Antidepressant Paroxetine may attenuate myocardial fibrosis in post MI setting: JAMA
Antidepressant Paroxetine may be worth gold for heart attack patients as it may attenuate myocardial fibrosis in post MI setting, finds JAMA study.
Dysregulation of G-protein–coupled receptor kinases (GRK) plays a central role in the progression of left ventricular remodeling after ischemic injury. In this regard, researchers Piilgrim et al explored the role of selective serotonin reuptake inhibitor paroxetine which has an off target inhibitory role on GRK2, in mitigating adverse left ventricular remodeling in patients presenting with acute anterior myocardial infarction.
The authors found that treatment with paroxetine did not improve left ventricular ejection fraction compared with placebo but patients in the paroxetine arm experienced a greater reduction in late gadolinium enhancement compared with those receiving placebo, indicating attenuation of myocardial fibrosis. The findings were published today in JAMA Cardiology.
Earlier in a mouse model, paroxetine treatment has been demonstrated to mitigate sympathetic overdrive, reverse myocardial remodeling, and improve left ventricular function. The aim of the present study was to prospectively investigate the efficacy of paroxetine-mediated GRK2 inhibition to mitigate adverse left ventricular remodeling in patients presenting with acute myocardial infarction.
In this double-blind, placebo-controlled randomized clinical trial 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. 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.
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.
At the end of trial period, the extent of LVEF recovery was comparable in patients treated with paroxetine or placebo. There were no significant differences in changes of left ventricular dimensions and volumes. In contrast, patients treated with paroxetine had greater reduction in late gadolinium enhancement (by approximately 9%), indicating attenuation of myocardial fibrosis and scar formation after myocardial infarction.
In contrast with the mouse model, in which treatment was started 2 weeks after inducing acute myocardial infarction, patients in this study were included 48 to 96 hours after primary percutaneous coronary revascularization and paroxetine was started on top of guideline-directed optimal medical therapy less than 7 days after percutaneous coronary revascularization.
In conclusion, in this randomized clinical trial, a 3-month course of paroxetine treatment following acute myocardial infarction did not lead to an improvement in left ventricular ejection fraction compared with placebo but a beneficial effect on late gadolinium enhancement paves way for future research in this arena.
Source: JAMA Cardiology: doi:10.1001/jamacardio.2021.2247
