https://immattersacp.org/weekly/archives/2016/10/04/1.htm

Prescription NSAIDs associated with heart failure risk, study finds

A 19% increased risk for hospital admission for heart failure was found to be associated with any use of NSAIDs in the preceding 14 days versus past use of any NSAIDs. Diclofenac, ibuprofen, indomethacin, ketorolac, naproxen, nimesulide, piroxicam, etoricoxib, and rofecoxib were associated with increased risk for hospital admission.


Prescription nonsteroidal anti-inflammatory drugs (NSAIDs) may increase risk for heart failure, a European study has found.

Researchers performed a nested case-control study using population health care databases from the Netherlands, Italy, Germany, and the United Kingdom to evaluate the cardiovascular safety of NSAIDs and to determine the risk for hospital admission for heart failure associated with individual NSAID use. The study included adults who began taking NSAIDs in 2000-2010. Those who were admitted to the hospital for heart failure were matched with controls by age, sex, and year of cohort entry in risk-set sampling. The main outcome measure was association between risk for hospital admission for heart failure and use of 27 NSAIDs (23 traditional drugs and 4 selective cyclooxygenase-2 [COX-2] inhibitors), with dose-response relationship between use of NSAIDs and heart failure risk as a secondary outcome measure. The study was published online on Sept. 28 by BMJ.

The authors matched 92,163 heart failure admissions with 8,246,403 controls. Mean age was 77 years and 76 years, respectively, and approximately 45% of each group were men. Overall, 9.1% of cases and 2.5% of controls had a history of heart failure diagnosis. Cases were more likely than controls to have comorbid conditions and to have received treatment with other drugs, such as anticoagulants and nitrates. Overall, 16,081 cases (17.4%) and 1,193,537 matched controls (14.4%) currently used NSAIDs.

A 19% increased risk for hospital admission for heart failure was found to be associated with any use of NSAIDs in the preceding 14 days (adjusted odds ratio [OR], 1.19; 95% CI, 1.17 to 1.22) versus past use of any NSAIDs, defined as at least 183 days previously. Seven traditional NSAIDs (diclofenac, ibuprofen, indomethacin, ketorolac, naproxen, nimesulide, and piroxicam) and 2 COX-2 inhibitors (etoricoxib and rofecoxib) were associated with increased risk for hospital admission. (Nimesulide and etoricoxib are not approved for use in the United States. Rofecoxib was withdrawn from the market in 2004 due to safety concerns.) Odds ratios were lowest for naproxen (1.16; 95% CI, 1.07 to 1.27) and highest for ketorolac (1.83; 95% CI, 1.66 to 2.02). Current use of any NSAID was associated with a 24% higher risk of heart failure than past use (odds ratio, 1.24; 95% CI, 1.12 to 1.36).

The dose-response analysis included 25,179 cases and 2,083,706 controls. Very high doses of diclofenac, etoricoxib, indomethacin, piroxicam, and rofecoxib (i.e., 2 or more defined daily dose equivalents) were associated with a doubled risk for heart failure; however, the authors noted that some of the confidence intervals for these odds ratios were wide. For indomethacin and etoricoxib, an association was seen between increased heart failure risk and doses of 0.9 to 1.2 defined daily dose equivalents. No association was seen between common doses of celecoxib and risk for heart failure admission, but the authors cautioned that they could not exclude the possibility of an increased risk at very high doses.

The authors noted that their study may not have captured all exposure to NSAIDs because it did not assess use of over-the-counter products. In addition, they said, some outcomes may have been misclassified, the dose-response analysis may have been underpowered for some dose classes, and heterogeneous patient characteristics at baseline and residual confounding may have affected their results. However, they concluded that increased risk for heart failure admission is associated with both traditional NSAIDs and selective COX-2 inhibitors and that the risk appears to vary according to drug and dose.

An accompanying editorial said the current study adds to existing evidence on the link between NSAID use and heart failure risk and provides new evidence regarding a dose-response relationship but did not provide data on excess absolute risk, making it harder to explain the findings to patients. However, the editorialists said that since NSAIDs are widely used, “even a small increase in cardiovascular risk is a concern for public health.” The availability of NSAIDs over the counter “fuels the common misconception that NSAIDs are harmless drugs that are safe for everyone,” they wrote. “Therefore, a more restricted policy by regulatory authorities on the availability of NSAIDs and requirements for healthcare professionals providing advice on their use and potential harm is warranted.”