NSAIDs Vary in How Much They Raise Heart-Failure Hospitalization Risk

Larry Hand

September 30, 2016

MILAN, ITALY — The risk of hospitalization for heart failure with current use of nonsteroidal anti-inflammatory drugs (NSAIDs) varies with the use of individual NSAIDs, according to new research[1].

Dr Giovanni Corrao (University of Milano-Bicocca, Italy) and colleagues conducted a nested case-control study of five population-based healthcare databases from four countries: the Netherlands, Italy, Germany, and the United Kingdom.

Overall, they identified 92,163 hospital admissions for HF between 2000 and 2010 and matched that with more than 8.2 million controls by risk-set sampling according to sex, year of cohort entry, and age. More than 17% (16,081) of cases and just under 15% (1.19 million) of matched controls were current NSAID users.

The results were published online September 28, 2016 in the BMJ.

Dr Sanjay Kaul (Cedars Sinai Medical Center, Los Angeles), an expert who was not involved in the study, told heartwire from Medscape that it presents "nothing new other than the observation of a dose-response relationship and the differential risk across NSAIDs."

Researchers assessed the association between risk of hospital admission for HF with use of 27 NSAIDs (23 traditional NSAIDs and four COX-2 inhibitors) plus the dose-response relation.

They found that current use of any NSAID during the previous 14 days was associated with a 19% increase in risk of hospital admission for HF (adjusted odds ratio 1.19; 95% CI 1.17–1.22) compared with past use of any NSAID within 183 days.

Risk varied by individual NSAID, and researchers identified nine of the agents as posing significantly increased risk and three others (sulindac, acemetacin, and dexibuprofen) associated with risks that were raised but not significantly.

The researchers also found that current use of very high doses of diclofenac, etoricoxib, indomethacin, piroxicam, and rofecoxib carried more than a twofold risk compared with past use. They also found no significant differences between individuals with or without previous HF.

NSAIDs With Significantly Increased Risk of HF Admission

NSAID OR Men, n=41,652 OR Women, n=50,511
Indomethacin 1.71 1.25
Diclofenac 1.21 1.19
Ketoralac 1.86 1.96
Piroxicam 1.34 1.31
Ibuprofen 1.18 1.16
Naproxen 1.24 1.15
Rofecoxib 1.35 1.37
Etoricoxib 1.80 1.45
Nimesulide 1.31 1.17

In an accompanying editorial[2], Dr Gunnar H Gislason (Copenhagen University Hospital, Denmark) and Dr Christian Torp-Pedersen (Aalborg University, Denmark) wrote, "Owing to the widespread use of NSAIDs, even a small increase in cardiovascular risk is a concern for public health."

"However, the clinical perspective of the study was limited: it reported only odds ratios and did not provide data on excess absolute risk," they wrote.

"As pointed out by the editorialists, without knowing the absolute excess risk, it is hard to understand the clinical implications of these findings," Kaul told heartwire.

He continued, "Fortunately, the results of the PRECISION trial, a randomized, double-blind, parallel-group study of cardiovascular safety in osteoarthritis or rheumatoid arthritis patients with or at high risk for cardiovascular disease comparing celecoxib with naproxen and ibuprofen, will be presented at the [American Heart Association] meeting in November. This trial is likely to yield a more reliable estimate of cardiovascular risk and address the issue of differential risk among the three NSAIDs."

The study was funded by the European Community's seventh Framework Program. Corrao reported collaborating with advisory boards of Novartis and Roche and participating in projects funded by GlaxoSmithKline.

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