Addition of simvastatin to carvedilol non responders: A new pharmacological therapy for treatment of portal hypertension

Abstract

AIMTo determine whether addition of simvastatin could be an important pharmacological rescue therapy for carvedilol non-responders.METHODSOne hundred and two consecutive patients of cirrhosis of liver with significant portal hypertension were included. Hepatic venous pressure gradient (HVPG) was measured at the base line and after proper optimization of dose; chronic response was assessed at 3 mo. Carvedilol non-responders were given simvastatin 20 mg per day (increased to 40 mg per day at day 15). Carvedilol plus simvastatin was continued for 1 mo and hemodynamic response was again measured at 1 mo.RESULTSA total of 102 patients with mean age of 58.3 ± 6.6 years were included. Mean baseline HVPG was 16.75 ± 2.12 mmHg and after optimization of dose and reassessment of HVPG at 3 mo, mean reduction of HVPG from baseline was 5.5 ± 1.7 mmHg and 2.8 ± 1.6 mmHg among responders and non-responders respectively (P < 0.001). Addition of simvastatin to carvedilol non-responders resulted in significant response in 16 patients (42.1%) and thus overall response with carvedilol and carvedilol plus simvastatin was seen in 78 patients (80%). Two patients were removed in chronic protocol study with carvedilol and three patients were removed in carvedilol plus simvastatin study due to side effects.CONCLUSIONAddition of simvastatin to carvedilol non-responders may prove to be an excellent rescue therapy in patients with portal hypertension.

Comprehensive evaluation of effects and safety of statin on the progression of liver cirrhosis: a systematic review and meta-analysis

“…Five studies [21, 24, 26, 32, 35] reported parameters of hepatic portal vessel pressure with follow-up duration less than 3 months. In these studies, three important hepatic portal hemodynamic indexes, hepatic venous pressure gradient (HVPG), free hepatic vein pressure (FHVP), and wedged hepatic venous pressures (WHVP) which could reflect the degree of portal hypertension, were included.…”

“…a hepatic venous pressure gradient (HVPG); b wedged hepatic venous pressures (WHVP); c free hepatic vein pressure (FHVP). 5 studies ( a ) and 3 studies ( b & c ) - Abraldes et al, [21]; Bishnu et al, [24]; Elwan et al, [26]; Pollo-Flores et al, [32]; and Wani et al, [35]…”

“…Previous investigation indicated that statin could improve the resilience and compliance of portal vessels by promoting the production of vascular endothelium-derived relaxing factor, namely, nitric oxide [48–52]. Furthermore, clinical studies hinted that statin could mitigate hepatic portal hypertension as well with a short therapeutic duration (mean value of follow-up period: 3 months) [21, 24, 26, 32, 35]. Moreover, statin was proved to function as a kind of free radical eliminated agent which could relieve oxidative stress reaction in liver cirrhosis progression [53, 54].…”

Simvastatin is Efficacious in Treating Cirrhosis

“…In contrast, Bishnu et al31 reported that atorvastatin combined with propranolol reduced HVPG levels, relative to propranolol alone, in patients with liver cirrhosis. Notably, simvastatin treatment increased the response rate to about 80% even patients who did not respond to carvedilol in the treatment of portal hypertension, whereas the average HVPG decreased by 5.5±1.7 mm Hg compared with the baseline 32. Simvastatin can acutely increase the level of hepatic vein NOx, enhance the effects of β-blockers on portal pressure, and reduce portal vein pressure to some extent 33.…”

Regression of portal hypertension: underlying mechanisms and therapeutic strategies

“…Importantly, the decrease in HVPG was further augmented when statins were used in combination with propranolol. Similarly, a study investigating simvastatin addition to carvedilol non-responders had positive results, increasing the number of patients with hemodynamic response [ 78 ]. In contrast, a recent study in the same patient category, using carvedilol in combination with simvastatin over a period of 3 months failed to show any additional benefit of combination therapy in reducing HVPG [ 79 ].…”