Statin use linked to ‘sharp 86% risk reduction’ for primary sclerosing cholangitis in IBD
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Key takeaways:
- Protection against PSC was reported in both ulcerative colitis (HR = 0.21) and Crohn’s disease (HR = 0.15).
- No differences were reported between men (HR = 0.22) and women (HR = 0.16).
WASHINGTON — Statin use was associated with up to a 90% risk reduction for new-onset primary sclerosing cholangitis among patients with inflammatory bowel disease, according to data presented at Digestive Disease Week.
“We all take care of patients with liver disease and we know what a significant burden [primary sclerosing cholangitis (PSC)] is,” Chiraag Kulkarni, MD, a third-year fellow in gastroenterology and hepatology at Stanford University, told attendees. “These patients have a significantly elevated risk of advanced fibrosis and cirrhosis and significantly elevated risk of multiple cancers.”
He continued, “Despite this, we have no proven effective medical therapy for PSC. However, over the last decade, there is growing evidence that statins may be beneficial in liver disease.”
Using a large, nationwide database, Kulkarni and colleagues conducted a retrospective study of 33,813 patients with IBD to investigate the association between statin exposure (n = 8,813 patients) and development of PSC.
Over a median follow-up of approximately 44.5 months after IBD diagnosis, 181 patients developed PSC, including eight patients (0.09%) in the statin arm and 173 (0.69%) in the control arm. Propensity score-matched analysis showed statins were associated with a lower risk for PSC onset (HR = 0.14; 95% CI, 0.06-0.33).
“We calculated an E-value of 5.5, suggesting that the results are unlikely to be confounded,” Kulkarni said. “For those who are unfamiliar, E-value measures on a ratio scale the strength of unmeasured compounding that would have to be present and be associated with both the treatment, in this case statins, and the outcome, PSC, to negate the observed association. The higher the E-value, the less likely it is to be unmeasured confounding.”
Findings were consistent across all age groups, Kulkarni noted, with a 90% risk reduction reported among patients younger than 50 years (HR = 0.1; 95% CI, 0.01-0.83).
Further, statin use was associated with protection against PSC in both ulcerative colitis (HR = 0.21; 95% CI, 0.08-0.56) and Crohn’s disease (HR = 0.15; 95% CI, 0.03-0.65), according to subgroup analyses. No differences in statin effect were reported among men (HR = 0.22; 95% CI, 0.08-0.59) vs. women (HR = 0.16; 95% CI, 0.04-0.7).
Even with a statin induction lag time of 12 months, there was an 84% risk reduction (HR = 0.16; 95% CI, 0.07-0.51) for new-onset PSC.
“Statin use is associated with a sharp 86% risk reduction in the risk of new-onset PSC among patients with IBD,” Kulkarni said. “The magnitude of the effect size in 80% to 90% reduction is very consistently seen in a variety of ways.”
Perspective
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Muyiwa Awoniyi, MD, PhD
Evaluating the impact of statin use on PSC among patients with IBD is challenging due to multiple factors. One must recognize that PSC occurs in only 7.5% to 15.1% of these individuals.
The study evaluated PSC in eight patients with IBD with statin exposure, the results of which are limited in their population generalizability. The study also does not mention the duration that patients were exposed to statins, which could affect the delayed effects on PSC progression. Furthermore, patients younger than 50 years are not commonly prescribed statins, mainly due to younger patients’ more favorable health profiles.
A previous study examined statin use in Taiwan and reported that usage trends are more prevalent in older adults.
The retrospective nature of this study may have inherent biases in the selection and screening processes. This could contribute to flawed associations between statin use and PSC incidence, as seen in other studies exploring statin benefits in diverse conditions. These discrepancies also have been demonstrated in previous studies assessing the effects of anti-inflammatory therapies on PSC prognosis.
However, promising retrospective findings often do not translate into successful prospective outcomes. Previously published PSC research has shown us that initial retrospective enthusiasm often needs to be balanced with rigorous scientific validation to ensure patient safety and effective treatment strategies.
This study demonstrates the need for further research to determine the direct effect of statins on PSC incidence. A larger patient cohort and study design that evaluates the long-term impact of statin use are crucial. Existing evidence suggests statins can reduce inflammatory markers, such as CRP levels, which may improve liver health.
Nonetheless, direct causation between statin use and reduced PSC incidence requires more targeted research.
References:
Alexopoulou E, et al. J Pediatr Gastroenterol Nutr. 2012;doi:10.1097/MPG.0b013e31825bb3dc.
Hsieh HC, et al. BMJ Open. 2017;doi:10.1136/bmjopen-2016-014150.
Kaneohe T, et al. Mediators Inflamm. 2022;doi:10.1155/2022/8732360.
Lindor KD, et al. Hepatology. 2009;doi:10.1002/hep.23082.
Lunder AK, et al. Gastroenterology. 2016;doi:10.1053/j.gastro.2016.06.021.
Olsson R, et al. Gastroenterology. 2005;doi:10.1053/j.gastro.2005.08.017.
Poupon R, et al. Lancet. 1987;doi:10.1016/s0140-6736(87)91610-2.
Ryou IS, et al. Front Med (Lausanne). 2022;doi:10.3389/fmed.2022.1024780.
Stiehl A. Scand J Gastroenterol Suppl. 1994;doi:10.3109/00365529409103626.
Triantos CK, et al. Aliment Pharmacol Ther. 2011;doi:10.1111/j.1365-2036.2011.04822.x.
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Kulkarni C, et al. Statin use is associated with reduction in primary sclerosing cholangitis (PSC) among patients with IBD. Presented at: Digestive Disease Week; May 18-21, 2024; Washington (hybrid).
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