Intestinal cholesterol absorption, treatment with atorvastatin, and cardiovascular risk in hemodialysis patients.

Silbernagel, Günther; Fauler, Günter; Genser, Bernd; Drechsler, Christiane; Krane, Vera; Scharnagl, Hubert; Grammer, Tanja B; Baumgartner, Iris; Ritz, Eberhard; Wanner, Christoph; März, Winfried (2015). Intestinal cholesterol absorption, treatment with atorvastatin, and cardiovascular risk in hemodialysis patients. Journal of the American College of Cardiology, 65(21), pp. 2291-2298. Elsevier 10.1016/j.jacc.2015.03.551

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BACKGROUND Hemodialysis patients are high absorbers of intestinal cholesterol; they benefit less than other patient groups from statin therapy, which inhibits cholesterol synthesis. OBJECTIVES This study sought to investigate whether the individual cholesterol absorption rate affects atorvastatin's effectiveness to reduce cardiovascular risk in hemodialysis patients. METHODS This post-hoc analysis included 1,030 participants in the German Diabetes and Dialysis Study (4D) who were randomized to either 20 mg of atorvastatin (n = 519) or placebo (n = 511). The primary endpoint was a composite of major cardiovascular events. Secondary endpoints included all-cause mortality and all cardiac events. Tertiles of the cholestanol-to-cholesterol ratio, which is an established biomarker of cholesterol absorption, were used to identify high and low cholesterol absorbers. RESULTS A total of 454 primary endpoints occurred. On multivariate time-to-event analyses, the interaction term between tertiles and treatment with atorvastatin was significantly associated with the risk of reaching the primary endpoint. Stratified analysis by cholestanol-to-cholesterol ratio tertiles confirmed this effect modification: atorvastatin reduced the risk of reaching the primary endpoint in the first tertile (hazard ratio [HR]: 0.72; p = 0.049), but not the second (HR: 0.79; p = 0.225) or third tertiles (HR: 1.21; p = 0.287). Atorvastatin consistently significantly reduced all-cause mortality and the risk of all cardiac events in only the first tertile. CONCLUSIONS Intestinal cholesterol absorption, as reflected by cholestanol-to-cholesterol ratios, predicts the effectiveness of atorvastatin to reduce cardiovascular risk in hemodialysis patients. Those with low cholesterol absorption appear to benefit from treatment with atorvastatin, whereas those with high absorption do not benefit.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Cardiovascular Disorders (DHGE) > Clinic of Angiology

UniBE Contributor:

Silbernagel, Günther and Baumgartner, Iris

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0735-1097

Publisher:

Elsevier

Language:

English

Submitter:

Catherine Gut

Date Deposited:

03 Jul 2015 09:45

Last Modified:

30 Oct 2015 08:00

Publisher DOI:

10.1016/j.jacc.2015.03.551

PubMed ID:

26022817

Uncontrolled Keywords:

cholestanol; mortality; randomized controlled trial; statin

BORIS DOI:

10.7892/boris.70077

URI:

https://boris.unibe.ch/id/eprint/70077

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