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Managing Hyperkalemia in High-Risk Patients in Long-Term Care
Rajeev Kumar, MD, FACP; Leo Kanev, MD; Steven D. Woods, PharmD; Melanie Brenner, PharmD; and Bernie Smith, RPh, MBA, MHA

Managing Hyperkalemia in High-Risk Patients in Long-Term Care

Rajeev Kumar, MD, FACP; Leo Kanev, MD; Steven D. Woods, PharmD; Melanie Brenner, PharmD; and Bernie Smith, RPh, MBA, MHA
HF is a leading cause of death, hospitalizations, and rehospitalizations in patients 65 years and older in the United States.9,40,41 A study assessing hospitalizations for HF in the Medicare population (mean age, 80 years) during a 5-year period showed that approximately one in 4 patients were readmitted to a hospital within 30 days of the initial hospitalization, and the most common cause of readmission was cardiovascular disease.40 Another study showed that the most frequent reason for all-cause 30-day hospital readmissions in the elderly—costing approximately $1.7 billion—was congestive HF.42 In a 2004 national survey of skilled nursing facilities (SNFs), 4% to 5% of the long-term residents were reported to have a primary diagnosis of HF, with many more having HF as a secondary diagnosis.43,44 Although the exact prevalence of HF in SNF residents is unknown, it has been estimated to be approximately 30% to 40%.45,46 Furthermore, an observational study assessing the clinical outcomes in Medicare patients hospitalized for HF showed that the rates of rehospitalization and death were significantly higher in patients who were discharged to a SNF versus home.47

RAASI therapy is well known to reduce the risk of death and hospitalization in patients with HF and reduced ejection fraction (HFrEF).48-52 Available data suggest that ACEIs and ARBs have similar effects in the young and the elderly. A study of ACEIs showed previously that the reduction in mortality and hospitalizations was consistent among older and younger age groups and more evident in patients with a left ventricular ejection fraction (LVEF) of 25% or less.53 In a more recent study (CHARM [Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity]), candesartan (an ARB) resulted in similar relative reductions in the risk of cardiovascular death or hospitalization, regardless of age.1,54 ARBs seem to be better tolerated than ACEIs.55-57 The ELITE II trial compared losartan (an ARB) and captopril (an ACEI) in older patients (mean age, 71 years) with an LVEF of 40% or less, and showed that the two drugs were equally effective in improving survival, but losartan was better tolerated.56

The benefit of blocking the RAAS does not end with the ACEIs and ARBs. The mineralocorticoid receptor antagonists (MRAs) spironolactone and eplerenone also provide an increased benefit in the elderly patients with HF. The Randomized Aldactone Evaluation Study (RALES) demonstrated a 30% reduction in mortality when spironolactone was added to standard-of-care treatment in patients with severe HF.48 Following the publication of results from RALES, there was a significant increase in the use of spironolactone in older patients, with a corresponding increase in hyperkalemia and hyperkalemia-related hospitalizations and deaths.58,59 The EMPHASIS HF (Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure) trial showed that eplerenone decreased the risk of cardiovascular death and hospitalization even in patients with mild, New York Heart Association (NYHA) class II HF, and these benefits remained in subgroups of older patients.50 However, in the older patients and in those with CKD, there was a noted increase in the incidence of moderate hyperkalemia (serum K+ level >5.5 mEq/L).60

The American Heart Association (AHA) guidelines for the management of HF recommend using an ACEI or ARB with a beta-blocker in patients with HFrEF.61,62 If the patient remains NYHA class II or greater, provided that eGFR is greater than 30 mL/min/1.73 m2 and serum K+ level is less than 5.0 mEq/L, it is further recommended to add an MRA to the treatment regimen.61,62 The guidelines of the European Society of Cardiology (ESC) also recommend prescribing an ACEI or ARB, in addition to a beta-blocker, for symptomatic patients with HFrEF to reduce the risk of HF hospitalization and death.63 An MRA is recommended for patients with HFrEF who remain symptomatic.63

Recently, the AHA and the Heart Failure Society of America developed specific guidelines for the management of HF in SNFs. These guidelines, similarly, recommend ACEIs, ARBs, and MRAs as
preferred therapy in patients with HFrEF, in addition to restricting sodium to achieve euvolemia (Table 144).44 In all guidelines, caution is advised when prescribing these therapies in patients with low blood pressure, increased serum creatinine, or elevated serum K+.44,61-63 Current guidelines recommend RAASI dose modifications with increasing serum K+ levels. The most recent 2016 ESC guidelines recommend a short-term cessation of K+-retaining agents and RAASIs to manage severe hyperkalemia (serum K+ level >6.0 mEq/L).63 However, this should be minimized and the RAASI therapy should be carefully reintroduced as soon as possible to resume its beneficial effects.63

Treatments for Acute Hyperkalemia
Treatment strategies for acute hyperkalemia are designed to prevent or minimize the adverse electrophysiological effects on the heart and remove the patient from immediate danger.64 These include intravenous administration of calcium to restore the resting membrane potential of cardiac cells when electrocardiographic changes are present, and pharmacologic treatments such as insulin and beta-adrenergic agonists that shift K+ to the intracellular space.64 The effect of these agents can be observed within 30 minutes, but they do not decrease total body K+, thus necessitating the removal of K+ through other nonacute approaches. These approaches include dialysis, increased renal excretion through forced diuresis, and increasing the gastrointestinal (GI) removal with short-term use of a K+-binding agent. These measures are useful emergency and in-hospital therapies for acute hyperkalemia, but are unsuitable for the chronic hyperkalemia that is typically seen in patients with CKD and/or HF who are on RAASIs.

Management of Chronic Hyperkalemia
The strategy to manage chronic hyperkalemia in the elderly is fundamentally different from the strategy for acute hyperkalemia. The management of chronic hyperkalemia usually begins with the elimination of any potential causes, including high dietary K+ and medications such as nonsteroidal anti-inflammatory drugs and RAASIs.3 Other interventions include dietary education, a thorough review of prescribed and other medications, and alkali replacement, if acidotic.3 Unfortunately, the class of medication most associated with hyperkalemia—RAASIs—is also the most beneficial to patients with CKD and HF.

Treatment guidelines for the management of CKD and HF outline the importance of RAAS inhibition in these patient populations and provide some guidance on managing hyperkalemia when it develops.26,28,61,62 There is an urgent need to update the guidelines, as the current guidelines were written prior to the advent of newer K+ binders that can be taken on a daily basis. In the past, chronic hyperkalemia in patients with CKD and/or HF was typically managed by reducing or discontinuing RAASIs. The following sections review the standard approaches to hyperkalemia management, and newly approved and investigational therapies for the daily management of hyperkalemia.

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