COX-2-specific inhibitors and the kidney: effect on hypertension and oedema.
Recent studies have investigated the renal and cardiovascular safety of celecoxib and rofecoxib. Both agents have been studied in long-term safety trials: the Celecoxib Long-Term Safety Study (CLASS) and Vioxx Gastrointestinal Outcomes Research Study (VIGOR). Renal safety was investigated in CLASS and the results indicated that celecoxib (even at the supratherapeutic 800 mg daily doses used in CLASS) is associated with lower rates of renal side effects than conventional non-steroidal anti-inflammatory drugs (NSAIDs). The renal safety of celecoxib was also assessed in healthy elderly subjects. In these subjects, celecoxib administration was associated with minimal effects on glomerular filtration rate compared with naproxen, while urinary sodium and prostaglandin E2 excretion were similar. Celecoxib and rofecoxib were compared with each other in two studies of elderly hypertensive patients with osteoarthritis (OA). These patients were treated with usual therapeutic doses of celecoxib (200 mg daily) or rofecoxib (25 mg daily). In the first study, celecoxib treatment had a significantly lower incidence of peripheral oedema than rofecoxib (4.9% versus 9.5%, P = 0.014). The second study confirmed the results of the initial study: the incidence of oedema was again lower with celecoxib than with rofecoxib (4.7% versus 7.7%, P < 0.05). Rofecoxib use was also associated with significantly greater mean and clinically relevant increases in systolic blood pressure than celecoxib. The CLASS study, which evaluated cardiovascular safety, showed that celecoxib treatment was not associated with an increase in myocardial infarction (MI) compared with non-selective NSAIDs (incidence in all patients was 0.3% for celecoxib and 0.3% for conventional NSAIDs). In a 12-week study of celecoxib (the Successive Celecoxib Efficacy and Safety Studies, SUCCESS-1) in more than 13000 patients with OA, combined doses of celecoxib (200 mg and 400 mg daily) and conventional NSAIDs (naproxen 1000 mg daily and diclofenac 100 mg daily) were again associated with similar rates of cardiovascular adverse events, including MI. However, in the VIGOR trial, treatment with rofecoxib was associated with a significantly higher rate of MI compared with naproxen (0.4% compared with 0.1% in the naproxen group, P < 0.05). In summary, celecoxib may have safety and tolerability advantages compared with non-selective NSAIDs studied and may have some cardiorenal benefits compared with rofecoxib.
Whelton
Andrew
A
Universal Clinical Research Center, Inc., Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. huntvalley@aol.com
D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D004487:Edema / Q000188:drug therapy*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D007668:Kidney / Q000187:drug effects*; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases; D012449:Safety
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases