Is a treat-to-target approach to lipid-lowering therapy appropriate in patients with chronic kidney disease? A prospective French cohort study

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 (&lt; 2.6 and &lt; 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. Graphic abstract: <fig id="Figa" position="anchor"> <graphic position="anchor" specific-use="HTML" mime-subtype="PNG" href="MediaObjects/40620_2021_1086_Figa_HTML.png" id="MO1"></graphic> </fig>