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Original Investigation
July 14, 2021

Effect of Paroxetine-Mediated G-Protein Receptor Kinase 2 Inhibition vs Placebo in Patients With Anterior Myocardial Infarction: A Randomized Clinical Trial

Author Affiliations
  • 1Department of Cardiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
  • 2Clinical Trials Unit, University of Bern, Bern, Switzerland
  • 3Department of Anaesthesiology and Pain Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
JAMA Cardiol. Published online July 14, 2021. doi:10.1001/jamacardio.2021.2247
Key Points

Question  Does treatment with paroxetine mitigate adverse left ventricular remodeling in patients presenting with acute anterior myocardial infarction?

Findings  In this double-blind, placebo-controlled randomized clinical trial allocating patients after acute anterior myocardial infarction to treatment with paroxetine or placebo, no difference was found in recovery of left ventricular ejection fraction at 12 weeks. In contrast, patients in the experimental arm experienced a greater reduction in late gadolinium enhancement compared with those receiving placebo, indicating attenuation of myocardial fibrosis.

Meaning  In this trial, in patients with acute myocardial infarction, treatment with paroxetine did not improve left ventricular ejection fraction compared with placebo.


Importance  Left ventricular remodeling following acute myocardial infarction results in progressive myocardial dysfunction and adversely affects prognosis.

Objective  To investigate the efficacy of paroxetine-mediated G-protein–coupled receptor kinase 2 inhibition to mitigate adverse left ventricular remodeling in patients presenting with acute myocardial infarction.

Design, Setting, and Participants  This double-blind, placebo-controlled randomized clinical trial was conducted at Bern University Hospital, Bern, Switzerland. Patients with acute anterior ST-segment elevation myocardial infarction with left ventricular ejection fraction (LVEF) of 45% or less were randomly allocated to 2 study arms between October 26, 2017, and September 21, 2020.

Interventions  Patients in the experimental arm received 20 mg of paroxetine daily; patients in the control group received a placebo daily. Both treatments were provided for 12 weeks.

Main Outcomes and Measures  The primary end point was the difference in patient-level improvement of LVEF between baseline and 12 weeks as assessed by cardiac magnetic resonance tomography. Secondary end points were changes in left ventricular dimensions and late gadolinium enhancement between baseline and follow-up.

Results  Fifty patients (mean [SD] age, 62 [13] years; 41 men [82%]) with acute anterior myocardial infarction were randomly allocated to paroxetine or placebo, of whom 38 patients underwent cardiac magnetic resonance imaging both at baseline and 12 weeks. There was no difference in recovery of LVEF between the experimental group (mean [SD] change, 4.0% [7.0%]) and the control group (mean [SD] change, 6.3% [6.3%]; mean difference, −2.4% [95% CI, −6.8% to 2.1%]; P = .29) or changes in left ventricular end-diastolic volume (mean difference, 13.4 [95% CI, −12.3 to 39.0] mL; P = .30) and end-systolic volume (mean difference, 11.4 [95% CI, −3.6 to 26.4] mL; P = .13). Late gadolinium enhancement as a percentage of the total left ventricular mass decreased to a larger extent in the experimental group (mean [SD], −13.6% [12.9%]) compared with the control group (mean [SD], −4.5% [9.5%]; mean difference, −9.1% [95% CI, −16.6% to −1.6%]; P = .02).

Conclusions and Relevance  In this trial, treatment with paroxetine did not improve LVEF after myocardial infarction compared with placebo.

Trial Registration  ClinicalTrials.gov Identifier: NCT03274752

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