Reviewer: Dr. Songül Akkoyun

Name of the Study : Patiromer for the Management of Hyperkalemia in Subjects Receiving a Renin-angiotensin aldosterone system inhibitor for Heart failure with reduced ejection fraction- DIAMOND

Presented Congress: ACC 22

Background
Renin angiotensin aldosterone system inhibitor (RAASi) are linked with an increased risk for hyperkalemia and guideline-based medical therapy (GDMT) management of patients using RAASi drugs have difficulties. Elderity, diabetes and chronic renal failure are conditions that predispose to hyperkalemia. New potassium binders are used for a while in the management of hyperkalemia; however, it is unknown whether these drugs supply long-term benefit for optimizing medical therapy in patients with low ejection fraction heart failure (HFrEF).

Objective
It was aimed to investigate the efficacy of patiromer  for treatment of hyperkalemia due to RAASi drugs in patients with HFrEF with a history of hyperkalemia.

Method
DIAMOND trial was a randomized, parallel study. Patients with HFrEF (left ventricular ejection fraction ?%40) and symptoms of New York Heart Association (NYHA) class II-IV, or with beta-blocker therapy intolerance or on beta-blocker therapy were included to study. Also patients with had active hyperkalemia or whose RAASi dose was reduced due to history of hyperkalemia were included to study. Acute decompensated heart failure, systolic blood pressure <90 mmHg, estimated glomerular filtration rate <30 ml/min/1.73 2, and major cardiovascular event in the last 4 weeks were exclusion criteria.
Patients who met the screening criteria were included in the single-blind run-in phase. During the run-in phase, patients were started on patiromer, angiotensin converting enzyme inhibitor/angiotensin receptor blocker/angiotensin receptor–neprilysin inhibitor was optimized, and mineralocorticoid receptor antagonist (MRA) was started or optimized (up to 12 week). The patiromer was titrated to a maximum of three packs per day (8.4 g/pack) to provide optimal doses of RAASi that would not develop hyperkalemia.
1:1 double-blind randomization was performed as either the patiromer continuation (n=439) or placebo (n=439) (patiromer withdrawal) group. Follow-up duration was 13 weeks. The mean age of the patients participating in the study was 67. %26 of  patients were female, %42 of patients were diabetic. Mean serum potassium level was 4.6 mEq/L

The primary endpoint was the change in serum potassium levels between the patiromer and placebo groups. The secondary endpoints included hyperkalemia events with a potassium value >5.5 mEq/L, providing to continue MRA at the target dose, investigator-reported adverse events of hyperkalemia, hyperkalemia-related clinical endpoints and novel RAASi use score (all-cause mortality, cardiovascular hospitalization or use of extensive heart failure medications) (0-8 points scale).

Results The adjusted mean change in serum potassium level at the end of the study (primary endpoint) was 0.03 mEq/L (%95 confidence interval [CI] : -0.01- 0.07) in patiromer group and 0.13 mEq/L (%95 CI: 0.09-0.16) in control group (p<0.001).
All secondary endpoints favored the patiromer. The rate of patients with serum potassium level >5.5 mEq/L was %13.9 in patiromer group and %19.4 in control group (p=0.006). Reduction in MRA dose below target dose was %13.9 in patiromer group and %18.9 in control group (p=0.006). The hyperkalemia-related clinical outcome success ratio was 1.53 (p<0.001), and the novel RAASi usage score success ratio was 1.25 (p = 0.048).

Conclusion
In patients with HFrEF optimized with RAASi therapy, the use of patiromer resulted in maintenance of lower potassium levels, reducing the risk of hyperkalemia and increment in guideline-recommended RAASi therapy.

Interpretation
Patiromer was found to be beneficial in patients with HFrEF and a history of hyperkalemia. Patiromer maintained low serum potassium levels and was associated with a lower incidence of severe hyperkalemia (>5.5 mEq/L) compared to the control group. Patiromer excused the optimization of RAASi doses against guideline-based medical therapy for %85 of study participants. Concomitant usage of RAASi agents with the potassium-sequestrant patiromer appears to protect patients against hyperkalemia sufficiently, thus they can take more RAASi treatment at higher doses. More randomized and controlled study needed though.