Main characteristics of studies included in the within 12-month network meta-analysis
| Study name . | Year . | Total patients . | Clinical settings . | First strategy (type and dose) . | Second strategy (type and dose) . | Primary efficacy endpoint . | % patients undergoing PCI or CABG . | % patients with ACS . |
|---|---|---|---|---|---|---|---|---|
| APPRAISE-2 | 2011 | 7392 | Patients with ACS with at least two high-risk features | Apixaban 5 mg b.i.d. (2.5 mg b.i.d. if eGFR < 40 mL/min) combined with standard antiplatelet therapy (ASA +/− P2Y12i) | Standard antiplatelet therapy (ASA +/− P2Y12i) | Cardiovascular death, MI, or ischaemic stroke | • PCI: 3255 pts, 44%• CABG: 55 pts, 0.7% | 100% |
| ATLAS ACS 2-TIMI 51 | 2012 | 15 526 | Patients with ACS | • Rivaroxaban 5 mg b.i.d. combined with standard antiplatelet therapy (ASA +/− P2Y12i)• Rivaroxaban 2.5 mg b.i.d. combined with standard antiplatelet therapy (ASA +/− P2Y12i) | Standard antiplatelet therapy (ASA +/− P2Y12i) | Cardiovascular death, MI, or any stroke | • PCI: 9631 pts, 62%• CABG: 10 pts, 0.1% | 100% |
| CARDIFF-I | 1979 | 1705 | Patients with AMI | Aspirin 300 mg | Placebo | All-cause death | NA | 100% |
| CARDIFF-II | 1979 | 1682 | Patients with AMI | Aspirin 300 mg three times daily | Placebo | All-cause death, cardiovascular death, non-fatal MI | NA | 100% |
| CARS | 1997 | 8803 | Patients with AMI | • Warfarin 1 mg and aspirin 80 mg• Warfarin 3 mg and aspirin 80 mg | Aspirin 160 mg | Cardiovascular death, non-fatal MI, non-fatal ischaemic stroke | NA | 100% |
| CHAMP | 2002 | 5059 | Patients with AMI | Warfarin (INR 1.5–2.5) and aspirin 81 mg | Aspirin 162 mg | All-cause death | NA | 100% |
| CREDO | 2002 | 2116 | Patients with stable CAD, unstable angina or recent MI | 12-month DAPT (clopidogrel 75 mg and aspirin 381–25 mg) | 1-month DAPT (clopidogrel 75 mg and aspirin 81–325 mg) followed by aspirin alone | All-cause death, MI, or stroke | • PCI: 1818 pts, 85.9%• CABG: 83 pts, 3.9% | 67% |
| CURE | 2001 | 12 562 | Patients with ACS without ST-segment elevation | Clopidogrel 75 mg and aspirin 75–325 mg | Aspirin 75–325 mg | Cardiovascular death, non-fatal MI, or non-fatal stroke | • PCI: 2658 pts, 21.2%• CABG: 2072 pts, 16.5% | 100% |
| Elderly-ACS 2 | 2018 | 1443 | Patients >74 years old with ACS undergoing PCI | Prasugrel 5 mg and aspirin 75–100 mg | Clopidogrel 75 mg and aspirin 75–100 mg | All-cause mortality, MI, disabling stroke, or rehospitalization for cardiovascular causes or bleeding | PCI: 1433 pts, 99% | 100% |
| EXCELLENT | 2012 | 1443 | Patients undergoing PCI | 6-month DAPT (aspirin 100–200 mg and clopidogrel 75 mg) followed by aspirin alone | 12-month DAPT (aspirin 100–200 mg and clopidogrel 75 mg) | Cardiac death, MI, or TVR | PCI: 100% | 52% |
| GEMINI-ACS | 2017 | 3037 | Patients with ACS | Rivaroxaban 2.5 mg b.i.d. and P2Y12i (clopidogrel 75 mg or ticagrelor 90 mg b.i.d.) | Aspirin 100 mg and P2Y12i (clopidogrel 75 mg or ticagrelor 90 mg b.i.d.) | Cardiovascular death, MI, stroke, or definite ST | • PCI: 2647 pts, 87%• CABG: 9 pts, 0.01% | 100% |
| GLASSY | 2020 | 7585 | Patients with stable CAD or ACS undergoing PCI | 1-month DAPT (aspirin 75–100 mg and 90 ticagrelor mg b.i.d.) followed by 23-month ticagrelor 90 mg b.i.d. monotherapy | 12-month DAPT (aspirin 75–100 mg and clopidogrel in stable CAD or ticagrelor 90 mg b.i.d. in ACS) followed by aspirin alone for 12 months | All-cause mortality, non-fatal MI, non-fatal stroke, or urgent TVR | PCI: 100% | 51% |
| I-LOVE-IT 2 | 2016 | 1829 | Patients with stable CAD or ACS undergoing PCI | 6-month DAPT (aspirin 100 mg and clopidogrel 75 mg) followed by aspirin alone | 12-month DAPT (aspirin 100 mg and clopidogrel 75 mg) | Cardiac death, target vessel MI, or clinically indicated TLR | PCI: 100% | 86% |
| ISAR-REACT5 | 2019 | 4018 | Patients with ACS | Aspirin 75–100 mg and ticagrelor 75 mg b.i.d. | Aspirin 75–100 mg and prasugrel 10 mg (5 mg in patients >75 years old or <60 kg) | All-cause mortality, MI, or stroke | • PCI: 3377 pts, 84%• CABG: 93 pts, 2% | 100% |
| ISAR-SAFE | 2015 | 4000 | Patients on DAPT (aspirin and clopidogrel) 6 month after PCI for both stable CAD and ACS | 6-month of aspirin 81–200 mg and clopidogrel 75 mg (a total length of 12-month DAPT) | 6-month of aspirin 81–200 mg and placebo (a total length of 6-month DAPT) | All-cause death, MI, definite or probable ST, stroke, or TIMI major bleeding | PCI: 100% | 40% |
| ISIS-2 | 1988 | 17 187 | Patients with suspected AMI | Aspirin 162.5 mg | Placebo | All-cause death | NA | 100% |
| ITALIC | 2015 | 1894 | Patients undergoing PCI | 6-month DAPT (aspirin 100 mg and clopidogrel 75 mg) followed by aspirin alone | 24-month DAPT (aspirin 100 mg and clopidogrel 75 mg) | All-cause death, MI, repeat emergency TVR, stroke, or TIMI major bleeding | PCI: 100% | 23% |
| IVUS-XPL | 2016 | 1400 | Patients with stable CAD or ACS undergoing PCI | 6-month DAPT (aspirin 100 mg and clopidogrel 75 mg) followed by aspirin alone | 12-month DAPT (aspirin 100 mg and clopidogrel 75 mg) | All-cause death, MI, stroke, or TIMI major bleeding | PCI: 100% | 49% |
| MASTER-DAPT | 2021 | 4579 | HBR patients with stable CAD or ACS undergoing PCI | Abbreviated therapy (immediate discontinuation of DAPT one month after PCI) | Standard therapy (at one month after PCI: continuation of DAPT for at least two additional months) | Death from any cause, MI, stroke, or major bleeding, and death from any cause, MI, or stroke | PCI:100% | 48% |
| NIPPON | 2017 | 3773 | Patients with stable CAD or ACS undergoing PCI | 6-month DAPT (aspirin 81–162 mg and clopidogrel 75 mg) followed by aspirin alone | 18-month DAPT (aspirin 81–162 mg and clopidogrel 75 mg) | All-cause death, MI, cerebrovascular events, or major bleeding | PCI: 100% | 33% |
| ONE-MONTH DAPT | 2021 | 3020 | Patients with stable CAD or ACS undergoing PCI | 1-month DAPT (aspirin 100 mg and clopidogrel 75 mg) followed by aspirin alone | 6–12 months DAPT (aspirin 100 mg and clopidogrel 75 mg) followed by aspirin alone | Cardiac death, nonfatal MI, TVR, stroke, or major bleeding | PCI:100% | 40% |
