NSAIDs and Cardiovascular Risk

Chances are excellent that you've probably taken an NSAID, a nonsteroidal anti-inflammatory medication, and you're in good company.  Almost everyone has taken one of this class of pain relievers at least once, and if survey data are to be believed, at any one time about a quarter of adults in the United States use these medications once per week or more.  That's a lot of NSIAD use, and it's worth reviewing that this class would include aspirin, ibuprofen, and naproxen, available over the counter (OTC) domestically and in many countries around the world.  How do these drugs compare with another major player in the OTC pain reliever world, acetaminophen or paracetamol?  Their mechanisms of action are different: NSAIDs work by inhibiting both cyclooxygenase-1 and 2, abbreviated COX-1 and COX-2, both enzymes, and thereby down regulating the production of thromboxanes and prostaglandins, which are involved in inflammation and pain.  Acetaminophen inhibits only COX-2, as does the prescription pain reliever celecoxib. As such these latter two may result in less gastrointestinal bleeding.  So what's the issue Rick and I discuss on PodMed this week?  The FDA has issued a report on the cardiovascular risk represented by NSAIDs, and since so many people are taking them, it's worth taking a look at the report.

The most recent data cited in the report is a meta-analysis of  280 placebo-controlled and 474 active-controlled NSAID trials, representing about 200,000 subjects in many comparisons and study designs. Sixty-eight percent of subjects were female, and 79% Caucasian, with a mean age of 61 years. Most people taking the medications had osteoarthritis (63%), with the next most common condition rheumatoid arthritis (20%). Lots of other data regarding comorbidities, concomitant use of gastroprotective medications or more than one NSAID was also examined when available.  The conclusion of the analysis was that use of these drugs did increase the risk of a vascular event by three in a thousand person years of treatment, with one fatal event. Ibuprofen was associated with a two-fold increased risk in major coronary events but not a statistically significant increase in major vascular events. Naproxen was not associated with major vascular events or vascular death, to which I quipped to Rick that I wish I had purchased stock in Naprosen prior to this report's release.

Gastrointestinal bleeds were also assessed and surprise!  were higher in the ibuprofen group.  Here's the take home as far as I'm concerned:  if you said to me as a patient in chronic pain that I had a very small but real increased risk for stroke and heart attack when I took NSAIDs or COX-2 inhibitors, and I juxtaposed that against daily pain relief, I would chose the small risk every time.  Rick responds to that with the current belle of the ball idea, "shared decision making."  He opines that this is one ideal time to educate the patient on both risks and benefits, ideally tailored to their specific situation, and then stand back and let the patient decide.  My own view of shared decision making is less sanguine, but I do agree that fair or not, its time has come and this may be the perfect illustration of when it should be used.

Other topics this week include a look at childhood obesity in the US in NEJM, the implications of the new cholesterol screening guidelines in Annals of Internal Medicine, and evaluating the potential for child abuse in fractures, in Pediatrics.  Until next week, y'all live well.

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