This review summarizes evidence on the cardiovascular safety of non-aspirin NSAIDs, highlighting that selective COX-2 inhibitors and diclofenac increase the risk of cardiovascular complications.
Do non-aspirin NSAIDs increase the risk of cardiovascular complications?
This position paper by the European Society of Cardiology highlights the significant cardiovascular risks associated with both selective COX-2 inhibitors and traditional non-aspirin NSAIDs.
Non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs) have been used in clinical practice for more than a century and are among the most widely used drugs worldwide for the treatment of pain, fever, and inflammation.1,2 For decades, it has been known that many of these drugs can cause fluid retention and elevate blood pressure,3 thus increasing cardiovascular risk particularly in heart failure patients.4 However, the main worry in relation to the use of these agents has been gastrointestinal bleeding.5 Newer selective COX-2 inhibitors (coxibs) were developed as NSAIDs with reduced gastrointestinal toxicity, but retained analgesic and anti-inflammatory properties. Coxibs were tested in accordance to modern drug development regulations with large numbers of patients included in clinical trials. These trials demonstrated that rofecoxib,6–8 celecoxib,9 valdecoxib,10 and parecoxib10 increased the risk of cardiovascular complications. As a result, coxibs currently have very limited indications for use. Paradoxically, an older and relatively selective COX-2 inhibitor, diclofenac,11 continues to be one of the most widely used drugs worldwide and is in most countries sold over the counter.1 Mixed COX-1/COX-2 inhibitors such as ibuprofen and naproxen are also used widely and, without solid evidence, assumed to be safe. Given the current uncertainty regarding the safety of this class of agents and the rapidly accumulating data on their cardiovascular risks, this review summarizes the current evidence from randomized and observational studies on the cardiovascular safety of non-aspirin NSAIDs and presents a position for their use. Non-steroidal anti-inflammatory drugs exhibit their anti-inflammatory effect by inhibiting COX, which is the rate-limiting enzyme in prostaglandin synthesis ( Figure 1 ).12 There are …
“The problem, as expected, is that these drugs are sold over-the-counter without any advice on side effects or the harmful effects. And even though they are sold in low dosages, the message is wrong. If you have an average individual, somebody who doesn't have this knowledge [about the risks], they're trusting the healthcare authorities or regulators that the drugs are safe to use. That's the problem. It gives a misconception that the drugs are safe.”
Schmidt et al. (Wed,) conducted a review in Cardiovascular risk associated with NSAID use. Non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs) was evaluated. This review summarizes evidence on the cardiovascular safety of non-aspirin NSAIDs, highlighting that selective COX-2 inhibitors and diclofenac increase the risk of cardiovascular complications.