Nonsteroidal Anti-inflammatory Drugs and Hypertension. The Risks in Perspective

Prostaglandins play an important role in cardiovascular homeostasis. Among other things, they promote vasodilation and enhance sodium excretion. Since they act as local hormones, it is difficult to assess their activity in the intact organism. Nonsteroidal anti-inflammatory drugs (NSAIDs) block the synthesis of prostaglandins, and thus may interfere with circulatory control. Indeed, many reports show that blood pressure may rise during treatment with one of these drugs. However, meta-analyses of such reports indicate that the rise in mean arterial pressure is relatively small, being approximately 5 mm Hg. At the present time, it is not known whether this confers any risk in terms of cardiovascular complications. Moreover, the trials on which this information is based are of relatively short duration. Whether the increment in blood pressure following administration of NSAIDs is sustained over time has not been established. Also, there is insufficient information regarding whether there are any special subgroups in the population who are at risk of developing hypertension during exposure to NSAIDs. Some data suggest that elderly people and patients with pre-existing hypertension carry an increased risk, notably when they are receiving antihypertensive treatment. Available data suggest that not all NSAIDs are equal as far as their effect on blood pressure is concerned. Sulindac, and perhaps also aspirin, seem to be less troublesome in this respect than other NSAIDs. This also applies to their effects on the kidney. Unfortunately, the mechanisms whereby NSAIDs may raise blood pressure are not fully understood. Interference with both the control of vascular resistance and the regulation of extracellular volume homeostasis has been incriminated, but several other putative mechanisms such as moderation of adrenergic activity or resetting of the baroreceptor response may also be involved. For the practising physician, it is wise to balance the risk of an increase in blood pressure against the expected benefit of treatment with an NSAID. In patients with (treated) hypertension and in the elderly, the benefits may not always outweigh the admittedly small risk. Should the physician nevertheless decide to prescribe an NSAID, frequent measurement of blood pressure may be necessary during the first weeks of treatment.