| OPTIMA-C | 2017 | 1368 | Patients undergoing PCI | 6-month DAPT (aspirin 100 mg and clopidogrel 75 mg) followed by aspirin alone | 12-month DAPT (aspirin 100 mg and clopidogrel 75 mg) | Cardiac death, target vessel-related, MI, ischaemia-driven TLR | PCI: 100% | 51% |
| OPTIMIZE | 2013 | 3119 | Patients with stable CAD or low-risk ACS undergoing PCI | 3-month DAPT (aspirin 100–200 mg and clopidogrel 75 mg) followed by aspirin alone | 12-month DAPT (aspirin 100–200 mg and clopidogrel 75 mg) | All-cause death, MI, stroke, or major bleeding | PCI: 100% | 32% |
| PLATO | 2010 | 13 408 | Patients with ACS with planned invasive strategy | Aspirin 75–100 mg and ticagrelor 90 mg b.i.d. | Aspirin 75–100 mg and clopidogrel 75 mg b.i.d. | Cardiovascular death, MI, or stroke | • PCI: 10 298 pts, 77%• CABG: 782 pts, 6% | 100% |
| POPULAR AGE | 2020 | 1002 | Patients >70 years old with NSTE-ACS | Clopidogrel 75 mg combined with local antithrombotic therapy (aspirin 86%) | Ticagrelor 90 mg b.i.d. on top of local antithrombotic therapy (Aspirin 86%) | All-cause death, MI, stroke, major, or minor bleeding | • PCI: 474 pts, 47%• CABG: 165 pts, 16% | 100% |
| PRAGUE-18 | 2016 | 1230 | Patients with AMI undergoing primary-PCI | Prasugrel 10 mg (5 mg in patients >75 years old or <60 kg) and aspirin 100 mg | Ticagrelor 90 mg b.i.d. and aspirin 100 mg | All-cause death, MI, stroke, major bleeding, or urgent TVR | PCI: 1220 pts, 99% | 100% |
| PRASFIT-ACS | 2014 | 1363 | Patients with ACS undergoing PCI | Prasugrel 3.75 mg and aspirin 81–100 mg | Clopidogrel 75 mg and aspirin 81–100 mg | Cardiovascular death, non-fatal MI, or non-fatal ischaemic stroke | PCI: 100% | 100% |
| PRODIGY | 2012 | 1970 | Patients with stable CAD or ACS at 1-month after PCI | 6-month DAPT (clopidogrel 75 mg and aspirin 80–160 mg) followed by aspirin alone | 24-month DAPT (clopidogrel 75 mg and aspirin 80–160 mg) | All-cause death, non-fatal MI, cerebrovascular accident | PCI: 100% | 74% |
| RACS | 2007 | 1004 | Patients with ACS undergoing PCI | 1-month DAPT (clopidogrel 75 mg and aspirin 75–325 mg) followed by aspirin alone | 6-month DAPT (clopidogrel 75 mg and aspirin 75–325 mg) | All-cause death, MI, or stroke | PCI: 100% | 100% |
| RESET | 2012 | 2117 | Patients undergoing PCI | 3-month DAPT (clopidogrel 75 mg and aspirin 100 mg) followed by aspirin alone | 12-month DAPT (clopidogrel 75 mg and aspirin 100 mg) | Cardiovascular death, MI, ST, ischaemia-driven TVR, or bleeding | PCI: 100% | 55% |
| SECURITY | 2014 | 1399 | Patients with stable or unstable angina undergoing PCI | 6-month DAPT (clopidogrel 75 mg and aspirin) followed by aspirin alone | 12-month DAPT (clopidogrel 75 mg and aspirin) | All-cause death, MI, stroke, definite or probable ST, BARC 3 or 5 bleeding | PCI: 100% | 38% |
| SMART-CHOICE | 2019 | 2993 | Patients with stable CAD or ACS undergoing PCI | Aspirin and a P2Y12i for 3 months followed by P2Y12i monotherapy | 12-month DAPT (aspirin and P2Y12i) | All-cause death, MI, or stroke | PCI: 100% | 58% |
| SMART-DATE | 2018 | 2712 | Patients with ACS undergoing PCI | 6-month DAPT (aspirin 100 mg and P2Y12i; clopidogrel 75 mg in 80% of patients) followed by aspirin alone | 12-month DAPT (aspirin 100 mg and P2Y12i; clopidogrel 75 mg in 80% of patients) | All-cause death, MI, or stroke | PCI: 100% | 100% |
| STOPDAPT-2 ACS | 2021 | 4136 | Patients with ACS undergoing PCI | 1-month DAPT (aspirin and clopidogrel 75 mg or prasugrel 3.75 mg) followed by clopidogrel 75 mg monotherapy | 12-month DAPT (aspirin and clopidogrel 75 mg) | Cardiovascular death, MI, definite ST, any stroke, TIMI major or minor bleeding | PCI: 100% | 100% |
| TALOS AMI | 2021 | 2697 | AMI patients without adverse events one month after successful PCI treated with aspirin and ticagrelor | Aspirin 100 mg and ticagrelor 90 mg twice daily | Aspirin 100 mg and clopidogrel 75 mg daily | Cardiovascular death, MI, stroke, or BARC type 2, 3, or 5 bleeding | PCI: 100% | 100% |
| TenBerg et al. | 2000 | 1058 | Patients with symptomatic CAD with planned PCI | VKA (INR 2.1–4.8) and aspirin 100 mg | Aspirin 100 mg | All-cause death, MI, TLR, or stroke | PCI: 100% | 0% |
| TICAB | 2019 | 1893 | Patients with stable CAD or ACS undergoing CABG | Ticagrelor 90 mg b.i.d. | Aspirin 100 mg | Cardiovascular death, MI, stroke, or repeat revascularization | CABG: 100% | 31% |
| TICO | 2020 | 3056 | Patients with ACS undergoing PCI | 3-month DAPT (clopidogrel 90 mg b.i.d. and aspirin 100 mg) followed by ticagrelor alone | 12-month DAPT (clopidogrel 90 mg b.i.d. and aspirin 100 mg) | All-cause death, MI, ST, stroke, TVR, or TIMI major bleeding | PCI: 100% | 100% |
| TREAT | 2019 | 3799 | Patients with STEMI receiving fibrinolytic therapy | Ticagrelor 90 mg b.i.d. and aspirin 75–100 mg | Clopidogrel 75 mg and aspirin 75–100 mg | Cardiovascular death, MI, or stroke | • PCI: 2132 pts, 56%• CABG: 71 pts, 1.9% | 100% |
| TRILOGY ACS | 2012 | 7243 | Patients with ACS managed conservatively | Prasugrel 10 mg (5 mg in patients >75 years old or <60 kg) and aspirin 100 mg | Clopidogrel 75 mg and aspirin 100 mg | Cardiovascular death, non-fatal MI, or non-fatal stroke | Among 7243 patients <75 years old:• PCI: 427 pts, 5.9%• CABG: 170 pts, 2.3% | 100% |
| TRITON-TIMI 38 | 2007 | 13 608 | Patients with ACS undergoing PCI | Prasugrel 10 mg and aspirin 75–162 mg | Clopidogrel 75 mg and aspirin 75–162 mg | Cardiovascular death, non-fatal MI, or non-fatal stroke | • PCI: 99%• CABG: 1% | 100% |
| TWILIGHT | 2019 | 7119 | High-risk patients undergoing PCI | 3-month DAPT (ticagrelor 90 mg b.i.d. and aspirin 81–100 mg) followed by 12-month of ticagrelor monotherapy | 3-month DAPT (ticagrelor 90 mg b.i.d. and aspirin 81–100 mg) followed by 12-month of ticagrelor and aspirin | All-cause death, non-fatal MI, non-fatal stroke | PCI: 100% | 65% |
| VACS | 1983 | 1266 | Patients with unstable angina | Aspirin 324 mg | Placebo | All-cause death or acute MI | NA | 100% |
| Study name . | Year . | Total patients . | Clinical settings . | First strategy (type and dose) . | Second strategy (type and dose) . | Primary efficacy endpoint . | % patients undergoing PCI or CABG . | % patients with ACS . |
|---|---|---|---|---|---|---|---|---|
