Clinical Implications of Nonopioid Analgesia for Relief of Mild-to-Moderate Pain in Patients with or at Risk for Cardiovascular Disease

Nonopioid analgesics, which include acetaminophen, aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), and cyclooxygenase-2 (COX-2)–specific inhibitors (coxibs), are frequently used for the relief of mild-to-moderate pain. Although all of these agents are effective at controlling pain, inhibition of prostaglandins (PGs) by NSAIDs may result in untoward cardiorenal effects, including hypertension, fluid and electrolyte abnormalities, congestive heart failure, acute renal failure, and nephrotic syndrome. Individuals with an increased risk for cardiorenal effects from NSAIDs (eg, the elderly, and those with hypertension, cardiac disease, or gouty nephropathy) should be monitored for early onset of edema, destabilization of blood pressure control, and/or onset of congestive heart failure when started on NSAID therapy. Because acetaminophen has a different mechanism of action from the conventional NSAIDs, it does not inhibit peripheral PGs at recommended dosing and therefore appears to have a more favorable cardiovascular and gastrointestinal safety profile. This review discusses the effects of acetaminophen, traditional NSAIDs, and coxibs on fluid and electrolytes, blood pressure, congestive heart failure, and renal function, as well as their consequences in patients with or at risk for cardiovascular disease (CVD). It also summarizes information on the mechanisms by which NSAID-induced cardiovascular adverse events develop, and it provides recommendations for the use of nonopioid analgesics for relief of mild-to-moderate pain in patients with or at risk for CVD.