Friday, September 21, 2012

Study Finds NSAID Use Risky After Heart Attack

NSAIDsFor heart attack victims, subsequent use of NSAIDs can be hazardous, according to research evidence from Denmark. Use of the drugs may increase the risk of a second heart attack or even death for at least 5 years, and caution regarding NSAID use in this patient population is advised at all times.

Writing in the journal Circulation from the American Heart Association, researchers at Copenhagen University Hospital note that cardiovascular risk after a first heart attack (myocardial infarction, or MI) usually declines rapidly during the first year [Olsen et al. 2012]. However, they wanted to know if using nonsteroidal anti-inflammatory drugs (NSAIDs) would alter that cardiovascular risk in the first year and thereafter.

Using nationwide registries of hospitalization and drug dispensing from pharmacies in Denmark, the investigators identified patients aged 30 years or older admitted with first-time MI during 1997–2009 and their subsequent NSAID use. Then, they calculated incidence rates of overall death and a composite endpoint of coronary (heart-related) death or nonfatal recurrent MIs associated with NSAID use in 1-year time intervals up to 5 years after inclusion in the study.

Of the roughly 99,000 cardiac patients included, approximately 44,000 (44%) were prescribed NSAIDs after their first recorded MI. In this total population, there were about 37,000 deaths from any cause and 29,000 coronary deaths or nonfatal recurrent MIs during the 5 years of followup.

Relative to those patients with prior MI not taking NSAIDs, and after ruling out other risk factors, the use of any NSAID in the years following MI was associated with a significant 59% increased risk of death from any cause within 1 year after a first heart attack (hazard ratio [HR]=1.59; 95% confidence interval [CI], 1.49–1.69). After 5 years the risk increased further to 63% among those with an NSAID prescription (HR=1.63; 95% CI, 1.52–1.74).

More specifically, among patients prescribed NSAIDs after a first heart attack, the risk of a second heart attack or of dying from coronary heart disease significantly increased by 30% after 1 year (HR=1.30; CI 1.22–1.39) and 41% after 5 years (HR=1.41; 95% CI, 1.28–1.55). [As the confidence intervals suggest, all hazard ratios were statistically significant at the P<0.001 level.]

The researchers conclude that the use of NSAIDs is associated with persistently increased coronary risk regardless of time elapsed after a first-time MI. They advise that, consistent with other reports of the adverse cardiovascular effects of NSAIDs, their data provide further evidence that using COX-2-selective and non-selective NSAIDs in this patient population may increase the risk of severe adverse cardiac events.

COMMENTARY: We have previously written about cardiovascular risks of NSAIDs in UPDATES [here] and [here]. In prior research by this same team from Denmark [see UPDATE here] they had found that even short-term treatment with most NSAIDs (up to 14 weeks) was associated with increased risk of death or recurrent MI in patients with prior MI.

In this present study, the authors duly note that large epidemiological investigations such as this cannot definitively determine cause-effect relationships, and there always is a chance of unknown confounding factors influencing outcomes. Yet, for endpoints like death or myocardial infarction, randomized placebo controlled trials are impractical and unethical; so, it is necessary to rely on observational approaches.

Furthermore, this study relied on data regarding prescribed NSAIDs. In Denmark, aspirin is available over-the-counter (OTC) and was not considered as a separate category. Ibuprofen is the only other NSAID available OTC, but only in low doses and it is more commonly prescribed for patients in higher doses. In all cases, there was a presumption that patients were adherent with their prescribed NSAID regimens.

Considering the cardiac risks, the authors express concerns about OTC availability of nonselective NSAIDs in many countries and that healthcare providers should consider alternatives to NSAIDs according to individual patient risk factors. In this study, as in others, naproxen was found to have the most favorable cardiovascular safety profile among NSAIDs and might be preferred if NSAID therapy cannot be avoided. Still, the high risk of gastrointestinal bleeding linked to naproxen should be taken into account.

MortalityIn a prior UPDATE [here], using compiled data from various sources and conservative estimates, we had developed a proportional comparison of annual mortality rates linked to acetaminophen (APAP), opioids, and NSAIDs (see graph). Clearly, NSAID-related mortality might be of much greater concern than the other two classes of analgesics. And, while acetaminophen may have a lower death rate, it is a significant cause of acute liver failure and a source of considerable, albeit often treatable, morbidity. We also have observed that acetaminophen overdoses lead to more than 78,000 emergency department visits each year in the United States alone, and the majority (70%) are due to intentional self-harm attempts.

As we have noted in the past, all analgesics carry risks and all can be misused or abused in some fashion. NSAIDs and acetaminophen are far from being safe and in some respects may be more hazardous than opioids analgesics. It is ironic that potentially dangerous acetaminophen and NSAIDs are so easily obtainable for the asking at any pharmacy or grocery store in the U.S., while more effective and relatively safe opioids — if properly used only as directed — are among the most regulated and restricted drugs in all of medicine.

REFERENCE: Olsen AMS, Fosbøl EL, Lindhardsen J, et al. Long-Term Cardiovascular Risk of NSAID Use According to Time Passed After First-Time Myocardial Infarction: A Nationwide Cohort Study. Circulation. 2012(Sep 10); online ahead of print [available here].

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