Risk for heart failure admissions increased with select NSAIDs, higher doses

The cardiovascular (CV) risks of NSAIDs are well known, with data showing these agents increase the risk of myocardial infarction, stroke, and heart failure.

Use of NSAIDs was associated with an increased risk for heart failure admissions, and this risk doubled for select NSAIDs used at higher doses, according to results of a large observational study of real-world data published in The British Medical Journal.1

The cardiovascular (CV) risks of NSAIDs are well known, with data showing these agents increase the risk of myocardial infarction, stroke, and heart failure. These risks have been demonstrated to increase with longer durations of use and with higher doses. Little is known, however, about the risk of heart failure with individual NSAIDs and cyclooxygenase-2 (COX-2) inhibitors.

New study data   

A nested case-control study was conducted to assess the risk of heart failure admissions with recent use of specific NSAIDs and COX-2 inhibitors using data from the Safety of Non-Steroidal Anti-Inflammatory (SOS) Drugs Project.1 Data from the SOS project included information on more than 37 million people from four European countries (i.e., the Netherlands, Italy, Germany, and the United Kingdom) gathered from 1999 to 2010. All patients who started NSAIDs during the follow-up period were selected for the analysis. Cases were defined as those being admitted for heart failure during the follow-up period (n = 92,163) and were matched with up to 100 controls on the basis of sex, age, and date of entry in the analysis (n = 8,246,403).

A total of 27 NSAIDs were assessed, with 23 being traditional NSAIDs and 4 being COX-2 inhibitors. Results of the analysis showed that current use of any NSAID, defined as use in the preceding 14 days, was associated with an approximately 20% higher risk for heart failure admissions compared with past use (odds ratio [OR] 1.19 [95% CI 1.17–1.22]). Specifically, this risk was increased with seven traditional NSAIDs (i.e., diclofenac, ibuprofen, indomethacin, ketorolac, naproxen, nimesulide, and piroxicam) and two COX2 inhibitors (i.e., etoricoxib and rofecoxib). The risk was greatest for ketorolac (OR 1.83), followed by etoricoxib and indomethacin (ORs 1.51 each). In addition, higher doses of select NSAIDs were associated with a doubling in the risk of heart failure admissions. Celecoxib was not associated with an increased risk of heart failure admissions when given at commonly used doses.

In an accompanying editorial, the authors noted that the current analysis adds to the bulk of evidence linking NSAID use with increased risk of heart failure.2 They commented, however, that this study only reported odds ratios, and information on absolute risks would have been more meaningful. The authors wrote, “For patients who do need NSAID treatment, it is important to consider the different risk profiles of the individual drugs.” They concluded that given the widespread use of NSAIDs and their OTC availability, even a small increase in CV risk is a real concern for public health. On the basis of the available evidence, clinicians should evaluate the risk–benefit ratio of using NSAIDs and strive to use the lowest effective dose for the shortest duration of time.

Visit www.pharmacytoday.org for the full article in the upcoming December 2016 issue of Pharmacy Today.



1.      BMJ. 2016;354:i4857.

2.      BMJ. 2016;354,i5163.