TABLE 1.
Randomized controlled trials testing antiplatelet de-escalation strategies in patients with acute coronary syndrome undergoing PCI.
| Study name | Number of patients enrolled | Timing of de-escalation | Primary endpoint | Limitations | Follow-up duration |
| Shortening DAPT | |||||
| Aspirin monotherapy | |||||
| DAPT-STEMI (2018) |
1,100 | 6 months | All death, MI, any revascularization, stroke, and TIMI major bleeding | Non-inferiority design Primary endpoint including both ischemic and bleeding outcomes |
18 months |
| SMART-DATE (2018) |
2,712 | 6 months | All death, MI or stroke | Non-inferiority design Short DAPT was associated with a doubled risk of MI and with a 50% increased risk of ST East Asian population |
18 months |
| REDUCE (2019) |
1,496 | 3 months | All death, MI, ST, stroke, target vessel revascularization and BARC 2–5 bleeding | Non-inferiority design Primary endpoint including both ischemic and bleeding outcomes Short DAPT was associated with a doubled risk of ST and a 62% increased risk of CV death |
12 months |
| Clopidogrel monotherapy | |||||
| STOPDAPT-2-ACS (2022) |
4,169 | 1–2 months |
CV death, MI, stroke, ST and TIMI major or minor bleeding |
Non-inferiority design Primary endpoint not met Primary endpoint including both ischemic and bleeding outcomes Short DAPT was associated with a 50% increase in the composite of CV death, MI, ST and stroke and a nearly doubled risk of MI East Asian population |
12 months |
| Ticagrelor monotherapy | |||||
| GLOBAL-LEADERS (ACS sub-study) | 3,750 | 1 month |
All death or MI |
Sub-study of a RCT |
24 months |
| TWILIGHT (ACS sub-study) |
4,614 | 3 months |
All death or MI and BARC 2–5 bleeding |
Sub-study of a RCT Primary endpoint including both ischemic and bleeding outcomes Randomization limited to uneventful patients after 3 months of standard DAPT |
15 months |
| TICO (2020) |
3,056 | 3 months |
TIMI major bleeding, all-cause death, MI, ST, stroke, and target-vessel revascularization |
Primary endpoint including both ischemic and bleeding outcomes Low ischemic risk patients East Asian population |
12 months |
| Mitigating P2Y12 inhibition | |||||
| Guided | |||||
| Platelet function-guided | |||||
| ANTARCTIC (2016) |
877 | 14 days (and 28 days) |
CV death, MI, stroke, ST, urgent revascularization and BARC 2–5 bleeding |
Primary endpoint not met Primary endpoint including both ischemic and bleeding outcomes Use of prasugrel 5 mg rather than prasugrel 10 mg Randomization 14 days after ACS |
12 months |
| TROPICAL-ACS (2017) |
2,610 | 7 days (and 14 days) |
CV death, MI, stroke, and BARC 2–5 bleeding |
Non-inferiority design Primary endpoint including both ischemic and bleeding outcomes |
12 months |
| Genotype-guided | |||||
| POPular Genetics (2019) |
2,488 | < 2 days |
Death from any cause, MI, definite ST, stroke, or major bleeding defined according to PLATO criteria and PLATO major or minor bleeding | Non-inferiority design Primary endpoint including both ischemic and bleeding outcomes |
12 months |
| Unguided | |||||
| Unguided clopidogrel | |||||
| TOPIC (2017) |
646 | 1 month |
CV death, urgent revascularization, stroke and BARC 2–5 bleeding |
Non-inferiority design Primary endpoint including both ischemic and bleeding outcomes Relatively small trial |
12 months |
| TALOS-MI (2021) |
2,697 | 1 month |
CV death, MI, stroke and BARC 2–5 bleeding |
Non-inferiority design Primary endpoint including both ischemic and bleeding outcomes East Asian population |
12 months |
| Reduced dose of P2Y12 inhibitor | |||||
| HOST-REDUCE-POLYTHEC-ACS (2020) |
3,429 | 1 month |
All death, MI, ST, repeat revascularization, stroke and BARC 2–5 bleeding |
Non-inferiority design Primary endpoint including both ischemic and bleeding outcomes East Asian population |
12 months |
ACS, acute coronary syndrome; DAPT, dual antiplatelet therapy; TIMI, Thrombolysis in Myocardial Infarction; MI, myocardial infarction; CV, cardiovascular; ST, stent thrombosis; PFT, platelet function test; BARC, Bleeding Academic Research Consortium; PLATO, Platelet Inhibition and Patient Outcomes; RCT, randomized controlled trial; PCI, percutaneous coronary intervention.