Key Points
- Optimal medical therapy for patients with Heart Failure with Reduced Ejection Fraction (HFrEF) compromises of renin-angiotensin-aldosterone-system inhibitors that often cause hyperkalemia.
- If hyperkalemia cannot be mitigated with alternative methods, dose reductions, which compromise the effect of the optimal therapies, are often employed.
- Patirometer, which binds to potassium in exchange for calcium, was shown to help mitigate hyperkalemia in patients with HFrEF on RAAS-i.
Patients with Heart Failure with Reduced Ejection fraction have an array of medications available to help improve their condition, part of guideline-directed medical therapy. These medications include renin-angiotensin-aldosterone-system inhibitors (RAAS-i), which have the side effect of raising potassium levels in serum. When patients are placed on both an ACE inhibitor and mineralocorticoid antagonist, which not a rare occurrence, the risk of hyperkalemia increases. When faced with hyperkalemia, clinicians generally respond by decreasing or stopping the RAAS-i, potentially compromising the beneficial effects of GDMT.
Enter patiroemeter: a potassium binder that works by eliminating potassium in stool. In a late breaking clinical trials session at the 71st American College of Cardiology’s Scientific Sessions, Dr. Javed Butler (Baylor University Medical Center, Dallas, TX), presented findings from the DIAMOND trial, in which patients with heart failure and hyperkalemia were given patirometer then randomized to continue the drug or withdraw it and replace it with placebo.
This double blinded clinical trial enrolled patients with heart failure and hyperkalemia while on RAAS-i, or normokalemia with a history of hyperkalemia leading to RAAS-i dose reduction. During a single blinded run-in period, all patients were given patiroemeter while GDMT, including ACE-i and MRA, was optimized. Participants were then either continued on patirometer or had it replaced with placebo during the double blinded treatment portion of the study. The primary endpoint of the study, intiailly time to first heart failure hospitalization or cardiovascular death, was changed due to the COVID-19 pandemic to an adjusted mean change in serum potassium to the end of the study, Secondary endpoints included time to first hyperkalemia event, time to reduction of MRA dose below target dosing, a win-ratio for morbidity and mortality adjusted outcomes, and a win-ratio of novel RAASi use.
878 patients underwent randomization and approximately 360 patients in each arm continued to completion. There was a clinically significant reduction in the mean change of serum potassium (+0.3 vs +0.13 mEq/L) in those who took patirometer (between group difference -0.1 (-0.13 to -0.07, p<0.001). The secondary endpoints of hyperkalemia events and lack of durable enablement of MRA target dosing, all favored patirometer as well.
During a panel discussion, Dr. Javed Butler warned of adding another drug without cause, stating “we should avoid polypharmacy and undue burden on our patients, but when hyperkalemia affects our ability to give targeted doses of known beneficial drugs, there is no reason, aside from possibly financial, that patirometer should not be prescribed”.
