NSAID CV Risk Persists for at Least Five Years Post-MI

September 13, 2012

September 11, 2012 (Copenhagen, Denmark) — The latest study to investigate the effect of nonsteroidal anti-inflammatory drugs (NSAIDs) in patients with a previous MI has found that the increased cardiovascular risk associated with these drugs persists for at least five years after the MI [1].

The study, published online in Circulation on September 10, 2012, was led by Dr Anne-Marie Schjerning Olsen (Copenhagen University Hospital Gentofte, Denmark).

She commented to heartwire : "We know that MI patients have an increased risk of a subsequent MI and that this decreases with time. We have also shown before that the risk of recurrent events is higher in patients taking an NSAID, but we have not known before how this risk varies with time. In this study, we show that the increased cardiovascular risk with an NSAID appears to remain constant with time after MI. In other words the risk appears to be similarly elevated at one year post-MI and five years post-MI.

"So NSAIDs are still dangerous to patients with a history of MI, even five years after their event. I would say there is no safe treatment window for these patients, and even short-term treatment with an NSAID is hazardous," Schjerning Olsen added.

She said many patients and doctors are unaware of this risk. "The American Heart Association issued guidelines in 2007 discouraging use of NSAIDs in patients with prior MI, but in our study 44% of the MI patients were still taking NSAIDs in 2009; the message has obviously not gotten through."

Better Education Needed

Noting that use of NSAIDs in Denmark has not declined at all since the cardiovascular hazards have been reported, either in MI patients or in the whole population, Schjerning Olsen called for better education, particularly of general practitioners, who tend to prescribe these drugs to many patients.

She suggested that the widespread availability of several NSAIDs without prescription is another factor that allows patients to believe these drugs are safe. "In Denmark, we only have low-dose ibuprofen available without prescription, and this is one of the safer ones regarding cardiovascular side effects, although it is associated with GI bleeding. But in many countries, several NSAIDs are available over the counter, including diclofenac, which had the highest cardiovascular risk in our study--even higher than rofecoxib [Vioxx, Merck], which has been withdrawn. Diclofenac should definitely not be available without a prescription for this reason."

For the study, Schjerning Olsen and her colleagues used national hospital and pharmacy registries in Denmark to identify 99 187 patients who had a first MI between 1997 and 2009 and track their NSAID use in subsequent years.

They found that 43 608 patients had had at least one prescription for an NSAID after the index MI, and these patients had a persistently increased risk of death and coronary death or nonfatal recurrent MI out to at least five years after the initial MI, which remained after adjustment for other factors.

Hazard Ratio (95% CI) of Death and CHD Death/MI in Patients Taking NSAIDs vs Those Not Taking NSAIDs

Time (y)


CHD death/MI


1.59 (1.49–1.69)

1.30 (1.22–1.39)


1.63 (1.52–1.74)


Of the individual NSAIDs used, diclofenac was associated with the highest risk of a cardiovascular event, with a hazard ratio of 2.07–2.73 over the five-year follow-up. The selective COX-2 inhibitors rofecoxib and celecoxib (Celebrex, Pfizer) were the next in line, with hazard ratios of 1.73–2.17 and 1.55–1.87, respectively.

As in previous studies, the current research found that naproxen was the NSAID with the lowest relative cardiovascular risk (HR 1.02–1.85). The authors write: "The results might indicate that naproxen should be preferred if NSAID treatment cannot be avoided." But they caution that, like ibuprofen, naproxen was associated with a high risk of gastrointestinal bleeding, which is associated with poor prognosis in MI patients. They therefore advocate "a very conservative approach to using NSAIDs among patients with MI."