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Primer: Non-steroidal anti-inflammatory drugs (NSAIDS) are known to be harmful in patients with myocardial infarctions. In fact, in 2007 the American Heart Association formally discouraged their use in this population subset. We also know that MI risk and the risk of death after a first MI is increased in the first year but returns to baseline after about 5 years – it is important to determine at what time-point during the post-MI period NSAID most increases the risk of further coronary events, in order to guide clinical decision making. This study examines cardiovascular risk associated with NSAID use over time since first-time MI to answer this question.
This [retrospective] study: 99,187 patients in a Danish registry were included. All were 30+ years old with a first-time MI between 1997-2009. Authors then obtained drug prescription records for each patient, using a validated method to estimate daily dosages for each patient. The primary endpoints included unadjusted rates of death as well as a composite point of coronary death or incidence of nonfatal recurrent MI. 44% of patients were prescribed NSAIDS after the first MI. 37% of the cohort died and 29% experienced a primary outcome in 5 years of follow-up. Patients using any NSAID after MI had an increased risk of death: hazard ratio (HR) of 1.59 (CI 1.49-1.69) after the first year and HR 1.63 (CI 1.52-1.74) after 5 years. Risk of coronary death of non-fatal recurrent MI were also statistically significantly increased in the NSAID groups on par with the data above.
In sum: The authors build on prior research and demonstrate a proportional increase in risk of death as well as coronary death/nonfatal MI in patients receiving NSAIDS after their first MI. This risk appears in the first year after MI but persists nearly unchanged for 5 years post-MI. This is in contrast to post-MI patients not taking NSAIDS, as the risk of subsequent MI declines to baseline over the same time period. Causality, however cannot be established with the study design. Clinically, there might be a greater push to limit NSAID use among post-MI patients and consider alternatives. Still, large scale comparative trials of various analgesic substances is warranted to better parse out which medications have the safest profiles for this subset of the population.
The study did not consider indications for the use of the NSAIDs in the subjects, introducing possible confounding. In addition, the study assumes adherence by every patient to their prescribed medication, but of course it is very possible patients did not adhere to the drugs prescribed – there is no way to determine this given the study design.
Click to read the study in Circulation
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