- Nov 3, 2010
NSAIDs work by inhibiting a family of chemicals, known as prostaglandins, which are produced within the body’s cells by the enzyme cyclooxygenase (COX). Prostaglandins promote inflammation, pain, and fever; as well as support the blood clotting function of platelets; and protect the lining of the stomach from the damaging effects of acid. Although there are two COX enzymes, called COX-1 and COX-2, both enzymes produce prostaglandins that promote inflammation, pain, and fever. However, only COX-1 produces prostaglandins that support platelet blood clotting and provide protection for the lining of the stomach.
Because NSAIDs block COX enzymes and reduce prostaglandins, not only do they reduce inflammation, pain, and fever, but also reduce both protection for the stomach lining and the support for platelets, which can cause stomach ulcers and bleeding. The drugs are available in both prescription and over-the-counter formulations, and include such brand names as Advil, Motrin, Voltarin, and Vioxx, among others.
The most commonly prescribed NSAIDs in the study were ibuprofen (Advil, Motrin) and diclofenac (Cataflam, Voltaren) among the 83,697 heart attack survivors whose records were analyzed by the research team. Study participants had an average age of 68, of whom 63 percent were men, and 42.3 percent had at least one prescription for an NSAID. Findings revealed that those who used certain NSAIDs for one week had an increased risk of 45 percent for suffering another heart attack, and the risk was heightened to 55 percent after three months’ use.
Almost all of the NSAIDs in the study were linked to an increased risk of a recurrent heart attack or death, with the highest risk noted among those who took diclofenac. Only naproxen (Aleve), was not found to be associated with a greater risk of death or recurrent heart attack in the study, although it has been linked to gastrointestinal bleeding.
According to the study’s lead author, Anne-Marie Schjerning Olsen, of Copenhagen University in Denmark, “We were surprised that commonly used NSAIDs such as diclofenac, which in some countries is available over the counter without any expert advice on potential side effects, were associated with increased risk ... and the risk continued to persist during the course of treatment.”
Regarding the results of the analysis, Olsen said “Overall, NSAID treatment was associated with a statistically significant increased risk of death.” She went on to explain, “Our results indicate that there is no apparent safe therapeutic window for NSAIDs in patients with prior heart attack.”
As for aspirin, an NSAID with blood-thinning properties that blocks the COX-1 enzyme, because it has long been considered useful in preventing heart attacks when used in low doses, Olsen agreed with other experts that at the low dose typically given to patients, taking a daily aspirin should pose no added risk for recurrence of heart attack.
Back in 2004, The U.S. Food and Drug Administration (FDA) banned the NSAID rofecoxib (Vioxx), due to findings that it raised the rate of heart attacks and strokes among those taking it. In addition, the FDA recently issued a warning against the use of diclofenac by patients recovering from heart surgery.
In a 2007 statement, The American Heart Association also advised physicians about the risks of NSAID use among heart patients and provided a stepped care approach. The statement also advised that extra caution needed to be taken regarding the use of NSAIDs by noting that they should “be limited to patients for whom there are not appropriate alternatives, and then, only in the lowest dose and for the shortest duration necessary.”
Olsen concluded, “A very conservative approach to use NSAIDs in patients with prior heart attack is warranted. If NSAID therapy is necessary for patients with known heart attack, the doctors should choose an NSAID less selective for COX-2 and a minimum for the shortest period.”