Key result
Ticagrelor shows no benefit over prasugrel for 12-month major cardiovascular events in diabetic patients undergoing PCI.
Why the study?
Although prasugrel is preferred over ticagrelor after PCI, its applicability to patients with diabetes remained unresolved, and no prior meta-analysis had pooled all available contemporary RCTs in diabetes.
Does ticagrelor reduce major adverse cardiovascular events (death, myocardial infarction, or stroke) compared to prasugrel in patients with diabetes undergoing percutaneous coronary intervention?
Meta-Analysis (n=2,942)
Randomized controlled trials
Does ticagrelor reduce major adverse cardiovascular events (death, myocardial infarction, or stroke) compared to prasugrel in patients with diabetes undergoing percutaneous coronary intervention?
In patients with diabetes undergoing PCI, ticagrelor and prasugrel result in comparable 12-month rates of MACE and major bleeding, indicating that the ischemic advantage of prasugrel seen in the general PCI population does not extend to diabetic patients.
Answers are grounded in this paper and cite their sources.
Comparable MACE rates support either agent in diabetic PCI patients; challenges extension of prasugrel's ischemic advantage to this subgroup.
Background: Prasugrel is preferred over ticagrelor after percutaneous coronary intervention (PCI), a position reinforced by a recent network meta-analysis of 15 randomized controlled trials (RCTs) reporting fewer major adverse cardiovascular events (MACE) with prasugrel. Its applicability to diabetes remains unresolved: in the ISAR-REACT 5 trial, the prasugrel advantage was restricted to patients without diabetes (significant treatment-by-diabetes interaction), and no prior meta-analysis has pooled all the available contemporary RCTs in diabetes. Hypothesis: Prasugrel’s ischemic advantage in the overall PCI population is absent in patients with diabetes, in whom ticagrelor and prasugrel confer comparable ischemic and bleeding outcomes. Methods: We searched PubMed, Embase, and Cochrane through May 2026 and identified three RCTs comparing prasugrel with ticagrelor in patients with diabetes undergoing PCI. These included the prespecified diabetic substudy of ISAR-REACT 5, the diabetic stratum of PRAGUE-18, and TUXEDO-2, the first trial restricted to diabetes. Endpoints, assessed at 12 months, were the ischemic composite of death, myocardial infarction, or stroke (MACE) and major bleeding (BARC types 3-5). Hazard ratios (HRs) were pooled using random-effects models with prediction intervals; heterogeneity was assessed using I2, and robustness was evaluated with leave-one-out analysis. Results: Among 2,942 patients with diabetes (1,488 ticagrelor, 1,454 prasugrel), MACE did not differ between agents (pooled HR, 1.02; 95% CI, 0.78-1.33; P =.90; I 2 =0%) and was unchanged on leave-one-out analysis. Major bleeding (BARC 3-5) was numerically higher with ticagrelor but nonsignificant (pooled HR, 1.30; 95% CI, 0.93-1.81; P =.12; I 2 =0%). Conclusions: Consistent with our hypothesis, ticagrelor and prasugrel were comparable for ischemic events in patients with diabetes undergoing PCI, with no significant difference in major bleeding. The prasugrel advantage evident in the overall population does not extend to diabetes, where antiplatelet selection may instead be governed by bleeding risk, tolerability, and cost.
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Mahajan et al. (2026) conducted a meta-analysis in Diabetes undergoing percutaneous coronary intervention (n=2,942). Ticagrelor vs. Prasugrel was evaluated on Ischemic composite of death, myocardial infarction, or stroke (MACE) (HR 1.02, 95% CI 0.78-1.33, p=.90). Ticagrelor and prasugrel resulted in comparable 12-month major cardiovascular events rates in patients with diabetes undergoing PCI.
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