| APPRAISE-2 | 2011 | 7392 | Patients with ACS with at least two high-risk features | Apixaban 5 mg b.i.d. (2.5 mg b.i.d. if eGFR < 40 mL/min) combined with standard antiplatelet therapy (ASA +/− P2Y12i) | Standard antiplatelet therapy (ASA +/− P2Y12i) | Cardiovascular death, MI, or ischaemic stroke | • PCI: 3255 pts, 44%• CABG: 55 pts, 0.7% | 100% |
| ATLAS ACS 2-TIMI 51 | 2012 | 15 526 | Patients with ACS | • Rivaroxaban 5 mg b.i.d. combined with standard antiplatelet therapy (ASA +/− P2Y12i)• Rivaroxaban 2.5 mg b.i.d. combined with standard antiplatelet therapy (ASA +/− P2Y12i) | Standard antiplatelet therapy (ASA +/− P2Y12i) | Cardiovascular death, MI, or any stroke | • PCI: 9631 pts, 62%• CABG: 10 pts, 0.1% | 100% |
| CARDIFF-I | 1979 | 1705 | Patients with AMI | Aspirin 300 mg | Placebo | All-cause death | NA | 100% |
| CARDIFF-II | 1979 | 1682 | Patients with AMI | Aspirin 300 mg three times daily | Placebo | All-cause death, cardiovascular death, non-fatal MI | NA | 100% |
| CARS | 1997 | 8803 | Patients with AMI | • Warfarin 1 mg and aspirin 80 mg• Warfarin 3 mg and aspirin 80 mg | Aspirin 160 mg | Cardiovascular death, non-fatal MI, non-fatal ischaemic stroke | NA | 100% |
| CHAMP | 2002 | 5059 | Patients with AMI | Warfarin (INR 1.5–2.5) and aspirin 81 mg | Aspirin 162 mg | All-cause death | NA | 100% |
| CREDO | 2002 | 2116 | Patients with stable CAD, unstable angina or recent MI | 12-month DAPT (clopidogrel 75 mg and aspirin 381–25 mg) | 1-month DAPT (clopidogrel 75 mg and aspirin 81–325 mg) followed by aspirin alone | All-cause death, MI, or stroke | • PCI: 1818 pts, 85.9%• CABG: 83 pts, 3.9% | 67% |
| CURE | 2001 | 12 562 | Patients with ACS without ST-segment elevation | Clopidogrel 75 mg and aspirin 75–325 mg | Aspirin 75–325 mg | Cardiovascular death, non-fatal MI, or non-fatal stroke | • PCI: 2658 pts, 21.2%• CABG: 2072 pts, 16.5% | 100% |
| Elderly-ACS 2 | 2018 | 1443 | Patients >74 years old with ACS undergoing PCI | Prasugrel 5 mg and aspirin 75–100 mg | Clopidogrel 75 mg and aspirin 75–100 mg | All-cause mortality, MI, disabling stroke, or rehospitalization for cardiovascular causes or bleeding | PCI: 1433 pts, 99% | 100% |
| EXCELLENT | 2012 | 1443 | Patients undergoing PCI | 6-month DAPT (aspirin 100–200 mg and clopidogrel 75 mg) followed by aspirin alone | 12-month DAPT (aspirin 100–200 mg and clopidogrel 75 mg) | Cardiac death, MI, or TVR | PCI: 100% | 52% |
| GEMINI-ACS | 2017 | 3037 | Patients with ACS | Rivaroxaban 2.5 mg b.i.d. and P2Y12i (clopidogrel 75 mg or ticagrelor 90 mg b.i.d.) | Aspirin 100 mg and P2Y12i (clopidogrel 75 mg or ticagrelor 90 mg b.i.d.) | Cardiovascular death, MI, stroke, or definite ST | • PCI: 2647 pts, 87%• CABG: 9 pts, 0.01% | 100% |
| GLASSY | 2020 | 7585 | Patients with stable CAD or ACS undergoing PCI | 1-month DAPT (aspirin 75–100 mg and 90 ticagrelor mg b.i.d.) followed by 23-month ticagrelor 90 mg b.i.d. monotherapy | 12-month DAPT (aspirin 75–100 mg and clopidogrel in stable CAD or ticagrelor 90 mg b.i.d. in ACS) followed by aspirin alone for 12 months | All-cause mortality, non-fatal MI, non-fatal stroke, or urgent TVR | PCI: 100% | 51% |
| I-LOVE-IT 2 | 2016 | 1829 | Patients with stable CAD or ACS undergoing PCI | 6-month DAPT (aspirin 100 mg and clopidogrel 75 mg) followed by aspirin alone | 12-month DAPT (aspirin 100 mg and clopidogrel 75 mg) | Cardiac death, target vessel MI, or clinically indicated TLR | PCI: 100% | 86% |
| ISAR-REACT5 | 2019 | 4018 | Patients with ACS | Aspirin 75–100 mg and ticagrelor 75 mg b.i.d. | Aspirin 75–100 mg and prasugrel 10 mg (5 mg in patients >75 years old or <60 kg) | All-cause mortality, MI, or stroke | • PCI: 3377 pts, 84%• CABG: 93 pts, 2% | 100% |
| ISAR-SAFE | 2015 | 4000 | Patients on DAPT (aspirin and clopidogrel) 6 month after PCI for both stable CAD and ACS | 6-month of aspirin 81–200 mg and clopidogrel 75 mg (a total length of 12-month DAPT) | 6-month of aspirin 81–200 mg and placebo (a total length of 6-month DAPT) | All-cause death, MI, definite or probable ST, stroke, or TIMI major bleeding | PCI: 100% | 40% |
| ISIS-2 | 1988 | 17 187 | Patients with suspected AMI | Aspirin 162.5 mg | Placebo | All-cause death | NA | 100% |
| ITALIC | 2015 | 1894 | Patients undergoing PCI | 6-month DAPT (aspirin 100 mg and clopidogrel 75 mg) followed by aspirin alone | 24-month DAPT (aspirin 100 mg and clopidogrel 75 mg) | All-cause death, MI, repeat emergency TVR, stroke, or TIMI major bleeding | PCI: 100% | 23% |
| IVUS-XPL | 2016 | 1400 | Patients with stable CAD or ACS undergoing PCI | 6-month DAPT (aspirin 100 mg and clopidogrel 75 mg) followed by aspirin alone | 12-month DAPT (aspirin 100 mg and clopidogrel 75 mg) | All-cause death, MI, stroke, or TIMI major bleeding | PCI: 100% | 49% |
| MASTER-DAPT | 2021 | 4579 | HBR patients with stable CAD or ACS undergoing PCI | Abbreviated therapy (immediate discontinuation of DAPT one month after PCI) | Standard therapy (at one month after PCI: continuation of DAPT for at least two additional months) | Death from any cause, MI, stroke, or major bleeding, and death from any cause, MI, or stroke | PCI:100% | 48% |
| NIPPON | 2017 | 3773 | Patients with stable CAD or ACS undergoing PCI | 6-month DAPT (aspirin 81–162 mg and clopidogrel 75 mg) followed by aspirin alone | 18-month DAPT (aspirin 81–162 mg and clopidogrel 75 mg) | All-cause death, MI, cerebrovascular events, or major bleeding | PCI: 100% | 33% |
| ONE-MONTH DAPT | 2021 | 3020 | Patients with stable CAD or ACS undergoing PCI | 1-month DAPT (aspirin 100 mg and clopidogrel 75 mg) followed by aspirin alone | 6–12 months DAPT (aspirin 100 mg and clopidogrel 75 mg) followed by aspirin alone | Cardiac death, nonfatal MI, TVR, stroke, or major bleeding | PCI:100% | 40% |
| OPTIMA-C | 2017 | 1368 | Patients undergoing PCI | 6-month DAPT (aspirin 100 mg and clopidogrel 75 mg) followed by aspirin alone | 12-month DAPT (aspirin 100 mg and clopidogrel 75 mg) | Cardiac death, target vessel-related, MI, ischaemia-driven TLR | PCI: 100% | 51% |
| OPTIMIZE | 2013 | 3119 | Patients with stable CAD or low-risk ACS undergoing PCI | 3-month DAPT (aspirin 100–200 mg and clopidogrel 75 mg) followed by aspirin alone | 12-month DAPT (aspirin 100–200 mg and clopidogrel 75 mg) | All-cause death, MI, stroke, or major bleeding | PCI: 100% | 32% |
