Some people take nonsteroidal anti-inflammatory drugs (NSAIDs) every day either for chronic pain, inflammation, or both. A survey of medication use in the United States showed that ibuprofen was taken by 17 percent of adults, aspirin by 17 percent and naproxen by 3.5 percent of adults in the preceding week.

For most, an occasional NSAID shouldn't cause a problem. However, NSAIDs are not without side effects, such as upset stomach, ulcers and bleeding in the gastrointestinal (GI) tract, and reduced blood flow to the kidneys — which could compromise these blood-filtering organs over time.

NSAID use is also known to approximately double the risk of hospital admission due to heart failure and increase systolic blood pressure by an average of 2-3 mmHg. In fact, it has been accepted that using NSAIDs increases the risk of acute myocardial infarction (MI).

A large study in 2013 found that there was a relative increase in cardiovascular risk — mainly attributed to coronary events — of approximately 33 percent in patients using high-dose diclofenac (greater than 150 mg), COX-2 inhibitors (celecoxib, rofecoxib, etoricoxib and lumiracoxib) and high-dose ibuprofen. But the timing of the risk, the effect dose, treatment duration and risks between NSAIDs has been unclear.

A new study published this month in the British Medical Journal adds new insight to what is already known about NSAID use and risk of heart attack.

Researchers — led by Michèle Bally, Ph.D., an epidemiologist in the Department of Pharmacy and Research Center, Centre hospitalier de l'Université de Montréal — performed an individual patient data meta-analysis of studies from healthcare databases to determine the complex time course for risk of acute MI and the effects of dose and of duration of continuous use for the main NSAIDs. The pooled data comprised 61,460 cases and 385,303 controls for a total number of 446,763 individuals.

By using the Bayesian statistical approach, which indicates probability, researchers compared adjusted odds ratios of acute MI for past use, recent use and five dose-duration categories of current NSAIDs, with nonuse of any NSAID in the year before the index date, for each study and for the pooled studies.

The researchers were interested in celecoxib, the three main traditional NSAIDs (diclofenac, ibuprofen and naproxen) and rofecoxib. Studies were limited to those conducted before rofecoxib (Vioxx, Merck) was withdrawn from the market because of safety concerns related to an increased risk for cardiovascular events.

For current NSAID use, the increase in MI risk compared with not using these drugs was 20 percent to 50 percent. There was a significantly increased risk for MI associated with current use for all traditional NSAIDs, including naproxen. The risk for acute MI for celecoxib did not appear to be greater than that for traditional NSAIDs and was lower than that for rofecoxib.

The study showed a rapid onset of MI risk in the first week of NSAID use. The probability of increased risk was greater than 90 percent for all NSAIDs: 92.4 percent for celecoxib, 97.3 percent for ibuprofen, 98.6 percent for diclofenac and 98.8 percent for both naproxen and rofecoxib. Higher doses were associated with increased MI risk.

Use for 8 to 30 days at a high dose was harmful for ibuprofen (greater than 1,200 mg/day), naproxen (greater than 750 mg/day) and rofecoxib (greater than 25 mg/day). However, according to Bally, longer duration of treatment did not appear to be associated with greater risk for MI, although the risk does not go away.

The large sample size of this study and the use of "real world" data add to the strengths of the study in supporting a growing body of evidence that both COX-2 inhibitors and nonselective NSAIDs are associated with a small increase in cardiovascular risk, especially at higher doses. Bally cautions about the perception that painkillers are benign and advises individuals to discuss their cardiovascular baseline risk with their physicians.