Cardiovascular mortality with oral potassium-binders in patients with CKD and heart failure

Abstract Introduction Hyperkalemia is an inherent consequence of advancing chronic kidney disease (CKD) as a result of the kidney’s decreased ability to excrete potassium. Heart failure patients with concomitant CKD may not tolerate maximum doses of guideline-directed medical therapies (GDMT) like ACE inhibitors (ACEi), angiotensin receptor blockers (ARB), angiotensin receptor/neprilysin inhibitors (ARNI) and mineralocorticoid receptor antagonists (MRA) due to dose-limiting hyperkalemia. Many randomized controlled trials in heart failure exclude patients with advanced CKD. Two oral therapies exist to manage hyperkalemia - patiromer sorbitex calcium and sodium zirconium cyclosilicate. This study aims to identify the potassium-binder with better outcomes as defined by less readmissions, hyperkalemia episodes, and death. Purpose This project was undertaken to better understand the impact of using potassium-binders in CKD patients with heart failure. Improved management of hyperkalemia will be an avenue for optimization of GDMT in this population. Methods and materials The TriNetX research network was used for this study. Two cohorts of patients were created by using International Classification of Disease 10 (ICD-10) codes and CPT codes. Both cohorts consisted of patients with no prior history of hyperkalemia within 30 days of hospital discharge at which time one cohort was prescribed patiromer and the other received sodium zirconium cyclosilicate. Each cohort was prohibited from exposure to the other medication. The cohorts were balanced by propensity score matching and the greedy nearest neighbor algorithm for age, race, gender, ethnicity. They were also balanced for systolic and diastolic heart failure diagnoses, and for each individual stage of CKD (1 through 5 and end stage). They were also balanced for use of ACEi, ARBs, and MRAs. This resulted in 8,921 patients in each arm. They were then evaluated for the outcomes of hospital readmission, hyperkalemia episodes (>6.1 mmol/L), and death within 12 months. Results Patients treated with patiromer were more likely to be hospitalized over the following twelve months (44% vs 40%, RR 1.11, 95% CI (1.07,1.15), p value <0.0001). They were also more likely to experience hyperkalemia (11.7% vs 9.2%, RR 1.27, 95% CI (1.16,1.38), p value <0.0001). Patiromer was also associated with slightly greater all cause mortality (27% vs 25%, RR 1.08, 95% CI (1.03,1.13), p value 0.0021). Discussion This study demonstrates patiromer has more readmissions and hyperkalemia episodes along with greater mortality. In conclusion, sodium zirconium cyclosilicate was found to have better outcomes compared to that of patiromer. Further studies are necessary to better understand the utility of using sodium zirconium cyclosilicate as maintenance therapy for hyperkalemia in order to maximize GDMT in CKD patients with heart failure.