| PLATO | 2010 | 13 408 | Patients with ACS with planned invasive strategy | Aspirin 75–100 mg and ticagrelor 90 mg b.i.d. | Aspirin 75–100 mg and clopidogrel 75 mg b.i.d. | Cardiovascular death, MI, or stroke | • PCI: 10 298 pts, 77%• CABG: 782 pts, 6% | 100% |
| POPULAR AGE | 2020 | 1002 | Patients >70 years old with NSTE-ACS | Clopidogrel 75 mg combined with local antithrombotic therapy (aspirin 86%) | Ticagrelor 90 mg b.i.d. on top of local antithrombotic therapy (Aspirin 86%) | All-cause death, MI, stroke, major, or minor bleeding | • PCI: 474 pts, 47%• CABG: 165 pts, 16% | 100% |
| PRAGUE-18 | 2016 | 1230 | Patients with AMI undergoing primary-PCI | Prasugrel 10 mg (5 mg in patients >75 years old or <60 kg) and aspirin 100 mg | Ticagrelor 90 mg b.i.d. and aspirin 100 mg | All-cause death, MI, stroke, major bleeding, or urgent TVR | PCI: 1220 pts, 99% | 100% |
| PRASFIT-ACS | 2014 | 1363 | Patients with ACS undergoing PCI | Prasugrel 3.75 mg and aspirin 81–100 mg | Clopidogrel 75 mg and aspirin 81–100 mg | Cardiovascular death, non-fatal MI, or non-fatal ischaemic stroke | PCI: 100% | 100% |
| PRODIGY | 2012 | 1970 | Patients with stable CAD or ACS at 1-month after PCI | 6-month DAPT (clopidogrel 75 mg and aspirin 80–160 mg) followed by aspirin alone | 24-month DAPT (clopidogrel 75 mg and aspirin 80–160 mg) | All-cause death, non-fatal MI, cerebrovascular accident | PCI: 100% | 74% |
| RACS | 2007 | 1004 | Patients with ACS undergoing PCI | 1-month DAPT (clopidogrel 75 mg and aspirin 75–325 mg) followed by aspirin alone | 6-month DAPT (clopidogrel 75 mg and aspirin 75–325 mg) | All-cause death, MI, or stroke | PCI: 100% | 100% |
| RESET | 2012 | 2117 | Patients undergoing PCI | 3-month DAPT (clopidogrel 75 mg and aspirin 100 mg) followed by aspirin alone | 12-month DAPT (clopidogrel 75 mg and aspirin 100 mg) | Cardiovascular death, MI, ST, ischaemia-driven TVR, or bleeding | PCI: 100% | 55% |
| SECURITY | 2014 | 1399 | Patients with stable or unstable angina undergoing PCI | 6-month DAPT (clopidogrel 75 mg and aspirin) followed by aspirin alone | 12-month DAPT (clopidogrel 75 mg and aspirin) | All-cause death, MI, stroke, definite or probable ST, BARC 3 or 5 bleeding | PCI: 100% | 38% |
| SMART-CHOICE | 2019 | 2993 | Patients with stable CAD or ACS undergoing PCI | Aspirin and a P2Y12i for 3 months followed by P2Y12i monotherapy | 12-month DAPT (aspirin and P2Y12i) | All-cause death, MI, or stroke | PCI: 100% | 58% |
| SMART-DATE | 2018 | 2712 | Patients with ACS undergoing PCI | 6-month DAPT (aspirin 100 mg and P2Y12i; clopidogrel 75 mg in 80% of patients) followed by aspirin alone | 12-month DAPT (aspirin 100 mg and P2Y12i; clopidogrel 75 mg in 80% of patients) | All-cause death, MI, or stroke | PCI: 100% | 100% |
| STOPDAPT-2 ACS | 2021 | 4136 | Patients with ACS undergoing PCI | 1-month DAPT (aspirin and clopidogrel 75 mg or prasugrel 3.75 mg) followed by clopidogrel 75 mg monotherapy | 12-month DAPT (aspirin and clopidogrel 75 mg) | Cardiovascular death, MI, definite ST, any stroke, TIMI major or minor bleeding | PCI: 100% | 100% |
| TALOS AMI | 2021 | 2697 | AMI patients without adverse events one month after successful PCI treated with aspirin and ticagrelor | Aspirin 100 mg and ticagrelor 90 mg twice daily | Aspirin 100 mg and clopidogrel 75 mg daily | Cardiovascular death, MI, stroke, or BARC type 2, 3, or 5 bleeding | PCI: 100% | 100% |
| TenBerg et al. | 2000 | 1058 | Patients with symptomatic CAD with planned PCI | VKA (INR 2.1–4.8) and aspirin 100 mg | Aspirin 100 mg | All-cause death, MI, TLR, or stroke | PCI: 100% | 0% |
| TICAB | 2019 | 1893 | Patients with stable CAD or ACS undergoing CABG | Ticagrelor 90 mg b.i.d. | Aspirin 100 mg | Cardiovascular death, MI, stroke, or repeat revascularization | CABG: 100% | 31% |
| TICO | 2020 | 3056 | Patients with ACS undergoing PCI | 3-month DAPT (clopidogrel 90 mg b.i.d. and aspirin 100 mg) followed by ticagrelor alone | 12-month DAPT (clopidogrel 90 mg b.i.d. and aspirin 100 mg) | All-cause death, MI, ST, stroke, TVR, or TIMI major bleeding | PCI: 100% | 100% |
| TREAT | 2019 | 3799 | Patients with STEMI receiving fibrinolytic therapy | Ticagrelor 90 mg b.i.d. and aspirin 75–100 mg | Clopidogrel 75 mg and aspirin 75–100 mg | Cardiovascular death, MI, or stroke | • PCI: 2132 pts, 56%• CABG: 71 pts, 1.9% | 100% |
| TRILOGY ACS | 2012 | 7243 | Patients with ACS managed conservatively | Prasugrel 10 mg (5 mg in patients >75 years old or <60 kg) and aspirin 100 mg | Clopidogrel 75 mg and aspirin 100 mg | Cardiovascular death, non-fatal MI, or non-fatal stroke | Among 7243 patients <75 years old:• PCI: 427 pts, 5.9%• CABG: 170 pts, 2.3% | 100% |
| TRITON-TIMI 38 | 2007 | 13 608 | Patients with ACS undergoing PCI | Prasugrel 10 mg and aspirin 75–162 mg | Clopidogrel 75 mg and aspirin 75–162 mg | Cardiovascular death, non-fatal MI, or non-fatal stroke | • PCI: 99%• CABG: 1% | 100% |
| TWILIGHT | 2019 | 7119 | High-risk patients undergoing PCI | 3-month DAPT (ticagrelor 90 mg b.i.d. and aspirin 81–100 mg) followed by 12-month of ticagrelor monotherapy | 3-month DAPT (ticagrelor 90 mg b.i.d. and aspirin 81–100 mg) followed by 12-month of ticagrelor and aspirin | All-cause death, non-fatal MI, non-fatal stroke | PCI: 100% | 65% |
| VACS | 1983 | 1266 | Patients with unstable angina | Aspirin 324 mg | Placebo | All-cause death or acute MI | NA | 100% |
Abbreviations: ACS, acute coronary syndrome; AMI, acute myocardial infarction; ASA, aspirin; BARC, Bleeding Academic Research Consortium; CABG, coronary artery bypass grafting; CAD, coronary artery disease; DAPT, dual antiplatelet therapy; eGFR, estimated glomerular filtration rate; HBR, high bleeding risk; INR, international normalized ratio; MI, myocardial infarction; NSTE-ACS, non-ST segment elevation acute coronary syndrome; PCI, percutaneous coronary intervention; P2Y12i, P2Y12 inhibitor; ST, stent thrombosis; STEMI, ST-segment elevation myocardial infarction; TIMI, thrombolysis in myocardial infarction; TLR, target lesion revascularization; TVR, target vessel revascularization; VKA, vitamin-K antagonist.
