NSAIDs and Blood Pressure

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Abstract
The use of nonsteroidal anti-inflammatory drugs (NSAIDs) and antihypertensive medication increases with age to 26% and >50%, respectively, among the elderly. Overall, 12 to 15% of elderly individuals take at least 1 NSAID and an antihypertensive medication concurrently. A large case-control study of older individuals demonstrated that recent users of NSAIDs had a 1.7-fold increase in risk of initiating antihypertensive therapy compared with non-users. A community-based epidemiological study revealed that NSAID use significantly predicted the presence of hypertension (odds ratio 1.4, 95% confidence interval 1.1 to 1.7) in the elderly. Furthermore, among those taking antihypertensive agents in the 65+ Rural Health Study, in Iowa, US, individuals also taking NSAIDs had a mean systolic blood pressure (BP) 4.9mm Hg higher than non-users of NSAIDs. The hypertensive effect of NSAIDs varies depending on the specific NSAID used and the type of antihypertensive agent, if they are taken concurrently. While the results of randomised, controlled trials in the elderly have been conflicting, 2 meta-analyses involving younger adults have revealed that NSAID use produces a clinically significant increment in mean BP of 5.0mm Hg, which is most marked in patients with controlled hypertension. Stratification by NSAID type has revealed that piroxicam and indomethacin had the greatest, and sulindac the least, pressor effect. While the mechanism(s) of the pressor effect remain speculative, salt and water retention, caused by several factors operating in parallel, coupled with an increased total peripheral vascular resistance via increased renal endothelin-1 synthesis, are potentially important. A 5 to 6mm Hg increase in diastolic BP maintained over a few years may be associated with a 67% increase in total stroke occurrence and a 15% increase in events associated with coronary heart disease. Clinicians should strive to avoid excessive use of NSAID treatment and consider alternative, well-tolerated therapeutic options, including simple analgesics and physical therapy. For patients who require concomitant NSAID and antihypertensive treatment, clinicians should be aware of the greater hypertensive effect of indomethacin and piroxicam compared with alternative NSAIDs, and the potential for relatively greater antagonism by NSAIDs of the BP-lowering effect of β-blockers compared with other antihypertensives. Finally, the progress of each patient should be monitored by careful BP measurement particularly during the initiation of NSAID therapy.