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

Abstract

Introduction: Thienopyridines are a class of antiplatelet drugs widely used in cardiovascular disease prevention and treatment. There is recent concern regarding the safety of thienopyridines because of possible malignancy risk. Therefore, we performed a systematic review and meta-analysis to evaluate the association between thienopyridine exposure and malignancy. Methods:We searched MEDLINE and EMBASE in March 2016 for studies which evaluated incident cancer and cancer mortality with and without exposure to thienopyridines. Relevant studies were identified, data were extracted and analysed with random effects meta-analysis.Results: A total of 9 studies (6 randomised controlled trials and 3 cohort studies) with 311,595 participants were included. The cancer event rate during the study period with clopidogrel and prasugrel was 1.56%. When compared to standard aspirin or placebo, thienopyridines are not significantly associated with cancer mortality and event rate OR 1.12 [95% CI 0.80-1.56, n=3] and OR 0.92 [95% CI 0.52-1. 64, n=2] respectively. Further analyses examining clopidogrel only showed no significant association with cancer event rate or malignancy related death. When comparing prasugrel to 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. 3 Key points:• Cancer-related mortality is not linked to thienopyridines with contemporary data• Standardisation of cancer-end points in trials will reduce adjudication bias• Cohort studies can be used to supplement trial findings due to longer follow-up 4

Clopidogrel and Low-Dose Aspirin, Alone or Together, Reduce Risk of Colorectal Cancer

“…Recently, some concerns have been raised about an increase of noncardiovascular and cancer-related mortality associated with long-term (!30 mo) DAPT use (low-dose aspirin plus either clopidogrel or prasugrel). 21 Echoing such concerns, the Food and Drug Administration released a safety note in 2014 that was updated 1…”

Antithrombotic Agents and Cancer

“…In the first one, an increase in solid tumors was associated with the use of prasugrel, whereas in the second trial, higher rates of death, due to both cancer and trauma, were detected in patients treated with clopidogrel. However, a systematic review and meta-analysis on cancer event rate and mortality following thienopyridine use showed that there is no increased risk with the use of P2Y 12 -R antagonists [ 94 ]. These results supported a previous meta-analysis conducted by the Food and Drug Administration of all the long-term RCTs on dual antiplatelet therapy with aspirin and clopidogrel given for 12 months or longer, which stated that the P2Y 12 -R antagonist did not modify the risk of cancer-related deaths [ 95 ].…”

P2Y12 Receptors in Tumorigenesis and Metastasis

“…Similar results were obtained on the analysis of cancer mortality. On the whole, these data do not support concerns for a class effect of thienopyridines in increasing the cancer event rate and/or mortality ( Kotronias et al, 2017 ).…”