Patiromer Limits Impact of RAAS Inhibitor-Related Hyperkalemia in HF

WASHINGTON — Use of the potassium-binding agent patiromer (Veltassa) allowed more heart failure patients at risk for hyperkalemia to remain on optimal therapy with renin-angiotensin-aldosterone system inhibitors (RAAS), including mineralocorticoids, the randomized DIAMOND trial showed.

For the study’s revised primary endpoint, patiromer led to a significant reduction in potassium levels by study end versus placebo (P<0.001), Javed Butler, MD, of Baylor University Medical Center in Dallas, reported here.

And overall, 21.6% of patients on patiromer needed to reduce mineralocorticoids, a mainstay of heart failure therapy, as compared to 26.7% of those assigned placebo (HR 0.74, 95% CI 0.57-0.97, P=0.030), he noted in his oral presentation at the annual scientific session of the American College of Cardiology (ACC).

More patients in the patiromer group were able to remain on at least 50% of their target dose of mineralocorticoids and angiotensin inhibitors (92% vs 87% with placebo, P=0.015), said Butler, and numerically fewer patients on the study arm discontinued their mineralocorticoid or angiotensin drugs than those in the placebo group.

RAAS inhibitors are standard of care for patients with heart failure with reduced ejection fraction (HFrEF), as the treatments tend to reduce symptoms, reduce heart failure hospitalizations, and reduce cardiovascular and all-cause mortality.

However, noted Butler, RAAS inhibitors are associated with an increased risk of hyperkalemia, particularly among older patients and those with concomitant chronic kidney disease and/or diabetes. Hyperkalemia, or even the perceived risk of hyperkalemia, is associated with suboptimal RAAS inhibitor use, particularly, suboptimal use of mineralocorticoid receptor antagonists, explained Butler.

The DIAMOND trial was designed to assess whether patiromer in patients with HFrEF and either hyperkalemia or a history of hyperkalemia due to RAAS inhibitor therapy can simultaneously control potassium levels, enable optimal RAAS inhibitor therapy, and improve clinical outcomes.

Patiromer was selected because the potassium-binding agent appears to be well tolerated and efficacious in treating hyperkalemia and maintaining normokalemia, said Butler. While prior studies have suggested that the drug may also enable RAAS inhibitor use, experience in patients with heart failure was limited.

Butler explained that the COVID-19 upended the trial’s original primary endpoint — time to cardiovascular death or first hospitalization for a cardiovascular event. Given the need for close patient monitoring, the shift in hospitalization due to the pandemic, and concerns about laboratory testing availability and whether patiromer supplies could be maintained, the researchers altered the study to instead look at the treatment’s effect on potassium-related events.

In total, 878 patients with HFrEF were randomized. Average age of the participants was 67 years, more than 70% were women, and the average left ventricular ejection fraction was 33%.

“Clearly these were not the results we wanted to see, but these data are still pretty valuable,” said ACC-designated discussant Craig Beavers, PharmD, of Baptist Health System in Paducah, Kentucky.

During a press briefing, Beavers said the findings were consistent with patiromer trials in other populations and offer clinicians a tool to help keep patients on the therapies they need to be on.