DIAMOND trial: Patiromer for management of hyperkalemia in HFrEF

DIAMOND trial: Patiromer for management of hyperkalemia in HFrEF

Patiromer is a nonabsorbed potassium binder used in the treatment of hyperkalemia. Earlier it was tested in patients with chronic kidney disease who were receiving inhibitors of the renin-angiotensin-aldosterone system (RAAS). It was found that patiromer treatment was associated with a decrease in serum potassium levels compared to placebo and a reduction in the recurrence of hyperkalemia  [1].

DIAMOND trial was designed to evaluate patiromer for the management of hyperkalemia in patients receiving RAAS inhibitors for heart failure with reduced ejection fraction (HFrEF) [2]. 1195 patients with RAAS inhibitor related current or previous hyperkalemia were enrolled in the 12 week run-in phase with patiromer and optimization of RAAS inhibitor therapy. Aim was to achieve recommended dose of angiotensin converting enzyme inhibitor/angiotensin receptor blocker/angiotensin receptor-neprilysin inhibitor, and 50 mg of mineralocorticoid receptor antagonist spironolactone or eplerenone.

878 patients who achieved the target doses of RAAS inhibitor therapy were randomized to either patiromer or placebo in a double blind pattern [3]. Primary endpoint was the mean difference in serum potassium from randomization between patiromer and placebo arms. Secondary endpoints specified were hyperkalemic events with serum potassium value above 5.5 mEq/L, durable enablement of MRA at target dose, investigator reported adverse events of hyperkalemia, hyperkalemia related clinical end points and an overall RAAS inhibitor use score on 0-8 point scale. RAAS inhibitor use score comprised of all cause death, occurrence of cardiovascular hospitalization or usage of comprehensive heart failure medication [2].

The median follow up was 27 weeks and adjusted mean change in potassium was +0.03 mmol/L in the patiromer group and +0.13 mmol/L in the placebo group (P<0.001). The risk of hyperkalemia, reduction of MRA dose and the total adjusted hyperkalemia events/100 person years were lower with patiromer. Hyperkalemia related morbidity adjusted events and total RAAS inhibitor use score favoured the patiromer arm. Adverse events were similar between the groups. It was concluded that concurrent use of patiromer with high-dose MRAs reduces the risk of recurrent hyperkalemia [3].

An interesting observation pointed out by an accompanying editorial to the DIAMOND trial was that about 80% of patients with HFrEF and a history of hyperkalemia did not experience recurrent hyperkalemia in the absence of patiromer. This was even when challenged with doses of MRAs that are probably higher than those needed to reduce mortality [4].

References

1. Weir MR, Bakris GL, Bushinsky DA, Mayo MR, Garza D, Stasiv Y, Wittes J, Christ-Schmidt H, Berman L, Pitt B; OPAL-HK Investigators. Patiromer in patients with kidney disease and hyperkalemia receiving RAAS inhibitors. N Engl J Med. 2015 Jan 15;372(3):211-21. doi: 10.1056/NEJMoa1410853. Epub 2014 Nov 21. PMID: 25415805.
2. Butler J, Anker SD, Siddiqi TJ, Coats AJS, Dorigotti F, Filippatos G, Friede T, Göhring UM, Kosiborod MN, Lund LH, Metra M, Moreno Quinn C, Piña IL, Pinto FJ, Rossignol P, Szecsödy P, Van Der Meer P, Weir M, Pitt B. Patiromer for the management of hyperkalaemia in patients receiving renin-angiotensin-aldosterone system inhibitors for heart failure: design and rationale of the DIAMOND trial. Eur J Heart Fail. 2022 Jan;24(1):230-238. doi: 10.1002/ejhf.2386. Epub 2021 Dec 9. PMID: 34800079; PMCID: PMC9300159.
3. Butler J, Anker SD, Lund LH, Coats AJS, Filippatos G, Siddiqi TJ, Friede T, Fabien V, Kosiborod M, Metra M, Piña IL, Pinto F, Rossignol P, van der Meer P, Bahit C, Belohlavek J, Böhm M, Brugts JJ, Cleland JG, Ezekowitz J, Bayes-Genis A, Gotsman I, Goudev A, Khintibidze I, Lindenfeld J, Mentz RJ, Merkely B, Montes EC, Mullens W, Nicolau JC, Parkhomenko A, Ponikowski P, Seferovic PM, Senni M, Shlyakhto E, Cohen-Solal A, Szecsödy P, Jensen K, Dorigotti F, Weir MR, Pitt B. Patiromer for the management of hyperkalemia in heart failure with reduced ejection fraction: the DIAMOND trial. Eur Heart J. 2022 Jul 28:ehac401. doi: 10.1093/eurheartj/ehac401. Epub ahead of print. PMID: 35900838.
4. Packer M. Potassium Binders for Patients With Heart Failure? The Real Enlightenment of the DIAMOND Trial. Eur Heart J. 2022 Jul 28:ehac399. doi: 10.1093/eurheartj/ehac399. Epub ahead of print. PMID: 35900836.