Ticagrelor or Clopidogrel Monotherapy vs Dual Antiplatelet Therapy After Percutaneous Coronary Intervention
Authors: Valgimigli Marco , Gragnano Felice , Branca Mattia , Franzone Anna , da Costa Bruno R. , Baber Usman , Kimura Takeshi , Jang Yangsoo , Hahn Joo-Yong , Zhao Qiang , Windecker Stephan , Gibson Charles M. , Watanabe Hirotoshi , Kim Byeong-Keuk , Song Young Bin , Zhu Yunpeng , Vranckx Pascal , Mehta Shamir , Ando Kenji , Hong Sung Jin , Gwon Hyeon-Cheol , Serruys Patrick W. , Dangas George D. , McFadden Eùgene P. , Angiolillo Dominick J. , Heg Dik , Calabrò Paolo , Jüni Peter , Mehran Roxana ,   Single Versus Dual Antiplatelet Therapy (Sidney-3) Collaboration
Published: March 2024

Importance

Among patients undergoing percutaneous coronary intervention (PCI), it remains unclear whether the treatment efficacy of P2Y12 inhibitor monotherapy after a short course of dual antiplatelet therapy (DAPT) depends on the type of P2Y12 inhibitor.

Objective

To assess the risks and benefits of ticagrelor monotherapy or clopidogrel monotherapy compared with standard DAPT after PCI.

Data Sources

MEDLINE, Embase, TCTMD, and the European Society of Cardiology website were searched from inception to September 10, 2023, without language restriction.

Study Selection

Included studies were randomized clinical trials comparing P2Y12 inhibitor monotherapy with DAPT on adjudicated end points in patients without indication to oral anticoagulation undergoing PCI.

Data Extraction and Synthesis

Patient-level data provided by each trial were synthesized into a pooled dataset and analyzed using a 1-step mixed-effects model. The study is reported following the Preferred Reporting Items for Systematic Review and Meta-Analyses of Individual Participant Data.

Main Outcomes and Measures

The primary objective was to determine noninferiority of ticagrelor or clopidogrel monotherapy vs DAPT on the composite of death, myocardial infarction (MI), or stroke in the per-protocol analysis with a 1.15 margin for the hazard ratio (HR). Key secondary end points were major bleeding and net adverse clinical events (NACE), including the primary end point and major bleeding.

Results

Analyses included 6 randomized trials including 25 960 patients undergoing PCI, of whom 24 394 patients (12 403 patients receiving DAPT; 8292 patients receiving ticagrelor monotherapy; 3654 patients receiving clopidogrel monotherapy; 45 patients receiving prasugrel monotherapy) were retained in the per-protocol analysis. Trials of ticagrelor monotherapy were conducted in Asia, Europe, and North America; trials of clopidogrel monotherapy were all conducted in Asia. Ticagrelor was noninferior to DAPT for the primary end point (HR, 0.89; 95% CI, 0.74-1.06; P for noninferiority = .004), but clopidogrel was not noninferior (HR, 1.37; 95% CI, 1.01-1.87; P for noninferiority &amp;gt; .99), with this finding driven by noncardiovascular death. The risk of major bleeding was lower with both ticagrelor (HR, 0.47; 95% CI, 0.36-0.62; P &amp;lt; .001) and clopidogrel monotherapy (HR, 0.49; 95% CI, 0.30-0.81; P = .006; P for interaction = 0.88). NACE were lower with ticagrelor (HR, 0.74; 95% CI, 0.64-0.86, P &amp;lt; .001) but not with clopidogrel monotherapy (HR, 1.00; 95% CI, 0.78-1.28; P = .99; P for interaction = .04).

Conclusions and Relevance

This systematic review and meta-analysis found that ticagrelor monotherapy was noninferior to DAPT for all-cause death, MI, or stroke and superior for major bleeding and NACE. Clopidogrel monotherapy was similarly associated with reduced bleeding but was not noninferior to DAPT for all-cause death, MI, or stroke, largely because of risk observed in 1 trial that exclusively included East Asian patients and a hazard that was driven by an excess of noncardiovascular death.