Use of antidepressants and the risk of acute myocardial infarction, and non-cardioembolic ischemic stroketwo nested case-control studies in a primary health care database

Resumo

Aim: this research included two studies, the primary objective for the first one is to investigate the association between antidepressants use and the risk of Acute Myocardial Infarction (AMI). And the primary objective for the second study to assess the association of SSRIs and other antidepressant subgroups with ischemic stroke (IS) of probable noncardioembolic origin. Methods: For the first study: A nested case-control study was conducted using a primary care database over the period 2002-2015. From a defined primary cohort composed of patients aged 40-99 years, and had no record of cancer or a previous AMI, incident AMI cases was identified and randomly selected five controls per case, matched to cases for exact age, sex and index date. Exposure to antidepressants were categorized as current-, recent-, past- and non-users. conditional logistic regression was used to calculate Adjusted Odds Ratio (AOR) and 95% Confidence Interval (CI) in order to assess the association between the current use of different antidepressants subgroups and AMI as compared to non-use. Dose and duration effects were explored. For the second study: A nested case-control study was conducted using a primary care database over the period 2002-2015. From a defined cohort composed of patients aged between 40 and 99 years and had no record of cancer or a previous stroke (any type of stroke). Incident non cardioembolic stroke cases were identified and randomly selected five controls per case, matched to cases for exact age, sex and index date. Antidepressants were divided in 6 pharmacological subgroups according to their mechanism of action. Antidepressant use was categorized as current-, recent-, past- and non-users. The current use of SSRIs was compared to non-use, past use and current use of other antidepressants through a conditional logistic regression model to obtain adjusted odds ratios (AORs) and 95% confidence intervals (95%CI). Only initiators of SSRIs and other antidepressants were considered. Results: for the first study: A total 24,155 incident AMI cases and 120,775 controls were included. The current use of antidepressants as a group was associated with a reduced risk (AOR=0.86; 95% CI:0.81-0.91), but mainly driven by Selective Serotonin Reuptake Inhibitors (SSRIs) (AOR=0.86; 95% CI:0.81-0.93). A reduced risk was also observed with trazodone (AOR=0.76;95%CI:0.64-0.91), and clomipramine (AOR=0.62;95%CI:0.40-0.96), whereas no significant effect was observed with other antidepressants. A duration-dependent effect was suggested for SSRIs, trazodone and clomipramine, while there was no clear dosedependency. For the second study: A total of 8,296 non-cardioembolic IS cases and 37,272 matched controls were included. Of them, 255 (3.07%) were current users of SSRIs among cases and 834 (2.24%) among controls, the current use of SSRIs as compared to non-users showed an AOR of 1.14 (95%CI:0.97-1.34), 0.94 (95%CI:0.77-1.13) as compared to past-users and 0.74 (95%CI:0.58-0.93) as compared to current users of other antidepressants. No relevant differences were found by duration (≤1year, >1year), sex, age (<70, ≥70 years old) and background vascular risk in both AMI and non-cardioembolic IS. Conclusions: The first study suggests that current use of antidepressants interfering selectively with the reuptake of serotonin, and those antagonizing the 5-HT2A receptor, are associated with a decrease in AMI risk and should be the antidepressants of choice in patients at cardiovascular risk. The second study showed that use of SSRIs was not associated with an increased risk of non- cardioembolic ischemic stroke. On the contrary, as compared to other antidepressants, SSRIs appeared to be protective.