Risks Associated With Diclofenac Initiation

Patients initiating diclofenac may have an increased risk for cardiovascular events compared with individuals using paracetamol, other traditional nonsteroidal anti-inflammatory drugs (NSAIDs), or those not taking NSAIDs, according to a study published in the British Medical Journal.

The study included 252 Danish nationwide cohort studies conducted between 1996 and 2016. Participants were adults without malignancy, schizophrenia, dementia, or cardiovascular, kidney, liver, or ulcer diseases. Cox proportional hazards regression analysis was used to calculate the intention-to-treat hazard ratio of major cardiovascular events within 30 days of drug initiation. The study included 1,370,832 patients initiating diclofenac, 3,878,454 individuals initiating ibuprofen, 291,490 initiating naproxen, 764,781 healthcare-seeking paracetamol initiators matched by propensity score, and 1,303,209 healthcare-seeking non-initiators also matched by propensity score.

The rate of adverse events among diclofenac initiators was 50% greater than that among non-initiators (incidence rate ratio [IRR], 1.5; 95% CI, 1.4-1.7), 20% greater compared with paracetamol or ibuprofen initiators (IRR, 1.2 for both; 95% CI, 1.1-1.3), and 30% greater compared with naproxen initiators (IRR, 1.3; CI, 1.1-1.5).

Diclofenac initiators vs non-initiators had increased event rates for each component of the combined end point: 1.2 for atrial fibrillation/flutter, 1.6 for ischemic stroke, 1.7 for heart failure, 1.9 for myocardial infarction, and 1.0 for cardiac death. Diclofenac initiators had an increased risk for upper gastrointestinal bleeding at 30 days, with a 4.5-fold risk compared with individuals not initiating diclofenac, a 2.5-fold risk compared with individuals initiating ibuprofen or paracetamol, and a similar risk compared with individuals initiating naproxen.

“It is time to acknowledge the potential health risk of diclofenac and to reduce its use,” the researchers wrote. “Diclofenac should not be available over the counter, and when prescribed, should be accompanied by an appropriate front package warning about its potential risks.”

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Reference

Schmidt M, Sorensen HT, Pedersen L. Diclofenac use and cardiovascular risks: series of nationwide cohort studies.  BMJ. 2018;362:k3426.