TY  - JOUR
AB  - INTRODUCTION: Frailty is associated with a higher risk of adverse outcomes. It is believed that people with a higher frailty index may be less tolerant to new treatments, often leading to inappropriate prescribing. This post hoc analysis of FIDELITY, a prespecified, pooled analysis of the FIDELIO-DKD and FIGARO-DKD phase 3 clinical trials, investigated the efficacy and safety of finerenone versus placebo according to baseline frailty index. METHODS: Between September 2015 and October 2018, 12,990 people with chronic kidney disease (CKD) and type 2 diabetes (T2D) receiving the maximum tolerated dose of a renin-angiotensin system inhibitor were randomized to receive finerenone 10 or 20 mg once daily or placebo. Baseline frailty index was calculated using the Rockwood cumulative deficit approach including 30 clinical characteristics. Primary efficacy outcomes included a kidney (kidney failure, sustained decrease of ≥57% in estimated glomerular filtration rate [eGFR], or kidney-related death) and a cardiovascular (CV) composite outcome (CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure). Changes in urine albumin-to-creatinine ratio (UACR) and eGFR were measured across the study period. RESULTS: Overall, kidney and CV event rates increased with increasing frailty. Finerenone reduced the risk of primary kidney and CV composite outcomes irrespective of baseline frailty (P interaction=0.93 and 0.35, respectively). Compared with placebo, finerenone also demonstrated significant reductions in UACR across all frailty subgroups (P<0.01 for all visits) and significant attenuation of eGFR decline from baseline to month 48 in the three most frail quartiles (>Q1 to ≤Q2, P=0.001; >Q2 to ≤Q3, P<0.001; >Q3, P<0.001, respectively). The incidence of serious adverse events and hyperkalemia increased with increasing frailty in both treatment arms. CONCLUSION: Finerenone reduced the risk of CV and kidney events in people with CKD and T2D versus placebo irrespective of baseline frailty status. REGISTRATION: FIDELIO-DKD (NCT02540993) and FIGARO-DKD (NCT02545049).
AU  - Rossing, P.*
AU  - Birkenfeld, A.L.
AU  - Fioretto, P.*
AU  - McGill, J.B.*
AU  - Anker, S.D.*
AU  - Pitt, B.*
AU  - Rohwedder, K.*
AU  - Scalise, A.*
AU  - Scott, C.*
AU  - Filippatos, G.*
C1  - 74283
C2  - 57124
CY  - 1401 H Street Nw, Suite 900, Washington, Dc 20005, United States
SP  - 968-977
TI  - Finerenone and clinical outcomes in chronic kidney disease and type 2 diabetes by frailty Iidex: FIDELITY post hoc analysis.
JO  - Clin. J. Am. Soc. Nephrol.
VL  - 20
IS  - 7
PB  - Amer Soc Nephrology
PY  - 2025
SN  - 1555-9041
ER  - 

TY  - JOUR
AB  - BACKGROUND AND OBJECTIVES: Hemodialysis patients with type 2 diabetes exhibit an excessive cardiovascular risk and regularly receive heparin. We tested whether antibodies to the platelet factor 4-heparin complex (PF4-H-AB) contribute to outcome. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In 1255 hemodialysis patients with type 2 diabetes, the German Diabetes Dialysis Study evaluated the effect of atorvastatin (20 mg/d) versus placebo. In a post hoc analysis, the association among PF4-H-ABs, biochemistry, and prespecified, centrally adjudicated end points (combined cardiovascular end point [CVE], all-cause mortality, sudden death, myocardial infarction, stroke) was investigated. RESULTS: During 4 years, 460 patients reached the CVE; 605 died, 159 of sudden death. Myocardial infarction and stroke occurred in 199 and 97 patients, respectively. Positive PF4-H-AB status was found in 231 (18.7%) of 1236 tested patients and was associated with lower albumin, higher C-reactive protein, and arrhythmia. In a multivariate model adjusted for demographics, comorbidities, and biochemistry, PF4-H-ABs were associated with sudden death. No significant association between PF4-H-ABs and all-cause mortality, myocardial infarction, stroke, or the CVE was observed. Detecting an interaction between acetylsalicylic acid and PF4-H-ABs regarding sudden death and mortality, we found that the association between PF4-H-ABs and outcomes was restricted to patients with acetylsalicylic acid use, most likely because of indication bias. CONCLUSIONS: In hemodialysis patients who have type 2 diabetes and are treated with acetylsalicylic acid, PF4-H-ABs are associated with sudden and all-cause death. Further studies are needed to elucidate this association.
AU  - Krane, V.*
AU  - Berger, M.*
AU  - Lilienthal, J.*
AU  - Winkler, K.*
AU  - Schambeck, C.*
AU  - Wanner, C.*
AU  - German Diabetes and Dialysis Study Investigators
C1  - 4452
C2  - 28055
SP  - 874-881
TI  - Antibodies to platelet factor 4-heparin complex and outcome in hemodialysis patients with diabetes.
JO  - Clin. J. Am. Soc. Nephrol.
VL  - 5
IS  - 5
PB  - American Society of Nephrology
PY  - 2010
SN  - 1555-9041
ER  -