Table 1.

Summary of randomized controlled trials comparing standard versus extended durations of DAPT after coronary stent insertion, as well as after MI

STUDYPOPULATIONINTERVENTION OR COMPARATOROUTCOMES
Extended DAPT after coronary stent insertion
  • ARCTIC-Interruption,2 2014
  • N = 1259 patients from France with DES (41.5% with G1DES)

  • Indication for PCI: excluded patients who underwent primary PCI for STEMI; included indications not defined at baseline

  • DAPT 18 to 30 mo vs 12 mo

  • Type of P2Y12 inhibitors: 90% clopidogrel and 10% prasugrel

  • Primary end point (death, MI, ST, stroke, or urgent revascularization): not statistically significant

  • Major bleeding (STEEPLE): not statistically significant

  • Major or minor bleeding: 2% vs 1%; HR = 0.26 (95% CI 0.07–0.91); P = .04; NNH = 100 per 29 mo

  • DAPT,3 2014
  • N = 9961 patients with DES (27% with G1DES)

  • Approximately 90% from North America

  • There was no benefit with extended DAPT in individuals with a BMS

  • Indication for PCI: 38% stable angina, approximately 17% UA, 15.5% NSTEMI, 10.5% STEMI, and 20% other

  • DAPT 30 mo vs 12 mo

  • Type of P2Y12 inhibitors: 65% clopidogrel and 35% prasugrel

  • Coprimary end points:

    • -Stent thrombosis: 0.4% vs 1.4%; HR = 0.29 (95% CI 0.17–0.48); P < .001; NNT = 100 per 30 mo

    • -MACCE*: 4.3% vs 5.9%; HR = 0.71 (95% CI 0.59–0.85); P < .001; NNT = 63 per 30 mo

  • Moderate-severe bleeding (GUSTO): 2.5% vs 1.6%; HR = 1.61 (95% CI 1.21–2.16); P = .001; NNH = 112 per 30 mo

  • All-cause mortality at 30 mo: 2% vs 1.5%; HR = 1.36 (95% CI 1–1.85); P = .052

  • All-cause mortality at 33 mo (ie, 3 mo once DAPT complete): 2.3% vs 1.8%; HR = 1.36 (95% CI 1.02–1.82); P = .004; NNH = 200 per 33 mo

  • DES-LATE,4 2014
  • N = 5045 patients from Korea with DES (approximately 64% with G1DES)

  • Indication for PCI: 39% stable angina, 38% UA, 10.5% NSTEMI, and 12.5% STEMI

  • DAPT 36 mo vs 12 mo

  • Type of P2Y12 inhibitor: 100% clopidogrel

  • Primary end point (death from CV causes, MI, stroke): not statistically significant

  • Stent thrombosis: not statistically significant

  • Major bleeding (TIMI): not statistically significant

  • OPTIDUAL,5 2016
  • N = 1385 patients from France with DES (approximately 34% with G1DES)

  • Indication for PCI: 32.2% stable angina, 21% silent ischemia, 15.6% NSTEMI, 11.3% STEMI, 9.2% UA, and 10.7% other

  • DAPT 48 mo vs 12 mo (mean follow-up 33.4 mo)

  • Type of P2Y12 inhibitor: 100% clopidogrel

  • Primary end point: net adverse clinical events (death, MI, stroke, or major bleeding): not statistically significant

  • Major bleeding (ISTH): not statistically significant

  • Trial was stopped early owing to slow recruitment (enrolled 70.4% of target sample size)

Extended DAPT after MI
  • CHARISMA,17,18 2006
  • N = 15 603 patients from 32 countries; study organized in the United States

  • 31.7% had a history of a MI

  • 22.8% had a history of PCI

  • DAPT vs ASA alone for a median of 28 mo

  • Type of P2Y12 inhibitor: 100% clopidogrel

  • Primary end point (CV death, MI, stroke):

    • -Overall, not statistically significant

    • -Subgroup analysis of those with prior MI: 6.6% vs 8.3%; RR = 0.77 (95% CI 0.61–0.98); P = .031; NNT = 59 per 28 mo

  • Major bleeding (GUSTO): not statistically significant

  • Moderate bleeding: 2.1% vs 1.3%; RR = 1.61 (95% CI 1.27–2.08); P < .001; NNH = 125 per 28 mo

  • PEGASUS-TIMI 54,19 2015
  • N = 21 162 (18% of population from North America; mean 1.7 y between index MI and enrolment)

  • 83% had a history of PCI with the index MI (41% with BMS, 39% with DES)

  • Type of MI: 53.6% STEMI, 40.6% NSTEMI, 5.8% unknown

  • DAPT 1 to 3 y after MI vs placebo (median follow-up of 33 mo)

  • Type of P2Y12 inhibitor during PEGASUS: one-third of patients used 90 mg of ticagrelor twice daily, one-third used 60 mg of ticagrelor twice daily, and one-third received placebo

  • Before enrolment, 94% of patients were using clopidogrel for the first 12 mo after their MI

  • Primary end point (CV death, MI, or stroke):

    • -High-dose ticagrelor vs placebo: 7.85% vs 9.04%; HR = 0.85 (95% CI 0.75–0.96); P = .008; NNT = 84 per 3 y

    • -Low-dose ticagrelor vs placebo: 7.77% vs 9.04%; HR = 0.84 (95% CI 0.74–0.95); P = .004; NNT = 79 per 3 y

  • Major bleeding (TIMI):

    • -High-dose ticagrelor vs placebo: 2.6% vs 1.06%; HR = 2.69 (95% CI 1.96–3.7); P < .001; NNH = 65 per 3 y

    • -Low-dose ticagrelor vs placebo: 2.3% vs 1.06%; HR = 2.32 (95% CI 1.68–3.21); P < .001; NNH = 81 per 3 y

  • Discontinuation rates owing to dyspnea:

    • -High-dose ticagrelor vs placebo: 6.5% vs 0.79%; HR = 8.89 (95% CI 6.65–11.88); P < .001; NNH = 18 per 3 y

    • -Low-dose ticagrelor vs placebo: 4.55% vs 0.79%; HR = 6.06 (95% CI 4.5–8.15); P < .001; NNH = 27 per 3 y

  • ARCTIC-Intervention—Assessment by a double Randomization of a Conventional antiplatelet strategy versus a monitoring-guided strategy for drug-eluting stent implantation and, of Treatment Interruption versus Continuation 1 year after stenting-Interruption, ASA—acetylsalicylic acid, BMS—bare-metal stent, CHARISMA—Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance, CV—cardiovascular, DAPT—dual antiplatelet therapy, DES—drug-eluting stent, DES-LATE—Optimal Duration of Clopidogrel Therapy with DES to Reduce Late Coronary Arterial Thrombotic Event, G1DES—first-generation drug-eluting stent, GUSTO—Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Arteries, HR—hazard ratio, ISTH—International Society on Thrombosis and Hemostasis, MACCE—major adverse cardiovascular and cerebrovascular events, MI—myocardial infarction, NNH—number needed to harm, NNT—number needed to treat, NSTEMI—non–ST-segment elevation MI, OPTIDUAL—OPTImal DUAL antiplatelet therapy, PCI—percutaneous coronary intervention, PEGASUS-TIMI 54—Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin–Thrombolysis in Myocardial Infarction 54, RR—relative risk, ST—stent thrombosis, STEEPLE—Safety and Efficacy of Enoxaparin in PCI Patients, STEMI—ST-segment elevation MI, TIMI—thrombolysis in myocardial infarction, UA—unstable angina.

  • * Major adverse cardiovascular and cerebrovascular events including death, MI, or stroke.