Q&A: The Evolving Treatment Landscape of Hyperkalemia

SEPTEMBER 30, 2017
Randy Lieberman, MD
What is hyperkalemia and are there are any signs/symptoms?
Hyperkalemia is a condition in which the level of potassium in the blood is elevated. In healthy people, even with excess dietary potassium, the body is able to maintain a normal physiologic blood potassium level via the kidney and GI tract, with the excess potassium naturally excreted. Hyperkalemia typically results from three situations, alone or in combination, in which some aspect of the kidney’s physiologic function is reduced and the GI tract cannot handle the excess potassium: 1) the patient is taking medications that block the kidney’s normal ability to manage potassium, 2) the patient is suffering from intrinsic kidney disease or 3) blood perfusion to the kidney is reduced. In these cases, the patient is at high risk for developing hyperkalemia because the body’s natural mechanisms to control potassium are being blocked. The traditional concern with hyperkalemia is the potential for a ventricular arrhythmia, which may lead to sudden death. Symptoms of hyperkalemia are generally very minimal and, unfortunately, hyperkalemia can lead to a fatal arrhythmia with little or no warning signs.

Why are some heart failure patients at risk of developing elevated blood potassium levels, or hyperkalemia?
Heart failure patients with reduced systolic function (HFrEF) -- by nature of their underlying etiology -- have many of the above-mentioned risks for developing hyperkalemia. HFrEF patients often have decreased perfusion of the kidney due to lowered cardiac output, renal vascular disease and/or diabetes, reducing the body’s ability to appropriately filter or excrete potassium. 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure recommends renin‐angiotensin system inhibition with an angiotensin‐converting enzyme inhibitor or an angiotensin receptor blocker or ARNI to improve symptoms and reduce mortality. Further recommendations include use of an aldosterone antagonist. Unfortunately, these critically necessary agents for reducing HFrEF mortality and morbidity also reduce the kidney’s physiologic ability to excrete potassium, thereby putting the patient at risk for developing hyperkalemia. It is important to understand that the “normal” kidney in combination with the back-up of the GI tract can adapt to the challenge of these medications and maintain a physiologic blood potassium level. Only in patients with some combination of intrinsic kidney disease or reduced renal blood flow do these medications result in hyperkalemia.

What are the greatest challenges in treating patients with hyperkalemia, particularly those who are also diagnosed with heart failure?
The greatest challenge in treating patients with HFrEF is achieving the optimal guideline dosage of renin-angiotensin aldosterone system (RAAS) inhibitors or other medications. Beyond patients’ symptoms limiting titration to goal, an abnormal lab report (Cr, GFR, K) may be perceived by the physician as too risky to initiate, maintain or titrate these proven lifesaving medical therapies. As a result, upwards of 30-50% of HFrEF patients are not on optimal therapy. Until recently, when a patient had a significant reduction in kidney function (Cr, GFR) or an elevated potassium level, the accepted practice for reducing the risk of hyperkalemia was not to initiate, stop or reduce these lifesaving medications. Medical evidence has demonstrated that sub-optimal doses of these medications result in a loss of their effectiveness and mortality benefits. Until now, physicians essentially had to choose which was worse: the risk of having hyperkalemia and a possible arrhythmia or the risk of stopping the heart failure medicine and allowing the patient’s underlying condition to progress. This is the paradox that we were dealing with for many years. To summarize, the most frustrating challenge for managing a patient with HFrEF has been having to let lifesaving medical therapy sit on the shelf because of the lack of effective chronic therapy to overcome the roadblock hyperkalemia represented.

How has the treatment landscape for hyperkalemia evolved over the past decade?
As I mentioned, for the past decade physicians managed the risk of hyperkalemia by eliminating or reducing the dose of heart failure (HFrEF) medicines such as RAAS inhibitors, per guideline recommendations. We never really had an effective chronic treatment to manage the condition. The other treatments for managing hyperkalemia, such as Kayexalate, are difficult for patients to tolerate and have a number of potentially serious side effects. Veltassa® (patiromer), which was approved in the United States in 2015, is the first new medicine for the treatment of hyperkalemia in more than 50 years. Veltassa is effective in lowering potassium levels and maintaining them within the normal range and it is well-tolerated and easy for patients to take. Importantly, in the clinical studies leading to FDA approval of Veltassa, the hyperkalemia patients (K: 5.0-6.5) were treated in the outpatient setting and remained on a RAAS inhibitor up to 52 weeks. The ability to directly treat hyperkalemia has the potential to essentially eliminate one of the significant challenges in the management of heart failure.

How have the recent advances in hyperkalemia treatment impacted how you treat your patients?
For me, having an option to manage hyperkalemia that does not involve eliminating or reducing the dose of the patient’s RAAS inhibitor has revolutionized not only how I treat my patients with heart failure but also those with hypertension and diabetes. Achieving the optimal dose of RAAS inhibitors recommended by the guidelines for patients with HFrEF, hypertension, diabetes and chronic kidney disease has been proven in clinical trials to reduce the progression of kidney disease and the need for dialysis, as well as reduce the risk of progressive heart failure and overall cardiovascular mortality. The option for me to manage the risk of hyperkalemia with Veltassa gives me the opportunity to achieve the optimal dose of RAAS inhibitor therapy and reduce the risk of hyperkalemia.  

What are you most excited about in regard to future developments in hyperkalemia treatment?
In the future, I’m hopeful that as cardiologists and nephrologists increase their comfort level in managing hyperkalemia, they will be able to push the envelope further in utilizing heart failure medicines particularly in our end-stage disease patients where we are normally very cautious. As more experience is gained, the ultimate goal is for primary care doctors to become familiar and confident in managing their patients with hyperkalemia using Veltassa. A significant population of heart failure and diabetic/hypertensive patients are cared for by primary care doctors who play a critical role in helping achieve the goal of reversing and improving our patients’ heart failure and renal failure. Ultimately, the medical community must gain a greater comfort in managing a patient’s hyperkalemia vs. being guided by fear. I believe that the ability to manage and treat hyperkalemia will allow us to optimize how we utilize the full range of heart failure medicines in our patients. In conclusion, while new medications will evolve, we currently have excellent therapies and need to utilize Veltassa to overcome the hurdle hyperkalemia presents to applying lifesaving therapies to our patients.
 
Randy A. Lieberman, MD, completed his residency training in internal medicine at Vanderbilt University School of Medicine in Nashville, Tennessee and Case Western Reserve in Cleveland, Ohio, where he completed fellowships in cardiology, electrophysiology, and pediatric electrophysiology. 

Dr Lieberman is the Director of cardiac electrophysiology at the Detroit Medical Center and Professor of Medicine at Wayne State University Medical School in Detroit, Michigan. He is board certified in internal medicine, cardiovascular disease, and cardiac electrophysiology. 

Dr Lieberman specializes in the diagnosis and treatment of cardiac rhythm disorders (arrhythmias) and heart failure and has a special interest in the treatment of atrial fibrillation and heart failure. He is a world-recognized expert in cardiac ablation, cardiac implantable electronic devices, cardiac resynchronization therapy and the precise placement of cardiac pacing electrodes within the heart. A sought-after lecturer and educator, Dr Lieberman travels the world teaching the latest cardiac pacemaker techniques. As a researcher, he has helped develop new techniques and technologies that are changing the way physicians treat arrhythmias and heart failure. He has published many studies, abstracts, and book chapters. 

Director of Electrophysiology Detroit Medical Center 
Director, Cardiac Electrophysiology Department of Cardiology 
Detroit Medical Center 
Wayne State University Medical School 
Detroit, Michigan 

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