Simvastatin plus beta blocker improves survival of cirrhotic patients with variceal bleeding

The addition of simvastatin to a nonselective beta blocker results in better survival among cirrhotic patients with variceal bleeding, reports a study presented at EASL 2023.

“Initial studies exploring the addition of simvastatin, a readily accessible and safe medication, to beta blockers in cirrhotic patients with index variceal bleeding have shown potential benefits in terms of liver generation of nitric oxide and hepatic endothelial dysfunction,” according to the researchers, led by Dr Jemimah Andrea Fajardo from St Luke’s Medical Center in Quezon City, Philippines.

“We therefore assessed the efficacy of simvastatin with a nonselective beta blocker in improving survival for cirrhotic patients with variceal bleed through a systematic review and meta-analysis,” they added.

Three randomized trials including a total of 361 patients with variceal bleeding met the eligibility criteria. A significant survival benefit was observed among patients who received simvastatin therapy (risk ratio [RR], 0.43, 95 percent confidence interval [CI], 0.26‒0.73; p=0.002). [EASL 2023, abstract SAT-520]

Rebleeding was also assessed as a secondary outcome. Fajardo and her team observed a trend towards benefit (RR, 0.72, 95 percent CI, 0.47‒1.09; p=0.12), but the results did not reach statistical significance.

“Among cirrhotic patients with variceal bleeding, the addition of simvastatin provides a significant benefit in survival, but not in rebleeding,” the researchers said. “However, there remains a need for larger studies with more participants to strengthen this evidence, and a deeper look into its safety profile in cirrhotic patients specifically.”

In this study, Fajardo and colleagues conducted a comprehensive systematic search of the following databases: PubMed, Cochrane, and Google Scholar. They identified clinical studies that explored the use of statin plus beta blocker in improving survival in patients with cirrhosis.

All available abstracts and full text papers were screened and reviewed independently by two reviewers. Studies were selected based on inclusion and exclusion criteria set by the researchers. To assess possible bias in each study, the Cochrane Risk of Bias tool was used. Additionally, RevMan 5.4 and GRADEPro were utilized to evaluate the obtained data.

Finally, the researchers examined the dichotomous outcomes using relative risk with 95 percent CI and the primary and secondary outcomes, namely survival improvement and rebleeding, respectively.

“Around 60 percent of patients with decompensated liver cirrhosis have esophageal varices with a high propensity to bleed, which is the major cause of death in these patients,” Fajardo and colleagues noted. “Pharmacological treatment in addition to endoscopic intervention has been documented to prevent variceal bleeding.”

Efficacy of simvastatin

In another systematic review and meta-analysis, simvastatin was found to reduce the mortality rates among patients with liver cirrhosis by suppressing incidences of fatal bleeding. [J Clin Gastroenterol 2022;56:e303-e312]

In this study, 554 relevant articles were identified, of which nine (n=648 participants) were included in the meta-analysis. In four studies, simvastatin significantly lowered the overall death rate (RR, 0.46, 95 percent CI, 0.29‒0.73; p<0.01). It also reduced the incidence of fatal bleeding (RR, 0.35, 95 percent CI, 0.13‒0.95; p=0.04) and levels of cholesterol (mean difference [MD], ‒31.48, 95 percent CI, ‒52.80 to ‒10.15; p<0.01), and triglyceride (MD, ‒25.88, 95 percent CI, ‒49.90 to ‒1.86; p=0.03).

“Statins can improve prognosis of patients with liver cirrhosis by suppressing inflammation and lowering portal pressure,” the investigators said. [J Clin Gastroenterol 2022;56:e303-e312]