No topic chronic kidney illness (CKD) stage, the potassium-binding agent patiromer (Veltassa) improved serum potassium ranges in sufferers with heart failure, in step with a prespecified CKD subanalysis from the DIAMOND trial.
In a subgroup of sufferers with heart failure with reduced ejection part plus CKD, and hyperkalemia on account of renin-angiotensin-aldosterone machine inhibitors (RAASi), patiromer seriously reduced serum potassium versus placebo, reported Matthew Weir, MD, of the College of Maryland College of Medication in Baltimore.
Patiromer used to be related to particularly famous reductions in potassium in these with decrease eGFR:
- ≥60 mL/min/1.732: -0.07 mEq/L when put next 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 slack-breaking findings of this subanalysis at the Nationwide Kidney Foundation Spring Clinical Meetings. High-line findings from the DIAMOND trial had been presented at the annual scientific session of the American College of Cardiology (ACC) factual a couple of days prior.
In CKD sufferers in both baseline eGFR teams — above and below 60 mL/min/1.732 — sufferers seen extra favorable hyperkalemia-related outcomes with patiromer, including longer time to cardiovascular loss of life, much less cardiovascular hospitalizations, and much less of an lengthen in serum potassium from baseline.
In sufferers with serum potassium ranges above 5.5 mmol/L, patiromer used to be additionally in a location to lengthen the time to first hyperkalemic match and the time to dose reduction in mineralocorticoid receptor antagonist (MRA) below target (50 mg of spironolactone or eplerenone). Use of the binder used to be in a location to diminish the prospect of recurrent hyperkalemia negative events.
Moreover, patiromer used to be additionally properly-tolerated, with a same chance of treatment emergent negative events between the active treatment and placebo teams.
“This in actuality is a terrific replacement to permit MRA use in corpulent dose in folk even with reduced GFR,” Weir acknowledged at some stage in a presentation of the findings.
These findings are rather welcome, as elevated potassium is one in all the necessary reasons for reducing or flat out stopping RAASi treatment in sufferers with chronic heart failure and CKD, he underscored. No longer handiest are RAASi and MRA agents underutilized — even “unacceptably low” for sufferers with CKD — nevertheless they’re additionally regularly “largely underdosed.”
“There is a rationalization for it — we are chance negative,” Weir acknowledged. “We are serious about potassium ranges and chance for cardiac arrhythmia and even loss of life.”
“The hyperkalemia charges in sufferers with heart failure and reduced ejection part are astronomical. Right here’s the scientific conundrum for us all: we like illness-bettering, existence-sustaining therapies where we like a effort of potassium mitigation. And here’s the accrued steadiness we deserve to stroll with our sufferers,” he acknowledged, referencing the pickle of weighing the dangers and benefits of RAASi with hyperkalemia.
He pointed out that the complete necessary guidelines, including KDIGO, suggest managing serum creatinine and potassium with dose adjustments barely than discontinuing RAASi, which will be a “closing resort.”
Weir acknowledged the DIAMOND trial used to be designed in relate to search out out if potassium mitigation would allow for better use of corpulent-dose MRA on prime of appropriate doses of angiotensin-converting enzyme (ACE) inhibitor, angiotensin II receptor blocker (ARB), or angiotensin receptor-neprilysin inhibitor (ARNi) in relate to diminish chance of cardiovascular match.
Carried out during 418 world websites, contributors within the trial had heart failure with reduced ejection part with hospitalization for it interior 12 months, serum potassium above 5.0 mEq/L or historical previous of hyperkalemia at some stage within the 12 months leading to RAASi discontinuation. These with an eGFR below 30 mL/min/1.732 had been excluded.
In this subgroup of sufferers with CKD, 439 had been randomized to acquire placebo (212 with an eGFR <60 and 227 with a increased eGFR) and 439 randomized to placebo (202 with eGFRs <60 and 237 with increased eGFR).
All contributors underwent a single-blinded trip-in segment for up to 12 weeks at some stage in which patiromer used to be started at a dose of 8.4 g per day. ACEi/ARB/ARNi had been optimized, and MRA used to be initiated and optimized. Then, half of of sufferers persevered on patiromer and half of withdrew to placebo.
Among sufferers within the patiromer neighborhood, the everyday age used to be 67 years, 26% had been women, and 36% had atrial fibrillation. The moderate baseline eGFR used to be 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 accepted that there used to be handiest a exiguous share of sufferers on an SGLT2 inhibitor (about 3-4%) at some stage within the trial, though a famous proportion had been on a loop diuretic.
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Kristen Monaco is a team creator, specializing in endocrinology, psychiatry, and nephrology data. Primarily based entirely mostly out of the Recent York City location of work, she’s worked at the company since 2015.
Disclosures
The examine used to be supported by Vifor Pharma.
Weir reported relationships with Vifor Pharma and AstraZeneca.
