes undergoing percutaneous coronary intervention: the SCOPE registry. EuroIntervention. 2017;13:459–466.
  • Cuisset T, Deharo P, Quilici J, et al. Benefit of switching dual antiplatelet therapy after acute coronary syndrome: the TOPIC (timing of platelet inhibition after acute coronary syndrome) randomized study. Eur Heart J. 2017;38:3070–3078.
  • Sibbing D, Aradi D, Jacobshagen C, et al. Guided de-escalation of antiplatelet treatment in patients with acute coronary syndrome undergoing percutaneous coronary intervention (TROPICAL-ACS): a randomised, open-label, multicentre trial. Lancet. 2017;390:1747–1757.
  • Sibbing D, Aradi D, Alexopoulos D, et al. Updated expert consensus statement on platelet function and genetic testing for guiding P2Y12 receptor inhibitor treatment in percutaneous coronary intervention. JACC Cardiovasc Interv. 2019;12:1521–1537.
  • Moon JY, Franchi F, Rollini F, et al. Role of genetic testing in patients undergoing percutaneous coronary intervention. Expert Rev Clin Pharmacol. 2018;11:151–164.
  • Claassens DMF, Vos GJA, Bergmeijer TO, et al. A genotype-guided strategy for oral P2Y12 inhibitors in primary PCI. N Engl JMed. 2019; Epub ahead of print.
  • Capodanno D, Angiolillo DJ. Antithrombotic pharmacotherapy in the elderly: general issues and clinical conundrums. Curr Treat Options Cardiovasc Med. 2012;14:57–68.
  • Capodanno D, Angiolillo DJ. Antithrombotic therapy in the elderly. J Am Coll Cardiol. 2010;56:1683–1692.
  • Capranzano P, Angiolillo DJ. Tailoring P2Y12 inhibiting therapy in elderly patients with myocardial infarction undergoing primary percutaneous coronary intervention. J Am Heart Assoc. 2019;8:e014000.
  • Armstrong PC, Leadbeater PD, Chan MV, et al. In the presence of strong P2Y12 receptor blockade, aspirin provides little additional inhibition of platelet aggregation. J Thromb Haemost. 2011;9:552–561.
  • Capodanno D, Mehran R, Valgimigli M, et al. Aspirin-free strategies in cardiovascular disease and cardioembolic stroke prevention. Nat Rev Cardiol. 2018;15:480–496.
  • Lopes RD, Heizer G, Aronson R, et al. Antithrombotic therapy after acute coronary syndrome or PCI in atrial fibrillation. N Engl J Med. 2019;380:1509–1524.
  • Lopes RD, Hong H, Harskamp RE, et al. Safety and efficacy of antithrombotic strategies in patients with atrial fibrillation undergoing percutaneous coronary intervention. JAMA Cardiol. 2019;4:747–755.
  • Capodanno D, Huber K, Mehran R, et al. Management of antithrombotic therapy in atrial fibrillation patients undergoing PCI. J Am Coll Cardiol. 2019;74:83–99.
  • Cannon CP, Bhatt DL, Oldgren J, et al. Dual antithrombotic therapy with dabigatran after PCI in atrial fibrillation. N Engl J Med. 2017;377:1513–1524.
  • Gibson CM, Mehran R, Bode C, et al. Prevention of bleeding in patients with atrial fibrillation undergoing PCI. N Engl J Med. 2016;375:2423–2434.
  • Capodanno D. Angiolillo DJ.Dual antithrombotic therapy for atrial fibrillation and PCI. Lancet. 2019;394:1300–1302.
  • Angiolillo DJ, Goodman SG, Bhatt DL, et al. Antithrombotic therapy in patients with atrial fibrillation treated with oral anticoagulation undergoing percutaneous coronary intervention. Circulation. 2018;138:527–536.
  • Ohman EM, Roe MT, Steg PG, et al. Clinically significant bleeding with low-dose rivaroxaban versus aspirin, in addition to P2Y12 inhibition, in acute coronary syndromes (GEMINI-ACS-1): a double-blind, multicentre, randomised trial. Lancet. 2017;389:1799–1808.
  • Vranckx P, Valgimigli M, Jüni P, et al. Ticagrelor plus aspirin for 1 month, followed by ticagrelor monotherapy for 23 months vs aspirin plus clopidogrel or ticagrelor for 12 months, followed by aspirin monotherapy for 12 months after implantation of a drug-eluting stent: a multicentre, open-la. Lancet. 2018;392:940–949.
  • Hahn JY, Song YB, Oh JH, et al. Effect of P2Y12 inhibitor monotherapy vs dual antiplatelet therapy on cardiovascular events in patients undergoing percutaneous coronary intervention. JAMA. 2019;321:2428–2437.
  • 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. JAMA. 2019;321:2414–2427.
  • Mehran R, Baber U, Sharma SK, et al. Ticagrelor with or without aspirin in high-risk patients after PCI. N Engl J Med. 2019; Epub ahead of print.
  • Raposeiras-Roubín S, Faxén J, Íñiguez-Romo A, et al. Development and external validation of a post-discharge bleeding risk score in patients with acute coronary syndrome: the BleeMACS score. Int J Cardiol. 2018;254:10–15.
  • Mathews R, Peterson ED, Chen AY, et al. In-hospital major bleeding during ST-elevation and non-ST-elevation myocardial infarction care: derivation and validation of a model from the action registry®-GWTGTM. Am J Cardiol. 2011;107:1136–1143.
  • Simonsson M, Winell H, Olsson H, et al. Development and validation of a novel risk score for in-hospital major bleeding in acute myocardial infarction:—the SWEDEHEART score. J Am Heart Assoc. 2019;8:e012157.
  • Fox KA, Dabbous OH, Goldberg RJ, et al. Prediction of risk of death and myocardial infarction in the six months after presentation with acute coronary syndrome: prospective multinational observational study (GRACE). Br Med J. 2006;333:1091–1094.
  • Baber U, Mehran R, Giustino G, et al. Coronary thrombosis and major bleeding after PCI with drug-eluting stents risk scores from Paris. J Am Coll Cardiol. 2016;67:2224–2234.
  • Yeh RW, Secemsky EA, Kereiakes DJ, et al. Development and validation of a prediction rule for benefit and harm of Dual antiplatelet therapy beyond 1 year after percutaneous coronary intervention. JAMA. 2016;315:1735–1749.
  • Costa F, Van Klaveren D, Feres F, et al. Dual antiplatelet therapy duration based on ischemic and bleeding risks after coronary stenting. J Am Coll Cardiol. 2019;73:741–754.
  • Lindholm D, Hagström E, James SK, et al. Growth differentiation factor 15 at 1 month after an acute coronary syndrome is associated with increased risk of major bleeding. J Am Heart Assoc. 2017;6:e005580.
  • Damani SB, Topol EJ. The case for routine genotyping in dual-antiplatelet therapy. J Am Coll Cardiol. 2010;56:109–111.

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