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Ticagrelor or Clopidogrel Monotherapy vs. DAPT After PCI
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- This systematic review and patient-level meta-analysis of trials compares prolonged DAPT vs. P2Y12 monotherapy with either ticagrelor or clopidogrel after 1-3 months of DAPT among patients undergoing PCI.
- When compared to DAPT, ticagrelor monotherapy was noninferior for the composite primary endpoint (HR, 0.89; 95% CI, 0.74-1.06; p for noninferiority = 0.004) and associated with significantly less bleeding (HR, 0.47; 95% CI, 0.36-0.62; p < 0.001).
- On the other hand, when compared to DAPT, clopidogrel monotherapy was inferior to DAPT (HR, 1.37; 95% CI, 1.01-1.87; for noninferiority > 0.99) for ischemic outcomes but associated with lower bleeding rates (HR, 0.49; 95% CI, 0.30-0.81; p = 0.006; p for interaction = 0.88).
Study Questions:
What are the risks and benefits of ticagrelor monotherapy or clopidogrel monotherapy compared with standard dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI)?
Methods:
Included studies were randomized clinical trials comparing P2Y12 inhibitor monotherapy with DAPT on adjudicated endpoints in patients without indication to oral anticoagulation undergoing PCI. Patient-level data provided by each trial were synthesized into a pooled dataset and analyzed using a one-step mixed-effects model. The primary objective was to determine noninferiority of ticagrelor or clopidogrel monotherapy versus DAPT on the composite of death, myocardial infarction, or stroke in the per-protocol analysis with a 1.15 margin for the hazard ratio (HR). Key secondary endpoints were major bleeding and net adverse clinical events (NACE), including the primary endpoint and major bleeding.
Results:
Analyses included six randomized trials including 25,960 patients undergoing PCI, of whom 24,394 patients (12,403 patients receiving DAPT; 8,292 patients receiving ticagrelor monotherapy; 3,654 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 endpoint (HR, 0.89; 95% confidence interval [CI], 0.74-1.06; p for noninferiority = 0.004), but clopidogrel was not noninferior (HR, 1.37; 95% CI, 1.01-1.87; p for noninferiority > 0.99), 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 < 0.001) and clopidogrel monotherapy (HR, 0.49; 95% CI, 0.30-0.81; p = 0.006; p for interaction = 0.88). NACE were lower with ticagrelor (HR, 0.74; 95% CI, 0.64-0.86, p < 0.001) but not with clopidogrel monotherapy (HR, 1.00; 95% CI, 0.78-1.28; p = 0.99; for interaction = 0.04).
Conclusions:
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 one trial that exclusively included East Asian patients and a hazard that was driven by an excess of noncardiovascular death.
Perspective:
The authors present a systematic review and patient-level meta-analysis of trials comparing prolonged DAPT versus P2Y12 monotherapy with either ticagrelor or clopidogrel after 1-3 months of DAPT among patients undergoing PCI. When compared to DAPT, ticagrelor monotherapy was noninferior for the composite primary endpoint (HR, 0.89; 95% CI, 0.74-1.06; p for noninferiority = 0 .004) and associated with significantly less bleeding (HR, 0.47; 95% CI, 0.36-0.62; p < 0.001). On the other hand, when compared to DAPT, clopidogrel monotherapy was inferior to DAPT (HR, 1.37; 95% CI, 1.01-1.87; p for noninferiority > 0.99) for ischemic outcomes but associated with lower bleeding rates (HR, 0.49; 95% CI, 0.30-0.81; p = 0.006; p for interaction = 0.88). There are several limitations that preclude broad clinical application of these findings (predominantly male cohort, considerable heterogeneity in trial design and study population). The questions surrounding optimal type and duration of antiplatelet therapy post-PCI that balances ischemic and bleeding risk remains unanswered and will need further investigation.
Clinical Topics: Invasive Cardiovascular Angiography and Intervention
Keywords: Percutaneous Coronary Intervention, Platelet Aggregation Inhibitors
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