Dataset Information

The Potential Anti-remodeling Effect of Paroxetine After Myocardial Infarction May Be Blunted by Beta-Blockers.

ABSTRACT:

Background

Left ventricular (LV) remodeling consists in maladaptive changes in cardiac geometry and function following an insult such as ST-segment elevation myocardial infarction (STEMI). Interventions able to prevent LV remodeling after a STEMI are expected to improve the outcome of this condition. Paroxetine has inhibitory effects on GRK2, also known as beta-adrenergic receptor kinase 1 (ADRBK1). This drug does not yield beneficial effects on LV remodeling in patients with STEMI and LV ejection fraction ≤ 45%.

Methods

We compared the molecular effects of paroxetine and drugs for neurohormonal antagonism (beta-blockers, angiotensin converting enzyme inhibitors/angiotensin receptor blockers, mineralocorticoid receptor antagonists), using a bioinformatic approach integrating transcriptomic data in a swine model of post-MI and available evidence from the literature and massive public databases.

Results

Among standard therapies for MI, beta-blockers are the only ones acting directly upon GKR2, but the mechanism of action overlaps with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers with respect to the AT2R-mediated anti-hypertensive response. Moreover, beta-blockers could have anti-fibrotic and anti-inflammatory effects through the regulation of myocyte-specific enhancer factors, endothelins and chemokines.

Conclusion

The additive benefit of paroxetine on the background of the standard therapy for STEMI, which includes beta-blockers, is expected to be limited. Nonetheless, paroxetine becomes particularly interesting when a beta-blocker is contraindicated (for example, in hypotensive individuals) or poorly tolerated.

SUBMITTER: Iborra-Egea O

PROVIDER: S-EPMC9309347 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

The Potential Anti-remodeling Effect of Paroxetine After Myocardial Infarction May Be Blunted by Beta-Blockers.

Iborra-Egea Oriol O Aimo Alberto A Martini Nicola N Galvez-Monton Carolina C Burchielli Silvia S Panichella Giorgia G Passino Claudio C Emdin Michele M Bayes-Genis Antoni A

Frontiers in cardiovascular medicine 20220711

<h4>Background</h4>Left ventricular (LV) remodeling consists in maladaptive changes in cardiac geometry and function following an insult such as ST-segment elevation myocardial infarction (STEMI). Interventions able to prevent LV remodeling after a STEMI are expected to improve the outcome of this condition. Paroxetine has inhibitory effects on GRK2, also known as beta-adrenergic receptor kinase 1 (ADRBK1). This drug does not yield beneficial effects on LV remodeling in patients with STEMI and L ...[more]

PMID: 35898267

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Project description:Objectives: Rheumatoid arthritis (RA) is an independent nontraditional risk factor for incidence of myocardial infarction (MI) and post-MI outcome is impaired in the RA population. Use of beta-blockers improves the long-term survival after MI in the general population while the protective effect of beta-blockers in RA patients is not clear. We investigate the impact of beta-blockers on the long-term outcome of MI among RA patients. Methods: We identified RA subjects from the registries for catastrophic illness and myocardial infarction from 2003 to 2013. The enrolled subjects were divided into three groups according to the prescription of beta-blockers (non-user, non-selective, and β1-selective beta-blockers). The primary endpoint was all-cause mortality. We adjusted clinical variables and utilized propensity scores to balance confounding bias. Cox proportional hazards regression models were used to estimate the incidence of mortality in different groups. Results: A total of 1,292 RA patients with myocardial infarction were enrolled, where 424 (32.8%), 281 (21.7%), and 587 (45.5%) subjects used non-user, non-selective, and β1-selective beta-blockers, respectively. Use of beta-blockers was associated with lower risk of all-cause mortality after adjustment with comorbidities, medications (adjusted hazard ratio [HR] 0.871; 95% confidence interval [CI] 0.727-0.978), and propensity score (HR 0.882; 95% CI 0.724-0.982). Compared with β1-selective beta-blockers, treatment with non-selective beta-blockers (HR 0.856; 95% CI 0.702-0.984) was significantly related to lower risk of mortality. The protective effect of non-selective beta-blockers remained in different subgroups including sex and different anti-inflammatory drugs. Conclusion: Use of beta-blockers improved prognosis in post-MI patients with RA. Treatment with non-selective beta-blockers was significantly associated with reduced risk of mortality in RA patients after MI rather than β1-selective beta-blockers.

Dataset Information

The Potential Anti-remodeling Effect of Paroxetine After Myocardial Infarction May Be Blunted by Beta-Blockers.

Background

Methods

Results

Conclusion

Publications

The Potential Anti-remodeling Effect of Paroxetine After Myocardial Infarction May Be Blunted by Beta-Blockers.

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