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

Significance: It remains uncertain whether the effectiveness of P2Y12 inhibitor monotherapy following a brief dual antiplatelet therapy (DAPT) regimen post-percutaneous coronary intervention (PCI) varies depending on the type of P2Y12 inhibitor used.

Objective: To evaluate the advantages and disadvantages of ticagrelor monotherapy or clopidogrel monotherapy compared to standard DAPT after PCI.

Data Sources: A search was conducted on MEDLINE, Embase, TCTMD, and the European Society of Cardiology website from inception to September 10, 2023, with no language restrictions.

Study Selection: This analysis included randomized clinical trials comparing P2Y12 inhibitor monotherapy with DAPT, focusing on adjudicated endpoints in patients without indications for oral anticoagulation undergoing PCI.

Data Extraction and Synthesis: Patient-level data from each trial were amalgamated into a pooled dataset and analyzed using a one-step mixed-effects model. The study adhered to the Preferred Reporting Items for Systematic Review and Meta-Analyses of Individual Participant Data.

Main Outcomes and Measures: The primary aim was to establish the noninferiority of ticagrelor or clopidogrel monotherapy versus DAPT concerning the composite of death, myocardial infarction (MI), or stroke, with a 1.15 margin for the hazard ratio (HR). Major bleeding and net adverse clinical events (NACE), comprising the primary endpoint and major bleeding, were key secondary endpoints.

Results: The analysis encompassed six randomized trials involving 25,960 patients undergoing PCI, with 24,394 patients retained in the per-protocol analysis (12,403 receiving DAPT; 8292 receiving ticagrelor monotherapy; 3654 receiving clopidogrel monotherapy; 45 receiving prasugrel monotherapy). Ticagrelor monotherapy trials were conducted across Asia, Europe, and North America, whereas clopidogrel monotherapy trials were exclusively conducted in Asia. Ticagrelor demonstrated noninferiority to DAPT for the primary endpoint (HR, 0.89; 95% CI, 0.74-1.06; P for noninferiorityโ€‰=โ€‰.004), whereas clopidogrel did not (HR, 1.37; 95% CI, 1.01-1.87; P for noninferiorityโ€‰>โ€‰.99), primarily due to noncardiovascular death. Both ticagrelor (HR, 0.47; 95% CI, 0.36-0.62; Pโ€‰<โ€‰.001) and clopidogrel monotherapy (HR, 0.49; 95% CI, 0.30-0.81; Pโ€‰=โ€‰.006; P for interactionโ€‰=โ€‰0.88) were associated with lower major bleeding risk. NACE were reduced with ticagrelor (HR, 0.74; 95% CI, 0.64-0.86, Pโ€‰<โ€‰.001) but not with clopidogrel monotherapy (HR, 1.00; 95% CI, 0.78-1.28; Pโ€‰=โ€‰.99; P for interactionโ€‰=โ€‰.04).

Conclusion and Relevance: This systematic review and meta-analysis indicate that ticagrelor monotherapy is noninferior to DAPT for all-cause death, MI, or stroke and superior for major bleeding and NACE. Clopidogrel monotherapy also reduced bleeding but was not noninferior to DAPT for all-cause death, MI, or stroke, primarily due to observations in one trial involving exclusively East Asian patients and an excess of noncardiovascular death hazard.

https://jamanetwork.com/journals/jamacardiology/article-abstract/2816711


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