Abstract
Background
Statins reduce cardiovascular risk. Patients with cirrhosis have decreased hepatic clearance of statins and potentially increased risk for complications. No studies assess mortality in patients with biopsy-confirmed cirrhosis.
Aim
Compare mortality in patients with cirrhosis on statins to those not on statins.
Methods
A retrospective cohort study evaluated patients from 1988 to 2011 at Partners Healthcare Hospitals. The Partners Research Patient Data Registry identified patients with biopsy-proven cirrhosis on statins at biopsy and at least 3 months following. Controls were matched 1:2 by age, gender and Child–Pugh class. Decompensation was defined as ascites, jaundice/bilirubin >2.5 mg/dL, and/or hepatic encephalopathy or variceal hemorrhage. Primary outcome was mortality. Secondary outcome was decompensation in baseline-compensated patients. Chi-square and two-way ANOVA testing compared groups. Cox proportional hazards models for mortality controlled for age, Child–Pugh class, diabetes, coronary artery disease, non-alcoholic steatohepatitis and hepatocellular carcinoma. Kaplan–Meier curves graphed mortality.
Results
Eighty-one statin users and 162 controls were included. Median follow-up: 36 months in statin users and 30 months in controls. 70.4 % of patients were Child–Pugh A. Model for End-Stage Liver Disease (MELD), albumin, varices and beta-blocker use were not significantly different between groups. Statin users had lower mortality on multivariate analysis (HR 0.53, p = 0.01), and Child–Pugh A patients had longer survival on Kaplan–Meier analysis. Cox multivariate analysis for decompensation showed lower risk of decompensation with statins while increased decompensation with low albumin, high MELD score and beta-blocker use.
Conclusions
In patients with cirrhosis, statin therapy is not associated with increased mortality and may delay decompensation.
Similar content being viewed by others
References
Targher G, Bertolini L, Padovani R, Rodella S, Acaro G, Day C. Differences and similarities in early atherosclerosis between patients with nonalcoholic steatohepatitis and chronic hepatitis B and C. J Hepatol. 2007;46:1126–1132.
Longo M, Crosignani A, Battezzati PM, et al. Hyperlipidaemic state and cardiovascular risk in primary biliary cirrhosis. Gut. 2002;51:265–269.
Loria P, Lonardo A, Bellentani S, et al. Non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease: an open question. Nutr Metab Cardiovasc Dis.. 2007;17:684–698.
Kalaitzakis E, Rosengren A, Skommevik T, Bjornsson E. Coronary artery disease in patients with liver cirrhosis. Dig Dis Sci. 2010;55:467–475.
Tiukinhoy-Laing SD, Rossi JS, Bayram M, et al. Cardiac hemodynamic and coronary angiographic characteristics of patients being evaluated for liver transplantation. Am J Cardiol. 2006;98:178–181.
Raval Z, Harinstein ME, Skaro AI, et al. Cardiovascular risk assessment of the liver transplant candidate. J Am Coll Cardiol. 2011;58:223–231.
Palmer SC, Craig JC, Navaneethan SD, Tonelli M, Pellegrini F, Strippoli GF. Benefits and harms of statin therapy for persons with chronic kidney disease: a systematic review and meta-analysis. Ann Intern Med. 2012;157:263–275.
Wiesbauer F, Heinze G, Mitterbauer C, Harnoncourt F, Horl WH, Oberbrauer R. Statin use is associated with prolonged survival of renal transplant recipients. J Am Soc Nephrol. 2008;19:2211–2218.
Frohlich GM, Rufiback K, Enseleit F, et al. Statins and the risk of cancer after heart transplantation. Circulation. 2012;126:440–447.
Douglas I, Evans S, Smeeth L. Effect of statin treatment on short term mortality after pneumonia episode: cohort study. BMJ. 2011;42:1642.
Poynter JN, Gruber SB, Higgins PDR, et al. Statins and the risk of colorectal cancer. N Engl J Med. 2005;352:2184–2192.
Boudreau DM, Gardner JS, Malone KE, Heckbert SR, Blough DK, Daling JR. The association between 3-hydroxy-3-methylglutaryl coenzyme A inhibitor use and breast carcinoma risk among postmenopausal women: a case-control study. Cancer. 2004;100:2308–2316.
Friis S, Poulsen AH, Johnsen SP, et al. Cancer risk among statin users: a population-based cohort study. Int J Cancer. 2005;114:643–647.
Marcella SW, David A, Ohman-Strickland PA, Carson J, Rhoads GG. Statin use and fatal prostate cancer: a matched case-control study. Cancer. 2012;118:4046–4052.
El-Serag HB, Johnson ML, Hachem C, Morgana RO. Statins are associated with a reduced risk of hepatocellular carcinoma in a large cohort of patients with diabetes. Gastroenterology. 2009;136:1601–1608.
