Statin Therapy in Patients With Cirrhosis
Statin Therapy in Patients With Cirrhosis
Cardiovascular disease is one of the leading causes of death among patients with cirrhosis and following liver transplantation. Although 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors ('statins') reduce the risk of cardiovascular events, fears about hepatotoxicity have historically led to underuse in patients with liver disease. In addition, the pharmacokinetics of statins can be significantly altered in cirrhosis, creating challenges with their use in liver disease. However, emerging data from randomised controlled trials and observational studies suggest that statin therapy appears to be safe and effective in patients with chronic liver disease and compensated cirrhosis. The cardiovascular risk benefits as well as the potential pleiotropic benefits of statins warrants strong consideration of use of statin therapy in patients with cirrhosis.
Cardiovascular disease (CVD) is a significant cause of morbidity and mortality among patients with all aetiologies of cirrhosis. Several studies have reported CVD as the leading cause of non-liver-related mortality among patients with cirrhosis both in the transplant and non-transplant setting. With the rising prevalence of cirrhosis from non-alcoholic fatty liver disease (NAFLD), the incidence of CVD among patients with cirrhosis is likely to rise as these patients are at an increased risk of CVD and frequently carry additional CVD risk factors including dyslipidaemia, diabetes mellitus and the metabolic syndrome.
3-Hydroxy-3-methyl-glutaryl-CoA reductase inhibitors, or 'statins', represent a major breakthrough in the treatment and prevention of CVD and have been employed in clinical practice for more than 20 years. High-quality evidence from large randomised controlled trials supports the use of statins in primary and secondary prevention of CVD. However, patients with liver disease were excluded from these trials limiting data on the role of statin therapy in this population. Concern about hepatotoxicity has historically led to decreased use of statins among patients with liver disease.
Recent studies have demonstrated the efficacy and safety of statin therapy among patients with liver disease and cirrhosis. Emerging evidence suggests multiple beneficial effects of statins in these patients independent of their lipid-lowering effects. Improvement in portal hypertension, reduction in the incidence of hepatocellular carcinoma (HCC) and delays in hepatic decompensation have been associated with statin therapy among patients with cirrhosis. In this review, we will explore the burden of CVD among patients with cirrhosis, review available evidence on the safety and efficacy of statins in this population, and summarise recent studies demonstrating the pleiotropic effects of statins among patients with cirrhosis.
Abstract and Introduction
Abstract
Cardiovascular disease is one of the leading causes of death among patients with cirrhosis and following liver transplantation. Although 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors ('statins') reduce the risk of cardiovascular events, fears about hepatotoxicity have historically led to underuse in patients with liver disease. In addition, the pharmacokinetics of statins can be significantly altered in cirrhosis, creating challenges with their use in liver disease. However, emerging data from randomised controlled trials and observational studies suggest that statin therapy appears to be safe and effective in patients with chronic liver disease and compensated cirrhosis. The cardiovascular risk benefits as well as the potential pleiotropic benefits of statins warrants strong consideration of use of statin therapy in patients with cirrhosis.
Introduction
Cardiovascular disease (CVD) is a significant cause of morbidity and mortality among patients with all aetiologies of cirrhosis. Several studies have reported CVD as the leading cause of non-liver-related mortality among patients with cirrhosis both in the transplant and non-transplant setting. With the rising prevalence of cirrhosis from non-alcoholic fatty liver disease (NAFLD), the incidence of CVD among patients with cirrhosis is likely to rise as these patients are at an increased risk of CVD and frequently carry additional CVD risk factors including dyslipidaemia, diabetes mellitus and the metabolic syndrome.
3-Hydroxy-3-methyl-glutaryl-CoA reductase inhibitors, or 'statins', represent a major breakthrough in the treatment and prevention of CVD and have been employed in clinical practice for more than 20 years. High-quality evidence from large randomised controlled trials supports the use of statins in primary and secondary prevention of CVD. However, patients with liver disease were excluded from these trials limiting data on the role of statin therapy in this population. Concern about hepatotoxicity has historically led to decreased use of statins among patients with liver disease.
Recent studies have demonstrated the efficacy and safety of statin therapy among patients with liver disease and cirrhosis. Emerging evidence suggests multiple beneficial effects of statins in these patients independent of their lipid-lowering effects. Improvement in portal hypertension, reduction in the incidence of hepatocellular carcinoma (HCC) and delays in hepatic decompensation have been associated with statin therapy among patients with cirrhosis. In this review, we will explore the burden of CVD among patients with cirrhosis, review available evidence on the safety and efficacy of statins in this population, and summarise recent studies demonstrating the pleiotropic effects of statins among patients with cirrhosis.
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