Cardiovascular Risk and NSAID Use

Nonsteroidal anti-inflammatory drugs (NSAIDs) are very commonly used by and are very important pain and inflammation reducers for people with arthritis. However, concerns over the cardiovascular safety of selective and nonselective NSAIDs led the US Food and Drug Administration to put a warning on all NSAID labels. A better understanding of which NSAID users are at greatest risk of having a cardiovascular disease (CVD) event – such as heart attack or stroke – is essential for physicians and people with arthritis.

What Problem Was Studied?

Selective NSAIDs = nonsteroidal anti-inflammatory drugs that selectively inhibit the action of the enzyme cycooxygenase 2. At the time this study was conducted, three of these medications were available in the US: celecoxib, rofecoxib and valdecoxib. Only celecoxib (Celebrex) is currently available.

 Nonselective NSAIDs = nonsteroidal anti-inflammatory drugs that inhibit the action of both cyclooxygenase 1 and cyclooxygenase 2. In this study, the medications of interest were diclofenac (Cataflam, Voltaren), ibuprofen (Motrin, Advil, Nuprin) and naproxen (Naprosyn, Aleve, Anaprox).

Investigators from Brigham and Women’s Hospital in Boston – including Arthritis Foundation-funded scientist Daniel H. Solomon, MD – sought to identify potentially important commonalities and differences among NSAID users who had CVD events.

What Was Done in the Study?

Using a US Medicare database, the research team identified 76,082 selective NSAID users, 53,014 nonselective NSAID users and 46,558 nonusers. Information was then gathered regarding specific medication used, cardiovascular event (hospitalization due to myocardial infarction [MI, heart attack], stroke or congestive heart failure [CHF] or death due to cardiovascular disease) and the following clinical data: age, sex, prior MI, prior CHF, prior stroke, high blood pressure, diabetes, any cardiovascular risk factor, chronic kidney disease, rheumatoid arthritis, chronic obstructive pulmonary disease (COPD), statin use and angiotensin-converting enzyme (ACE) inhibitor use.

What Were the Study Results?

Of the 175,654 people included, 7,262 cardiovascular events occurred over the course of the study. Seven patient characteristics were identified as increasing the risk of having a negative event when using NSAIDs: age 80 years or older, high blood pressure, prior MI, prior CVD (MI, CHF or stroke), rheumatoid arthritis, chronic renal disease and COPD.

When Dr. Solomon and team compared the incidence rates of CVD event by specific medication, they found that, within certain population subgroups, rofecoxib and ibuprofen users experienced substantially higher rates of CVD event than nonusers. For example, among people who had a prior MI, rofecoxib and ibuprofen users were at much greater risk of sustaining another CVD event than those who took no NSAIDs.

What Does This Mean for People With Arthritis?

Although the study did reveal that certain people with specific risk factors who take NSAIDs do have a higher likelihood of experiencing heart attack, stroke or congestive heart failure, the majority of the public who takes these effective medications are not at increased risk. Dr. Solomon concludes, “These results should bolster physicians’ and patients’ confidence that most selective and nonselective NSAIDs are not associated with an elevated risk of CVD events in many patient subgroups using typical doses.”

Solomon DH, Glynn RJ, Rothman KJ, et al. Subgroup analyses to determine cardiovascular risk associated with nonsteroidal antiinflammatory drugs and coxibs in specific patient groups. Arthritis Rheum (Arthritis Care Res) 2008;59:1097-104.

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