Influence of diabetes on platelet inhibition in patients with acute coronary syndrome treated with prasugrel or ticagrelor

Background Patients with diabetes are at an increased risk of ischaemic events following percutaneous coronary intervention (PCI) and may benefit from more intensive antiplatelet therapy. While prasugrel has been shown to inhibit platelets more effectively than ticagrelor in patients with acute coronary syndromes (ACS) who are managed invasively, it is unclear whether diabetes affects this differential effect. Purpose To evaluate platelet reactivity in patients with and without diabetes treated with prasugrel or ticagrelor. Methods The ISAR-REACT 5 was a randomized controlled trial of prasugrel- versus ticagrelor-based strategy with a pre-specified analysis according to the presence or absence of diabetes mellitus. Eligible for the platelet function sub-study were patients who were P2Y12 inhibitor-naïve and underwent PCI in 2 study centres. Patients who received glycoprotein IIb/IIIa inhibitors were excluded. The platelet function test (PFT) was assessed by Multiplate analyzer within 24 hours after receipt of the loading dose (LD) of the assigned treatment. The primary endpoint was adenosine diphosphate (ADP)-induced platelet aggregation expressed in aggregation units [AU] x min. Secondary endpoints included ischemic events (composite of death, myocardial infarction, or stroke) and bleeding events (BARC type 3-5) at 12 months. Results A total of 597 patients were included, of whom 129 with and 468 without diabetes. Patients with diabetes exhibited an overall higher cardiovascular risk profile compared with those without diabetes, characterized by a higher prevalence of hypertension and prior PCI, more frequent use of aspirin, angiotensin-converting enzyme inhibitors, and statins, but a lower likelihood of current smoking. The ADP-induced platelet aggregation at baseline did not differ between patients with and without diabetes (880 [25th; 75th percentiles, 565;1097] vs. 826 [608;1110] AU x min, respectively, p = 0.92). The presence of diabetes did not affect inhibition of platelet aggregation by prasugrel (102 [57.8;142] vs. 106 [58.8;183] AU x min for no diabetes, p = 0.34) by ticagrelor (130 [75.0;213] vs. 138 [78.5;207] AU x min for no diabetes, p = 0.61), p for interaction = 0.68. The 12-month rate of ischemic events was 14.9% among patients with diabetes and 13.1% among those without diabetes treated with prasugrel, and 13.1% and 14.2%, respectively, among patients treated with ticagrelor (p for interaction = 0.14). Bleeding rates among patients with and without diabetes were 13.4% and 5.5% with prasugrel, and 11.5% and 8.9% with ticagrelor, respectively (p for interaction = 0.31). Conclusions Among patients with ACS undergoing PCI, the presence of diabetes did not affect the inhibition of platelet aggregation achieved through randomised treatment with prasugrel or ticagrelor.