Main characteristics of studies included in the within 12-month network meta-analysis
| Study name . | Year . | Total patients . | Clinical settings . | First strategy (type and dose) . | Second strategy (type and dose) . | Primary efficacy endpoint . | % patients undergoing PCI or CABG . | % patients with ACS . |
|---|---|---|---|---|---|---|---|---|
| APPRAISE-2 | 2011 | 7392 | Patients with ACS with at least two high-risk features | Apixaban 5 mg b.i.d. (2.5 mg b.i.d. if eGFR < 40 mL/min) combined with standard antiplatelet therapy (ASA +/− P2Y12i) | Standard antiplatelet therapy (ASA +/− P2Y12i) | Cardiovascular death, MI, or ischaemic stroke | • PCI: 3255 pts, 44%• CABG: 55 pts, 0.7% | 100% |
| ATLAS ACS 2-TIMI 51 | 2012 | 15 526 | Patients with ACS | • Rivaroxaban 5 mg b.i.d. combined with standard antiplatelet therapy (ASA +/− P2Y12i)• Rivaroxaban 2.5 mg b.i.d. combined with standard antiplatelet therapy (ASA +/− P2Y12i) | Standard antiplatelet therapy (ASA +/− P2Y12i) | Cardiovascular death, MI, or any stroke | • PCI: 9631 pts, 62%• CABG: 10 pts, 0.1% | 100% |
| CARDIFF-I | 1979 | 1705 | Patients with AMI | Aspirin 300 mg | Placebo | All-cause death | NA | 100% |
| CARDIFF-II | 1979 | 1682 | Patients with AMI | Aspirin 300 mg three times daily | Placebo | All-cause death, cardiovascular death, non-fatal MI | NA | 100% |
| CARS | 1997 | 8803 | Patients with AMI | • Warfarin 1 mg and aspirin 80 mg• Warfarin 3 mg and aspirin 80 mg | Aspirin 160 mg | Cardiovascular death, non-fatal MI, non-fatal ischaemic stroke | NA | 100% |
| CHAMP | 2002 | 5059 | Patients with AMI | Warfarin (INR 1.5–2.5) and aspirin 81 mg | Aspirin 162 mg | All-cause death | NA | 100% |
| CREDO | 2002 | 2116 | Patients with stable CAD, unstable angina or recent MI | 12-month DAPT (clopidogrel 75 mg and aspirin 381–25 mg) | 1-month DAPT (clopidogrel 75 mg and aspirin 81–325 mg) followed by aspirin alone | All-cause death, MI, or stroke | • PCI: 1818 pts, 85.9%• CABG: 83 pts, 3.9% | 67% |
| CURE | 2001 | 12 562 | Patients with ACS without ST-segment elevation | Clopidogrel 75 mg and aspirin 75–325 mg | Aspirin 75–325 mg | Cardiovascular death, non-fatal MI, or non-fatal stroke | • PCI: 2658 pts, 21.2%• CABG: 2072 pts, 16.5% | 100% |
| Elderly-ACS 2 | 2018 | 1443 | Patients >74 years old with ACS undergoing PCI | Prasugrel 5 mg and aspirin 75–100 mg | Clopidogrel 75 mg and aspirin 75–100 mg | All-cause mortality, MI, disabling stroke, or rehospitalization for cardiovascular causes or bleeding | PCI: 1433 pts, 99% | 100% |
| EXCELLENT | 2012 | 1443 | Patients undergoing PCI | 6-month DAPT (aspirin 100–200 mg and clopidogrel 75 mg) followed by aspirin alone | 12-month DAPT (aspirin 100–200 mg and clopidogrel 75 mg) | Cardiac death, MI, or TVR | PCI: 100% | 52% |
| GEMINI-ACS | 2017 | 3037 | Patients with ACS | Rivaroxaban 2.5 mg b.i.d. and P2Y12i (clopidogrel 75 mg or ticagrelor 90 mg b.i.d.) | Aspirin 100 mg and P2Y12i (clopidogrel 75 mg or ticagrelor 90 mg b.i.d.) | Cardiovascular death, MI, stroke, or definite ST | • PCI: 2647 pts, 87%• CABG: 9 pts, 0.01% | 100% |
| GLASSY | 2020 | 7585 | Patients with stable CAD or ACS undergoing PCI | 1-month DAPT (aspirin 75–100 mg and 90 ticagrelor mg b.i.d.) followed by 23-month ticagrelor 90 mg b.i.d. monotherapy | 12-month DAPT (aspirin 75–100 mg and clopidogrel in stable CAD or ticagrelor 90 mg b.i.d. in ACS) followed by aspirin alone for 12 months | All-cause mortality, non-fatal MI, non-fatal stroke, or urgent TVR | PCI: 100% | 51% |
| I-LOVE-IT 2 | 2016 | 1829 | Patients with stable CAD or ACS undergoing PCI | 6-month DAPT (aspirin 100 mg and clopidogrel 75 mg) followed by aspirin alone | 12-month DAPT (aspirin 100 mg and clopidogrel 75 mg) | Cardiac death, target vessel MI, or clinically indicated TLR | PCI: 100% | 86% |
| ISAR-REACT5 | 2019 | 4018 | Patients with ACS | Aspirin 75–100 mg and ticagrelor 75 mg b.i.d. | Aspirin 75–100 mg and prasugrel 10 mg (5 mg in patients >75 years old or <60 kg) | All-cause mortality, MI, or stroke | • PCI: 3377 pts, 84%• CABG: 93 pts, 2% | 100% |
| ISAR-SAFE | 2015 | 4000 | Patients on DAPT (aspirin and clopidogrel) 6 month after PCI for both stable CAD and ACS | 6-month of aspirin 81–200 mg and clopidogrel 75 mg (a total length of 12-month DAPT) | 6-month of aspirin 81–200 mg and placebo (a total length of 6-month DAPT) | All-cause death, MI, definite or probable ST, stroke, or TIMI major bleeding | PCI: 100% | 40% |
| ISIS-2 | 1988 | 17 187 | Patients with suspected AMI | Aspirin 162.5 mg | Placebo | All-cause death | NA | 100% |
| ITALIC | 2015 | 1894 | Patients undergoing PCI | 6-month DAPT (aspirin 100 mg and clopidogrel 75 mg) followed by aspirin alone | 24-month DAPT (aspirin 100 mg and clopidogrel 75 mg) | All-cause death, MI, repeat emergency TVR, stroke, or TIMI major bleeding | PCI: 100% | 23% |
| IVUS-XPL | 2016 | 1400 | Patients with stable CAD or ACS undergoing PCI | 6-month DAPT (aspirin 100 mg and clopidogrel 75 mg) followed by aspirin alone | 12-month DAPT (aspirin 100 mg and clopidogrel 75 mg) | All-cause death, MI, stroke, or TIMI major bleeding | PCI: 100% | 49% |
| MASTER-DAPT | 2021 | 4579 | HBR patients with stable CAD or ACS undergoing PCI | Abbreviated therapy (immediate discontinuation of DAPT one month after PCI) | Standard therapy (at one month after PCI: continuation of DAPT for at least two additional months) | Death from any cause, MI, stroke, or major bleeding, and death from any cause, MI, or stroke | PCI:100% | 48% |
| NIPPON | 2017 | 3773 | Patients with stable CAD or ACS undergoing PCI | 6-month DAPT (aspirin 81–162 mg and clopidogrel 75 mg) followed by aspirin alone | 18-month DAPT (aspirin 81–162 mg and clopidogrel 75 mg) | All-cause death, MI, cerebrovascular events, or major bleeding | PCI: 100% | 33% |
| ONE-MONTH DAPT | 2021 | 3020 | Patients with stable CAD or ACS undergoing PCI | 1-month DAPT (aspirin 100 mg and clopidogrel 75 mg) followed by aspirin alone | 6–12 months DAPT (aspirin 100 mg and clopidogrel 75 mg) followed by aspirin alone | Cardiac death, nonfatal MI, TVR, stroke, or major bleeding | PCI:100% | 40% |
