Introduction: With recent advances in interventional cardiology where percutaneous coronary intervention (PCI) has become the most preferred invasive strategy and with advances in adjunctive pharmacotherapy, several newer oral P2Y12 inhibitors have reached the market. In this analysis, we aimed to compare the cardiovascular outcomes and bleeding events which were associated with the use of cangrelor versus clopidogrel in patients with type 2 diabetes mellitus (T2DM) 48 h after PCI.
Methods: The electronic databases MEDLINE (PubMed), www.ClinicalTrials.gov , EMBASE, and Cochrane central were searched for relevant publications comparing canagrelor with clopidogrel during PCI. Patients with T2DM were extracted. Adverse cardiovascular outcomes and bleeding events at 48 h follow-up were considered as the end points. This meta-analysis was carried out with the latest RevMan software (5.30). Odds ratios (OR) and 95% confidence intervals (CI) were used to represent the data.
Results: This analysis consisted of a total number of 5031 participants with T2DM (enrolled between the years 2006 and 2012). Compared to clopidgrel, use of cangrelor in these patients with T2DM was not associated with significantly different primary end point (OR 0.94, 95% CI 0.75-1.16; P = 0.55), myocardial infarction (OR 0.96, 95% CI 0.76-1.20; P = 0.71), all-cause death (OR 0.70, 95% CI 0.25-1.96; P = 0.49), ischemia-driven revascularization (OR 0.66, 95% CI 0.32-1.36; P = 0.26), and stent thrombosis (OR 0.45, 95% CI 0.17-1.17; P = 0.10). Thrombolysis in myocardial infarction (TIMI)-defined major and minor bleedings were similarly manifested: (OR 1.02, 95% CI 0.38-2.74; P = 0.96) and (OR 1.39, 95% CI 0.70-2.79; P = 0.35), respectively. Global use of strategies to open occluded arteries (GUSTO)-defined moderate and severe bleeding were also not significantly different: (OR 1.36, 95% CI 0.70-2.67; P = 0.37) and (OR 1.21, 95% CI 0.41-3.59; P = 0.74), respectively. However, GUSTO-defined mild bleeding and acute catheterization and urgent intervention triage strategy (ACUITY)-defined major and minor bleedings were significantly in favor of clopidogrel in comparison to cangrelor in these patients with T2DM: (OR 1.28, 95% CI 1.09-1.50; P = 0.003), (OR 1.43, 95% CI 1.05-1.94; P = 0.02), and (OR 1.23, 95% CI 1.04-1.46; P = 0.02), respectively. Other bleeding outcomes were not significantly different.
Conclusions: In these patients with T2DM, cangrelor was comparable to clopidogrel in terms of efficacy at 48 h following PCI. However, it was associated with significantly higher mild GUSTO bleeding and major and minor ACUITY bleeding, therefore requiring further workups on its safety side. This hypothesis should be explored further and confirmed in other forthcoming trials based strictly on patients with T2DM.
Keywords: Antiplatelet agents; Cangrelor; Cardiovascular disease; Clopidogrel; Percutaneous coronary intervention; Type 2 diabetes mellitus.