1. Paroxetine’s G-protein receptor kinase 2 inhibitory activity was not shown to alter anterior myocardial infarction left ventricle ejection fraction, left ventricular end-diastolic diameter, or end-systolic diameter, but improved late gadolinium enhancement compared to a placebo group at 12 weeks after anterior myocardial infarction.
2. Paroxetine was not found to significantly alter mortality or adverse effects compared to placebo.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Remodeling after myocardial infarction (MI) involves scar formation, ventricular dilation, and deterioration of contractile functions. This is signaled by intracellular signals including G-protein receptor kinases (GRK). Preclinical studies have demonstrated that inhibiting GRK2 may attenuate maladaptive responses. This study investigated the efficacy of paroxetine, a selective serotonin reuptake inhibitor that also inhibits GRK2, at reducing left ventricular cardiac remodeling, measured as change in left ventricular ejection fraction (LVEF) from baseline to 12 weeks using imaging in MI patients. This study also measured change in left ventricular end-diastolic and end-systolic volumes and change in late gadolinium enhancement. Patients randomized into paroxetine or placebo were comparable for their time to treat their MI. While LVEF improved between post-MI and 12 weeks, the paroxetine group did not improve more than the control group. Similarly, the paroxetine and control group did not differ on how patients improved on left ventricular end-diastolic diameter, or end-systolic diameter, echocardiograms findings, or mortality. The treatment group did, however, have improved late gadolinium enhancement percentage compared to the control group. This study was limited by being significantly underpowered due to higher attrition (24%) than anticipated (10%) in the power calculation. Additionally, participants had only moderate levels of LVEF reduction which limited the sensitivity of the study to detect differences based on treatment.
Click to read the study in JAMA Cardiology
Relevant Reading: Hypothesis: Paroxetine, a G Protein-Coupled Receptor Kinase 2 (GRK2) Inhibitor Reduces Morbidity and Mortality in Patients With Heart Failure
In-Depth [randomized controlled trial]: This study was an analysis of data from the Paroxetine-Mediated GRK2 Inhibition to reduce cardiac remodeling after acute myocardial infarction (CARE-AMI) double-blind, randomized controlled trial. Participants had MI with LVEF of ≤45% received either 20 mg paroxetine (measured at 12 weeks) or placebo in addition to guideline-directed medical treatment. Randomization was done using sequential boxes. Left ventricular ejection fraction was assessed at baseline and 12 weeks via transthoracic echocardiography and magnetic resonance imaging. 50 anterior wall MI patients (age = 62±13 years, 82% men) were eligible to undergo randomization and 38 completed the imaging (the subset of whom did not differ on any patient characteristics compared to the whole sample). Importantly, the randomized groups were comparable on door-to-balloon time and symptom onset to balloon inflation time. LVEF improved from baseline to 12 weeks treatment in both the paroxetine (4.0±7.0%) and control (6.3±6.3%) groups, however, the treatment did not significantly improve LVEF compared to the control group (-2.4%, 95% CI = -6.8% to 2 .1%]; P = 0.29). The treatment and control group did not differ on improvement from baseline to 12 weeks treatment in terms of left ventricular end-diastolic diameter (-0.2mm, 95% CI = -4.8 to 4.3; P = 0.92) or end-systolic diameter (3.6 mm, 95% CI = -1.7 to 8.8; P = 0.18). Late gadolinium enhancement significantly decreased more in the experimental group (-13.6±12.9%) compared with the control group (-4.5±9.5%) (-9.1%, 95% CI = -16.6% to -1.6%; P = 0.02). Echocardiograms at follow-up were comparable between the experimental and control group. As none of the participants died during the trial, there was no mortality difference between the experimental and control group.
Image: PD
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