Lancet:非甾体类抗炎药增加血管和消化道风险

　　英国一项荟萃分析表明，大剂量双氯芬酸的血管风险与昔布类相当，布洛芬可能亦为如此，大剂量萘普生的相关性血管风险则低于其他非甾体类抗炎药（NSAID）。尽管这种药物增加血管和消化道危险，但这些危险的大小可预测，进一步指导临床决策。论文于5月30日在线发表于《柳叶刀》（Lancet）。

　　此项荟萃分析共纳入280项NSAID与安慰剂的对比试验（124513例受试者，68342人年），以及474项一种NSAID与其他NSAID的对比试验（229296例受试者，165456人年）。主要转归为严重血管事件（非致命性心肌梗死、非致命性卒中或血管性死亡）、严重冠脉时间（非致命性心肌梗死或冠脉性死亡）、卒中、死亡、心力衰竭和上消化道并发症（穿孔、梗阻或出血）。

　　结果显示，昔布类[比率（RR）1.37]或双氯芬酸（RR 1.41）使严重血管事件增加约1/3，主要归咎于严重冠脉事件增多。

　　布洛芬亦可显著增加严重冠脉事件（RR 2.22，P=0•0253），但未增加严重血管事件。

　　与安慰剂相比，在1000例接受为期1年昔布类或双氯芬酸治疗的患者中，严重血管事件患者增加3例，其中1例为致命性。萘普生未显著增加严重血管事件。昔布类（RR 1.58）和双氯芬酸（RR 1.65）可显著增加血管性死亡，布洛芬致上述效应不显著，萘普生则无此效应。严重血管事件的比例效应独立于包括血管风险在内的基线特征。

　　所有NSAID均大致使心衰风险倍增。所有NSAID治疗均使上消化道并发症增多（昔布类、双氯芬酸、布洛芬、萘普生RR分别为1.81、1.89、3.97和4.22）。

　　NSAID主要血管和冠脉事件的危险表

　　注：图表来源于Medscape报道（Risk for CVD Events with NSAIDs Can Be Predicted）

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

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.