What Price Pain Relief?

Abstract

Chronic pain affects more than 50 million Americans and results in more than 25 million physician visits a year for lower back pain alone.1 The burden is particularly great in the elderly, in whom associated cardiovascular disease is the leading cause of death. Nonselective, nonaspirin, nonsteroidal antiinflammatory agents (NSAIDs) are effective analgesic, antiinflammatory, and antipyretic agents, but associated gastrointestinal toxicity led to the development and widespread use of selective cyclooxygenase (COX)-2 inhibitors. Originally introduced for use in chronic conditions such as osteoarthritis, they are today used to mitigate acute pain in numerous conditions. Their benefit was presumed to be from their selective inhibition of COX 2, which along with COX-1 is responsible for the conversion of arachidonic acid to prostaglandin H2. Adverse events associated with NSAIDs were attributed to their inhibition of COX 1, which downstream would normally result in the production of prostaglandins responsible for maintenance of gastrointestinal integrity.2 More recent investigations, however, have identified that both COX-1 and COX-2 are involved in vascular hemostasis, and selective COX-2 inhibitors can have net prothrombotic effects. COX-2 inhibitors lower levels of prostacyclin, a platelet inhibitor and vasodilator, whereas uninhibited COX-1 action results in continued thromboxane A2 production, which promotes platelet aggregation.3 There is mounting evidence that nonselective NSAIDs, previously thought to be neutral or beneficial for risk of cardiovascular disease, may also confer harm because of each agent’s relative COX-1/COX-2 prothrombotic effects and potential to reduce glomerular filtration, exacerbate congestive heart failure, and raise blood pressure.4 Article p 2906 In this issue of Circulation , Gislason and colleagues5 report on the risk of death and reinfarction associated with the use of both nonselective, nonaspirin NSAIDs and selective COX-2 inhibitors in post–myocardial infarction (MI) patients in Denmark. The advanced database system in Denmark is …