The majority of patients with heart failure with reduced ejection fraction (HFrEF) and renin-angiotensin-aldosterone system inhibitor (RAASi)-related hyperkalemia had significantly lower K+ levels when taking patiromer compared with a placebo, based on findings from the DIAMOND trial presented April 3 at ACC.22.

The trial initially screened 1,642 patients with HFrEF and either a history of hyperkalemia or current hyperkalemia related to RAASi use at 389 medical centers in 21 countries. For the first part of the study, 1,195 patients meeting the eligibility criteria entered a run-in phase for optimization of RAASi therapy and patiromer treatment for up to 12 weeks. Of those, 1,038 patients completed the run-in phase and 878 patients who had achieved optimized RAASi therapy were randomized to continue taking patiromer or switch to a placebo (patiromer withdrawal).

Researchers followed the patients for a median of 27 weeks. Although neither the study participants nor their treating clinicians knew whether they were taking patiromer or a placebo, their clinicians did know patients' K+ levels over time and were able to adjust RAASi doses accordingly. As a result, many of the treating clinicians lowered the RAASi dosage for patients in the placebo arm. However, even though they were receiving more and higher doses of RAASi medications, the patients who continued taking patiromer still had lower K+ levels, on average, compared to those taking a placebo, meeting the study's primary endpoint. They also had a 35% relative risk reduction in the total number of hyperkalemia events.

"On the basis of these results, unless accessibility or affordability of medications is an issue, there's no good reason not to use potassium binders to optimize heart failure medical therapy," said Javed Butler, MD, MPH, MBA, FACC, the study's lead author. "For cases where hyperkalemia is the dominant reason for not giving guideline-directed RAASi therapy, I think what we are achieving with patiromer is an enablement strategy to allow patients to get appropriate RAASi therapy while simultaneously lowering the risk of hyperkalemia."

The study also showed a favorable safety profile for patiromer, with comparable rates of adverse events in both study groups. Butler said that the trial was paused briefly to redesign its goals in response to the COVID-19 pandemic. The trial was initially designed to assess how the use of patiromer affected morbidity and mortality outcome, but was adjusted to focus on blood potassium levels and prespecified hierarchical endpoints assessing hyperkalemia episodes and RAASi use to better protect patient safety amid the complexities of conducting a clinical trial in high-risk patients during the pandemic.

Clinical Topics: Heart Failure and Cardiomyopathies, Acute Heart Failure

Keywords: ACC Annual Scientific Session, ACC22, Hyperkalemia, Renin-Angiotensin System, Stroke Volume, Heart Failure, Polymers, Angiotensin-Converting Enzyme Inhibitors

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