NSAID Initiation Contraindicated in New Myocardial Infarction or Heart Failure

Nonsteroidal anti-inflammatory drug (NSAID) use in patients with newly diagnosed myocardial infarction (MI) or heart failure (HF) is contraindicated, and the persistent high prevalence of this use is of significant concern and requires immediate attention, according to study findings published in the European Heart Journal Cardiovascular Pharmacotherapy.

Investigators in Denmark sought to determine if patients with first-time MI or HF have differing cardiovascular risk related to continuing or initiating NSAIDs. The primary outcome was a composite of all-cause death and new MI/HF admission.

The investigators conducted a cohort study using nationwide health registries from 1996 to 2018 that included all patients with first-time MI or HF who survived until 30 days after discharge (N=273,682). A total of 97,966 patients who receive NSAIDs were stratified by continuing users (17%) and initiating users (83%) determined by prescriptions filled less than 60 days before index diagnosis according to the Danish National Prescription Registry.

All NSAIDs are available by prescription in Denmark, over-the-counter sales of ibuprofen are restricted to individuals at least 18 years of age, 1 package/person/dispensing (since 2011), and pack sizes contain a maximum of 20 tablets (since 2013). Additionally, prescriptions are reimbursable so use of data from the Danish National Prescription Registry is a reasonable representation of NSAID use.

Continuing users vs initiators were older (median age, 72 vs 67 years), more often women (48% vs 39%), and had more severe comorbidity burden (20% vs 13%) reflected by prescribed opioids (27% vs 10%), prescribed acetaminophen (32% vs 13%), prescribed anti-ulcer medications (20% vs 12%), and osteoarthritis (22% vs 12%).

The investigators found the most frequently filled NSAID prescriptions (N=657,469) were ibuprofen (50%), diclofenac (20%), etodolac (8.5%), and naproxen (4.3%). Redeemed prescriptions (treatment intensity) declined during the study period from a median of 5 to 2. Continuing users vs initiators had a stronger overall treatment intensity (2 vs 1, in 2018).

The hazard ratio (HR) for the composite outcome was 1.25 (95% CI, 1.23-1.27) substantiated by initiator results (HR, 1.39; 95% CI, 1.36-1.41) and not by continuing users (HR, 1.03; 95% CI, 1.00-1.07).

The HR for the composite outcome among initiators was 1.63 (95% CI, 1.57-1.69) for diclofenac, 1.31 (95% CI, 1.27-1.35) for ibuprofen, and 1.19 (95% CI, 1.08-1.31) for naproxen.

Ibuprofen and naproxen showed no association with the composite outcome among continuing users (HR, 1.00; 95% CI, 0.96-1.05; and HR, 0.98; 95% CI, 0.86-1.12), and associated with a slightly increased outcome rate for diclofenac (HR, 1.11; 95% CI, 1.05-1.18).

These results were consistent with individual components of the composite outcome, for both MI and HF patients, through various sensitivity analyses.

Study limitations include the filled prescriptions being a proxy for adherence and possible unmeasured confounding.

“The persistent high-prevalent contraindicated NSAID use in patients with newly diagnosed MI or HF is a major public and clinical health concern that needs attention from healthcare authorities and relevant medical societies,” the investigators wrote. “…patients with [first-time] MI or HF represent a high-risk group, in which not even nonselective NSAIDs (ibuprofen and naproxen) seem safe to initiate and where other analgetic regimens therefore should be prioritized.”

Disclosure: One study author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.