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Meta-Analysis
. 2024 May 1;9(5):437-448.
doi: 10.1001/jamacardio.2024.0133.

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

Marco Valgimigli  1   2 , Felice Gragnano  3 , Mattia Branca  4 , Anna Franzone  5 , Bruno R da Costa  6 , Usman Baber  7 , Takeshi Kimura  8 , Yangsoo Jang  9 , Joo-Yong Hahn  10 , Qiang Zhao  11 , Stephan Windecker  2 , Charles M Gibson  12 , Hirotoshi Watanabe  8 , Byeong-Keuk Kim  13 , Young Bin Song  10 , Yunpeng Zhu  11 , Pascal Vranckx  14 , Shamir Mehta  15   16 , Kenji Ando  17 , Sung Jin Hong  13 , Hyeon-Cheol Gwon  10 , Patrick W Serruys  18 , George D Dangas  19 , Eùgene P McFadden  20   21 , Dominick J Angiolillo  22 , Dik Heg  4 , Paolo Calabrò  3 , Peter Jüni  6 , Roxana Mehran  19 ; Single Versus Dual Antiplatelet Therapy (Sidney-3) Collaboration
Affiliations
Meta-Analysis

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

Marco Valgimigli et al. JAMA Cardiol. .

Abstract

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 > .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.

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Conflict of interest statement

Conflict of Interest Disclosures: Drs Branca and Heg reported being employed by CTU Bern, University of Bern, which has a staff policy of not accepting honoraria or consultancy fees; however, CTU Bern is involved in design, conduct, or analysis of clinical studies funded by not-for-profit and for-profit organizations, including pharmaceutical and medical device companies. Dr Baber reported receiving personal fees from Amgen, Boston Scientific, AstraZeneca, and Abbott outside the submitted work. Dr Kimura reported receiving grants from Abbott during the conduct of the study. Dr Windecker reported receiving grants from Abbott, Abiomed, Amgen, AstraZeneca, Bayer, B. Braun, Biotronik, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardinal Health, CardioValve, Corids Medical, Corflow Therapeutics, CSL Behring, Daichi Sankyo, Edwards Lifesciences, Farapulse, Fumedica, Guerbet, Idorsia, Inari Medical, InfraRedx, Janssen-Cilag, Johnson & Johnson, Medalliance, Meducure, Medtronic, Merck Sharp & Dohm, Miracor Medical, Novartis, NovoNordisk, Organon, OrPha Suisse, Pharming Tech, Pfizer, Polares, Regeneron, Sanofi Aventis, Servier, Sinomed, Terumo, Vifor, and V-Wave (paid to institution) during the conduct of the study; and serving as an advisory board member, or member of the steering or executive group of trials funded by Abbott, Abiomed, Amgen, AstraZeneca, Bayer, Boston Scientific, Biotronik, Bristol Myers Squibb, Edwards Lifesciences, MedAlliance, Medtronic, Novartis, Polares, Recardio, Sinomed, Terumo, and V-Wave (with payments to the institution but no personal payments) and as an unpaid member of the Pfizer Research Award selection committee in Switzerland, Clinical Study Group of the Deutsches Zentrum für Herz Kreislauf-Forschung, and Advisory Board of the Australian Victorian Heart Institute; serving as vice president of the European Society of Cardiology and associate editor of JACC: Cardiovascular Interventions. Dr Gibson reported receiving personal fees from Bayer, Johnson and Johnson, Janssen, and AstraZeneca during the conduct of the study. Dr Watanabe reported receiving personal fees from Daiichi Sankyo, Pfizer, and Abbott outside the submitted work. Dr Vranckx reported receiving personal fees from AstraZeneca, Bayer, Daiichy Sankyo, Bristol Myers Squibb-Pfizer Alliance, Bristol Myers Squibb-Janssen Alliance, CSL Behring, and Novartis outside the submitted work. Dr Mehta reported receiving grants from Abbott, Amgen, and Janssen outside the submitted work. Dr Serruys reported receiving personal fees from SMT, Novartis, Merillife, Xeltis, and Philips/Volcano outside the submitted work. Dr McFadden reported receiving personal fees from Cardialysis BV Netherlands during the conduct of the study. Dr Angiolillo reported receiving personal fees from Abbott, Amgen, AstraZeneca, Bayer, Biosensors, Boehringer Ingelheim, Bristol-Myers Squibb, Chiesi, CSL Behring, Daiichi Sankyo, Eli Lilly, Haemonetics, Janssen, Merck, Novartis, PhaseBio, PLx Pharma, Pfizer, Sanofi, and Vectura and grants from Amgen, AstraZeneca, Bayer, Biosensors, Celo-Nova, CSL Behring, Daiichi Sankyo, Eisai, Eli Lilly, Gilead, Idorsia, Janssen, Matsutani Chemical Industry, Merck, Novartis, and the Scott R. MacKenzie Foundation (paid to institution) outside the submitted work. Dr Jüni reported serving as an unpaid member of steering groups for Abbott Vascular, and Terumo; serving as a paid expert witness for Hicks Morley Hamilton Stewart Storie, City of Toronto, and Baker McKenzie outside the submitted work. Dr Mehran reported receiving grants from Bayer, Boston Scientific, and Abbott outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Kaplan-Meier Estimates for Clinical Outcomes in Patients Receiving Ticagrelor Monotherapy or Dual Antiplatelet Therapy (DAPT)
BARC indicates Bleeding Academic Research Consortium; HR, hazard ratio.
Figure 2.
Figure 2.. Kaplan-Meier Estimates for Clinical Outcomes in Patients Receiving Clopidogrel Monotherapy or Dual Antiplatelet Therapy (DAPT)
BARC indicates Bleeding Academic Research Consortium; HR, hazard ratio.
See this image and copyright information in PMC

References

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