Non-steroidal anti-inflammatory drugs and risk of heart failure in four European countries: nested case-control study

NSAIDS and Heart Failure. Again dose and potency determine benefits and risks

The Safety of Non-steroidal Anti-inflammatory Drugs (SOS) Project Consortium (Andrea Arfè et. al. BMJ 28 September 2016) report on the association of NSAIDS with heart failure (HF). HF is a well-known risk with the use of NSAIDs.

The most important and interesting aspect of this study is the relative risk of the different NSAIDs, with higher heart failure risk found with ketorolac (odds ratio, 1.83), indomethacin (1.51), piroxicam (1.27), diclofenac (1.19), ibuprofen (1.18), and naproxen (1.16).

Higher doses were associated with greater risk. You can also observe that the higher the potency, the higher the risk. Paracelsus in action.

These finding are very similar to other reports on the side effects of NSAIDs as in our analysis in the BMJ ten years ago (1).
It is long known that all NSAIDs could produce some deaths per million prescriptions. The least potent, such as ibuprofen, had the lowest risk of death (1.5), the risk increasing with potency (naproxen 4.6, diclofenac 5.3, piroxicam 7.0, and indomethacin 7.1).

The odds ratios for adverse effects depend on the end point (cardiovascular or gastrointestinal), the reference parameters, and the dose: diclofenac (1.55, one study), naproxen (1.14 to 1.5, three studies), ibuprofen (1.09 to 1.24, two studies), celecoxib (0.43 to 1.26 in six studies, 1.25 in three).

It becomes again very clear that the cardiovascular toxicity of NSAIDs depends on their potency, dose and duration of the treatment. These fundamental elements should always be considered when we prescribe these important and useful drugs.

Prof. Enrique Sánchez Delgado, MD

Internal Medicine-Clinical Pharmacology and Therapeutics

Hospital Metropolitano Vivian Pellas, Managua

Reference:
1. - Sánchez Delgado Enrique. Life without COX 2 inhibitors. Risks and benefits are determined by dose and potency. BMJ 2006;332:1451-1452 (17 June)