Fiche publication
Date publication
mars 2022
Journal
Clinical journal of the American Society of Nephrology : CJASN
Auteurs
Membres identifiés du Cancéropôle Est :
Pr ROSSIGNOL Patrick
Tous les auteurs :
Massy Z, Merkling T, Wagner S, Girerd N, Essig M, Wanner C, Fellstrom B, Rossignol P, Zannad F
Lien Pubmed
Résumé
Statins are less efficacious in reducing cardiovascular disease risk in dialysis patients than in general population. Recent experimental data showed that phosphate excess promotes cellular de novo cholesterol synthesis through 3-hydroxy-3-methylglutaryl coenzyme A reductase activation. Whether this mechanism might account for dialysis patients' resistance to statins has not yet been explored. In the present post-hoc analysis we examined the efficacy of statin treatment according to serum phosphate levels in the dialysis patient participants of the AURORA trial (A Study to Evaluate the Use of Rosuvastatin in Subjects on Regular hemodialysis: An Assessment of Survival and Cardiovascular Events), using serum phosphate levels at baseline and during trial course. We first classified the patients by groups of similar phosphate trajectories over time, and tested whether phosphate as a longitudinal exposure (summarized by the identified trajectory groups) modulated the occurrence of major adverse cardiovascular events (MACE) and all-cause death. We replicate the analysis in 4D (Deutsche Diabetes Dialyse Studie) trial. In the AURORA trial, using multivariable analysis we found that the treatment effect of statin on MACE and all-cause death was significant and protective effects in patients with low values of serum phosphate and gradually faded for higher phosphate levels >5 mg/dL. A similar lack of statin treatment efficacy for both outcomes was observed with high baseline phosphate levels (>5 mg/dL). In the 4D trial, we found a comparable but not significant trend towards losing treatment efficacy in presence of high serum phosphate levels for both outcomes. Our results demonstrated the limited treatment efficacy of statins in dialysis patients in the presence of hyperphosphatemia.
Référence
Clin J Am Soc Nephrol. 2022 Mar 2;:
