Ticagrelor or Clopidogrel Monotherapy vs Dual Antiplatelet Therapy after Percutaneous Coronary Intervention: A Systematic Review and Patient-Level Meta-Analysis

Marco Valgimigli, Felice Gragnano, Mattia Branca, Anna Franzone, Bruno R. Da Costa, Usman Baber, Takeshi Kimura, Yangsoo Jang, Joo Yong Hahn, Qiang Zhao, Stephan Windecker, Charles M. Gibson, Hirotoshi Watanabe, Byeong Keuk Kim, Young Bin Song, Yunpeng Zhu, Pascal Vranckx, Shamir Mehta, Kenji Ando, Sung Jin HongHyeon Cheol Gwon, Patrick W. Serruys, George D. Dangas, Eùgene P. McFadden, Dominick J. Angiolillo, Dik Heg, Paolo Calabrò, Peter Jüni, Roxana Mehran

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Importance: Among patients undergoing percutaneous coronary intervention (PCI), it remains unclear whether the treatment efficacy of P2Y12inhibitor monotherapy after a short course of dual antiplatelet therapy (DAPT) depends on the type of P2Y12inhibitor. 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 P2Y12inhibitor 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 25960 patients undergoing PCI, of whom 24394 patients (12403 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 >.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 <.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 <.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.

Original languageEnglish
Pages (from-to)437-448
Number of pages12
JournalJAMA Cardiology
Issue number5
StatePublished - 8 May 2024


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