NSAIDs and increased blood pressure. What is the clinical significance?

Several randomised studies have demonstrated that various nonsteroidal anti-inflammatory drugs (NSAIDs) elevate blood pressure in normotensive and hypertensive individuals; however, these data have been contradicted by numerous negative studies. Two meta-analyses have demonstrated that, after pooling data drawn from published reports of randomised trials of younger adults, NSAID use produces a clinically significant increment in mean blood pressure of 5 mm Hg, most marked in patients with controlled hypertension. Stratification by NSAID type revealed that piroxicam, naproxen and indomethacin had the greatest, and sulindac the smallest, pressor effect. These data were supported by 2 large community studies involving elderly patients. Recent NSAID users had a 1.7-fold higher risk of requiring the initiation of antihypertensive therapy compared with nonusers; NSAID users also had a 40% increased risk of receiving a diagnosis of hypertension compared with nonusers. It is vital to determine the nature of the association in the elderly, 12 to 15% of whom are concurrently receiving an NSAID and an antihypertensive agent. Importantly, a 5 to 6 mm Hg increase in diastolic blood pressure maintained over a few years may be associated with a 67% increase in total stroke risk and a 15% increase in coronary heart disease events. While the mechanism(s) remain speculative, salt and water retention through several factors operating in parallel, coupled with increased total peripheral vascular resistance, via increased renal endothelin-1 synthesis, are potentially important. Clinicians should strive to avoid excessive use of NSAID treatment and consider well-tolerated therapeutic alternatives, including simple analgesics and physical therapy. For patients who require concomitant NSAID and antihypertensive treatment, physicians should be aware that indomethacin, naproxen and piroxicam may be associated with a greater pressor effect than many other NSAIDs, and that antagonism of beta-blockers may be greater than that of vasodilators (including ACE inhibitors and calcium antagonists) and diuretics. Finally, the progress of each patient should be monitored by careful blood pressure measurement, particularly during the period of initiation of NSAID therapy.