Statins may protect against primary sclerosing cholangitis in IBD patients

Patients with inflammatory bowel disease (IBD) who use statins appear to have a substantially reduced risk of primary sclerosing cholangitis (PSC), as shown in a retrospective study.

In a propensity-score matched analysis involving large data from a national database, statin use was associated with an 86-percent lower risk of PSC onset (hazard ratio [HR], 0.14, 95 percent confidence interval [CI], 0.06–0.33). [Kulkarni C, et al, DDW 2024]

“We calculated an E value, which was 5.5, suggesting that the results are unlikely to be due to confounding,” said lead researcher Dr Chiraag Kulkarni from Stanford University School of Medicine in Stanford, California, US.

When analysis was limited to IBD patients under the age of 50 years, a similar magnitude of protection against the onset of PSC was observed (HR, 0.10, 95 percent CI, 0.01–0.83).

“We take away two things from these. First is that the protective effect of statins occurs at ages where PSC is most likely to occur. The second is that the results we are observing are not due to a survival bias where that patients who simply survive to an age where statins are prescribed simply have a biologically predilection for developing PSC,” Kulkarni explained.

The protective benefit of statins on PSC onset was consistent across patient subgroups defined by IBD type (ulcerative colitis: HR, 0.21, 95 percent CI, 0.08–0.56; Crohn’s disease: HR, 0.15, 95 percent CI, 0.03–0.65) and sex (females: HR, 0.16, 95 percent CI, 0.04–0.70; males: HR, 0.22, 95 percent CI, 0.08–0.59).

Finally, Kulkarni and colleagues investigated the impact of a 12-month lag time, given the uncertainty regarding the optimal duration of statin therapy prior to a putative protective effect taking place. The analysis indicated that even with a 12-month delay, the risk of PSC onset remained low, with the estimate being very similar to the main analysis (HR, 0.16, 95 percent CI, 0.07–0.51).

How statins might prevent the onset of PSC in patients with IBD may involve two potential pathways, according to Kulkarni.

One is via the direct modulation of inflammation, he said. Statins may directly suppress inflammatory processes within the gut, and this aligns with evidence suggesting that statin use, specifically atorvastatin, was associated with a significant reduction in the need for colectomy in some IBD patients.

The other is through alterations in bile acid profiles. Patients with PSC often exhibit an abnormal bile acid profile, characterized by an excess of primary bile acids and a deficiency in secondary bile acids. Statins may help rectify this imbalance by promoting the production of beneficial secondary bile acids. This shift towards a healthier bile acid profile could potentially contribute to improved liver function and potentially prevent complications associated with PSC, as Kulkarni pointed out.

For the study, Kulkarni and colleagues used a large, representative national database and performed high dimensional propensity score matching to balance confounding factors between groups. However, the database had limited capture of dosage data, which precluded the performance of a secondary analysis to understand the impact of the intensity of statin therapy on the outcome. Also, the researchers were unable to assess compliance with statins.

The study included 33,813 patients, of which around 8,813 were statin users (53.2 percent female, 44.8 percent White) and 25,000 were nonusers (58.7 percent female, 54.0 percent White).