Michael Emmett M.D.

Packer, M., W. M. Armstrong, J. M. Rothstein and M. Emmett (2016). “Sacubitril-valsartan in heart failure: Why are more physicians not prescribing it?” Ann Intern Med 165(10): 735-736.

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What if you were a patient with heart failure with reduced ejection fraction and your physician did not prescribe sacubitril–valsartan, a new drug that could prolong your life? Clinical trial data supported the drug’s effectiveness, the U.S. Food and Drug Administration (FDA) expedited its approval, and U.S. guidelines recommended its use. Yet, you were stable while using several heart failure drugs, and the physician who saw you every 3 to 6 months never mentioned a newer medication, despite clinical trial data demonstrating mortality benefits of the drug in patients like you. You died suddenly one morning. Did your physician do anything wrong?

Emmett, M. and A. Mehta (2016). “Patiromer-an oral calcium-loaded potassium binder: Kalirrhea with calciuresis.” Clin J Am Soc Nephrol: 2016 Sep [Epub ahead of print].

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Until recently, the major way to bind K in the gastrointestinal (GI) tract and thereby enhance excretion in the stool was the administration of sodium polystyrene sulfonate, which is a poorly effective and potentially dangerous medication (1,2). Recently, two new K-binding agents have been developed (patiromer and zirconium cyclosilicate), and one (patiromer) has been approved for use by the Food and Drug Administration (FDA). A safe, oral, nonabsorbable K-binding agent should mitigate the hyperkalemia risk of RAAS blockers and thereby be very beneficial to patients who have been unable to tolerate optimal doses of these agents on that basis. However, while the GI K-binding agents which are currently available or in the developmental pipeline are relatively selective for K, they also bind other ions and substances. Also, these agents all release other cations when K (or another cation) is bound; patiromer releases calcium whereas sodium polystyrene sulfonate and zirconium cyclosilicate each release sodium.

Rossignol, P., M. Legrand, M. Kosiborod, S. M. Hollenberg, W. F. Peacock, M. Emmett, M. Epstein, C. P. Kovesdy, M. B. Yilmaz, W. G. Stough, E. Gayat, B. Pitt, F. Zannad and A. Mebazaa (2016). “Emergency management of severe hyperkalemia: Guideline for best practice and opportunities for the future.” Pharmacol Res 113(Pt A): 585-591.

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Hyperkalemia is a common electrolyte disorder, especially in chronic kidney disease, diabetes mellitus, or heart failure. Hyperkalemia can lead to potentially fatal cardiac dysrhythmias, and it is associated with increased mortality. Determining whether emergency therapy is warranted is largely based on subjective clinical judgment. The Investigator Network Initiative Cardiovascular and Renal Clinical Trialists (INI-CRCT) aimed to evaluate the current knowledge pertaining to the emergency treatment of hyperkalemia. The INI-CRCT developed a treatment algorithm reflecting expert opinion of best practices in the context of current evidence, identified gaps in knowledge, and set priorities for future research. We searched PubMed (to August 4, 2015) for consensus guidelines, reviews, randomized clinical trials, and observational studies, limited to English language but not by publication date. Treatment approaches are based on small studies, anecdotal experience, and traditional practice patterns. The safety and real-world effectiveness of standard therapies remain unproven. Prospective research is needed and should include studies to better characterize the population, define the serum potassium thresholds where life-threatening arrhythmias are imminent, assess the potassium and electrocardiogram response to standard interventions. Randomized, controlled trials are needed to test the safety and efficacy of new potassium binders for the emergency treatment of severe hyperkalemia in hemodynamically stable patients. Existing emergency treatments for severe hyperkalemia are not supported by a compelling body of evidence, and they are used inconsistently across institutions, with potentially significant associated side effects. Further research is needed to fill knowledge gaps, and definitive clinical trials are needed to better define optimal management strategies, and ultimately to improve outcomes in these patients.

Hundemer, G. L., A. Z. Fenves, K. M. Phillips and M. Emmett (2016). “Sodium thiosulfate and the anion gap in patients treated by hemodialysis.” Am J Kidney Dis 68(3): 499-500.

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Calciphylaxis is a syndrome of microvascular calcification and thrombosis leading to painful purpuric skin lesions that progress to necrotic ulcers. Calciphylaxis occurs primarily in patients with ESRD, for which its prevalence has been estimated at 1% annually, and carries a high mortality rate.1 and 2 Increasingly, sodium thiosulfate (STS) is used off-label for treating calciphylaxis. The STS mechanism of action in this condition is unknown. One postulated mechanism is by binding to calcium phosphate salts to form soluble calcium thiosulfate, though additional antioxidant, vasodilatory, and direct inhibitory actions on vascular calcification have been proposed.3, 4 and 5 Dosing of STS, which contains 12.7 mEq/g of sodium and thiosulfate, is empirical and typically 12.5 or 25 g is given during the final 30 to 60 minutes of a hemodialysis (HD) session. A retrospective study showed that 73% of patients treated for calciphylaxis with STS had clinical improvement, with 26% having complete resolution of skin lesions.6