Patiromer helps HFrEF patients to optimise RAAS inhibitors without hyperkalaemia

In the DIAMOND trial, 85% of the patients with heart failure with reduced ejection fraction (HFrEF) and renin-angiotensin-aldosterone system (RAAS)-inhibitor-related hyperkalaemia could optimise RAAS-inhibitor therapy when treated with patiromer, while sustaining normal levels of serum potassium.

RAAS inhibitors have a class 1 indication in the treatment of HFrEF but may increase the risk of hyperkalaemia [1]. Therefore, RAAS inhibitors, mineralocorticoid receptor antagonist (MRA) therapy, in particular, are often underused in patients who display RAAS inhibitor-related hyperkalaemia, resulting in an increased risk of cardiovascular events [2,3].

The DIAMOND trial (NCT03888066) included 1,038 participants with HFrEF and RAAS-inhibitor-related hyperkalaemia and a kidney function not more than mild or moderately impaired, who were subjected to a 12 week run-in phase to initiate patiromer, optimise RAAS-inhibitor therapy, and initiate/optimise MRA therapy. 85% (n=878) could be optimised, whereas 15% (n=160) of the participants could not be optimised. The 878 optimised participants were then randomised to continuance or withdrawal from patiromer (placebo) until the end of the study, approximately 1 year from baseline. The modified primary endpoint was the adjusted mean change in serum potassium in the study population. The results were presented by Prof. Stefan Anker (Charité Campus Virchow Clinic Berlin, Germany) and Dr Javed Butler (Baylor University Medical Center, TX, USA) [4,5].

The adjusted mean change in serum potassium at the end of study was significantly lower in participants on patiromer compared with participants receiving placebo (+0.03 mEq/L vs +0.13 mEq/L; P<0.001). This result was consistent across ejection fractions, baseline New York Heart Association (NYHA) class, history of hyperkalaemia, chronic kidney disease (CKD) stage, and other subgroups. Furthermore, participants on patiromer had a reduced risk of hyperkalaemia >5.5 mEq/L (HR 0.63; P=0.006) and showed fewer MRA dose-reduction-below-target events (HR 0.62; P=0.006) than participants on placebo.

The safety analysis did not reveal remarkable safety issues for patiromer and similar rates of serious adverse events were reported in the patiromer group (12.3%) and the placebo group (13.2%). Notably, hypomagnesemia did not occur more frequently in participants receiving patiromer (4.3%) compared with placebo (5.0%). However, Prof. Anker mentioned that this study was underpowered to conclusively assess safety.

Dr Butler added that the non-randomised participants were older, had a lower eGFR, were more frequently diabetic, and were using less RAAS inhibitors at baseline. Although an initial reduction in serum potassium was observed in the non-randomised participants during the run-in phase, they displayed fewer up-titrations of RAAS inhibitors and/or MRA therapy than the randomised participants. Finally, participants were mostly not randomised because they did not meet the randomisation criteria, experienced RAAS-inhibitor-related events or other adverse events, or because they withdrew from the study.

“Most patients with HFrEF and RAAS-inhibitor-related hyperkalaemia could achieve optimal doses of RAAS inhibitors, including an MRA, when treated with patiromer while maintaining normal serum potassium levels,” concluded Prof. Anker.

1. Seliger SL. Nephrol Dial Transplant. 2019;34:iii12–iii18.
2. Ouwerkerk W, et al. Eur Heart J 2017;38(24):1883–1890.
3. Trevisan M, et al. Eur J Heart Failure 2021;23(10):1698–1707.
4. Anker SD, et al. Patiromer For The Management Of Hyperkalemia In Subjects Receiving RAAS-Inhibitors For Heart Failure With Reduced Ejection Fraction: Results From The DIAMOND Trial. LBT Pharmacological treatment I, Heart Failure 2022, 21–24 May, Madrid, Spain.
5. Butler J, et al. DIAMOND Trial: Patriomer for the management of hyperkalemia in subjects receiving RAASi medications for heart failure with reduced ejection fraction. LBT Pharmacological treatment II, Heart Failure 2022, 21–24 May, Madrid, Spain.

 

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Posted on 28 July, 2022