Rofecoxib: increased risk of renal and cardiovascular effects
- PDF / 162,151 Bytes
- 1 Pages / 623.591 x 841.847 pts Page_size
- 16 Downloads / 181 Views
Increased cardiovascular risks In one paper, researchers compared the risks of serious CV events (predominantly myocardial infarction [MI]) with COX-2 inhibitors and individual NSAIDs.1 Included studies were observational, of case-control (n = 17) or cohort (6) design, and reported data on CV events with exposure to COX-2 inhibitors, NSAIDs, or both, with remote use or nonuse of the drugs as the reference exposure for calculating the relative risk (RR). Across all studies that included rofecoxib, the summary RR for CV events was 1.35 (95% CI 1.15, 1.59), and there was an apparent dose effect: the RRs for > 25 and ≤ 25 mg/day were 2.19 (1.64, 2.91) and 1.33 (1.00, 1.79), respectively. A risk was evident within the first 30 days of treatment (summary RR across three studies 1.66 (1.09, 2.51). There was no elevated risk of CV events with celecoxib (summary RR 1.06 [0.91, 1.23]). The summary RR for diclofenac was 1.40 (1.16, 1.70), for indomethacin was 1.30 (1.07, 1.60), for meloxicam was 1.25 (1.00, 1.55), for ibuprofen was 1.07 (0.97, 1.18), for piroxicam was 1.06 (0.70, 1.59), and for naproxen was 0.97 (0.87, 1.07).
• • •
1
high doses. The risk starts early, probably as soon as the first dose, and there is no immunity from risk in the first 18 months. Celecoxib also increases MI risk at dosages > 200 mg/day; the potential risk at lower dosages is less clear. A number of other NSAIDs increase MI risk, including diclofenac, meloxicam, indomethacin and, probably, ibuprofen. Meta-analyses of observational studies and randomised clinical trials show agreement that naproxen is neutral for MI risk.
1. McGettigan P, et al. Cardiovascular risk and inhibition of cyclooxygenase: a systematic review of the observational studies of selective and nonselective inhibitors of cyclooxygenase 2. JAMA: the Journal of the American Medical Association 296 (Suppl. 3): 1633-1644, No. 13, 4 Oct 2006. 2. Zhang J, et al. Adverse effects of cyclooxygenase 2 inhibitors on renal and arrhythmia events: meta-analysis of randomized trials. JAMA: the Journal of the American Medical Association 296 (Suppl. 3): 1619-1632, No. 13, 4 Oct 2006. 3. Graham DJ. COX-2 inhibitors, other NSAIDs, and cardiovascular risk: the seduction of common sense. JAMA: the Journal of the American Medical Association 296 (Suppl. 3): 1653-1656, No. 13, 4 Oct 2006. 801013669
» Editorial comment: On 30 Sep 2004, Merck & Co voluntary withdrew Vioxx [rofecoxib] from the market worldwide [see Reactions 1022: 2, 9 Oct 2004; 800969957].
. . . and adverse renal and arrhythmia risks In another paper, researchers aimed to quantify the risks for renal events (composite of peripheral oedema, hypertension and renal dysfunction) and arrhythmia events associated with COX-2 inhibitors, and potential class effects; they also explored the temporal consistency for these adverse effects.2 114 randomised, double-blind, clinical trials of COX-2 inhibitors with renal endpoints of interest and arrhythmia were included (116 094 patients). A pooled analysis of composite renal events showed subs
Data Loading...
