Is a treat-to-target approach to lipid-lowering therapy appropriate in patients with chronic kidney disease? A prospective French cohort study
Ziad A. Massy, Epiphane Kolla, Jean Ferrières, Éric Bruckert, Oriane Lambert, Nicolas Mansencal, Maurice Laville, Luc Frimat, Denis Fouque, Christian Combe, Roberto Pecoits‐Filho, Bénédicte Stengel, Sophie Liabeuf, CKD-REIN Collaborators
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: ). 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.