Systematic review and meta-analysis of optimal P2Y(12) blockade in dual antiplatelet therapy for patients with diabetes with acute coronary syndrome

BACKGROUND: Patients with diabetes are at increased risk of acute coronary syndromes (ACS) and their mortality and morbidity outcomes are significantly worse following ACS events, independent of other comorbidities. This systematic review sought to establish the optimum management strategy with focus on P2Y(12) blockade in patients with diabetes with ACS. METHODS: MEDLINE (1946 to present) and EMBASE (1974 to present) databases, abstracts from major cardiology conferences and previously published systematic reviews were searched to June 2014. Relevant randomised control trials with clinical outcomes for P2Y(12) inhibitors in adult patients with diabetes with ACS were scrutinised independently by 2 authors with applicable data was extracted for primary composite end point of cardiovascular death, myocardial infarction (MI) and stroke; enabling calculation of relative risks with 95% CI with subsequent direct and indirect comparison. RESULTS: Four studies studied clopidogrel in patients with diabetes, with two (3122 patients) having primary outcome data showing superiority of clopidogrel against placebo with RR0.84 (95% CI 0.72–0.99). Irrespective of management strategy, the newer agents prasugrel (2 studies) and ticagrelor (1 study) had a lower primary event rate compared with clopidogrel; RR 0.80 (95% CI 0.66 to 0.97) and RR 0.89 (95% CI 0.77 to 1.02), respectively. When ticagrelor was indirectly compared with prasugrel, there was a trend to an improved primary outcome with prasugrel (RR 1.11 (95% CI 0.94 to 1.31)) particularly in those managed with percutaneous coronary intervention (PCI) (RR 1.23 (95% CI 0.95 to 1.59)). Prasugrel demonstrated a statistical superiority with prevention of further MI with RR 1.48 (95% CI 1.11 to 1.97). This was not at the expense of increased major thrombolysis in MI (TIMI) bleeding rates RR 0.94 (95% CI 0.59 to 1.51). CONCLUSIONS: This meta-analysis shows the addition of a P2Y(12) inhibitor is superior to placebo, with a trend favouring the use of prasugrel in patients with diabetes with ACS, particularly those undergoing PCI.