RESEARCH - Older NSAIDs and acetaminophen boost cardiovascular risk

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Older NSAIDs and acetaminophen boost cardiovascular risk

Rheumawire

Mar 17, 2006

Gandey

Boston, MA - Amid a flurry of concern over selective COX-2 inhibitors, many

doctors have been switching patients to traditional nonsteroidal

anti-inflammatory drugs (NSAIDs). But a new large prospective study suggests

that even the old mainstays of pain relief may be problematic. In a

Circulation paper published online March 13, 2006, researchers report that

regular use of analgesics, including over-the-counter drugs, can

significantly increase the risk of major cardiovascular events [1].

" Our study emphasizes the importance of examining even the drugs we've been

using for a long time, because they may not be as safe as we've assumed, "

lead author Dr Chan (Massachusetts General Hospital and Harvard

Medical School, Boston, MA) told rheumawire. " People are taking these

products more often and for longer periods of time, and this is not

something that should be undertaken lightly. "

The researchers point out that NSAIDs inhibit antithrombotic prostacyclins

in much the same way as COX-2 selective inhibitors. Although nonselective

NSAIDs also inhibit COX-1, which synthesizes the prothrombotic thromboxane

A2, the relative balance between COX-1 and COX-2 activity is critical for

vascular homeostasis. They suggest that all NSAIDs may in fact shift the

equilibrium toward thrombosis and vasoconstriction.

In the present analysis, Chan and his team examined the influence of NSAIDs

and acetaminophen on the risk of major cardiovascular events, which they

characterize as nonfatal myocardial infarction, fatal coronary heart

disease, and stroke. They studied more than 70 900 women enrolled in the

Nurses' Health Study who were free of known cardiovascular disease or

cancer.

The women, aged 44 to 69 years, provided medication data biennially from

1990. During 12 years of follow-up, the investigators confirmed 2041 major

cardiovascular events. After adjusting for risk factors, they found that

women who frequently used NSAIDs had a relative risk for a cardiovascular

event of 1.44 (95% CI 1.27-1.65) compared with nonusers.

The women who frequently used acetaminophen had a relative risk for a

cardiovascular event of 1.35 (95% CI 1.14-1.59). " Moreover, " the researchers

write, " we observed significant dose-response relations. " Compared with

nonusers, the relative risk for a cardiovascular event among women who used

15 or more tablets per week was 1.86 (95% CI 1.27-2.73) for NSAIDs and 1.68

(95% CI, 1.10-2.58) for acetaminophen.

The researchers also found that the elevated risk associated with frequent

NSAID use was particularly evident among current smokers (relative risk

1.82, 95% CI 1.38-2.42) and was absent among never smokers.

Moderate use not linked to substantial risk

The investigators found that women taking NSAIDs or acetaminophen only

occasionally-roughly 1 to 21 days per month-did not experience a significant

increase in the risk of cardiovascular events. During an interview with

rheumawire, Chan noted that infrequent casual analgesic use did not appear

to pose a danger, but he said that patients using over-the-counter pain

relievers on a more regular basis should consult a doctor.

He points to a number of strengths and limitations to the present study. His

group looked at a large number of patients and followed them for a long

period of time. But, he notes, the study is observational and analgesic use

was self-selected.

" Despite the strong biological plausibility of our results, " the researchers

write, " it is possible that our findings could be related to the reason for

which participants used NSAIDs or acetaminophen. " But, they add, high doses

of these agents, including aspirin, were primarily used for analgesia and

did not appear to increase the risk of cardiovascular events among

high-frequency aspirin users.

The investigators note that although they cannot completely exclude residual

confounding by factors associated with frequent analgesic intake, their

findings remained significant even after they carefully controlled for known

cardiovascular risk indicators as well as common reasons for chronic

analgesic use.

" At this point, our understanding of the cardiovascular risks associated

with analgesics is still fairly crude, " Chan said. " Moving forward, we will

need more clarification on who the specific at-risk patient populations

might be or what risk factors need to be taken into account. "

Chan says he hopes this study will trigger enough questions in people's

minds to help spur future research. " It is important that we continue to add

to the body of literature and raise people's awareness. "

Source

1. Chan AT, Manson JE, Albert CM, et al. Nonsteroidal

antiinflammatory drugs, acetaminophen, and the risk of cardiovascular

events. Circulation 2006; DOI: 10.1161/CIRCULATIONAHA.105.595793. Available

at: http://circ.ahajournals.org.

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