In the subsequent extended phase of the study, patients on ZS-9 t.i.d. in the acute phase were rerandomized to once-daily ZS-9 or placebo for 12 days. Patients on ZS-9 at 5 g or 10 g once daily maintained normokalemia, while those switched to placebo became hyperkalemic once again by day 12, according to Dr. El-Shahawy of the Academic Medical Research Institute, Los Angeles.
The side-effect profile of ZS-9 was similar to that of placebo, with no significant hypokalemia or GI side effects being noted, he added.
A large, long-term study of ZS-9 for maintenance of normokalemia is ongoing.
Dr. Fonarow noted that another, entirely different approach to reducing the risk of hyperkalemia involves the development of novel, nonsteroidal, cardioselective mineralocorticoid receptor antagonists.
He cited a promising phase II study of one such agent, known for now as BAY 94-8862. That study was conducted in patients with heart failure and mild to moderate chronic kidney disease. Patients assigned to the novel agent had significantly smaller rises in serum potassium than those randomized to spironolactone. Yet BAY 94-8862 reduced levels of B-type natriuretic peptide, amino-terminal brain natriuretic peptide, and albuminuria at least as much as did spironolactone, and with significantly lower rates of worsening renal failure (Eur. Heart J. 2013;34:2453-63).
Once new and better therapies for hyperkalemia enter clinical practice, Dr. Fonarow said, the priorities will be to get patients on RAAS inhibitor therapy who should be on it but now aren’t, as well as to augment dosing up to target levels in those now on suboptimal doses. But access to improved treatments for hyperkalemia also opens the door to another intriguing possibility.
“Could the ability to raise doses of RAAS inhibitors even higher than current target doses without causing hyperkalemia further enhance remodeling and improve clinical outcomes? That could indeed be the case. It’s something we’ll want to test in prospective trials,” he said.
Dr. Fonarow reported serving as a consultant to and/or advisory board member for Medtronic, Novartis, Johnson & Johnson, Bayer, and Amgen. Dr. El-Shahawy is on an advisory board for ZS Pharma and has received research grants from that company as well as Amgen, GlaxoSmithKline, Celgene, and Abbvie. Dr. Pitt reported serving as a consultant to Pfizer, Bayer, Lilly, Relypsa, and Sarfez.