Side effects of conventional nonsteroidal anti-inflammatory drugs and celecoxib: more similarities than differences.

To the Editor: Cyclooxygenase-2 (COX-2) inhibitors are a new class of nonsteroidal anti-inflammatory drugs (NSAIDs) with a reported benefit of less gastric and duodenal ulceration. Nevertheless, it has been shown that COX-2 inhibitors are not completely "ulcer-proof." (1) Whereas the gastrointestinal side effects of NSAIDs are a matter of concern and interest, the cardiovascular and renal side effects of these drugs are less well appreciated. NSAIDs, including both conventional and COX-2 inhibitors, inhibit the synthesis of prostaglandins. Pathophysiologically, NSAIDs may increase blood pressure by renal and extrarenal mechanisms such as the reninangiotensin pathway, alterations in sodium and water retention, inhibition of vasodilating prostaglandins, and production of various vasoconstricting factors, including endothelin-1 and P450-mediated metabolites of arachidonic acid. Thus, NSAIDs have been identified as risk factors for the development of hypertension. (2) Furthermore, NSAIDs antagonize the blood pressure-lowering effect of diuretics, [beta]-blockers, angiotensin-converting enzyme inhibitors, and AT-2-blockers. (3) In addition, NSAIDs aggravate heart failure by inducing water retention and by blunting the effects of diuretics, [beta]-blockers, and angiotensin-converting enzyme inhibitors. (4) The prevalence of cardiovascular and renal side effects is relatively high and does not seem to differ between conventional NSAIDs and COX-2 inhibitors. A comparison of celecoxib with diclofenac in 287 patients with arthritis, cardiovascular and renal side effects were found in a total of 79 patients (27.8%). These side effects were hypertension (16.6%), peripheral edema (5.2%), and renal failure (6.0%) and did not differ between patient groups. (5) On the basis of these findings, we suggest that NSAIDs, regardless of whether they are conventional or COX-2 inhibitors, should be used with caution in patients with cardiovascular disorders and that NSAID intake should be considered a potential reason for aggravation of heart failure or increased blood pressure.

References

(1.) Crawford AS, White JG. Celecoxib-induced upper gastrointestinal hemorrhage and ulceration. South Med J 2002;95:1444-1446.

(2.) Curhan GC, Willett WC, Rosner B, et al. Frequency of analgesic use and risk of hypertension in younger women. Arch Intern Med 2002;162:2204-2208.

(3.) Fogari R, Zoppi A, Carretta R, et al; Italian Collaborative Study Group. Effect of indomethacin on the antihypertensive efficacy of valsartan and lisinopril: A multicentre study. J Hypertens 2002;20:1007-1014.

(4.) Feenstra J, Heerdink ER, Grobbee DE, et al. Association of nonsteroidal anti-inflammatory drugs with first occurrence of heart failure and with relapsing heart failure: The Rotterdam Study. Arch Intern Med 2002;162:265-270.

(5.) Chan FK, Hung LC, Suen BY, et al. Celecoxib versus diclofenac and omeprazole in reducing the risk of recurrent ulcer bleeding in patients with arthritis. N Engl J Med 2002;347:2104-2110.

Claudia Stollberger, MD

Second Medical Department

Josef Finsterer, MD

Neurological Department

Krankenanstalt Rudolfstifung

Vienna, Austria