Do some inhibitors of COX-2 increase the risk of thromboembolic events? Linking pharmacology with pharmacoepidemiology

被引:34
作者
Clark, DWJ
Layton, D
Shakir, SAW
机构
[1] Univ Otago, Sch Med, Dept Prevent & Social Med, New Zealand Pharmacogvigilance Ctr, Dunedin, New Zealand
[2] Univ Otago, Sch Med Sci, Dept Pharmacol & Toxicol, Dunedin, New Zealand
[3] Drug Safety Res Unit, Southampton, Hants, England
[4] Univ Portsmouth, Fac Sci, Portsmouth, Hants, England
关键词
D O I
10.2165/00002018-200427070-00002
中图分类号
R1 [预防医学、卫生学];
学科分类号
1004 ; 120402 ;
摘要
Inhibitors of the cyclo-oxygenase (COX)-2 isoenzyme were developed with the expectation that their use would be accompanied by a reduction in adverse reactions thought to be mediated through COX-1 compared with conventional nonselective NSAIDs. However, the results of some clinical studies and other evidence have led to the hypothesis that use of COX-2 inhibitors may contribute to an increased risk of adverse thromboembolic (TE) events. In this review, we have evaluated the evidence from small-scale in vitro and in vivo pharmacological studies, clinical trials and large-scale pharmacoepidemiological studies and commented on the relationship between the pharmacological characteristics related to thromboembolic events and the clinical effects in large-scale clinical trials and pharmacoepidemiological studies. Overall, the pharmacological evidence suggests that a prothrombotic effect of COX-2 selective inhibitors is plausible. To date, despite the results from the Vioxx Gastrointestinal Outcome Research (VIGOR) study from which the clinical concern regarding cardiovascular TE risk arose, the published data from other randomised controlled trials (RCTs), retrospective observational studies and spontaneous reporting schemes provide a conflicting body of evidence on the TE risk with COX-2 inhibitors. Concerns that COX-2 inhibitors may be associated with prothrombotic effects remain and these need to be addressed in large scale, RCTs designed specifically to investigate the possibility of an excess of adverse cardiovascular outcomes in users of some or all selective COX-2 inhibitors, both with and without concomitant low-dose aspirin (acetylsalicylic acid). Consideration must also be given to other pathophysiological mechanisms for potential cardiovascular risk linked with inhibition of COX-2. In view of the evidence reviewed, it is recommended that selective COX-2 inhibitors should be prescribed with caution, only in patients with conditions for which these drugs have proven efficacy and with careful monitoring of outcomes and adverse events. This is particularly important in the elderly, in patients with cardiovascular/renal disease and in patients with other risk factors that might predispose them to adverse events.
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页码:427 / 456
页数:30
相关论文
共 98 条
[71]  
Rodríguez LAG, 2001, CLIN EXP RHEUMATOL, V19, pS41
[72]   Differential effects of aspirin and non-aspirin nonsteroidal antiinflammatory drugs in the primary prevention of myocardial infarction in postmenopausal women [J].
Rodríguez, LAG ;
Varas, C ;
Patrono, C .
EPIDEMIOLOGY, 2000, 11 (04) :382-387
[73]   Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis - The CLASS study: A randomized controlled trial [J].
Silverstein, FE ;
Faich, G ;
Goldstein, JL ;
Simon, LS ;
Pincus, T ;
Whelton, A ;
Makuch, R ;
Eisen, G ;
Agarwal, NM ;
Stenson, WF ;
Burr, AM ;
Zhao, WW ;
Kent, JD ;
Lefkowith, JB ;
Verburg, KM ;
Geis, GS .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2000, 284 (10) :1247-1255
[74]   Nonsteroidal anti-inflammatory drug use and acute myocardial infarction [J].
Solomon, DH ;
Glynn, RJ ;
Levin, R ;
Avorn, J .
ARCHIVES OF INTERNAL MEDICINE, 2002, 162 (10) :1099-1104
[75]  
Sperling R, 2001, ARTHRITIS RHEUM, V44, P1229, DOI 10.1002/1529-0131(200105)44:5<1229::AID-ANR209>3.0.CO
[76]  
2-E
[77]  
Stracher GB, 2002, GEOTIMES, V47, P4
[78]   Hypercoagulability in venous and arterial thrombosis [J].
Thomas, DP ;
Roberts, HR .
ANNALS OF INTERNAL MEDICINE, 1997, 126 (08) :638-644
[79]   Effect of cyclooxygenase-2 inhibition with rofecoxib on endothelial dysfunction and inflammatory markers in patients with coronary artery disease [J].
Title, LM ;
Giddens, K ;
McInerney, MM ;
McQueen, MJ ;
Nassar, BA .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2003, 42 (10) :1747-1753
[80]   Effects of cyclooxygenases inhibitors on vasoactive prostanoids and thrombin generation at the site of microvascular injury in healthy men [J].
Tuleja, E ;
Mejza, F ;
Cmiel, A ;
Szczeklik, A .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2003, 23 (06) :1111-1115