Unfortunately, confounding by indication is a common problem across these studies. Investigators have attempted to mitigate this effect by using a cohort of osteoarthritis or other inflammatory arthritis patients. Similarly, some studies have compared cardiovascular risk of NSAIDs with non-users of NSAIDs, which can also bias the results.
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Explore This IssueJuly 2018
Use of remote, recent and current users of NSAIDs instead of non-users could potentially reduce confounding. Finally, physician preferences of a particular NSAID, over-the-counter drug use and the effect of baby aspirin cannot be sufficiently accounted for in these studies.
NSAIDs are commonly used in routine clinical practice and, particularly, rheumatology practice. And perhaps for osteoarthritis, which is the most common form of arthritis, there are not many choices—clinicians are often forced to choose between NSAIDs and prescription opiates, both with their associated side effects. Also, clinicians must weigh other side effects such as GI toxicity (often much less with COX-2 inhibitors) and drug efficacy (recent meta-analysis suggests that diclofenac may be more effective) with cardiovascular toxicity.
Although the U.S. Food and Drug Administration warns for cardiovascular toxicity against all NSAIDs, naproxen’s cardiovascular safety has been demonstrated across clinical trials and observational trials. Celecoxib at lower doses has been shown to be safe from a cardiovascular standpoint, and it has a favorable GI safety prolife. Various observational studies have shown drugs that preferentially inhibit COX-2 over COX-1 (e.g., diclofenac, etodolac, meloxicam, etc.) have increased cardiovascular toxicity and should be avoided if possible. Finally, nabumetone seems to have remarkable GI safety, and initial observational studies have shown its cardiovascular safety.
In summary, current data suggest this reasonable pain treatment strategy:
- Start with nonsystemic NSAID analgesics, topical diclofenac or acetaminophen;
- Try naproxen next;
- Try celecoxib next, at a low (200 mg/day) dose; and finally
- Try other nonselective NSAIDs next, such as ibuprofen.
Deepan S. Dalal, MD, MPH, works in the Department of Medicine at Brown University Warren Alpert School of Medicine in Providence, R.I.
Maureen Dubreuil, MD, MS, works in the Department of Medicine at Boston University School of Medicine and the Division of Rheumatology in the Boston VA Healthcare system.
David T. Felson, MD, MPH, works in the Department of Medicine at Boston University School of Medicine and in the Arthritis Research UK Epidemiology Unit at the University of Manchester in Manchester, England.
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