Optimization of RAASi Therapy with New Potassium Binders for Patients with Heart Failure and Hyperkalemia: Rapid Review and Meta-Analysis.

Andrea Montagnani,Gualberto Gussoni,Stefania Frasson,Dario Manfellotto

doi:10.3390/jcm10235483

Andrea Montagnani, Gualberto Gussoni + Show 2 more

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https://doi.org/10.3390/jcm10235483

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Abstract

(1) Background: The objective of this rapid review is to assess whether new potassium binders (NPBs) could enable the optimization of RAASi therapy more than usual care or placebo in patients with or at risk of heart failure and hyperkalemia. (2) Methods: We searched for RCTs that included patients with or at risk of hyperkalemia and patients treated with Patiromer or sodium zirconium cyclosilicate (ZSC). The comparators were placebo, usual care, and potassium binders with different doses or different treatment protocols. We searched the Cochrane CENTRAL, MEDLINE, and ClinicalTrials.gov databases. The risk of bias was assessed using the Cochrane risk of bias tool for RCTs. Data were pooled using the random effects model, and the fixed effects model was used for sensitivity analysis. (3) Results: We included 12 studies with 2800 enrolled patients. Only three of these trials (412 patients) were included in the meta-analysis. NPBs seemed to have an effect on the optimization of MRA therapy, with an RR (95% CI) of 1.24 (1.09, 1.42) (moderate certainty evidence); Patiromer seemed to have an effect on MRA optimization, with an RR (95% CI) or 1.25 (1.08, 1.45) (high certainty evidence). ZSC seemed to have no effect on enabling MRA therapy, with an RR (95% CI) of 1.19 (0.89, 1.59) (low certainty evidence). The AEs in HF patients with hyperkalemia treated with Patiromer were GI disorders and hypomagnesemia. ZSC The AEs included chronic cardiac failure, hypokalemia, and edema. (4) Conclusions: This meta-analysis included three studies with a small number of patients and a short follow-up period (1–3 months). The evidence of the effect of NPBs on MRA optimization had a moderate certainty for imprecision. Data on the effect on MRA optimization and less severe AEs in long-term treatment seem to suggest the use of Patiromer for the optimization of MRA therapy in patients with or at risk of heart failure and hyperkalemia. Future adequately powered RCTs are needed to assess the benefits and potential harms of potassium binders.

Highlights

new potassium binders (NPBs) seemed to have an effect on the optimization of MRA therapy, with a risk ratio of 1.24 (1.09, 1.42); there was no heterogeneity (I2 = 0%, moderate certainty evidence)
Patiromer seems to have an effect on MRA optimization, while zirconium cyclosilicate (ZSC) seems to have no statistically significant effect
The results of our review indicated that NPBs seem to have an effect on MRA optimization with moderate certainty of evidence

Summary

Introduction

There is no universal cutoff for HK, but a level of 5.0 mEq/L is common [4]. HK is a life-threatening condition that leads to significant morbidity and mortality. A recent evaluation of medical records demonstrated an increase in all-cause mortality both with K+ values below the normal range and values higher than 5.5–6.0 mEq/L, with a clear effect of comorbidities, such as diabetes, heart failure, and CKD, considered individually or together [5]. In three pivotal clinical studies examining the efficacy of RAAS inhibitors in heart failure, HK occurred in these patients at a non-negligible frequency, patients with a high risk of HK (i.e., with impaired renal function) were excluded from the studies [6,7,8]

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