Effectiveness of Paroxetine Versus Non‐Paroxetine Selective Serotonin Reuptake Inhibitors on Mortality and Heart Failure Following Myocardial Infarction: An Active Comparator Population‐Based Cohort Study

BACKGROUND: Animal studies suggest that paroxetine, unlike other selective serotonin reuptake inhibitors (SSRIs), may attenuate post-myocardial infarction (MI) heart failure. We examine the effectiveness of paroxetine versus non-paroxetine SSRIs on the risk of post-MI mortality and heart failure in a clinical setting. METHOD: We conducted a nationwide population-based cohort study based on Danish medical registries. Using an active comparator design, we compared the effectiveness of paroxetine with non-paroxetine SSRI drugs on post-MI outcomes. This included all patients hospitalized for MI in Denmark during 1995-2020 who had redeemed an SSRI prescription within 90 days prior to admission and measured outcome variables after a 180-day follow-up period. We calculated cumulative incidences as a measure of risk and used Cox regression to compute hazard ratios (HRs) for all outcomes, adjusting for sex, age group, individual comorbidities, and comedications. RESULTS: We identified 13 053 patients receiving treatment with an SSRI at the time of hospital admission for MI. Cumulative incidences were lower for paroxetine SSRI users compared with non-paroxetine SSRI users for all-cause mortality (24.7% versus 33.8% (difference: -9.1% [95% CI: -12.4; -5.8])) and cardiovascular death (15.9% versus 22.7% (-6.8% [95% CI: -9.6; -4.0])), but not for heart failure (11.0% versus 11.8% (-0.7% [95% CI: -3.13; 1.65])). Adjusted hazard ratios (aHRs) showed no substantial differences for all-cause mortality (aHR 0.9 [95% CI: 0.8-1.1]), cardiovascular death (aHR 0.9 [95% CI: 0.8-1.1]), or heart failure (aHR 1.0 [95% CI: 0.8-1.3]). CONCLUSION: Paroxetine was not associated with clinically significant improvement in post-MI outcomes compared with non-paroxetine SSRI drugs.