On July 14, 2015 the Food and Drug Administration issued a warning that plans on asking manufacturers of non-steroidal anti-inflammatory drugs (NSAIDs) to change labels to reflect evidence of increased risk of heart attacks and strokes.
Most NSAIDs inhibit the activity of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2), and thereby, the synthesis of prostaglandins and thromboxanes. It is thought that inhibiting COX-2 leads to the anti-inflammatory, analgesic and antipyretic effects and that those NSAIDs that inhibit COX-1, particularly aspirin, may cause gastrointestinal bleeding and ulcers.
Non-steroidal anti-inflammatory drugs are widely used all over the world for their analgesic and antipyretic qualities and include Motrin IB, Aleve and Celebrex but not aspirin. In 2001, NSAIDs accounted for 70 million prescriptions and 30 billion over-the-counter doses annually in the United States.
Experts suggest that the warning reflected new evidence that there was risk even in small amounts and that everyone taking them should use them sparingly and for brief periods.
The FDA said that the drugs increased the risk of a heart attack and/or stroke soon after patients first started taking them, and that while the risk was higher for people with heart disease, it occurs even for people who had never had heart problems.
A meta-analysis of 280 trials of NSAIDs versus placebo (124 513 participants, 68 342 person-years) and 474 trials of one NSAID versus another NSAID (229 296 participants, 165 456 person-years) was published at Lancet in 2013.
Major vascular events were increased by about a third by a coxib or diclofenac, chiefly due to an increase in major coronary events. Ibuprofen also significantly increased major coronary events, but not major vascular events
Compared with placebo, of 1000 patients allocated to a coxib or diclofenac for a year, three more had major vascular events, one of which was fatal. Naproxen did not significantly increase major vascular events.
Vascular death increased significantly by coxibs and diclofenac, non-significantly by ibuprofen but not by naproxen. The proportional effects on major vascular events were independent of baseline characteristics, including vascular risk.
Heart failure risk was roughly doubled by all NSAIDs. All NSAID regimens increased upper gastrointestinal complications.
The data from these randomized trials suggest that vascular risks of high-dose diclofenac (Voltaren), and possibly ibuprofen (Advil, Motrin), are comparable to coxibs (Celebrex), whereas high-dose naproxen (Aleve) is associated with less vascular risk than other NSAIDs.
A conclusive answer could come from a large randomized trial, called Precision, that is comparing the rate of heart problems among patients with high cardiovascular risk for ibuprofen (Motrin IB), naproxen (Aleve) and celecoxib (Celebrex).
Patients who use over-the-counter medications, which have the lowest doses, should be aware that they probably increase their risk of a cardiovascular event by about 10 percent. Low-dose prescription medications were likely to increase the risk by about 20 percent and higher-level dose prescription medications by about 50 percent with significant variability in each estimate.
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