Even With CKD, Patiromer Helped Heart Failure Patients Keep Hyperkalemia at Bay

Regardless of chronic kidney disease (CKD) stage, the potassium-binding agent patiromer (Veltassa) improved serum potassium levels in patients with heart failure, according to a prespecified CKD subanalysis from the DIAMOND trial.

In a subgroup of patients with heart failure with reduced ejection fraction plus CKD, and hyperkalemia due to renin-angiotensin-aldosterone system inhibitors (RAASi), patiromer significantly reduced serum potassium versus placebo, reported Matthew Weir, MD, of the University of Maryland School of Medicine in Baltimore.

Patiromer was associated with especially large reductions in potassium in those with lower eGFR:

• ≥60 mL/min/1.73²: -0.07 mEq/L compared with placebo (95% CI -0.11 to -0.03)
• <60 mL/min/1.73²: -0.14 mEq/L (95% CI -0.18 to -0.09)
• ≥45 mL/min/1.73²: -0.08 mEq/L (95% CI -0.11 to -0.04)
• <45 mL/min/1.73²: -0.19 mEq/L (95% CI -0.26 to -0.12)

Weir presented the late-breaking findings of this subanalysis at the National Kidney Foundation Spring Clinical Meetings. Top-line findings from the DIAMOND trial were presented at the annual scientific session of the American College of Cardiology (ACC) just a few days prior.

In CKD patients in both baseline eGFR groups -- above and below 60 mL/min/1.73² -- patients saw more favorable hyperkalemia-related outcomes with patiromer, including longer time to cardiovascular death, less cardiovascular hospitalizations, and less of an increase in serum potassium from baseline.

In patients with serum potassium levels above 5.5 mmol/L, patiromer was also able to extend the time to first hyperkalemic event and the time to dose reduction in mineralocorticoid receptor antagonist (MRA) below target (50 mg of spironolactone or eplerenone). Use of the binder was able to cut the likelihood of recurrent hyperkalemia adverse events.

Moreover, patiromer was also well-tolerated, with a similar number of treatment emergent adverse events between the active therapy and placebo groups.

"This really is a remarkable opportunity to enable MRA use in full dose in people even with reduced GFR," Weir said during a presentation of the findings.

These findings are quite welcome, as elevated potassium is one of the principal reasons for reducing or flat out stopping RAASi therapy in patients with chronic heart failure and CKD, he underscored. Not only are RAASi and MRA agents underutilized -- even "unacceptably low" for patients with CKD -- but they're also often "largely underdosed."

"There's a reason for it -- we are risk adverse," Weir said. "We are concerned about potassium levels and risk for cardiac arrhythmia and even death."

"The hyperkalemia rates in patients with heart failure and reduced ejection fraction are substantial. This is the clinical conundrum for us all: we have disease-modifying, life-sustaining therapies where we have a concern of potassium mitigation. And this is the delicate balance we have to walk with our patients," he said, referencing the dilemma of weighing the risks and benefits of RAASi with hyperkalemia.

He pointed out that all the major guidelines, including KDIGO, recommend managing serum creatinine and potassium with dose adjustments rather than discontinuing RAASi, which would be a "last resort."

Weir said the DIAMOND trial was designed in order to determine if potassium mitigation would allow for better use of full-dose MRA on top of appropriate doses of angiotensin-converting enzyme (ACE) inhibitor, angiotensin II receptor blocker (ARB), or angiotensin receptor-neprilysin inhibitor (ARNi) in order to reduce risk of cardiovascular event.

Conducted across 418 international sites, participants in the trial had heart failure with reduced ejection fraction with hospitalization for it within 12 months, serum potassium above 5.0 mEq/L or history of hyperkalemia within the 12 months leading to RAASi discontinuation. Those with an eGFR below 30 mL/min/1.73² were excluded.

In this subgroup of patients with CKD, 439 were randomized to receive placebo (212 with an eGFR <60 and 227 with a higher eGFR) and 439 randomized to placebo (202 with eGFRs <60 and 237 with higher eGFR).

All participants underwent a single-blinded run-in phase for up to 12 weeks during which patiromer was started at a dose of 8.4 g per day. ACEi/ARB/ARNi were optimized, and MRA was initiated and optimized. Then, half of patients continued on patiromer and half withdrew to placebo.

Among patients in the patiromer group, the average age was 67 years, 26% were women, and 36% had atrial fibrillation. The average baseline eGFR was 62.6 mL/min/1.73² and 16% had stage 1 CKD, 36% had stage 2, 42% had stage 3, and 7% had stage 4.

Weir noted that there was only a small percentage of patients on an SGLT2 inhibitor (about 3-4%) during the trial, although a large proportion were on a loop diuretic.

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