Impact of a Multichannel Blocker in Attenuating Intramyocardial Artery Remodeling in Hypertensive Rats through Increased Nitric Oxide Bioavailability

Quintana‐Villamandos, Begoña; Delgado-Martos, María Jesús; Delgado-Baeza, Emilio

doi:10.1155/2019/6374582

Cited by 3 publications

(2 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The positive effects on progression, regression, and AF/AFL burden suggest that dronedarone may reverse atrial and ventricular remodeling. This suggestion is supported by results from animal studies of structural heart disease in which dronedarone was found to decrease remodeling through increased bioavailability of nitric oxide 19 and to cause regression of myocardial remodeling. 20–22 Moreover, dronedarone has previously been shown in the HESTIA study to reduce AF burden in patients with pacemakers who had paroxysmal or persistent AF.…”

Section: Discussionmentioning

confidence: 69%

Effect of dronedarone vs. placebo on atrial fibrillation progression: apost hocanalysis from ATHENA trial

et al. 2023

View full text Add to dashboard Cite

Aims This post hoc analysis of the ATHENA trial (NCT00174785) assessed the effect of dronedarone on the estimated burden of atrial fibrillation (AF)/atrial flutter (AFL) progression to presumed permanent AF/AFL, and regression to sinus rhythm (SR), compared with placebo. Methods and results The burden of AF/AFL was estimated by a modified Rosendaal method using available electrocardiograms (ECG). Cumulative incidence of permanent AF/AFL (defined as ≥6 months of AF/AFL until end of study) or permanent SR (defined as ≥6 months of SR until end of study) were calculated using Kaplan–Meier estimates. A log-rank test was used to assess statistical significance. Hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) were estimated using a Cox model, adjusted for treatment group. Of the 4439 patients included in this analysis, 2208 received dronedarone, and 2231 placebo. Baseline and clinical characteristics were well balanced between groups. Overall, 304 (13.8%) dronedarone-treated patients progressed to permanent AF/AFL compared with 455 (20.4%) treated with placebo (P < 0.0001). Compared with those receiving placebo, patients receiving dronedarone had a lower cumulative incidence of permanent AF/AFL (log-rank P < 0.001; HR: 0.65; 95% CI: 0.56–0.75), a higher cumulative incidence of permanent SR (log-rank P < 0.001; HR: 1.19; 95% CI: 1.09–1.29), and a lower estimated AF/AFL burden over time (P < 0.01 from Day 14 to Month 21). Conclusion These results suggest that dronedarone could be a useful antiarrhythmic drug for early rhythm control due to less AF/AFL progression and more regression to SR vs. placebo, potentially reflecting reverse remodeling. Clinical trial registration NCT00174785

show abstract

Section: Discussionmentioning

confidence: 69%

Effect of dronedarone vs. placebo on atrial fibrillation progression: apost hocanalysis from ATHENA trial

et al. 2023

View full text Add to dashboard Cite

show abstract

“…Several studies have shown that chronic treatment with antihypertensive drugs produces regression of coronary artery remodeling [ 5 , 6 , 7 , 8 , 9 ]. However, our group has demonstrated this beneficial effect with short-term treatment with antiarrhythmic drugs (esmolol and dronedarone) [ 10 , 11 , 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

Maintenance over Time of the Effect Produced by Esmolol on the Structure and Function of Coronary Arteries in Hypertensive Heart Diseases

et al. 2022

View full text Add to dashboard Cite

We previously observed that esmolol treatment for 48 h reduced vascular lesions in spontaneously hypertensive rats (SHRs). Therefore, we investigated whether this beneficial effect is persistent after withdrawal. Fourteen-month-old SHRs (SHR-Es) were treated with esmolol (300 μg/kg/min) or a vehicle for 48 h. Two separate groups were also given identical treatment, but they were then monitored for a further 1 week and 1 month after drug withdrawal. We analyzed the geometry and composition of the coronary artery, vascular reactivity and plasma redox status. Esmolol significantly decreased wall thickness (medial layer thickness and cell count), external diameter and cross-sectional area of the artery, and this effect persisted 1 month after drug withdrawal. Esmolol significantly improved endothelium-dependent relaxation by ACh (10−9–10−4 mol/L); this effect persisted 1 week (10−9–10−4 mol/L) and 1 month (10−6–10−4 mol/L) after withdrawal. Esmolol reduced the contraction induced by 5-HT (3 × 10−8–3 × 10−5 mol/L), and this effect persisted 1 week after withdrawal (10−6–3 × 10−5 mol/L). Esmolol increased nitrates and reduced glutathione, and it decreased malondialdehyde and carbonyls; this enhancement was maintained 1 month after withdrawal. This study shows that the effect of esmolol on coronary remodeling is persistent after treatment withdrawal in SHRs, and the improvement in plasma oxidative status can be implicated in this effect.

show abstract

Treatment of coronary microvascular dysfunction

Merz

Pepine

Shimokawa

et al. 2020

Cardiovascular Research

149

103

View full text Add to dashboard Cite

Contemporary data indicate that patients with signs and symptoms of ischaemia and non-obstructive coronary artery disease (INOCA) often have coronary microvascular dysfunction (CMD) with elevated risk for adverse outcomes. Coronary endothelial (constriction with acetylcholine) and/or microvascular (limited coronary flow reserve with adenosine) dysfunction are well-documented, and extensive non-obstructive atherosclerosis is often present. Despite these data, patients with INOCA currently remain under-treated, in part, because existing management guidelines do not address this large, mostly female population due to the absence of evidence-based data. Relatively small sample-sized, short-term pilot studies of symptomatic mostly women, with INOCA, using intense medical therapies targeting endothelial, microvascular, and/or atherosclerosis mechanisms suggest symptom, ischaemia, and coronary vascular functional improvement, however, randomized, controlled outcome trials testing treatment strategies have not been completed. We review evidence regarding CMD pharmacotherapy. Potent statins in combination with angiotensin-converting enzyme inhibitor (ACE-I) or receptor blockers if intolerant, at maximally tolerated doses appear to improve angina, stress testing, myocardial perfusion, coronary endothelial function, and microvascular function. The Coronary Microvascular Angina trial supports invasive diagnostic testing with stratified therapy as an approach to improve symptoms and quality of life. The WARRIOR trial is testing intense medical therapy of high-intensity statin, maximally tolerated ACE-I plus aspirin on longer-term outcomes to provide evidence for guidelines. Novel treatments and those under development appear promising as the basis for future trial planning.

show abstract

Impact of a Multichannel Blocker in Attenuating Intramyocardial Artery Remodeling in Hypertensive Rats through Increased Nitric Oxide Bioavailability

Cited by 3 publications

References 31 publications

Effect of dronedarone vs. placebo on atrial fibrillation progression: apost hocanalysis from ATHENA trial

Effect of dronedarone vs. placebo on atrial fibrillation progression: apost hocanalysis from ATHENA trial

Maintenance over Time of the Effect Produced by Esmolol on the Structure and Function of Coronary Arteries in Hypertensive Heart Diseases

Treatment of coronary microvascular dysfunction

Contact Info

Product

Resources

About