Cancer Event Rate and Mortality with Thienopyridines: A Systematic Review and Meta-Analysis

Introduction Thienopyridines are a class of antiplatelet drugs widely used in cardiovascular disease prevention and treatment. A recent concern has come to light regarding the safety of thienopyridines because of the possible risk of malignancy. We therefore performed a systematic review and meta-analysis to evaluate the association between thienopyridine exposure and malignancy. Method We searched the MEDLINE and EMBASE databases in March 2016 for studies that evaluated incident cancer and cancer mortality with and without exposure to thienopyridines. Relevant studies were identified, and data were extracted and analysed using random-effects meta-analysis. Result A total of nine studies (six randomised controlled trials and three cohort studies) that included 282,084 participants were included. The cancer event rate with clopidogrel and prasugrel was 3.25% and 1.58% respectively. When compared with standard aspirin or placebo, thienopyridines are not significantly associated with cancer mortality and event rate (odds ratio [OR] 1.12, 95% confidence interval [CI] 0.80-1.56, n = 3; and OR 0.92, 95% CI 0.52-1.64, n = 2, respectively. Further analyses examining clopidogrel showed no significant association with cancer event rate or malignancy-related death. When comparing prasugrel with clopidogrel, no significant association was noted for cancer event rate (OR 1.10, 95% CI 0.89-1.37, n = 2]. Subanalyses according to cancer location showed that thienopyridines are not significantly associated with malignancy mortality and/or incidence. Conclusions Our results suggest that there is currently insufficient evidence to suggest that thienopyridine exposure is associated with an increased risk of cancer event rate or mortality.