| OPTIMA-C | 2017 | 1368 | Patients undergoing PCI | 6-month DAPT (aspirin 100 mg and clopidogrel 75 mg) followed by aspirin alone | 12-month DAPT (aspirin 100 mg and clopidogrel 75 mg) | Cardiac death, target vessel-related, MI, ischaemia-driven TLR | PCI: 100% | 51% |
| OPTIMIZE | 2013 | 3119 | Patients with stable CAD or low-risk ACS undergoing PCI | 3-month DAPT (aspirin 100–200 mg and clopidogrel 75 mg) followed by aspirin alone | 12-month DAPT (aspirin 100–200 mg and clopidogrel 75 mg) | All-cause death, MI, stroke, or major bleeding | PCI: 100% | 32% |
| PLATO | 2010 | 13 408 | Patients with ACS with planned invasive strategy | Aspirin 75–100 mg and ticagrelor 90 mg b.i.d. | Aspirin 75–100 mg and clopidogrel 75 mg b.i.d. | Cardiovascular death, MI, or stroke | • PCI: 10 298 pts, 77%• CABG: 782 pts, 6% | 100% |
| POPULAR AGE | 2020 | 1002 | Patients >70 years old with NSTE-ACS | Clopidogrel 75 mg combined with local antithrombotic therapy (aspirin 86%) | Ticagrelor 90 mg b.i.d. on top of local antithrombotic therapy (Aspirin 86%) | All-cause death, MI, stroke, major, or minor bleeding | • PCI: 474 pts, 47%• CABG: 165 pts, 16% | 100% |
| PRAGUE-18 | 2016 | 1230 | Patients with AMI undergoing primary-PCI | Prasugrel 10 mg (5 mg in patients >75 years old or <60 kg) and aspirin 100 mg | Ticagrelor 90 mg b.i.d. and aspirin 100 mg | All-cause death, MI, stroke, major bleeding, or urgent TVR | PCI: 1220 pts, 99% | 100% |
| PRASFIT-ACS | 2014 | 1363 | Patients with ACS undergoing PCI | Prasugrel 3.75 mg and aspirin 81–100 mg | Clopidogrel 75 mg and aspirin 81–100 mg | Cardiovascular death, non-fatal MI, or non-fatal ischaemic stroke | PCI: 100% | 100% |
| PRODIGY | 2012 | 1970 | Patients with stable CAD or ACS at 1-month after PCI | 6-month DAPT (clopidogrel 75 mg and aspirin 80–160 mg) followed by aspirin alone | 24-month DAPT (clopidogrel 75 mg and aspirin 80–160 mg) | All-cause death, non-fatal MI, cerebrovascular accident | PCI: 100% | 74% |
| RACS | 2007 | 1004 | Patients with ACS undergoing PCI | 1-month DAPT (clopidogrel 75 mg and aspirin 75–325 mg) followed by aspirin alone | 6-month DAPT (clopidogrel 75 mg and aspirin 75–325 mg) | All-cause death, MI, or stroke | PCI: 100% | 100% |
| RESET | 2012 | 2117 | Patients undergoing PCI | 3-month DAPT (clopidogrel 75 mg and aspirin 100 mg) followed by aspirin alone | 12-month DAPT (clopidogrel 75 mg and aspirin 100 mg) | Cardiovascular death, MI, ST, ischaemia-driven TVR, or bleeding | PCI: 100% | 55% |
| SECURITY | 2014 | 1399 | Patients with stable or unstable angina undergoing PCI | 6-month DAPT (clopidogrel 75 mg and aspirin) followed by aspirin alone | 12-month DAPT (clopidogrel 75 mg and aspirin) | All-cause death, MI, stroke, definite or probable ST, BARC 3 or 5 bleeding | PCI: 100% | 38% |
| SMART-CHOICE | 2019 | 2993 | Patients with stable CAD or ACS undergoing PCI | Aspirin and a P2Y12i for 3 months followed by P2Y12i monotherapy | 12-month DAPT (aspirin and P2Y12i) | All-cause death, MI, or stroke | PCI: 100% | 58% |
| SMART-DATE | 2018 | 2712 | Patients with ACS undergoing PCI | 6-month DAPT (aspirin 100 mg and P2Y12i; clopidogrel 75 mg in 80% of patients) followed by aspirin alone | 12-month DAPT (aspirin 100 mg and P2Y12i; clopidogrel 75 mg in 80% of patients) | All-cause death, MI, or stroke | PCI: 100% | 100% |
| STOPDAPT-2 ACS | 2021 | 4136 | Patients with ACS undergoing PCI | 1-month DAPT (aspirin and clopidogrel 75 mg or prasugrel 3.75 mg) followed by clopidogrel 75 mg monotherapy | 12-month DAPT (aspirin and clopidogrel 75 mg) | Cardiovascular death, MI, definite ST, any stroke, TIMI major or minor bleeding | PCI: 100% | 100% |
| TALOS AMI | 2021 | 2697 | AMI patients without adverse events one month after successful PCI treated with aspirin and ticagrelor | Aspirin 100 mg and ticagrelor 90 mg twice daily | Aspirin 100 mg and clopidogrel 75 mg daily | Cardiovascular death, MI, stroke, or BARC type 2, 3, or 5 bleeding | PCI: 100% | 100% |
| TenBerg et al. | 2000 | 1058 | Patients with symptomatic CAD with planned PCI | VKA (INR 2.1–4.8) and aspirin 100 mg | Aspirin 100 mg | All-cause death, MI, TLR, or stroke | PCI: 100% | 0% |
| TICAB | 2019 | 1893 | Patients with stable CAD or ACS undergoing CABG | Ticagrelor 90 mg b.i.d. | Aspirin 100 mg | Cardiovascular death, MI, stroke, or repeat revascularization | CABG: 100% | 31% |
| TICO | 2020 | 3056 | Patients with ACS undergoing PCI | 3-month DAPT (clopidogrel 90 mg b.i.d. and aspirin 100 mg) followed by ticagrelor alone | 12-month DAPT (clopidogrel 90 mg b.i.d. and aspirin 100 mg) | All-cause death, MI, ST, stroke, TVR, or TIMI major bleeding | PCI: 100% | 100% |
| TREAT | 2019 | 3799 | Patients with STEMI receiving fibrinolytic therapy | Ticagrelor 90 mg b.i.d. and aspirin 75–100 mg | Clopidogrel 75 mg and aspirin 75–100 mg | Cardiovascular death, MI, or stroke | • PCI: 2132 pts, 56%• CABG: 71 pts, 1.9% | 100% |
| TRILOGY ACS | 2012 | 7243 | Patients with ACS managed conservatively | Prasugrel 10 mg (5 mg in patients >75 years old or <60 kg) and aspirin 100 mg | Clopidogrel 75 mg and aspirin 100 mg | Cardiovascular death, non-fatal MI, or non-fatal stroke | Among 7243 patients <75 years old:• PCI: 427 pts, 5.9%• CABG: 170 pts, 2.3% | 100% |
| TRITON-TIMI 38 | 2007 | 13 608 | Patients with ACS undergoing PCI | Prasugrel 10 mg and aspirin 75–162 mg | Clopidogrel 75 mg and aspirin 75–162 mg | Cardiovascular death, non-fatal MI, or non-fatal stroke | • PCI: 99%• CABG: 1% | 100% |
| TWILIGHT | 2019 | 7119 | High-risk patients undergoing PCI | 3-month DAPT (ticagrelor 90 mg b.i.d. and aspirin 81–100 mg) followed by 12-month of ticagrelor monotherapy | 3-month DAPT (ticagrelor 90 mg b.i.d. and aspirin 81–100 mg) followed by 12-month of ticagrelor and aspirin | All-cause death, non-fatal MI, non-fatal stroke | PCI: 100% | 65% |
| VACS | 1983 | 1266 | Patients with unstable angina | Aspirin 324 mg | Placebo | All-cause death or acute MI | NA | 100% |
| Study name . | Year . | Total patients . | Clinical settings . | First strategy (type and dose) . | Second strategy (type and dose) . | Primary efficacy endpoint . | % patients undergoing PCI or CABG . | % patients with ACS . |
|---|---|---|---|---|---|---|---|---|
