Ziad A Massy1,2,3,4, Sophie Liabeuf5,6, Epiphane Kolla7, Jean Ferrières8,9, Eric Bruckert10, Oriane Lambert7, Nicolas Mansencal11, Maurice Laville12, Luc Frimat13,14, Denis Fouque15, Christian Combe16,17, Roberto Pecoits-Filho18,19, Bénédicte Stengel7,20. 1. Centre for Research in Epidemiology and Population Health (CESP), Inserm UMRS 1018, Team 5, Villejuif, France. ziad.massy@aphp.fr. 2. University Versailles-Saint Quentin, Univ Paris-Saclay, 91190, Villejuif, France. ziad.massy@aphp.fr. 3. Department of Nephrology, CHU Ambroise Paré, APHP, 92104, Boulogne Billancourt Cedex, France. ziad.massy@aphp.fr. 4. Division of Nephrology, Ambroise Paré Hospital, 9 Avenue Charles de Gaulle, 92104, Boulogne Billancourt Cedex, France. ziad.massy@aphp.fr. 5. Pharmacology Department, Amiens University Hospital, 80054, Amiens, France. 6. MP3CV Laboratory, EA7517, University of Picardie Jules Verne, 80054, Amiens, France. 7. Centre for Research in Epidemiology and Population Health (CESP), Inserm UMRS 1018, Team 5, Villejuif, France. 8. Department of Cardiology, Toulouse Rangueil University Hospital (CHU), Toulouse, France. 9. Department of Epidemiology and Public Health, UMR INSERM 1027, INSERM-Université de Toulouse, Toulouse, France. 10. Service d'Endocrinologie Métabolisme et Prévention Cardiovasculaire, Unité Fonctionnelle d'Aphérèse, Institut E3M et IHU Cardiométabolique, Hôpital Pitié Salpêtrière, Paris, France. 11. Department of Cardiology, CHU Ambroise Paré, APHP, 92104, Boulogne Billancourt Cedex, France. 12. AURAL, 124 rue Villon, 69008, Lyon, France. 13. Nephrology Department, CHRU de Nancy, 54000, Vandoeuvre-lès-Nancy, France. 14. Lorraine University, APEMAC, 54000, Vandoeuvre-lès-Nancy, France. 15. Nephrology Department, Centre Hospitalier Lyon Sud, Université de Lyon, Carmen, 69495, Pierre-Bénite, France. 16. Service de Néphrologie Transplantation Dialyse Aphérèse, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France. 17. INSERM, U1026, Univ Bordeaux, Bordeaux, France. 18. DOPPS Program Area, Arbor Research Collaborative for Health, Ann Arbor, MI, USA. 19. School of Medicine, Pontificia Universidade Catolica do Parana, Curitiba, PR, Brazil. 20. Paris-Sud, Univ Paris-Saclay, Villejuif, France.
Abstract
BACKGROUND: Whereas European guidelines recommend adjusting lipid-lowering therapy (LLT) to meet prespecified targets ('treat-to-target') for low-density lipoprotein cholesterol (LDL-C), other guidelines do not ('fire and forget'). In a large observational prospective cohort, we sought to evaluate which strategy could be associated with better cardiovascular outcomes in chronic kidney disease (CKD). METHODS: In CKD-REIN, patients (CKD stages 3 and 4) on LLT were categorized according to achievement of LDL-C targets for high and very high cardiovascular risk (< 2.6 and < 1.8 mmol/L, respectively) at baseline. Primary outcome was fatal/non-fatal atheromatous cardiovascular disease (CVD). Secondary outcomes were non-atheromatous CVD, atheromatous or non-atheromatous CVD, and major adverse cardiovascular events. RESULTS: The population comprised 1521 patients (68 ± 12 years, 31% women, mean estimated glomerular filtration rate [eGFR] 35 mL/min/1.73 m2). Overall, 523 (34%) met their LDL-C targets at baseline. Median follow-up was 2.9 years (interquartile range 2.2-3.0). Incidence rates per 100 patient-years were 6.2% (95% confidence interval [CI] 5.5-7.0) for atheromatous CVD, 9.2% (8.3-10.1) for non-atheromatous CVD, 15.2% (14.0-16.4) for atheromatous/non-atheromatous CVD, and 6.3% (5.5-7.1) for major adverse cardiovascular events. Corresponding rates in patients who achieved targets were 6.6%, 9.8%, 16.1%, and 6.3%, respectively. Target achievement was not associated with risk of fatal/non-fatal atheromatous CVD (adjusted hazard ratio 1.04, 95% CI 0.76-1.44, p = 0.77) or fatal/non-fatal atheromatous or non-atheromatous CVD (0.98, 0.78-1.23, p = 0.91). CONCLUSIONS: These findings do not appear to support a treat-to-target approach in CKD patients on LLT, and may favor the hypothesis of an advantage of fire-and-forget. Randomized trials are needed to confirm this theory.
BACKGROUND: Whereas European guidelines recommend adjusting lipid-lowering therapy (LLT) to meet prespecified targets ('treat-to-target') for low-density lipoprotein cholesterol (LDL-C), other guidelines do not ('fire and forget'). In a large observational prospective cohort, we sought to evaluate which strategy could be associated with better cardiovascular outcomes in chronic kidney disease (CKD). METHODS: In CKD-REIN, patients (CKD stages 3 and 4) on LLT were categorized according to achievement of LDL-C targets for high and very high cardiovascular risk (< 2.6 and < 1.8 mmol/L, respectively) at baseline. Primary outcome was fatal/non-fatal atheromatous cardiovascular disease (CVD). Secondary outcomes were non-atheromatous CVD, atheromatous or non-atheromatous CVD, and major adverse cardiovascular events. RESULTS: The population comprised 1521 patients (68 ± 12 years, 31% women, mean estimated glomerular filtration rate [eGFR] 35 mL/min/1.73 m2). Overall, 523 (34%) met their LDL-C targets at baseline. Median follow-up was 2.9 years (interquartile range 2.2-3.0). Incidence rates per 100 patient-years were 6.2% (95% confidence interval [CI] 5.5-7.0) for atheromatous CVD, 9.2% (8.3-10.1) for non-atheromatous CVD, 15.2% (14.0-16.4) for atheromatous/non-atheromatous CVD, and 6.3% (5.5-7.1) for major adverse cardiovascular events. Corresponding rates in patients who achieved targets were 6.6%, 9.8%, 16.1%, and 6.3%, respectively. Target achievement was not associated with risk of fatal/non-fatal atheromatous CVD (adjusted hazard ratio 1.04, 95% CI 0.76-1.44, p = 0.77) or fatal/non-fatal atheromatous or non-atheromatous CVD (0.98, 0.78-1.23, p = 0.91). CONCLUSIONS: These findings do not appear to support a treat-to-target approach in CKD patients on LLT, and may favor the hypothesis of an advantage of fire-and-forget. Randomized trials are needed to confirm this theory.
Authors: Scott M Grundy; Neil J Stone; Alison L Bailey; Craig Beam; Kim K Birtcher; Roger S Blumenthal; Lynne T Braun; Sarah de Ferranti; Joseph Faiella-Tommasino; Daniel E Forman; Ronald Goldberg; Paul A Heidenreich; Mark A Hlatky; Daniel W Jones; Donald Lloyd-Jones; Nuria Lopez-Pajares; Chiadi E Ndumele; Carl E Orringer; Carmen A Peralta; Joseph J Saseen; Sidney C Smith; Laurence Sperling; Salim S Virani; Joseph Yeboah Journal: Circulation Date: 2018-11-10 Impact factor: 29.690