May 24, 2012

Statins Reduce Cirrhosis Deaths


By Kristina Fiore, Staff Writer, MedPage Today

Published: May 23, 2012

Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston and Dorothy Caputo, MA, BSN, RN, Nurse Planner

SAN DIEGO -- Giving statins to cirrhosis patients with heart disease appears to lower the risk of both hepatic decompensation and mortality, researchers said here.

In a small, retrospective study, significantly fewer cirrhosis patients on statins had decompensation compared with cirrhosis patients not on the cholesterol-lowering drugs (38.2% versus 50.62%, P=0.018), Sonal Kumar, MD, of Brigham & Women's Hospital in Boston, and colleagues reported at Digestive Disease Week here.

They also had significantly less mortality (P=0.043), she reported.

"Contrary to the prior belief that statins aren't safe in patients with cirrhosis, we found they actually may be beneficial in this population," Kumar said during a press briefing.

Clinicians have long been concerned that statins aren't safe in patients with severe liver disease, primarily because statins are metabolized in the liver and may put patients at greater risk of complications such as hepatic decompensation and liver failure.

Recent studies, however, have suggested that statins aren't harmful in these patients, and that they may even diminish morbidity and mortality for liver patients with heart disease, Kumar said.

So she and colleagues looked at data from the Partners Research Patient Data Registry on a total of 243 patients, 81 of whom were treated for dyslipidemia with statins for at least 3 months, and 162 who served as controls matched for age, gender, and liver disease severity.

The primary outcome was hepatic decompensation, defined as the development of ascites, jaundice, hepatic encephalopathy, or variceal hemorrhage.

The statin group was followed for a mean of 1,756 days and the control group for 1,503 days.

In each group, 70.4% of patients were Child-Pugh A and 29.6% were Child-Pugh B/C; factors such as MELD, albumin, presence of varices and beta-blocker use weren't significantly different between groups.

In multivariate analysis, statin therapy alone was significantly associated with a lower risk of decompensation, they reported (HR 0.44, 95% CI 0.27 to 0.71).

In addition, analyses showed an overall longer time to decompensation in patients on statins, they found (P=0.01), which was also present for patients with Child-Pugh A disease (P=0.04).

Kumar and colleagues also found that there was less all-cause mortality among cirrhotic patients on statins compared with those not on the drugs (37% versus 50.6%, P=0.043).

In multivariate analyses, statin use was significantly associated with lower mortality (OR 0.49, 95% CI 0.29 to 0.81). Coronary artery disease and non-alcoholic steatohepatitis, on the other hand, were associated with increased mortality, they reported (OR 2.62, 95% CI 1.78 to 3.86 and OR 1.61, 95% CI 1.03 to 2.52, respectively).

The researchers also saw a longer time to death in patients with Child-Pugh A disease who used statins (P=0.005).

Kumar said the beneficial effects on liver outcomes may be due to statins' ability to diminish portal pressure, which is associated with complications including jaundice and vomiting blood due to enlarged veins in the upper GI tract. That may be mediated via statins' known mechanism of increasing the production of nitric oxide, Kumar said.

She added that more prospective trials are needed, but Zobair Younossi, MD, of Inova Health System in Great Falls, Va., who attended the press briefing at which the data were presented, said evidence is amassing that statins are safe in liver disease patients.

"If you need to use them, you should use them, and not worry about the liver," Younossi said.

But Cam Patterson, MD, of the University of North Carolina at Chapel Hill, said in an email to MedPage Today that most physicians still have "second and third thoughts about using statins in patients with severe liver disease."

"This is a retrospective, nonrandomized study, so it would be a big mistake to use this study as a general advertisement that statins can be safely used in patients with severe liver disease or that patients with liver disease will do better and live longer if they receive statins," Patterson wrote.

"What this study does tell us," he added, "is that carefully selected patients with liver disease can be given statins and that they seem to tolerate them well."

Questions that still need to be answered before making broad recommendations for the use of statins in cirrhotic patients include assessing which patients will benefit most and finding out whether patients fare better with some statins more than others, Patterson said: "I hope that this small study provides an impetus for additional studies that will answer these questions."

Kumar reported no conflicts of interest.

Primary source: Digestive Disease Week
Source reference:
Kumar S, et al "Statin therapy decreases the risk of hepatic decompensation in cirrhosis" DDW 2012; Abstract 595.


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