Novel potassium binder effectively controls hyperkalaemia in HFrEF patients

In individuals receiving renin-angiotensin-aldosterone system inhibitor (RAASi) therapy for heart failure with reduced ejection fraction (HFrEF), the novel potassium binder patiromer effectively reduced serum potassium levels, the DIAMOND trial suggests, thus optimizing a guideline-directed RAASi therapy for these patients.

“RAASis are standard of care for patients with HFrEF. [However,] RAASis are associated with an increased risk of hyperkalaemia (HK), particularly among older patients and those with concomitant chronic kidney disease and/or diabetes,” noted Professor Javed Butler from the University of Mississippi Medical Center, Jackson, Mississippi, US, at ACC.22.

“[As such,] RAASi therapy is often down-titrated or discontinued* in patients with HFrEF and HK … [However,] failure to provide optimal RAASi therapy is associated with an increased risk of HF hospitalizations and death,” Butler continued.

“So the question is – as we do have novel potassium binders that are well tolerated – could we give these in the long run to optimize medical therapy for patients with HFrEF? That was the main aim of the DIAMOND trial,” Butler explained. “[We sought to] determine if patiromer can simultaneously control potassium levels, enable optimal RAASi therapy, and improve clinical outcomes.”

In the 12-week run-in phase of the trial, 1,195 HFrEF patients (mean age 67 years, 73 percent male) with a history of HK or current HK related to RAASi use were optimized on RAASi** therapy and patiromer. Following which, 878 patients who had achieved optimized RAASi therapy were randomized 1:1 to either continue patiromer or withdraw from it and transition to placebo. They were followed for a median 27 weeks. [ACC.22, Late-Breaking Clinical Trials III]

At end of study, there was a significant reduction in serum potassium levels from baseline in patiromer vs placebo recipients (between-group difference, –0.10 mEq/L; p<0.001). “The effect was consistent across all prespecified subgroups***,” said Butler.

All secondary endpoints also favoured patiromer over placebo: HK events with serum potassium >5.5 mmol/L (hazard ratio [HR], 0.63; p=0.006), reduction of MRA** dose below target (HR, 0.62; p=0.006) and total number of investigator-reported HK events (HR, 0.66; p<0.001). Patiromer also outdid placebo in terms of win ratio for HK-related outcomes (HR, 1.53; p<0.001) and overall RAASi use score (HR, 1.25; p=0.048).

Safety wise, adverse event (AE) rates were similar between the patiromer and the placebo arms (15.0 percent vs 10.7 percent [hypokalaemia], 4.3 percent vs 5.0 percent [hypomagnesemia], 4.3 percent vs 3.4 percent [diarrhoea], 2.5 percent vs 1.1 percent [constipation], and 0.9 percent for both [nausea]), as were the incidences of serious AEs (12.3 percent vs 13.2 percent) and AEs leading to withdrawal (2.7 percent vs 2.5 percent).

An enablement strategy

“You usually have better RAASi therapy and HK, or you avoid HK but do not optimize RAASi therapy. We took a look to see whether you can win on both,” said Butler. “We took a very comprehensive look at all levels of HK and all levels of RAASi therapy, and proved that you really do not have to compromise – you can get good therapy and also lower patients’ risk of HK.”

As the trial was stopped earlier, Butler noted that they did not have enough clinical events to make any conclusive comments about the clinical outcomes. “[Nonetheless,] it stands to reason that optimization of RAASi therapy without the concomitant risk of HK may, in the long run, lead to better outcomes for these patients.”

“[Based on our] results, unless accessibility or affordability of medications is an issue, there is no good reason not to use potassium binders to optimize HF medical therapy,” said Butler. “For cases where HK is the dominant reason for not giving guideline-directed RAASi therapy, I think what we [achieved] with patiromer is an enablement strategy to allow patients to get appropriate RAASi therapy while simultaneously lowering the risk of HK.”