Kotronias Rafail Angelos, Kwok Chun Shing, Wong Chun Wai, Kinnaird Tim, Zaman Azfar, Mamas Mamas A
Keele Cardiovascular Research Group, Keele University, Stoke-on-Trent, UK.
Oxford University Clinical Academic Graduate School, Oxford University, Oxford, UK.
Drug Saf. 2017 Mar;40(3):229-240. doi: 10.1007/s40264-016-0481-2.
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.
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.
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.
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.
噻吩并吡啶类是一类广泛用于心血管疾病预防和治疗的抗血小板药物。由于可能存在的恶性肿瘤风险,近期噻吩并吡啶类药物的安全性受到关注。因此,我们进行了一项系统评价和荟萃分析,以评估噻吩并吡啶类药物暴露与恶性肿瘤之间的关联。
我们于2016年3月检索了MEDLINE和EMBASE数据库,查找评估有或无噻吩并吡啶类药物暴露情况下的新发癌症和癌症死亡率的研究。识别出相关研究,并使用随机效应荟萃分析提取和分析数据。
共纳入9项研究(6项随机对照试验和3项队列研究),涉及282,084名参与者。氯吡格雷和普拉格雷的癌症事件发生率分别为3.25%和1.58%。与标准阿司匹林或安慰剂相比,噻吩并吡啶类药物与癌症死亡率和事件发生率无显著关联(优势比[OR]分别为1.12,95%置信区间[CI]为0.80 - 1.56,n = 3;以及OR为0.92,95%CI为0.52 - 1.64,n = 2)。进一步分析氯吡格雷显示,其与癌症事件发生率或恶性肿瘤相关死亡无显著关联。将普拉格雷与氯吡格雷比较时,癌症事件发生率无显著关联(OR为1.10,95%CI为0.89 - 1.37,n = 2)。根据癌症部位进行的亚组分析表明,噻吩并吡啶类药物与恶性肿瘤死亡率和/或发病率无显著关联。
我们的结果表明,目前尚无足够证据表明噻吩并吡啶类药物暴露与癌症事件发生率或死亡率增加有关。