Nonsteroidal anti-inflammatory drugs (NSAIDs) can be dangerous for patients with atrial fibrillation (AFib) when taken on top of oral anticoagulants, suggests a post hoc analysis of the RE-LY trial published in the Journal of the American College of Cardiology.
The trial was designed to compare dabigatran etexilate (DE) 150 and 110 mg twice daily with warfarin in patients with AFib. But in this analysis, researchers studied outcomes based on whether participants used a NSAID at any point during the study; 12.6 percent of the 18,113 patients took an NSAID along with the prescribed oral anticoagulant (OAC).
Compared to patients who never used NSAIDs during follow-up, those who did demonstrated average risk increases of 68 percent for major bleeding, 81 percent for gastrointestinal bleeding, 50 percent for stroke or systemic embolism and 64 percent for hospitalization. The rates of myocardial infarction were similarly low for both groups and NSAID use didn’t alter the comparative effectiveness of the OACs when evaluated against each other.
“The mechanism for the observed bleeding associated with NSAIDs was likely a result of its antiplatelet effects and a reduction in gastric mucosal protection,” wrote lead author Anthony P. Kent, MD, and colleagues. “Non-GI (gastrointestinal) bleeding represented 60 percent and GI bleeding represented 40 percent of major bleeding events among the NSAID group. NSAIDs are known to reduce the glomerular filtration rate, and DE is excreted approximately 80 percent via glomerular filtration.”
NSAIDs are easily available over-the-counter and are “frequently self-used in the community in conflict with labeling information,” according to the authors. Notably, they are often used for arthritis, which would make overlaps with OACs taken for heart problems more likely as the population ages.
Kent et al. noted the baseline stroke risk calculated by the CHA2DS2-VASc score was 3.6 both for patients who took and didn’t take NSAIDs. Hospitalization occurred in 20 percent of patients each year in the non-NSAID arm versus 29 percent who took NSAIDs.
“The present analysis … reinforces the evidence that NSAIDs are not innocuous medications,” Kent and coauthors wrote. “Thus, there is a need for careful clinical review of NSAID use in patients with atrial fibrillation who are receiving OAC therapy.”
AFib is estimated to affect up to 6.1 million Americans and more than 30 million people worldwide, according to the authors.
“Updated guidelines and better therapeutic interventions (nonpharmacological and pharmacological) are needed to address analgesia in patients with heart disease because current approaches with NSAIDs and opioids pose a risk to patients,” they wrote.
The analysis didn’t have data on which specific type of NSAID was used, the dosage or the reason for its use, the researchers acknowledged.
In a related editorial, two researchers said the increase in cardiovascular events associated with NSAIDs is likely related to anticoagulation being interrupted or stopped altogether in response to bleeding events. Outside of that, they said there is “little clarity” for which mechanisms contribute to the increase in events.
The landscape is just as muddy for what alternatives to NSAIDs and opioids could be used to manage pain in patients with both AFib and arthritis.
“Our best strategy is to tailor treatment on an individual basis to clinical need and predictable risks,” wrote Sam Schulman, MD, PhD, and James Aisenberg, MD. “NSAID use should be moderated when appropriate, and coxibs should be considered. Concurrent antiplatelet treatment, particularly dual antiplatelet treatment, increases bleeding risk in the setting of non-aspirin NSAID and anticoagulation, and should be carefully scrutinized.”