Lancet：常服止痛药增加心血管病风险

一个国际研究小组通过大规模调查发现，长期服用一些常规止痛药可能增加心血管疾病风险。研究人员提醒，关节炎患者等需长期服止痛药的人群更应注意保持良好生活习惯，控制此类风险。

英国牛津大学等机构研究人员在新一期《柳叶刀》杂志发表论文说，他们调查了超过35万人的医疗记录，考察了服用常规止痛药与心血管疾病间的关系。结果发现，长期服用双氯芬酸或布洛芬等非甾体抗炎药的人群患心脏病、中风等心血管疾病的风险会有所增加，特别是有相关病史或高血压等致病因素的人，其心血管疾病发病风险会更高。

领导这项研究的牛津大学教授科林·贝金特说，平均来看，每千名有心血管疾病患病风险的人中，每年会有8人发病，但如果这些人每天服用2400毫克布洛芬或150毫克双氯芬酸，则一年内会有11人发作心脏病或中风，且死亡率可高达三分之一。

研究人员说，关节炎患者等人群往往长期、大量服用止痛药物，因此他们更需注意戒烟、保持健康饮食、定期量血压等，以尽量降低心血管疾病风险。而医生在为患者选择止痛药物时也应注意考量其副作用。

不过研究人员也指出，这项研究只显示长期服用止痛药会增加心血管疾病风险，为缓解肌肉酸痛等而短期、低剂量服用止痛药者不必担心此类风险。

Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials

Coxib and traditional NSAID Trialists' (CNT) Collaboration

Background The vascular and gastrointestinal effects of non-steroidal anti-inflammatory drugs (NSAIDs), including selective COX-2 inhibitors (coxibs) and traditional non-steroidal anti-inflammatory drugs (tNSAIDs), are not well characterised, particularly in patients at increased risk of vascular disease. We aimed to provide such information through meta-analyses of randomised trials. Methods We undertook meta-analyses of 280 trials of NSAIDs versus placebo (124 513 participants, 68 342 person-years) and 474 trials of one NSAID versus another NSAID (229 296 participants, 165 456 person-years). The main outcomes were major vascular events (non-fatal myocardial infarction, non-fatal stroke, or vascular death); major coronary events (non-fatal myocardial infarction or coronary death); stroke; mortality; heart failure; and upper gastrointestinal complications (perforation, obstruction, or bleed). Findings Major vascular events were increased by about a third by a coxib (rate ratio [RR] 1·37, 95% CI 1·14—1·66; p=0·0009) or diclofenac (1·41, 1·12—1·78; p=0·0036), chiefly due to an increase in major coronary events (coxibs 1·76, 1·31—2·37; p=0·0001; diclofenac 1·70, 1·19—2·41; p=0·0032). Ibuprofen also significantly increased major coronary events (2·22, 1·10—4·48; p=0·0253), but not major vascular events (1·44, 0·89—2·33). Compared with placebo, of 1000 patients allocated to a coxib or diclofenac for a year, three more had major vascular events, one of which was fatal. Naproxen did not significantly increase major vascular events (0·93, 0·69—1·27). Vascular death was increased significantly by coxibs (1·58, 99% CI 1·00—2·49; p=0·0103) and diclofenac (1·65, 0·95—2·85, p=0·0187), non-significantly by ibuprofen (1·90, 0·56—6·41; p=0·17), but not by naproxen (1·08, 0·48—2·47, p=0·80). The proportional effects on major vascular events were independent of baseline characteristics, including vascular risk. Heart failure risk was roughly doubled by all NSAIDs. All NSAID regimens increased upper gastrointestinal complications (coxibs 1·81, 1·17—2·81, p=0·0070; diclofenac 1·89, 1·16—3·09, p=0·0106; ibuprofen 3·97, 2·22—7·10, p<0·0001; and naproxen 4·22, 2·71—6·56, p<0·0001). Interpretation The vascular risks of high-dose diclofenac, and possibly ibuprofen, are comparable to coxibs, whereas high-dose naproxen is associated with less vascular risk than other NSAIDs. Although NSAIDs increase vascular and gastrointestinal risks, the size of these risks can be predicted, which could help guide clinical decision making.