Introduction and aims Diabetic patients have increased platelet reactivity and are at an increased risk of Acute Coronary Syndromes (ACS). Furthermore, they are subject to relatively higher rates of mortality and morbidity independent of other co-morbidities. This systematic review sought to establish the optimum P2Y12 receptor antagonist therapy for this high risk population.
Methods We searched publications in databases (Medline (1946 to present) and Embase (1974 to present)) and abstracts from major cardiology conferences to 8th June 2014; for randomised control trials with clinical outcomes for P2Y12 inhibitors in adult diabetic patients with ACS. There were no date or language restrictions. Two authors independently evaluated the methodological quality of included studies and extracted the data. Meta-analysis was performed with statistical direct and indirect comparison. Studies were evaluated for the primary composite end point of cardiovascular death, non-fatal myocardial infarction and non-fatal stroke. In addition, the secondary outcome of bleeding was assessed.
Results 1162 studies were reviewed and 17 articles (7 study populations) satisfied protocol inclusion/exclusion criteria. Four studies compared clopidogrel to placebo in diabetic patients of which two had the required primary outcome data (n = 3122 patients). Results showed superiority of clopidogrel with a relative risk (RR) 0.84 (95% confidence interval (CI) 0.72–0.99). Irrespective of management strategy (invasive or medical) the newer agents prasugrel (2 studies) and ticagrelor (1 study) had a lower primary event rate compared to clopidogrel; RR 0.80 (95% CI 0.66–0.97) and RR 0.89 (95% CI 0.77–1.02) respectively. Therefore predictably both prasugrel and ticagrelor were superior when indirectly compared to placebo (Figure 1). Ticagrelor was indirectly compared to prasugrel showing a trend to an improved primary outcome with prasugrel (RR 1.11 (95% CI 0.94–1.31)) particularly in those managed with percutaneous coronary intervention (RR 1.23 (95% CI 0.95–1.59)). Prasugrel demonstrated a statistical superiority with prevention of further myocardial infarction with RR 1.48 (95% CI 1.11–1.97). This was not at the expense of increased major TIMI bleeding rates RR 0.94 (95% CI 0.59–1.51) (Figure 2).
Conclusions This meta-analysis shows that the addition of a P2Y12 Inhibitor is superior to placebo, with a trend favouring the use of prasugrel in diabetic patients with ACS, particularly those undergoing PCI. This supports the 2014 NICE (National Institute for Health and Care Excellence) guidance that determined the cost effectiveness of prasugrel to be dominant in comparison to clopidogrel.
- Acute Coronary Syndrome
- Diabetes Mellitus
- P2Y12 Receptor
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