Spotlight on statin therapy

Studies published in May found a potential benefit of statin therapy for three different conditions.

Statin use was linked to potential benefit in colorectal cancer, chronic liver disease, and cirrhosis in three recent studies.

In the first study, researchers in the Netherlands analyzed survival of 999 patients with colon cancer who had surgical resection from 2002 through 2008 and categorized them by statin use, as determined by a database network. Tissue microarray of cancer specimens was also conducted to determine protein levels and mutations. The study's primary outcome measures were overall mortality and cancer-specific mortality. Results were published early online by Gastroenterology on May 13.

Two hundred ten of 999 patients (21.0%) used statins after colon cancer diagnosis. Such use was statistically significantly associated with reduced risk of death from any cause (adjusted relative risk, 0.67; P=0.003) as well as death from cancer (adjusted relative risk, 0.66; P=0.007). When BMP signaling was considered, risk for all-cause death and death from cancer was reduced in patients whose tumors had intact BMP signaling versus those whose tumors did not (adjusted relative risk, 0.39 vs. 0.81, respectively; P<0.0001 for the interaction). Statin use did not appear to be associated with reduced risk for either outcome in patients with or without KRAS mutations.

The researchers noted that their study was retrospective and that differences in baseline characteristics between statin users and nonstatin users may have confounded their results, among other limitations. However, they concluded that in their study cohort, use of statins after diagnosis of colon cancer was associated with a lower risk for death, especially in patients whose tumors retained BMP signaling. They called for randomized controlled trials to confirm their findings.

Another study, published early online by Clinical Gastroenterology and Hepatology on May 4, was a systematic review and meta-analysis examining the association between statins and risk for cirrhosis and cirrhosis-related complications in patients with chronic liver disease. Thirteen studies published through March 2017 that reported on statin use and risk for cirrhosis, decompensated cirrhosis, improved portal hypertension, or death were included. Three were randomized controlled trials, and 10 were cohort studies.

A total of 121,058 patients with chronic liver disease were involved in the included studies, most (84.5%) with hepatitis C. Of these, 46% had used statins. The researchers found that statin use was associated with 46% lower risk for both hepatic decompensation and mortality in patients with cirrhosis and with a nonsignificantly lower risk for cirrhosis or fibrosis progression in patients with chronic liver disease but no cirrhosis. In the three randomized controlled trials, a 27% lower risk for variceal bleeding or progression of portal hypertension was found to be associated with statin use.

The authors noted that some of their evidence was based on observational studies and that some outcomes had substantial heterogeneity, among other limitations. However, they concluded that based on their results, moderate-quality evidence indicates that statins may have a beneficial effect on risk for hepatic decompensation, death, and variceal bleeding, especially in patients who are known to have compensated cirrhosis. In addition, they noted that low-quality evidence suggests that statins may be linked to mortality benefit in patients with chronic liver disease. They said their findings, when added to previous evidence, may suggest that statins can improve outcomes in patients with chronic liver disease at reasonable costs, but they noted that further studies are needed.

Finally, a study in Taiwan used a national health insurance database to evaluate the association between use of statins and risk for decompensation, death, and development of hepatocellular carcinoma in patients in the general population who had cirrhosis with different causes. Statin users served as the case cohort, while those who didn't use statins were matched using propensity scores. Results were published online May 8 by Hepatology.

A total of 1,350 patients with cirrhosis were included in the study. A statistically significant dose-dependent decrease in risk for decompensation, death, and hepatocellular carcinoma was seen with statin use in patients who had cirrhosis. In regression analysis, a statistically significant lower risk for decompensation (adjusted hazard ratio, 0.39; 95% CI, 0.25 to 0.62) and death (adjusted hazard ratio, 0.39; 95% CI, 0.21 to 0.72) was noted in statin users whose cirrhosis was caused by hepatitis B as well as in those whose cirrhosis was caused by hepatitis C (adjusted hazard ratio, 0.51; 95% CI, 0.29 to 0.93); however, this lower risk was of borderline statistical significance among statin users whose cirrhosis was related to alcohol (adjusted hazard ratio, 0.69; 95% CI, 0.45 to 1.07).

The study authors noted that they didn't examine the effect of statins on nonalcoholic steatohepatitis (NASH) and that they had no data available on adherence to statin prescriptions or laboratory values, among other limitations. However, they concluded that statins may be considered for use as adjuvant therapy to reduce risk for decompensation in patients with cirrhosis, but like the authors of the other two studies, they called for additional prospective trials to confirm their results.