NSAIDs and Increased Blood Pressure

Abstract

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.

Prostaglandin E2 modulation of blood pressure homeostasis: Studies in rodent models

“…This observation underscores the pro-hypertensive effects of blockade of all prostaglandin production and subsequent receptor activation by NSAIDs [11,24,25,26,27] consistent with the loss of a tonic vasodepressor PG effect. Although no selective EP2 antagonists are available, the pharmacology of EP vasodepressor response has been addressed with EP2 knockout mice.…”

Labor therapeutics and BMI as risk factors for postpartum preeclampsia: A case-control study

“…Although we abstracted discharge recommendations for the use of NSAIDs, we did not have data on the actual use of NSAIDs following discharge. NSAID use may influence the development of PPPE by decreasing renal blood flow and limiting the ability of the women to manage intravascular volume, resulting in an increased risk of PPPE [26, 27]. In addition, robust collection and reporting of urinary output were lacking; this data would assist in the determination of fluid balance in the peri-delivery period.…”

Nonsteroidal Anti-Inflammatory Drugs and the Kidney

“…COX-2 selective inhibitors have effects on blood pressure that are similar to those of nonselective NSAIDs [137,138,139,140,141,142,143]. In contrast, the cardiorenal safety database from the Celecoxib Long-term Arthritis Safety Study (CLASS) indicates that a supratherapeutic dose (400 mg b.i.d.)…”