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Published on: April 8, 2013
Carvedilol Combined With Ivabradine Improves Left Ventricular Diastolic Dysfunction, Clinical Progression, and
Madhumita Premkumar1, Devaraja Rangegowda1, Tanmay Vyas1
1Departments of Hepatology.
Insights
This study shows that combining carvedilol and ivabradine effectively improves left ventricular diastolic dysfunction (LVDD) in cirrhosis patients. Targeted heart rate reduction (THR) with these drugs also reduced complications and improved survival.
Area of Science:
- Cardiology
- Hepatology
- Pharmacology
Background:
- Left ventricular diastolic dysfunction (LVDD) is common in cirrhosis and impairs cardiac function.
- Targeted heart rate reduction (THR) may improve LVDD and clinical outcomes.
- Carvedilol and ivabradine offer a potential therapeutic strategy for THR in these patients.
Purpose of the Study:
- To evaluate the efficacy of carvedilol plus ivabradine for achieving THR.
- To assess the impact of this combination therapy on LVDD reversal and improvement.
- To determine the effect on clinical outcomes, including mortality, acute kidney injury, and encephalopathy.
Main Methods:
- A randomized controlled trial involving 189 cirrhosis patients with LVDD.
- Group A received carvedilol ± ivabradine to achieve THR (55-65 bpm), while Group B received standard care without beta-blockers.
- Patients were followed for 12 months, with assessments of LVDD, heart rate, and clinical events.
Main Results:
- THR was achieved in 93% of patients in Group A, with 61.5% responding to carvedilol alone and 86.9% with added ivabradine.
- LVDD reversed or improved in 55.9% of Group A patients, versus progression in 10.5% of Group B.
- Persistent THR at 1 year was associated with no mortality, while non-responders had increased mortality risk. Group B had higher rates of acute kidney injury and encephalopathy.
Conclusions:
- Combination therapy with carvedilol and ivabradine effectively achieves THR in cirrhosis patients with LVDD.
- This approach improves LVDD, reduces the risk of serious complications like acute kidney injury and encephalopathy, and is associated with improved survival.
- Targeted heart rate reduction is a promising strategy for managing cardiac dysfunction in patients with advanced liver disease.
Background:
Left ventricular diastolic dysfunction (LVDD) refers to impaired cardiac diastolic relaxation and may be improved by targeted heart rate reduction (THR). The authors evaluated whether a combination of carvedilol and ivabradine, an If channel blocker that reduces heart rate without affecting blood pressure, could improve LVDD and outcomes in cirrhosis.
Patients And Methods:
THR was defined as heart rate reduction to 55 to 65 beats per minute. Of 260 patients with cirrhosis, 189 (72%) with LVDD were randomized to THR [group (Gr.)A; n=94; carvedilol±ivabradine)] or standard care (Gr.B; n=95; no β-blockers) and followed for 12 months.
Results:
In Gr.A, THR was achieved at 4 weeks in 88 (93%) patients (responders, R): 48 (61.5%) with carvedilol alone and 40 (86.9%) of 46 patients with additional ivabradine. In Gr.A, LVDD reversed in 16 (20.5%) and improved from grade 2 to 1 in 34 (35.4%)], whereas in Gr.B, it progressed from grade 1 to 2 in 10 (10.5%) patients. At 12 months, 21 (11.1%) patients died, 6 (14%) in Gr.A and 15 (18%) in Gr.B (P=0.240), but no mortality was seen in those who had persistent THR at 1 year (n=78; P=0.000). In multivariate analysis, model for end-stage liver disease [hazard ratio (HR), 1.52; 95% confidence interval (CI), 1.22-2.75; P=0.034] and E-wave transmitral/early diastolic mitral annular velocity (HR, 1.28; 95% CI, 1.23-2.42; P=0.048) predicted 1-year mortality. Nonresponders had an increased mortality risk (HR, 1.3; 95% CI, 1.2-1.8; P=0.046) independent of age, gender, and baseline model for end-stage liver disease. Levels of norepinephrine, N terminal brain natriuretic peptide, plasma renin activity, and aldosterone were reduced (P<0.01) in responders. More patients in Gr.B developed acute kidney injury (odds ratio, 4.2; 95% CI, 2.8-10.5; P=0.027) and encephalopathy (odds ratio, 6.6; 95% CI, 1.9-9.7; P=0.040).
Conclusions:
Ivabradine combined with carvedilol improves LVDD, achieves THR more often and reduces risk of encephalopathy, acute kidney injury with improved survival in patients with cirrhosis.
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