DIAMOND Shines Bright on Patiromer for Curbing Hyperkalemia in HFrEF

WASHINGTON, DC—The oral potassium-binding agent patiromer (Veltassa; Vifor Pharma) may help keep hyperkalemia under control in heart failure with reduced ejection fraction (HFrEF) patients taking renin-angiotensin-aldosterone system inhibitors (RAASi), thus preventing the need to stop or lower current medication doses, the small DIAMOND trial shows.

“These data suggest that you can simultaneously control potassium and optimize RAASi therapy, and perhaps in the long run, it would improve clinical outcomes, but we did not have enough outcomes to make any definitive conclusion in that respect,” said Javed Butler, MD, MPH (Baylor Scott & White Research Institute, Dallas, TX), in his presentation of the study results at the American College of Cardiology 2022 Scientific Session earlier this week.

Hyperkalemia is a primary reason for discontinuing or lowering the dose of any RAASi therapy, including ACE inhibitors, ARBs, angiotensin receptor-neprilysin inhibitors (ARNIs), and mineralocorticoid receptor antagonists (MRAs). According to Butler, current guidelines recommend stopping RAASi therapy when blood potassium levels exceed 6 mmol/L, and lowering the doses and closely following patients if levels are between 5 and 6 mmol/L.

With the newly release HF guidelines stressing the importance of optimizing all guideline-directed medical therapy (GDMT) in HF as swiftly as possible, patiromer, which binds to potassium and decreases its absorption from the GI tract, may be a consideration in helping to keep patients at risk for hyperkalemia optimized, if further research can clarify how best to use this add-on management strategy, said Craig Beavers, PharmD (University of Kentucky, Lexington), commenting on the findings in a press briefing. While adding more medications in this population deserves serious consideration, Beavers said, it’s also important to strive for good versus bad polypharmacy.

“Good polypharmacy helps us meet goals and initiatives,” he said, adding that DIAMOND provides evidence that there are additional tools out there that might help clinicians to better meet therapy optimization goals.

Trial Challenges and Outcomes

The 389-center DIAMOND trial fell victim to the COVID-19 pandemic and was both paused and had its primary endpoint changed as a result. The initial trial was designed to assess patiromer’s impact on morbidity and mortality, but was changed to blood potassium levels and prespecified hierarchical endpoints assessing hyperkalemia episodes and RAASi use due to the complexities of compiling patient data during the pandemic. The trial initially screened 1,642 HFrEF patients with a history of hyperkalemia (60%) or current hyperkalemia related to RAASi therapy (40%). Initially, 1,195 patients meeting the eligibility criteria entered a run-in phase for optimization of RAASi therapy plus oral patiromer for up to 12 weeks. Of those, 1,038 patients completed the run-in phase and 878 (85%) achieved optimization of RAASi therapy. Those patients were then randomized to continue with patiromer or switch to placebo.

At a median of 27 weeks, the mean change in serum potassium levels was lower in the group that continued on patiromer versus placebo (P < 0.001). For the secondary endpoint of hyperkalemia events with serum potassium > 5.5 mmol/L, there was a reduction in favor of the patiromer group (HR 0.63; 95% CI 0.45-0.87). Similarly, for another secondary endpoint of time to reduction in MRA dose, there was risk reduction in favor of patiromer (HR 0.62; 95% CI 0.45-0.87). The total number of hyperkalemic events over the study period was 225 in the patiromer group and 316 in the placebo group (HR 0.66; 95% CI 0.53-0.81). A win ratio analysis of hyperkalemia-related outcomes also favored patiromer over placebo (HR 1.53; 95% CI 1.23-1.91), as did comprehensive RAASi use (HR 1.25; 95% CI 1.003-1.564).

Commenting on the study in the main session, James Januzzi Jr, MD (Massachusetts General Hospital, Boston), congratulated the researchers on completing the study under “absolutely terrible global conditions” for a trial requiring the kind of follow-up and monitoring that was initially intended. Januzzi added that hyperkalemia is one of the most common fears that clinicians articulate with regard to closing gaps in GDMT in HF patients.

He noted that despite the success of patiromer in lowering potassium levels in the treatment group,  a substantial percentage of placebo-treated patients did not develop hyperkalemia. Like Beavers, Januzzi said a main question now is when to potentially seek help in the form of patiromer and in whom.

“A lot of the patients in the placebo arm were able to tolerate RAASi therapy, which really makes the question that if you have one episode of hyperkalemia, do you reach out for a potassium binder or do you try again after some time and maybe the patients are able to tolerate it,” Butler said. “In terms of the clinical implication, what I would say is that I think it's pretty reasonable to try once again and see [because] . . .  maybe they can tolerate it right now and you don't need polypharmacy. But a critical issue is that if you have made up your mind that you're going to compromise RAASi therapy and whatever else you could have done [or] you have done . . . a strong consideration of a binder and not compromising RAASi therapy would be good.”