| APPRAISE-2 | 2011 | 7392 | Patients with ACS with at least two high-risk features | Apixaban 5 mg b.i.d. (2.5 mg b.i.d. if eGFR < 40 mL/min) combined with standard antiplatelet therapy (ASA +/− P2Y12i) | Standard antiplatelet therapy (ASA +/− P2Y12i) | Cardiovascular death, MI, or ischaemic stroke | • PCI: 3255 pts, 44%• CABG: 55 pts, 0.7% | 100% |
| ATLAS ACS 2-TIMI 51 | 2012 | 15 526 | Patients with ACS | • Rivaroxaban 5 mg b.i.d. combined with standard antiplatelet therapy (ASA +/− P2Y12i)• Rivaroxaban 2.5 mg b.i.d. combined with standard antiplatelet therapy (ASA +/− P2Y12i) | Standard antiplatelet therapy (ASA +/− P2Y12i) | Cardiovascular death, MI, or any stroke | • PCI: 9631 pts, 62%• CABG: 10 pts, 0.1% | 100% |
| CARDIFF-I | 1979 | 1705 | Patients with AMI | Aspirin 300 mg | Placebo | All-cause death | NA | 100% |
| CARDIFF-II | 1979 | 1682 | Patients with AMI | Aspirin 300 mg three times daily | Placebo | All-cause death, cardiovascular death, non-fatal MI | NA | 100% |
| CARS | 1997 | 8803 | Patients with AMI | • Warfarin 1 mg and aspirin 80 mg• Warfarin 3 mg and aspirin 80 mg | Aspirin 160 mg | Cardiovascular death, non-fatal MI, non-fatal ischaemic stroke | NA | 100% |
| CHAMP | 2002 | 5059 | Patients with AMI | Warfarin (INR 1.5–2.5) and aspirin 81 mg | Aspirin 162 mg | All-cause death | NA | 100% |
| CREDO | 2002 | 2116 | Patients with stable CAD, unstable angina or recent MI | 12-month DAPT (clopidogrel 75 mg and aspirin 381–25 mg) | 1-month DAPT (clopidogrel 75 mg and aspirin 81–325 mg) followed by aspirin alone | All-cause death, MI, or stroke | • PCI: 1818 pts, 85.9%• CABG: 83 pts, 3.9% | 67% |
| CURE | 2001 | 12 562 | Patients with ACS without ST-segment elevation | Clopidogrel 75 mg and aspirin 75–325 mg | Aspirin 75–325 mg | Cardiovascular death, non-fatal MI, or non-fatal stroke | • PCI: 2658 pts, 21.2%• CABG: 2072 pts, 16.5% | 100% |
| Elderly-ACS 2 | 2018 | 1443 | Patients >74 years old with ACS undergoing PCI | Prasugrel 5 mg and aspirin 75–100 mg | Clopidogrel 75 mg and aspirin 75–100 mg | All-cause mortality, MI, disabling stroke, or rehospitalization for cardiovascular causes or bleeding | PCI: 1433 pts, 99% | 100% |
| EXCELLENT | 2012 | 1443 | Patients undergoing PCI | 6-month DAPT (aspirin 100–200 mg and clopidogrel 75 mg) followed by aspirin alone | 12-month DAPT (aspirin 100–200 mg and clopidogrel 75 mg) | Cardiac death, MI, or TVR | PCI: 100% | 52% |
| GEMINI-ACS | 2017 | 3037 | Patients with ACS | Rivaroxaban 2.5 mg b.i.d. and P2Y12i (clopidogrel 75 mg or ticagrelor 90 mg b.i.d.) | Aspirin 100 mg and P2Y12i (clopidogrel 75 mg or ticagrelor 90 mg b.i.d.) | Cardiovascular death, MI, stroke, or definite ST | • PCI: 2647 pts, 87%• CABG: 9 pts, 0.01% | 100% |
| GLASSY | 2020 | 7585 | Patients with stable CAD or ACS undergoing PCI | 1-month DAPT (aspirin 75–100 mg and 90 ticagrelor mg b.i.d.) followed by 23-month ticagrelor 90 mg b.i.d. monotherapy | 12-month DAPT (aspirin 75–100 mg and clopidogrel in stable CAD or ticagrelor 90 mg b.i.d. in ACS) followed by aspirin alone for 12 months | All-cause mortality, non-fatal MI, non-fatal stroke, or urgent TVR | PCI: 100% | 51% |
| I-LOVE-IT 2 | 2016 | 1829 | Patients with stable CAD or ACS undergoing PCI | 6-month DAPT (aspirin 100 mg and clopidogrel 75 mg) followed by aspirin alone | 12-month DAPT (aspirin 100 mg and clopidogrel 75 mg) | Cardiac death, target vessel MI, or clinically indicated TLR | PCI: 100% | 86% |
| ISAR-REACT5 | 2019 | 4018 | Patients with ACS | Aspirin 75–100 mg and ticagrelor 75 mg b.i.d. | Aspirin 75–100 mg and prasugrel 10 mg (5 mg in patients >75 years old or <60 kg) | All-cause mortality, MI, or stroke | • PCI: 3377 pts, 84%• CABG: 93 pts, 2% | 100% |
| ISAR-SAFE | 2015 | 4000 | Patients on DAPT (aspirin and clopidogrel) 6 month after PCI for both stable CAD and ACS | 6-month of aspirin 81–200 mg and clopidogrel 75 mg (a total length of 12-month DAPT) | 6-month of aspirin 81–200 mg and placebo (a total length of 6-month DAPT) | All-cause death, MI, definite or probable ST, stroke, or TIMI major bleeding | PCI: 100% | 40% |
| ISIS-2 | 1988 | 17 187 | Patients with suspected AMI | Aspirin 162.5 mg | Placebo | All-cause death | NA | 100% |
| ITALIC | 2015 | 1894 | Patients undergoing PCI | 6-month DAPT (aspirin 100 mg and clopidogrel 75 mg) followed by aspirin alone | 24-month DAPT (aspirin 100 mg and clopidogrel 75 mg) | All-cause death, MI, repeat emergency TVR, stroke, or TIMI major bleeding | PCI: 100% | 23% |
| IVUS-XPL | 2016 | 1400 | Patients with stable CAD or ACS undergoing PCI | 6-month DAPT (aspirin 100 mg and clopidogrel 75 mg) followed by aspirin alone | 12-month DAPT (aspirin 100 mg and clopidogrel 75 mg) | All-cause death, MI, stroke, or TIMI major bleeding | PCI: 100% | 49% |
| MASTER-DAPT | 2021 | 4579 | HBR patients with stable CAD or ACS undergoing PCI | Abbreviated therapy (immediate discontinuation of DAPT one month after PCI) | Standard therapy (at one month after PCI: continuation of DAPT for at least two additional months) | Death from any cause, MI, stroke, or major bleeding, and death from any cause, MI, or stroke | PCI:100% | 48% |
| NIPPON | 2017 | 3773 | Patients with stable CAD or ACS undergoing PCI | 6-month DAPT (aspirin 81–162 mg and clopidogrel 75 mg) followed by aspirin alone | 18-month DAPT (aspirin 81–162 mg and clopidogrel 75 mg) | All-cause death, MI, cerebrovascular events, or major bleeding | PCI: 100% | 33% |
| ONE-MONTH DAPT | 2021 | 3020 | Patients with stable CAD or ACS undergoing PCI | 1-month DAPT (aspirin 100 mg and clopidogrel 75 mg) followed by aspirin alone | 6–12 months DAPT (aspirin 100 mg and clopidogrel 75 mg) followed by aspirin alone | Cardiac death, nonfatal MI, TVR, stroke, or major bleeding | PCI:100% | 40% |
| OPTIMA-C | 2017 | 1368 | Patients undergoing PCI | 6-month DAPT (aspirin 100 mg and clopidogrel 75 mg) followed by aspirin alone | 12-month DAPT (aspirin 100 mg and clopidogrel 75 mg) | Cardiac death, target vessel-related, MI, ischaemia-driven TLR | PCI: 100% | 51% |
| OPTIMIZE | 2013 | 3119 | Patients with stable CAD or low-risk ACS undergoing PCI | 3-month DAPT (aspirin 100–200 mg and clopidogrel 75 mg) followed by aspirin alone | 12-month DAPT (aspirin 100–200 mg and clopidogrel 75 mg) | All-cause death, MI, stroke, or major bleeding | PCI: 100% | 32% |
