The NSAID and CVD Balancing Act

An Expert Interview With Daniel Solomon, MD

Linda Brookes; Daniel Solomon, MD


August 30, 2011

In This Article

Cardiovascular Effects: Not All NSAIDS Are Alike

Medscape: Are all the issues about the cardiovascular safety of the COX-2 inhibitors clear now?

Dr. Solomon: No, there are many fundamental issues that are not settled. The comparative cardiovascular safety of celecoxib vs nonselective NSAIDs is still not clear. While high dosages of celecoxib (ie, at least 200 mg twice daily) are associated with cardiovascular risk compared with placebo,[13,14,15,16,17] the risk of lower dosages compared with nonselective NSAIDs is not known.

Medscape: What is known about the cardiovascular effects of traditional NSAIDs at present?

Dr. Solomon: Traditional NSAIDs are not all similar in their risk. Naproxen appears to be safest from a cardiovascular standpoint,[11,18,19,20,21,22] but it may be associated with more gastrointestinal bleeding. Agents, such as diclofenac, with greater COX-2 inhibition appear to be most risky on the cardiovascular system.

Medscape: How do the risks differ in patients with and without cardiovascular disease risk factors?

Dr. Solomon: This has not been well studied, but it appears that patients with more cardiovascular disease risk factors are at a heightened risk with nonselective and selective NSAIDs.[17] This needs further study.

Medscape: So in younger patients, say aged ≤ 50 years, with no other risk factors, presumably these drugs are safe?

Dr. Solomon: The baseline risk for cardiovascular events is lower in younger people who do not have cardiovascular risk factors. So, even if the risk is raised by 20%-50%, the absolute rate of events is still very low. It is bad if you are one of those people who has an event but, obviously, the vast majority do not have events. While cardiovascular morbidity is a big deal, especially at the population level, the truth is that patients come in asking for pain relief and providers want to help.

Medscape: There have been a number of meta-analyses published this year that looked at the cardiovascular safety of NSAIDs, including the network meta-analysis by Trelle and colleagues,[11] which concluded that all NSAIDs are associated with increased cardiovascular risk but that naproxen is safest in this respect.

Dr. Solomon: A network meta-analysis, such as the one by Trelle and colleagues,[11] takes data from randomized clinical trials and attempts to use the "transitive property" to make indirect comparisons across studies. So, if naproxen has been shown in one study to be safer than ibuprofen and in another study ibuprofen was safer than diclofenac, then naproxen is concluded to be safer than diclofenac. However, as I said in a recent commentary,[22] I am not certain that this meta-analysis has given us new insight. It was conducted using very rigorous methodology, with large numbers of people from randomized controlled trials, and so it adds to the literature. However, most doctors and patients are more interested in comparisons between active agents than comparisons with placebo. Moreover, overall safety (not just cardiovascular) and the benefit-risk ratio for analgesics would really help guide prescribing.

One can interpret the results of the Trelle study to say that all NSAIDs (selective and nonselective) are risky on the heart. However, as a rheumatologist, I treat patients who come in with joint pain. So the rheumatologist says, "Look, I have to give analgesics to people with arthritis and other chronic painful conditions; that is why they are coming in to see me. These drugs are useful for pain and a small risk is likely acceptable." All drugs have risks, so it's more about managing the risk through appropriate patient selection and good communication rather than complete risk avoidance.


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