Tsan YT, Lee CH, Wang JD, Chen PC. Statins and the risk of hepatocellular carcinoma in patients with hepatitis B virus infection. J Clin Oncol. 2012;30:623–630.
Russo MW, Jacobson IM. How to use statins in patients with chronic liver disease. Cleve Clin J Med.. 2004;71:58–62.
Stancu C, Sima A. Statins: mechanism of action and effects. J Cell Mol Med. 2001;5:378–387.
Parra JL, Reddy KR. Hepatotoxicity of hypolipidemic drugs. Clin Liver Dis. 2003;7:415–433.
Calderon RM, Cubeddu LX, Goldberg RB, Schiff ER. Statins in the treatment of dyslipidemia in the presence of elevated liver aminotransferase levels: a therapeutic dilemma. Mayo Clin Proc. 2010;85:349–356.
Argo CK, Loria P, Caldwell SH, Lonardo A. Statins in liver disease: a molehill, an iceberg or neither? Hepatology. 2008;48:662–669.
Vuppalanchi R, Teal E, Chalasani N. Patients with elevated baseline liver enzymes do not have higher frequency of hepatotoxicity from lovastatin than those with normal liver enzymes. Am J Med Sci. 2005;329:62–65.
Chalasani N. Statins and hepatotoxicity: focus on patients with fatty liver. Hepatology. 2005;41:690–695.
Onofrei MD, Butler KL, Fuke DC, Miller HB. Safety of statin therapy in patients with preexisting liver disease. Pharmacotherapy.. 2008;28:522–529.
Khorashadi S, Hasson NK, Cheung RC. Incidence of statin hepatotoxicity in patients with hepatitis C. Clin Gastroenterol Hepatol.. 2006;4:902–907.
Chalasani N, Aljadhey H, Kesterson J, Murray MD, Hall SD. Patients with elevated liver enzymes are not at higher risk for statin hepatotoxicity. Gastroenterology. 2004;126:1287–1292.
Lewis JH, Mortensen ME, Zweig S, et al. Efficacy and safety of high-dose pravastatin in hypercholesterolemic patients with well-compensated chronic liver disease: results of a prospective, randomized, double-blind, placebo-controlled, multicenter trial. Hepatology. 2007;46:1453–1463.
Avins AL, Manos MM, Zhao W. Hepatic effects of lovastatin exposure in patients with liver disease. Drug Saf. 2008;31:325–334.
Cohen DE, Anania FA, Chalasani N, National lipid association statin safety task force liver expert panel. An assessment of statin safety by hepatologists. Am J Cardiol. 2006;97:77C–81C.
Lewis JH. Clinical perspective: statins and the liver—harmful or helpful? Dig Dis Sci. 2012;57:1754–1763.
Trebicka J, Hennenberg M, Laleman W, et al. Atorvastatin lowers portal pressures in cirrhotic rats by inhibition of RhoA/Rho-kinase and activation of endothelial nitric oxide synthase. Hepatology. 2007;46:242–253.
Zafra C, Albrades JG, Turnes J, et al. Simvastatin enhances hepatic nitric oxide production and decreases the hepatic vascular tone in patients with cirrhosis. Gastroenterology. 2004;126:749–755.
Albrades JG, Lapillus A, Banares R, et al. Simvastatin lowers portal pressure in patients with cirrhosis and portal hypertension: a randomized controlled trial. Gastroenterology. 2009;136:1651–1658.
Morena M, Ramalho LN, Sancho-Bru P, et al. Atorvastatin attenuates angiotensin II-induced inflammatory actions in the liver. Am J Physiol Gastrointest Liver Physiol. 2009;296:G147–G156.
Cholesterol Treatment Trialists’ (CTT) Collaborators, Kearney PM, Blackwell L et al. Efficacy of cholesterol lowering therapy in 18,686 people with diabetes in 14 randomised trials of statins: a meta-analysis. Lancet 2008;371:117–125.
Tonelli M, Lloyd A, Clement F, et al. Efficacy of statins for primary prevention in people at low cardiovascular risk: a meta-analysis. CMAJ. 2011;183:E1189–E1202.
Tsochatzis EA, Bosch J, Burroughs AK. Prolonging survival in patients with cirrhosis: old drugs with new indications. Gastroenterology. 2010;139:1813–1815.
PDR Staff. Physicians’ desk reference. PDR Network; 2011.
Berzigotti A, Garcia-Tsao G, Bosch J, et al. Obesity is an independent risk factor for clinical decompensation in patients with cirrhosis. Hepatology. 2011;54:555–561.
Conflict of interest
None.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Kumar, S., Grace, N.D. & Qamar, A.A. Statin Use in Patients with Cirrhosis: A Retrospective Cohort Study. Dig Dis Sci 59, 1958–1965 (2014). https://doi.org/10.1007/s10620-014-3179-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10620-014-3179-2