| PLATO | 2010 | 13 408 | Patients with ACS with planned invasive strategy | Aspirin 75–100 mg and ticagrelor 90 mg b.i.d. | Aspirin 75–100 mg and clopidogrel 75 mg b.i.d. | Cardiovascular death, MI, or stroke | • PCI: 10 298 pts, 77%• CABG: 782 pts, 6% | 100% |
| POPULAR AGE | 2020 | 1002 | Patients >70 years old with NSTE-ACS | Clopidogrel 75 mg combined with local antithrombotic therapy (aspirin 86%) | Ticagrelor 90 mg b.i.d. on top of local antithrombotic therapy (Aspirin 86%) | All-cause death, MI, stroke, major, or minor bleeding | • PCI: 474 pts, 47%• CABG: 165 pts, 16% | 100% |
| PRAGUE-18 | 2016 | 1230 | Patients with AMI undergoing primary-PCI | Prasugrel 10 mg (5 mg in patients >75 years old or <60 kg) and aspirin 100 mg | Ticagrelor 90 mg b.i.d. and aspirin 100 mg | All-cause death, MI, stroke, major bleeding, or urgent TVR | PCI: 1220 pts, 99% | 100% |
| PRASFIT-ACS | 2014 | 1363 | Patients with ACS undergoing PCI | Prasugrel 3.75 mg and aspirin 81–100 mg | Clopidogrel 75 mg and aspirin 81–100 mg | Cardiovascular death, non-fatal MI, or non-fatal ischaemic stroke | PCI: 100% | 100% |
| PRODIGY | 2012 | 1970 | Patients with stable CAD or ACS at 1-month after PCI | 6-month DAPT (clopidogrel 75 mg and aspirin 80–160 mg) followed by aspirin alone | 24-month DAPT (clopidogrel 75 mg and aspirin 80–160 mg) | All-cause death, non-fatal MI, cerebrovascular accident | PCI: 100% | 74% |
| RACS | 2007 | 1004 | Patients with ACS undergoing PCI | 1-month DAPT (clopidogrel 75 mg and aspirin 75–325 mg) followed by aspirin alone | 6-month DAPT (clopidogrel 75 mg and aspirin 75–325 mg) | All-cause death, MI, or stroke | PCI: 100% | 100% |
| RESET | 2012 | 2117 | Patients undergoing PCI | 3-month DAPT (clopidogrel 75 mg and aspirin 100 mg) followed by aspirin alone | 12-month DAPT (clopidogrel 75 mg and aspirin 100 mg) | Cardiovascular death, MI, ST, ischaemia-driven TVR, or bleeding | PCI: 100% | 55% |
| SECURITY | 2014 | 1399 | Patients with stable or unstable angina undergoing PCI | 6-month DAPT (clopidogrel 75 mg and aspirin) followed by aspirin alone | 12-month DAPT (clopidogrel 75 mg and aspirin) | All-cause death, MI, stroke, definite or probable ST, BARC 3 or 5 bleeding | PCI: 100% | 38% |
| SMART-CHOICE | 2019 | 2993 | Patients with stable CAD or ACS undergoing PCI | Aspirin and a P2Y12i for 3 months followed by P2Y12i monotherapy | 12-month DAPT (aspirin and P2Y12i) | All-cause death, MI, or stroke | PCI: 100% | 58% |
| SMART-DATE | 2018 | 2712 | Patients with ACS undergoing PCI | 6-month DAPT (aspirin 100 mg and P2Y12i; clopidogrel 75 mg in 80% of patients) followed by aspirin alone | 12-month DAPT (aspirin 100 mg and P2Y12i; clopidogrel 75 mg in 80% of patients) | All-cause death, MI, or stroke | PCI: 100% | 100% |
| STOPDAPT-2 ACS | 2021 | 4136 | Patients with ACS undergoing PCI | 1-month DAPT (aspirin and clopidogrel 75 mg or prasugrel 3.75 mg) followed by clopidogrel 75 mg monotherapy | 12-month DAPT (aspirin and clopidogrel 75 mg) | Cardiovascular death, MI, definite ST, any stroke, TIMI major or minor bleeding | PCI: 100% | 100% |
| TALOS AMI | 2021 | 2697 | AMI patients without adverse events one month after successful PCI treated with aspirin and ticagrelor | Aspirin 100 mg and ticagrelor 90 mg twice daily | Aspirin 100 mg and clopidogrel 75 mg daily | Cardiovascular death, MI, stroke, or BARC type 2, 3, or 5 bleeding | PCI: 100% | 100% |
| TenBerg et al. | 2000 | 1058 | Patients with symptomatic CAD with planned PCI | VKA (INR 2.1–4.8) and aspirin 100 mg | Aspirin 100 mg | All-cause death, MI, TLR, or stroke | PCI: 100% | 0% |
| TICAB | 2019 | 1893 | Patients with stable CAD or ACS undergoing CABG | Ticagrelor 90 mg b.i.d. | Aspirin 100 mg | Cardiovascular death, MI, stroke, or repeat revascularization | CABG: 100% | 31% |
| TICO | 2020 | 3056 | Patients with ACS undergoing PCI | 3-month DAPT (clopidogrel 90 mg b.i.d. and aspirin 100 mg) followed by ticagrelor alone | 12-month DAPT (clopidogrel 90 mg b.i.d. and aspirin 100 mg) | All-cause death, MI, ST, stroke, TVR, or TIMI major bleeding | PCI: 100% | 100% |
| TREAT | 2019 | 3799 | Patients with STEMI receiving fibrinolytic therapy | Ticagrelor 90 mg b.i.d. and aspirin 75–100 mg | Clopidogrel 75 mg and aspirin 75–100 mg | Cardiovascular death, MI, or stroke | • PCI: 2132 pts, 56%• CABG: 71 pts, 1.9% | 100% |
| TRILOGY ACS | 2012 | 7243 | Patients with ACS managed conservatively | Prasugrel 10 mg (5 mg in patients >75 years old or <60 kg) and aspirin 100 mg | Clopidogrel 75 mg and aspirin 100 mg | Cardiovascular death, non-fatal MI, or non-fatal stroke | Among 7243 patients <75 years old:• PCI: 427 pts, 5.9%• CABG: 170 pts, 2.3% | 100% |
| TRITON-TIMI 38 | 2007 | 13 608 | Patients with ACS undergoing PCI | Prasugrel 10 mg and aspirin 75–162 mg | Clopidogrel 75 mg and aspirin 75–162 mg | Cardiovascular death, non-fatal MI, or non-fatal stroke | • PCI: 99%• CABG: 1% | 100% |
| TWILIGHT | 2019 | 7119 | High-risk patients undergoing PCI | 3-month DAPT (ticagrelor 90 mg b.i.d. and aspirin 81–100 mg) followed by 12-month of ticagrelor monotherapy | 3-month DAPT (ticagrelor 90 mg b.i.d. and aspirin 81–100 mg) followed by 12-month of ticagrelor and aspirin | All-cause death, non-fatal MI, non-fatal stroke | PCI: 100% | 65% |
| VACS | 1983 | 1266 | Patients with unstable angina | Aspirin 324 mg | Placebo | All-cause death or acute MI | NA | 100% |
Abbreviations: ACS, acute coronary syndrome; AMI, acute myocardial infarction; ASA, aspirin; BARC, Bleeding Academic Research Consortium; CABG, coronary artery bypass grafting; CAD, coronary artery disease; DAPT, dual antiplatelet therapy; eGFR, estimated glomerular filtration rate; HBR, high bleeding risk; INR, international normalized ratio; MI, myocardial infarction; NSTE-ACS, non-ST segment elevation acute coronary syndrome; PCI, percutaneous coronary intervention; P2Y12i, P2Y12 inhibitor; ST, stent thrombosis; STEMI, ST-segment elevation myocardial infarction; TIMI, thrombolysis in myocardial infarction; TLR, target lesion revascularization; TVR, target vessel revascularization; VKA, vitamin-K antagonist.
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