Nonsteroidal anti-inflammatory drugs (NSAIDs) have a variety of adverse effects. From a cardiovascular viewpoint, they can both raise the blood pressure and affect overall cardiovascular risk.
The effect of NSAIDs and acetaminophen on the blood pressure and the development of hypertension will be reviewed here. The cardiovascular effects of NSAIDs are discussed separately. (See "Nonselective NSAIDs: Adverse cardiovascular effects" and "COX-2 selective inhibitors: Adverse cardiovascular effects".)
NSAIDS AND BLOOD PRESSURE
All nonsteroidal anti-inflammatory drugs (NSAIDs) in doses adequate to reduce inflammation and pain can increase blood pressure in both normotensive and hypertensive individuals . The average rise in blood pressure is 3/2 mmHg but varies considerably [2-4]. In addition, NSAID use may reduce the effect of all antihypertensive drugs except calcium channel blockers . These effects may contribute to the increase in cardiovascular risk associated with the selective COX-2 inhibitors . (See "COX-2 selective inhibitors: Adverse cardiovascular effects".)
The prohypertensive effect is dose-dependent and probably involves inhibition of cyclooxygenase-2 (COX-2) in the kidneys, which reduces sodium excretion and increases intravascular volume . Low dose aspirin has no COX-2-inhibiting or prohypertensive effects. As an example, 75 mg/day of aspirin did not interfere with antihypertensive therapy, as compared with placebo, in 18,790 patients in the Hypertension Optimal Treatment (HOT) Study . However, these conclusions cannot be extended to larger doses of aspirin.
ACETAMINOPHEN AND BLOOD PRESSURE
Acetaminophen produces its analgesic effect by inhibiting the same cyclooxygenase, prostaglandin H2 synthase, that is the target of NSAID and aspirin . However, acetaminophen blocks this enzyme at its peroxidase catalytic rather than at the cyclooxygenase catalytic site. Therefore, the acetaminophen-mediated inhibition is sensitive to changes in the tissue peroxide levels; higher concentrations of peroxide in activated leukocytes and platelets block the effect of acetaminophen on inflammation and platelet thrombosis. However, acetaminophen is able to inhibit prostaglandins in the central nervous system, thus providing relief of pain and fever. Therefore, acetaminophen is not an NSAID or anti-thrombotic agent.