Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials.
Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials.
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DOI：
10.1016/s0140-6736(13)60900-9
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发表时间：
2013-08-31
期刊：
影响因子：
168.9
通讯作者：
Yau, F.
中科院分区：
文献类型：
--
作者：
Bhala, N.;Emberson, J.;Merhi, A.;Abramson, S.;Arber, N.;Baron, J. A.;Bombardier, C.;Cannon, C.;Farkouh, M. E.;FitzGerald, G. A.;Goss, P.;Halls, H.;Hawk, E.;Hawkey, C.;Hennekens, C.;Hochberg, M.;Holland, L. E.;Kearney, P. M.;Laine, L.;Lanas, A.;Lance, P.;Laupacis, A.;Oates, J.;Patrono, C.;Schnitzer, T. J.;Solomon, S.;Tugwell, P.;Wilson, K.;Wittes, J.;Baigent, C.;Adelowo, O.;Aisen, P.;Al-Quorain, A.;Altman, R.;Bakris, G.;Baumgartner, H.;Bresee, C.;Carducci, M.;Chang, D-M.;Chou, C-T.;Clegg, D.;Cudkowicz, M.;Doody, L.;El Miedany, Y.;Falandry, C.;Farley, J.;Ford, L.;GarciLosa, M.;Gonzalez-Ortiz, M.;Haghighi, M.;Hala, M.;Iwama, T.;Jajic, C.;Kerr, D.;Kim, H-S.;Kohne, C.;Koo, B-K.;Martin, B.;Meinert, C.;Muller, N.;Myklebust, G.;Neustadt, D.;Omdal, R.;Ozgocmen, S.;Papas, A.;Patrignani, P.;Pelliccia, F.;Roy, V.;Schlegelmilch, I.;Umar, A.;Wahlstrom, O.;Wollheim, F.;Yocum, S.;Zhang, X. Y.;Hall, E.;McGettigan, P.;Midgley, R.;Moore, R. A.;Philipson, R.;Curtis, S.;Reicin, A.;Bond, J.;Moore, A.;Essex, M.;Fabule, J.;Morrison, B.;Tive, L.;Davies, K.;Holland, L. E.;Merhi, A.;Yau, F.
非甾体类抗炎药（NSAID），包括选择性考克斯-2抑制剂（昔布类）和传统非甾体类抗炎药（tNSAID）的血管和胃肠道效应尚未得到充分表征，尤其是在血管疾病风险增加的患者中。我们旨在通过随机试验的荟萃分析提供此类信息。我们对280项NSAID与安慰剂的试验（124513例受试者，68342人-年）和474项NSAID与另一种NSAID的试验（229296例受试者，165456人-年）进行了荟萃分析。 主要结局为主要血管事件（非致死性心肌梗死、非致死性卒中或血管性死亡）;主要冠状动脉事件（非致死性心肌梗死或冠状动脉性死亡）;卒中;死亡率;心力衰竭;和上消化道并发症（穿孔、梗阻或出血）。主要血管事件增加了约三分之一的coxib（率比[RR] 1.37，95% CI 1.14 - 1.66; p= 0.0009）或双氯芬酸（1·41，1·12-1·78; p=0·0036），主要是由于主要冠状动脉事件的增加（昔布1.76，1.31 - 2.37; p= 0.0001;双氯芬酸1.70，1.19 - 2.41; p= 0.0032）。胰岛素还显著增加了主要冠状动脉事件（2.22，1.10 - 4.48; p= 0.0253），但不增加主要血管事件（1.44，0.89 - 2.33）。与安慰剂组相比，在1000名接受昔布或双氯芬酸治疗一年的患者中，有3名多发生了主要血管事件，其中1名是致命的。萘普生未显著增加主要血管事件（0.93，0.69 - 1.27）。昔布（1.58，99% CI 1.00 - 2.49; p= 0.0103）和双氯芬酸（1.65，0.95 - 2.85，p= 0.0187）显著增加血管死亡，布洛芬（1.90，0.56 - 6.41; p= 0.17）无显著增加，但萘普生（1.08，0.48 - 2.47，p= 0.80）无显著增加。对主要血管事件的比例效应与基线特征（包括血管风险）无关。所有NSAID的心力衰竭风险大约增加一倍。所有NSAID方案均增加了上消化道并发症（昔布1.81，1.17 - 2.81，p= 0.0070;双氯芬酸1.89，1.16 - 3.09，p= 0.0106;布洛芬3.97，2.22 - 7.10，p<0.0001;萘普生4.22，2.71 - 6.56，p<0.0001）。高剂量双氯芬酸（可能还有布洛芬）的血管风险与昔布相当，而高剂量萘普生的血管风险低于其他NSAID。尽管NSAID增加了血管和胃肠道风险，但这些风险的大小是可以预测的，这有助于指导临床决策。英国医学研究理事会和英国心脏基金会。
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. 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). 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). 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. UK Medical Research Council and British Heart Foundation.