Comparative Effectiveness of Ticagrelor vs. Prasugrel in Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention
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Background
Ticagrelor and prasugrel are recommended P2Y₁₂ inhibitors for patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI), yet uncertainty persists regarding their direct comparative evidence and guideline recommendations differ.
Methods
We conducted a multinational retrospective new-user cohort study across 7 claims and electronic health record databases. Adults with ACS undergoing first PCI who initiated ticagrelor or prasugrel were included; patients with prior major ischemic or hemorrhagic events or oral anticoagulant use were excluded. The primary outcome was 1-year major adverse cardiovascular events (MACE: all-cause mortality, acute myocardial infarction, or stroke). Secondary outcomes included net adverse clinical events (NACE) and individual components. Propensity scores were estimated using large-scale L1-regularized logistic regression and applied through stratification. Prespecified diagnostics (covariate balance, empirical equipoise, and systematic error) determined eligibility of each database for inclusion in meta-analysis. Database-specific hazard ratios (HRs) were combined using Bayesian random-effects meta-analysis.
Results
Among 7 participating databases, 3 met prespecified diagnostic criteria and were included in the primary meta-analysis, comprising 133,718 patients from one nationwide Korean claims database and two U.S. commercial claims databases (ticagrelor, 109,639; prasugrel, 24,079). For 1-year MACE, the pooled HR for ticagrelor versus prasugrel was 1.28 (95% credible interval [CrI], 0.89–1.88), with substantial between-database heterogeneity. Sensitivity analyses across alternative time-at-risk definitions and propensity score matching were consistent. No statistically credible differences were observed for NACE (HR 1.23, CrI 0.88–1.75), all-cause mortality (HR 1.17, CrI 0.78–1.77), cardiovascular mortality (HR 1.23, CrI 0.81–1.87), ischemic events (HR 1.28, CrI 0.88–1.90), hemorrhagic events (HR 1.01, CrI 0.72–1.39), acute myocardial infarction (HR 1.30, CrI 0.88–1.94), stroke (HR 1.09, CrI 0.73– 1.58), or gastrointestinal bleeding (HR 1.04, CrI 0.77–1.41). In a post hoc meta-analysis restricted to the two U.S. databases, the pooled HR for 1-year MACE was 1.49 (95% CrI 1.05–2.10).
Conclusions
In this pre-specified multinational observational study, no statistically credible difference in 1-year MACE was observed between ticagrelor and prasugrel in patients with ACS undergoing PCI. However, substantial cross-database heterogeneity warrants further investigation into context-specific comparative effectiveness and safety.
CLINICAL PERSPECTIVE
What is new?
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In a multinational new-user active comparator study across one nationwide Korean claims database and two U.S. commercial claims databases, ticagrelor and prasugrel did not show a statistically credible overall difference in 1-year MACE after PCI for ACS.
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Despite a prespecified protocol, standardized execution, and empirical calibration, substantial cross-database heterogeneity was observed, with neutral estimates in Korea and prasugrel-favoring ischemic signals in U.S. databases.
What are the clinical implications?
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These findings do not support superiority of ticagrelor or prasugrel for 1-year MACE across all health-care settings.
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Substantial cross-database heterogeneity argues against assuming that the comparative effectiveness and safety of ticagrelor and prasugrel are uniform across populations and care settings.
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Selection between ticagrelor and prasugrel should remain individualized, integrating individual patient risk profiles and local care considerations rather than presume a universally preferred agent.
