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

Pilgrim, Thomas; Vollenbroich, René; Deckarm, Sarah; Gräni, Christoph; Dobner, Stephan; Stark, Anselm W; Erne, Sophie A; Babongo Bosombo, Flora; Fischer, Kady; Stortecky, Stefan; Reusser, Nicole; Fürholz, Monika; Siontis, George C. M.; Heg, Dik; Hunziker, Lukas; Windecker, Stephan; Lanz, Jonas (2021). Effect of Paroxetine-Mediated G-Protein Receptor Kinase 2 Inhibition vs Placebo in Patients With Anterior Myocardial Infarction: A Randomized Clinical Trial. (In Press). JAMA cardiology American Medical Association 10.1001/jamacardio.2021.2247

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Intensive Care, Emergency Medicine and Anaesthesiology (DINA) > Clinic and Policlinic for Anaesthesiology and Pain Therapy
04 Faculty of Medicine > Department of Cardiovascular Disorders (DHGE) > Clinic of Cardiology
04 Faculty of Medicine > Pre-clinic Human Medicine > CTU Bern

UniBE Contributor:

Pilgrim, Thomas; Vollenbroich, René; Gräni, Christoph; Dobner, Stephan; Babongo Bosombo, Flora; Fischer, Kady Anne; Stortecky, Stefan; Fürholz, Monika; Siontis, Georgios; Heg, Dierik Hans; Hunziker Munsch, Lukas Christoph; Windecker, Stephan and Lanz, Jonas

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2380-6583

Publisher:

American Medical Association

Language:

English

Submitter:

Andrea Flükiger-Flückiger

Date Deposited:

27 Jul 2021 12:53

Last Modified:

27 Jul 2021 12:53

Publisher DOI:

10.1001/jamacardio.2021.2247

PubMed ID:

34259826

URI:

https://boris.unibe.ch/id/eprint/157667

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