Effect of initiation and rapid maximisation of RAASi in patients with CKD and heart failure with reduced ejection fraction – observations from the LIFT study, an ongoing trial

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Effect of initiation and rapid maximisation of RAASi in patients with CKD and heart failure with reduced ejection fraction – observations from the LIFT study, an ongoing trial
Debasish
Banerjee
Daniel Murphy danajmurphy@doctors.org.uk St George's University of London Renal Medicine London
Ella Tumelty ella.tumelty@stgeorges.nhs.uk St George's University of London Renal Medicine London
Tony Lopez tony.lopez1@nhs.net St George's University of London Renal medicine London
Simran Parmar simransingh.parmar@stgeorges.nhs.uk St George's University of London Renal medicine London
Sabba Hussain sabba.hussain@stgeorges.nhs.uk St George's University of London Renal medicine London
Isaac Chung isaac.chung1@nhs.net St George's University of London Renal medicine London
Harsha Addada m1800369@sgul.ac.uk St George's University of London Renal medicine London
Riny Paul riny.paul@stgeorges.nhs.uk St George's University Hospitals NHS Foundation Trust Renal medicine London
Sharirose Abat sharirose.abat@stgeorges.nhs.uk St George's University Hospitals NHS Trust Renal medicine London
Thomas McNally thomas.mcnally2@nhs.net St George's University of London Renal medicine London
Irina Chis Ster ichisste@sgul.ac.uk St George's University of London Infection and immunity London
Lisa Anderson lisa.anderson@stgeorges.nhs.uk St George's University Hospitals NHS Foundation Trust Cardiology London
Mahrukh Ayesha Ali mahrukh.ali@nhs.net St George's University Hospital NHS Foundation Trust Renal medicine London
 
 

The use of renin-angiotensin-aldosterone inhibitors (RAASi) in heart failure patients reduces hospital admissions and mortality; however, this is limited in CKD patients by hyperkalaemia, and concerns of worsening renal function. Novel potassium binders like Lokelma (sodium zirconium cyclosilicate – SZC) can potentially allow clinicians to achieve optimal dosing of RAASi. The LIFT study (Lokelma for maximization of RAASi in patients with CKD and HF) is a phase III, randomised controlled trial to evaluate the effect of Lokelma in allowing initiation and maximization of RAASi in patients with CKD and HF with reduced ejection fraction on nil or sub-optimal RAASi. The trial is ongoing and here we present some pre-liminary data and the data remains blinded.

The primary outcome is to assess the effect of Sodium Zirconium Cyclosilicate (ZS-9) and Placebo with respect to enabling patients to achieve the maximum (RAASi) dose while keeping [K+] < 5.6 mmol/L. Secondary outcomes include the number and maximum doses of ACEi/ARBs (Angiotensin Converting Enzyme inhibitors/angiotensin receptor blockers) and MRA (mineralocorticoid receptor blockers) achieved during the study period. Other secondary outcomes include time since randomisation to first occurrence of hyperkalaemia (K+>5.5 mmol/L) and/or severe hyperkalaemia (K+>6.0), number of hospital admissions and duration of hospital admissions during the study.

We present some longitudinal preliminary data regarding the up-titration of RAASi achieved for the 38 patients who have completed the trial so far, having started with none or sub-optimal RAASi. The mean age of participants is 73 years (SD=7). Of the 38 participants, 35 (92%) achieved up-titration to maximum tolerated dose in the treatment duration of 2 to 12 weeks. There was no significant change noted in eGFR, NTpro-BNP and troponin during the visits. The data exhibit unsurprising high variability as the results cannot be stratified by intervention arm at this moment.

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