THE IMPACT OF BASELINE FRAILTY, MULTIMORBIDITY, POLYPHARMACY AND HEALTH-RELATED QUALITY OF LIFE ON THE EFFECTS OF EMPAGLIFLOZIN: POST-HOC ANALYSES FROM THE EMPA-KIDNEY TRIAL
Dr Daniel Vincent O’Hara1,2
1NHMRC Clinical Trials Centre, University of Sydney, Camperdown, Australia, 2Department of Renal Medicine, Royal North Shore Hospital, St Leonards, Australia
Aim: To assess the impact of frailty, multimorbidity, polypharmacy and health-related quality of life (HRQoL) on the effects of empagliflozin.
Background: Chronic kidney disease (CKD) is associated with higher rates of frailty, multimorbidity, polypharmacy and low HRQoL, but the efficacy and safety of empagliflozin among people with these attributes are uncertain.
Methods: EMPA-KIDNEY was a double-blind trial randomising 6609 participants with CKD (eGFR 20- <45; or 45-<90ml/min/1.73m² with urinary albumin-to-creatinine ratio ≥22.6mg/mmol) to empagliflozin 10mg daily or placebo (Clinicaltrials.gov: NCT03594110). The primary outcome (kidney disease progression or cardiovascular death) was assessed after median 2.0 years follow-up in post-hoc subgroups by baseline multimorbidity, concomitant medication count, and HRQoL (EuroQoL EQ-5D-5L) in thirds. Baseline frailty was estimated through a multivariable regression model predicting hospitalisation risk. Effects on the primary and safety outcomes were assessed by pre-specified Cox regression models.
Results: Empagliflozin lowered the relative risk of the primary outcome by 28% (hazard ratio 0.72, 95%CI 0.64-0.82) with no significant heterogeneity by frailty, multimorbidity, polypharmacy or HRQoL (all Het P>0.05). Those in the highest categories of multimorbidity and polypharmacy, or with lowest HRQoL, had at least as much absolute benefit as those at the other extreme in each category, and across the frailty metric those with highest predicted hospitalisation risk had greatest estimated absolute benefit (trend P by frailty<0.001). There was no evidence of a difference in effect on safety outcomes by baseline frailty, multimorbidity, polypharmacy or HRQoL.
Conclusions: Absolute net benefits of empagliflozin in CKD are evident irrespective of baseline frailty, multimorbidity, polypharmacy and HRQoL, with potentially larger absolute benefits in those who are frail.
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Biography:
Dr Daniel O’Hara is a nephrologist and researcher with the University of Sydney and the NHMRC Clinical Trials Centre. Daniel’s research interests include initiatives to provide people living with chronic kidney disease and/or diabetes with a more consistent and high-quality standard of care. The pursuit of this goal includes working closely with patients as key stakeholders, developing programs to provide patient education and long-term support, investigating new medications and technologies that could improve long term health and wellbeing outcomes, and exploring strategies to improve the equity of healthcare in Australia and internationally.