NSAIDs and Cardiovascular Disease

Although more COX-2-selective NSAIDs appear to be associated with a higher risk of CV problems, the report recommends that patients taking any NSAID be monitored for hypertension in addition to edema, declining renal function, and GI bleeding. It also recommends that in patients who are at increased risk for a thrombotic event, low-dose aspirin(Drug information on aspirin) (ie, 81 mg/d) be considered, although it notes that this may not provide "sufficient protection" against these adverse events. The statement discusses whether NSAIDs can counteract the cardiac protective actions of aspirin and reports that at present, ibuprofen(Drug information on ibuprofen) is the only NSAID that has been found to do so; however, there is limited information on other NSAIDs with regard to this. It also notes that the addition of aspirin while the patient is taking an NSAID can increase the risk of GI distress and bleeding.

While reading the AHA statement, I experienced déjà vu. With the exception of recommending the use of narcotics before NSAIDs and the addition of the COX-2-selective agents at the bottom of the list, the guidelines are very similar to standard clinical practice up until the introduction of the latter drugs during the late 1990s. Before that, in patients for whom an NSAID was indicated but who were at risk for GI bleeding, a nonacetylated salicylate such as choline and magnesium salicylate (Trilisate) was recommended.

I do have several concerns about the AHA statement. It recommends dividing musculoskeletal problems into "those that result from tendonitis/bursitis, those that result from degenerative joint problems (eg, osteoarthritis), or those that result from inflammatory joint problems (eg, rheumatoid arthritis)," but it fails to note that there are many cases of pain, most notably low back pain, where it is less clear to what extent musculoskeletal problems are the cause.

It also does not discuss the use of topical agents. There is literature supporting the use of topical NSAIDs, capsaicin, and lidocaine(Drug information on lidocaine) transdermal 5% patch (Lidoderm) for musculoskeletal pain.⁴ All have the added benefit of being relatively unlikely to cause systemic adverse effects or to interact with other medications.

Finally, in supporting the use of tramadol(Drug information on tramadol), it does not note that the drug's analgesic effects appear primarily related to its inhibition of serotonin and norepinephrine(Drug information on norepinephrine) reuptake.

The tricyclic antidepressants (TCAs) also have been found to be beneficial in pain related to both osteoarthritis and rheumatoid arthritis, although their cardiac effects generally contraindicate their use in patients who have cardiac disease, especially conduction defects.⁵ Tramadol may be safer than TCAs for these patients, but it is a very weak serotonin-norepinephrine reuptake inhibitor (SNRI). Although there are limited reports on the use of the SNRIs venlafaxine (Effexor XR) and duloxetine(Drug information on duloxetine) (Cymbalta) in musculoskeletal pain, their effectiveness in other types of pain suggest that they may be beneficial and thus worthy of consideration.