Systolic blood pressure variability and effect of finerenone treatment in patients with chronic kidney disease and type 2 diabetes: a FIDELITY analysis
S Rajagopalan, P Rossing, B Pitt, S Anker, G Filippatos, Z Zheng, C Scott, S Al KindiAbstract
Introduction
High blood pressure (BP) variability is associated with increased aldosterone and mineralocorticoid receptor (MR) activation, and high visit-to-visit systolic BP (SBP) variability is associated with increased risks of cardiovascular (CV) events and chronic kidney disease (CKD). In FIDELITY, a prespecified pooled analysis of the phase III FIDELIO-DKD and FIGARO-DKD trials, the non-steroidal MR antagonist finerenone significantly reduced the risk of CV and adverse kidney outcomes vs placebo in patients with CKD and type 2 diabetes (T2D).
Purpose
This FIDELITY post hoc subanalysis evaluated the association between SBP variability and CV and kidney outcomes. Additionally, the finerenone treatment effect across levels of SBP variability was assessed.
Methods
Patients in FIDELITY were on optimised renin–angiotensin system inhibition and randomised 1:1 to finerenone or placebo. Outcomes included composite CV (CV death, non-fatal myocardial infarction, non-fatal stroke, or hospitalisation for heart failure) and composite kidney (kidney failure, sustained ≥57% decrease in estimated glomerular filtration rate from baseline over at least 4 weeks, or kidney-related death). SBP recorded at pre-screening, screening, baseline (pre-treatment) and up to 1 year from baseline after titration at month 1 (post-treatment) were used. The effect of finerenone vs placebo on outcomes was assessed across strata of pre- and post-treatment SBP variability (quartile 1 as the lowest and quartile 4 as the highest). SBP variability was estimated using standard deviation. A stratified Cox proportional hazards model was used to assess the associations of SBP variability with clinical outcomes and the finerenone treatment effects across SBP variability quartiles.
Results
Higher pre-treatment SBP variability was associated with increased probabilities of CV and kidney events over 3.5 years in both treatment groups (Fig). Over a median follow-up period of 3 years (interquartile range 2.3–3.8 years), finerenone reduced composite CV (hazard ratio [HR] 0.86; 95% confidence interval [CI] 0.78–0.95) and kidney outcomes (HR 0.76; 95% CI 0.66–0.88) vs placebo across SBP variability quartiles (pinteraction≥0.1741 and pinteraction≥0.5267, respectively). A trend was observed for a greater finerenone impact on CV outcomes at the highest levels of SBP variability (HR 0.72; 95% CI 0.60–0.87). Overall, finerenone and placebo showed comparable safety profiles.
Conclusions
In FIDELITY, higher SBP variability was associated with increased risk of adverse CV and kidney outcomes. Finerenone lowered the risk of CV and kidney outcomes vs placebo in patients with CKD and T2D irrespective of SBP variability. The treatment effect of finerenone is not modified by SBP variability and may confer benefit compared with placebo in those with high SBP variability.Figure 1