A new analysis confirms many of the risks and benefits of commonly used painkillers but quantifies them in ways that should help clinicians and patients make more informed decisions about using the drugs to treat chronic pain.
The meta-analysis, published online today in The Lancet, includes more than 600 clinical trials that evaluated about 353 000 patients. Researchers with the Coxib and traditional NSAID Trialists’ (CNT) Collaboration wanted to provide more reliable estimates of the effect that nonsteroidal anti-inflammatory drugs, known as NSAIDs, have on vascular and coronary events such as heart attacks, strokes, and death as well as on gastrointestinal complications including perforations, obstructions, or bleeding.
“There has been uncertainty about the nature and magnitude of these risks, and the relative safety of different NSAID regimens, especially in those at increased risk of coronary heart disease,” the researchers wrote.
They assessed risks associated with traditional NSAIDs such as ibuprofen, diclofenac, and naproxen as well as newer-generation formulations known collectively as coxibs because they selectively inhibit the COX-2 enzyme involved with pain and inflammation. COX-2 inhibitors were perceived to be as effective as traditional NSAIDs, with the added advantage of posing less risk of causing gastrointestinal upset. But subsequent studies showed they increased the risk of heart attacks and stroke, and the coxib rofecoxib was pulled from the market in 2004.
The new analysis showed that, compared with placebo, high doses of coxibs or diclofenac increased the risk of major vascular events, primarily heart attacks, by one-third. Ibuprofen more than doubled the risk of major coronary events compared with placebo but had no significant effect on the risk of vascular complications. High doses of naproxen weren’t associated with increased vascular or coronary risk.
All of the NSAIDs studied, including naproxen, roughly doubled the risk of being hospitalized because of congestive heart failure. All NSAIDs were linked with a 2- to 4-fold increased risk of gastrointestinal complications, primarily bleeding. The lowest risk was associated with using coxibs.
The overall results mean that, compared with placebo, about 3 excess major vascular events, including 1 death, could be expected annually in 1000 patients taking high-dose diclofenac or a coxib. But for every 1000 patients at high risk of major vascular events, taking a coxib or high-dose diclofenac would result in an additional 7 or 8 of those events occurring, about 2 that would be fatal.
The researchers said their findings “indicate that the effects of different regimens in particular patients can be predicted, which could help in guiding decisions about the clinical management of inflammatory disorders.”