Excess Mortality in Aspirin and Dipyrone (Metamizole) Co‐Medicated in Patients With Cardiovascular Disease: A Nationwide Study

BACKGROUND: Pain is a major issue in our aging society. Dipyrone (metamizole) is one of the most frequently used analgesics. Additionally, it has been shown to impair pharmacodynamic response to aspirin as measured by platelet function tests. However, it is not known how this laboratory effect translates to clinical outcome. METHODS AND RESULTS: We conducted a nationwide analysis of a health insurance database in Germany comprising 9.2 million patients. All patients with a cardiovascular event in 2014 and subsequent secondary prevention with aspirin were followed up for 36 months. Inverse probability of treatment weighting analysis was conducted to investigate the rate of mortality, myocardial infarction, and stroke/transient ischemic attack between patients on aspirin‐dipyrone co‐medication compared with aspirin‐alone medication. Permanent aspirin‐alone medication was given to 26,200 patients, and 5946 patients received aspirin–dipyrone co‐medication. In the inverse probability of treatment weighted sample, excess mortality in aspirin–dipyrone co‐medicated patients was observed (15.6% in aspirin‐only group versus 24.4% in the co‐medicated group, hazard ratio [HR], 1.66 [95% CI, 1.56–1.76], P<0.0001). Myocardial infarction and stroke/transient ischemic attack were increased as well (myocardial infarction: 1370 [5.2%] versus 355 [5.9%] in aspirin‐only and co‐medicated groups, respectively; HR, 1.18 [95% CI, 1.05–1.32]; P=0.0066, relative risk [RR], 1.14; number needed to harm, 140. Stroke/transient ischemic attack, 1901 [7.3%] versus 506 [8.5%] in aspirin‐only and co‐medicated groups, respectively; HR, 1.22 [95% CI, 1.11–1.35]; P<0.0001, RR, 1.17, number needed to harm, 82). CONCLUSIONS: In this observational, nationwide analysis, aspirin and dipyrone co‐medication was associated with excess mortality. This was in part driven by ischemic events (myocardial infarction and stroke), which occurred more frequently in co‐medicated patients as well. Hence, dipyrone should be used with caution in aspirin‐treated patients for secondary prevention.