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MSM

Health News Archive 232 - Arthritis
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COX-II Drug for Arthritis - Celebrex - Doubles Heart Attack Risk

A study by the Medical Research Institute of New Zealand and published in the March issue of the Journal of the Royal Society of Medicine found an increased risk of heart attack in patients taking Celebrex, a COX-2 inhibitor used to treat arthritis pain. Professor Richard Beasley of the Medical Institute recommended that regulators should re-examine the drug in light of the findings.

The research included two meta analysis.  In the first, 4,422 patients in four placebo-controlled studies showed a 2.25 times greater risk of heart attack taking celebrex than placebo, but no significant increase in the risk of cardiovascular deaths or stroke.  The second meta analysis included six studies of 12,780 patients and found almost double (1.88X) greater risk of heart attacks when Celebrex was compared with other treatments, including ibuprofen and paracetamol. Two other COX-2 drugs, Pfizer's Bextra and Merck's Vioxx, have been withdrawn from the market because of safety concerns.

Alternatives which lubricate the joints, increase cartilage growth, and increase cushioning in the joints include cetyl myristoleate (CMO), glucosamine and chondroitin, and hyaluronic acid.

Objectives: To examine whether the increased risk of cardiovascular events with rofecoxib represents a class effect of cyclooxygenase-2 (COX-2) specific inhibitors. Design: Systematic review and meta-analysis of randomized double-blind clinical trials of celecoxib of at least 6 weeks' duration and presented data on serious cardiovascular thromboembolic events. Data sources included six bibliographic databases, the relevant files of the United States Food and Drug Administration, and pharmaceutical company websites. Main outcome measures: Pooled fixed effects estimates of the odds ratios for risk of cardiovascular events with celecoxib compared with comparator treatment were calculated using the inverse variance weight method. The main outcome measure was myocardial infarction. Results: Four placebo-controlled trials with 4422 patients were included in the primary meta-analysis comparing celecoxib with placebo. The odds ratio of myocardial infarction with celecoxib compared to placebo was 2.26 (95%confidence interval 1.0 to 5.1). For composite cardiovascular events [odd ratio 1.38 (95% CI 0.91 to 2.10)], cardiovascular deaths [OR 1.06 (95% CI 0.38 to 2.95)] and stroke [OR 1.0(95% CI 0.51 to 1.84)] there was no significant increase in risk with celecoxib. The secondary meta-analysis which included a total of six studies (with placebo, diclofenac, ibuprofen, and paracetamol as comparators) of 12 780 patients, showed similar findings with a significant increased risk with celecoxib for myocardial infarction [OR 1.88 (95% CI 1.15 to 3.08)] but not other outcome measures. Conclusion: The available data indicate an increased risk of myocardial infarction with celecoxib therapy, consistent with a class effect for COX-2 specific inhibitors.

Source: Caldwell B, Aldington S, Weatherall M, Shirtcliffe P, Beasley R. Risk of cardiovascular events and celecoxib: a systematic review and meta-analysis. J R Soc Med. 2006 Mar;99(3):132-40.