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Patiromer HF Medication Optimization for Hyperkalemia
Quick Takes
- In patients with HFrEF and current or past hyperkalemia, patiromer use compared to placebo (for optimization of RAASi therapy) is effective in reducing serum potassium levels in both patients with current hyperkalemia and past hyperkalemia.
- The effect of patiromer may be better at preventing reduction in target MRA dose in patients with current hyperkalemia compared to past hyperkalemia.
Study Questions:
In this prespecified analysis of the DIAMOND trial, what is the effect of patiromer in patients with heart failure with reduced ejection fraction (HFrEF) when examining the current and past hyperkalemia subgroups?
Methods:
The DIAMOND (Patiromer for the Management of Hyperkalemia in Subjects Receiving RAASi Medications for the Treatment of Heart Failure) trial included patients with HFrEF and current or past hyperkalemia within the last year. Randomization occurred after a run-in phase where patiromer was started and renin-angiotensin-aldosterone system inhibitors (RAASi) were started and optimized. Patients with a successful run-in phase were randomized to continue patiromer or stop patiromer (control). The primary outcome of adjusted mean change in serum potassium was significantly lower in the patiromer group. Secondary outcomes also favored patiromer use with reduced hyperkalemia episodes and improved mineralocorticoid receptor antagonist (MRA) and other RAASi use.
This current study is a prespecified analysis of the DIAMOND trial comparing the placebo-corrected effects of patiromer on the primary and secondary outcomes between the current hypokalemia and past hyperkalemia subgroups.
Results:
After the run-in phase, 354 patients with current hyperkalemia and 524 patients with past hyperkalemia were randomized in the study. Compared to control, patiromer use in both the current hyperkalemia and past hyperkalemia subgroups led to lower serum potassium levels (adjusted mean change, -0.12 mmol/L; 95% confidence interval [CI], -0.17 to -0.07 for current hyperkalemia and -0.08 mmol/L; 95% CI, -0.12 to -0.05 for past hyperkalemia). The effect of patiromer on the primary outcome between subgroups was similar (p for interaction = 0.17). For the secondary outcomes, patiromer compared to control reduced hyperkalemia episodes and improved MRA target dose use in the current hyperkalemia subgroup, but the same benefit was not seen in the past hyperkalemia subgroup. For hyperkalemia episodes, there was no significant difference between the subgroups (p for interaction = 0.24). For the reduction of MRA dose below target, there was a difference between the current hyperkalemia (hazard ratio [HR], 0.45; 95% CI, 0.26-0.76) compared to the past hyperkalemia (HR, 0.85; 95% CI, 0.54-1.32) subgroups (p for interaction = 0.03). Adverse events were similar between the subgroups.
Conclusions:
In patients with HFrEF and current or past hyperkalemia, use of patiromer compared to placebo was effective in reducing serum potassium levels, with no significant difference between the current and past hyperkalemia subgroups. Patiromer may be better at preventing reduction in target MRA dose in the current hyperkalemia subgroup compared to past hyperkalemia.
Perspective:
Several studies have demonstrated the value of potassium binders like patiromer in facilitating the initiation and titration of RAASi for HFrEF management. Removing barriers, like hyperkalemia, to optimal HFrEF guideline-directed medical therapy will improve care for this patient population. The DIAMOND study also demonstrated that continuation of patiromer therapy will have a long-term benefit in maintaining lower serum potassium levels compared to medication withdrawal after RAASi optimization. It is encouraging that this benefit was seen in both the current and past hyperkalemia subgroups. Interestingly, patiromer appeared to have a larger effect on preventing reduction of MRA below target doses in patients with current hyperkalemia compared to past hyperkalemia. Further studies may be needed to clarify this discrepancy in benefit. Additional studies may also be needed to assess the impact of patiromer in the era of sodium-glucose cotransporter-2 inhibitor use, as this newer HFrEF therapy also has the potential to reduce risk of hyperkalemia.
Clinical Topics: Heart Failure and Cardiomyopathies, Prevention
Keywords: Heart Failure, Reduced Ejection Fraction, Hyperkalemia, Mineralocorticoid Receptor Antagonists, Renin-Angiotensin System
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