Carvedilol plus ivabradine improves LVDD, survival in cirrhosis

The combination of ivabradine and carvedilol improves left ventricular diastolic dysfunction (LVDD), achieves targeted heart rate reduction (THR) more often, and reduces the risk of encephalopathy, leading to improved survival in patients with cirrhosis, reveals a study.

The investigators randomized 189 cirrhotic patients with LVDD to THR (group A: n=94; carvedilol±ivabradine) or standard care (group B: n=95; no β-blockers) and followed them for 12 months. THR was defined as heart rate reduction to 55–65 beats per minute.

Eighty-eight patients (93 percent; responders) in group A achieved THR at 4 weeks: 48 (61.5 percent) with carvedilol alone and 40 (86.9 percent) of 46 patients with additional ivabradine. LVDD reversed in 16 (20.5 percent) and improved from grade 2 to 1 in 34 patients (35.4 percent) in group A. On the other hand, LVDD progressed from grade 1 to 2 in 10 patients (10.5 percent) in group B.

Twenty-one patients (11.1 percent) died at 12 months, six (14 percent) in group A and 15 (18 percent) in group B (p=0.240). However, there was no mortality seen in those who had persistent THR at 1 year (n=78; p=0.000).

Multivariate analysis revealed that model for end-stage liver disease (hazard ratio [HR], 1.52, 95 percent confidence interval [CI], 1.22–2.75; p=0.034] and E-wave transmitral/early diastolic mitral annular velocity (HR, 1.28, 95 percent CI, 1.23–2.42; p=0.048) were associated with 1-year mortality.

Mortality risk was higher among nonresponders (HR, 1.3, 95 percent CI, 1.2–1.8; p=0.046), independent of age, gender, and baseline model for end-stage liver disease. Responders, on the other hand, had reduced levels of norepinephrine, N terminal brain natriuretic peptide, plasma renin activity, and aldosterone (p<0.01).

More patients in group B developed acute kidney injury (odds ratio [OR], 4.2, 95 percent CI, 2.8–10.5; p=0.027) and encephalopathy (OR, 6.6, 95 percent CI, 1.9–9.7; p=0.040).

“LVDD refers to impaired cardiac diastolic relaxation and may be improved by THR,” the investigators noted.