Cardio risk for healthy people varies by specific NSAID

The use of certain nonsteroidal anti-inflammatory drugs (NSAIDs) by healthy people is associated with an increased risk of cardiovascular death, but naproxen (Aleve, Bayer Consumer) appears to have a safer cardiovascular risk profile, according to a study published online June 8 in Circulation: Cardiovascular Quality and Outcomes, as reported by HealthDay News.

Emil Loldrup Fosbøl, MD, of Gentofte University Hospital in Hellerup, Denmark, and colleagues compiled data from nationwide registers on more than 1 million healthy Danish subjects who had not been hospitalized for at least 5 years previous to their first NSAID prescription claim, and who had not claimed drug prescriptions for certain concomitant medications 2 years previously.

“This study is the first to [research] specific cardiovascular risk (risk of stroke, risk of coronary death or nonfatal myocardial infarction, and risk of cardiovascular death) in healthy people,” Dr. Fosbøl told Formulary. “Very few studies have been designed to answer the important question: Do NSAIDs also increase the cardiovascular risk among healthy people who use these drugs for minor complaints? This study is the first to confirm that the cardiovascular risk is indeed increased when healthy individuals use some of the drugs.”

The researchers assessed the risks for cardiovascular death, a composite of coronary death or nonfatal myocardial infarction, and fatal or nonfatal stroke linked to NSAID use.

The investigators discovered that use of either diclofenac (Voltaren, Novartis Pharmaceuticals) or rofecoxib (Vioxx, Merck & Co.), which was withdrawn in 2004 due to heart-related side effects, was associated with an increased risk of cardiovascular death (odds ratios [ORs], 1.91 and 1.66, respectively), with risk increasing for higher doses. Use of naproxen was not associated with increased risk for cardiovascular death (OR, 0.84). Ibuprofen (Advil, Wyeth Consumer Healthcare and Motrin, McNeil Consumer Healthcare) use was associated with a trend toward increased risk of stroke - either fatal or nonfatal (OR, 1.29).

“NSAID users should at a minimum be aware that some of these drugs have been linked to an increased risk of myocardial infarction and cardiovascular risk,” Dr. Fosbøl said. “This is especially important in over-the-counter retail, as most of the drugs are available OTC. Clinicians should make a critical assessment whether the indication for starting NSAID treatment is present before starting the treatment. This assessment should be made individually, taking factors such as heart disease, peptic ulcers, concomitant pharmacotherapy, and conventional risk factors of heart disease into account.”

Diclofenac is one of the most prescribed NSAIDs in Denmark and other northern European nations, Dr. Fosbøl said. Many studies have shown worrying results for this drug and many general practitioners have shifted patients receiving diclofenac to either ibuprofen or naproxen - or stopped NSAID treatment, he added.

“I believe that trials on diclofenac and cardiovascular risk in the general population are mandatory and could help clarify whether this drug is suited for OTC sale,” Dr. Fosbøl said. “Furthermore, studies on the importance of treatment duration would be highly informative as well.”