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

This report ignores a basic fact about people who have to take analgesics -- namely, that their pain is associated with stress. Stress is associated with hypertension, myocardial infarction and mood changes such as anger and depression that have been specifically linked to major cardiovascular events including cardiac failure. An example of stress related mood changes is increased anger, fatigue and depression during placebo periods in a crossover clinical trial of diclofenac in patients with chronic arthritis of the knees (1) while the association between anger and myocardial infarction is well documented. For example, in one report the relative risk of myocardial infarction in the 2 h after an episode of anger was 2.3 (95% confidence interval 1.7, 3.2 (2).

Stress is a common factor to chronic pain which could at least partly explain the uniformity of the report's finding across many analgesics. Where an analgesic is perceived to be stronger, such as diclofenac, it tends to be used in pain that has not responded to other analgesics so it is chronic and severe and involves greater stress levels. Such patients may have to use higher doses which is an alternative explanation of an apparent dose related effect.

Overall I am concerned that advice to avoid analgesics, or minimise their dose, could have the perverse effect of increasing risk of serious cardiovascular events by asking patients to undergo more pain, thereby increasing their stress.

1. Kilminster SG, Mould GP. Comparison of diclofenac spray and gel on knee joints of patients with osteoarthritic pain. Clin Drug Invest. 1999;5:345–54.
2. Mittleman MA, Maclure M, Sherwood JB, Mulry RP, Tofler GH, Jacobs SC, Friedman R, Benson H, Muller JE. Triggering of acute myocardial infarction onset by episodes of anger. Determinants of myocardial infarction onset. Circulation. 1995;92:1720–5. [PubMed]