News - Apr. 4, 2022

Presented at ACC.22 by Javed Butler, MD (Jackson, MS, USA)

Introduction and methods

Guideline-directed medical therapy (GDMT) can be difficult to achieve for patients on RAAS inhibitors, as RAASi are associated with an increased risk of hyperkalemia. This risk tends to be higher in older patients and those with comorbidities such as diabetes or CKD.

There are novel potassium binders available for the management of hyperkalemia, but it is unknown whether these provide benefit in the long run to optimize medical therapy in patients with heart failure and reduced ejection fraction (HFrEF). This was investigated in the DIAMOND trial.

Patients who had hyperkalemia on RAASi therapy or had a history of hyperkalemia due to RAASi therapy that resulted in downregulation of RAASi were enrolled in the study. First, 1195 patients entered the run-in phase, in which they were optimized on RAASi therapy, defined as requiring ≥50% doses of ACEi/ARB/ARNI and ≥50 mg dose of MRA, with the use of patiromer. 878 Patients that achieved optimized therapy were randomized to continuation of patiromer or to withdrawal of patiromer and switched to placebo in a double-blinded fashion.

When the trial was designed, the primary endpoint was determined as time to CV death or first CV hospitalization. But because of COVID-related issues, the primary endpoint was changes to the adjusted mean change in serum potassium levels at the end of the study.

End of study was in June 2021, average duration of follow-up was 266.6 days.

Results

• The adjusted mean change in potassium was 0.03 (95%CI: -0.01 to 0.07) in the patiromer group and 0.13 (95%CI: 0.09 to 0.16) in the placebo group; a between group difference of -0.10 (95%CI: -0.13 to -0.07), P<0.001).
• The secondary endpoints time to first event of hyperkalemia, time to lowering of MRA dose below target, total investigator-reported adverse events of hyperkalemia, win-ratio for morbidity and mortality adjusted hyperkalemia-related outcomes, the win ratio of novel RAASi use-score were all significantly changed in favor of patiromer.

Conclusion

Use of patiromer resulted in maintenance of lower levels of potassium in patients with HFrEF who were optimized on RAASi therapy, and reduced the risk of hyperkalemia, and enabled guideline-recommended RAASi therapy.

Discussion

The discussant Craig Beavers, PharmD (Lexington, KY, USA) said that the investigators did amazing work considering the pandemic. Although these were not the outcomes they aimed for in the first place, the data are still valuable. The findings are helpful to realize how to get patients over the barriers to get them on GDMT now that we have the tools. He concluded: “This trial helps to provide tools to get the best outcomes for our patients”.

– Our coverage of ACC.22 is based on the information provided during the congress –