What is the best DAPT de-escalation strategy for ACS patients undergoing PCI?

In a systematic review and network meta‐analysis, high- to low-potency dual‐antiplatelet therapy (DAPT) was associated with a 31% relative risk reduction of MACE compared with DAPT with aspirin plus clopidogrel for 12 months, with no increased bleeding risk.

This summary is based on the publication of Ullah W, Sandhyavenu H, Taha A, et al. - Antiplatelet Strategy for Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention: A Systematic Review and Network Meta‐Analysis. J Am Heart Assoc. 2024 Oct 15;13(20):e032490. doi: 10.1161/JAHA.122.032490.

Introduction and methods

Background

In patients with ACS undergoing PCI, dual‐antiplatelet therapy (DAPT) consisting of aspirin and a P2Y₁₂ inhibitor (prasugrel, ticagrelor, or clopidogrel) for 12 months is recommended (class I) by the 2021 ACC/AHA/SCAI guideline for coronary artery revascularization [1]. To mitigate the associated bleeding risk, several de-escalation strategies have been investigated, such as the use of aspirin in combination with the less potent P2Y₁₂ inhibitor clopidogrel, decreasing the dose of prasugrel, or switching to monotherapy after a mandated short duration of DAPT. Still, the optimal duration and choice of antiplatelet therapy in patients with ACS undergoing PCI remain controversial.

Aim of the study

The study aim was to assess the relative benefits and harms of DAPT de-escalation strategies in patients with ACS who have undergone PCI.

Methods

For this systematic review and network meta‐analysis, the authors performed a systematic search in the PubMed, Cochrane, and Embase databases until September 2022 to identify RCTs comparing the safety and efficacy of DAPT and any type of de-escalation strategy in patients presenting with ACS who had undergone PCI, with a follow-up duration ≥12 months.

In total, 32 studies were included (n=103,459), after which the studied treatments were categorized into 4 major strategies: (1) high‐potency DAPT (i.e., aspirin plus either prasugrel or ticagrelor) for 12 months; (2) high‐potency DAPT for 1–3 months, which was switched to low‐potency DAPT (aspirin plus clopidogrel) for a total duration of 12 months; (3) aspirin plus low‐dose prasugrel (3.75 or 5 mg instead of 10 mg) for 12 months; and (4) short-duration DAPT (i.e., discontinuation of 1 antiplatelet agent after a mandated period of DAPT). The latter category was further subdivided into 7 different strategies based on the initial duration of DAPT. For direct comparisons, the common control strategy was DAPT consisting of aspirin plus clopidogrel for 12 months.

Outcomes

The primary efficacy endpoint was MACE, defined as a composite outcome of all‐cause mortality, non-fatal MI, or non-fatal stroke. The primary safety endpoint were major bleeding events, which were mostly defined as Bleeding Academic Research Consortium score >2, major bleeding according to the Platelet Inhibition and Patient Outcomes criteria, or major bleeding according to the Thrombolysis in Myocardial Infarction criteria.

Main results

Efficacy

• Patients treated with high- to low-potency DAPT had a lower rate of MACE after a median follow-up time of 1 year than those receiving DAPT with aspirin plus clopidogrel for 12 months (risk ratio (RR): 0.69; 95%CI: 0.52–0.92), as did patients treated with DAPT with aspirin plus prasugrel for 12 months (RR: 0.84; 95%CI: 0.72–0.98).
• In contrast, DAPT for 1 month followed by clopidogrel monotherapy was associated with a higher MACE incidence compared with the control strategy (RR: 1.59; 95%CI: 1.06–2.39).
• The other comparison strategies had no significant effect on the MACE rate.

Safety

• Both DAPT containing prasugrel for 12 months (RR: 1.35; 95%CI: 1.09–1.66) and DAPT containing ticagrelor for 12 months (RR: 1.38; 95%CI: 1.17–1.62) were associated with higher rates of major bleeding at 1 year compared with the control strategy.
• Patients receiving 1-month DAPT followed by clopidogrel monotherapy had a lower major bleeding rate (RR: 0.41; 95%CI: 0.19–0.89).
• High- to low-potency DAPT did not increase the risk of major bleeding events (RR: 0.85; 95%CI: 0.63–1.15), nor did any of the other comparison strategies.

Net clinical benefit

• Overall, high- to low-potency DAPT showed the greatest beneficial effect due to a significant reduction in MACE risk with no increase in major bleeding risk, whereas 1-month DAPT followed by clopidogrel monotherapy showed the least efficacy with regard to MACE reduction, against a reduced bleeding risk.
• A bivariate outcome plot for the primary efficacy and safety endpoints visually confirmed that most de-escalation strategies were associated with a numerically lower, albeit statistically nonsignificant, risk of major bleeding events, whereas the tendency to reduce the MACE risk was heterogeneous.

Conclusion

This systematic review and network meta‐analysis of DAPT de-escalation strategies in ACS patients who have undergone PCI demonstrated high- to low-potency DAPT was associated with a 31% relative risk reduction of MACE compared with the control strategy (i.e., DAPT with aspirin plus clopidogrel for 12 months), with no increased risk of major bleeding events. In contrast, DAPT for 1 month followed by clopidogrel monotherapy showed the least efficacy with regard to MACE reduction.

Find this article online at J Am Heart Assoc.

Reference

1. Lawton JS, Tamis-Holland JE, Bangalore S, Bates ER, Beckie TM, Bischoff JM, Bittl JA, Cohen MG, DiMaio JM, Don CW, et al. 2021 ACC/AHA/SCAI guideline for coronary artery revascularization: executive summary: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2022;145:e4–e17. doi: 10.1161/CIR.0000000000001039