Key result
Patiromer increases 12-week spironolactone retention by an absolute ~20% in resistant hypertension with CKD.
Why the study?
Spironolactone effectively reduces blood pressure in uncontrolled resistant hypertension, but its use in patients with chronic kidney disease is restricted by hyperkalaemia. This study evaluated whether the potassium binder patiromer allows more persistent spironolactone use in patients with chronic kidney disease and resistant hypertension.
Does patiromer increase the proportion of patients remaining on spironolactone at week 12 in adults with resistant hypertension and chronic kidney disease?
RCT (n=295)
Double-blind
1:1 stratified by local potassium measurement and history of diabetes
Yes
Does patiromer increase the proportion of patients remaining on spironolactone at week 12 in adults with resistant hypertension and chronic kidney disease?
In patients with resistant hypertension and moderate-to-severe chronic kidney disease, the potassium binder patiromer significantly increased the proportion of patients able to maintain spironolactone therapy over 12 weeks by mitigating hyperkalaemia.
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“In the AMBER trial, compared with placebo, the potassium-binder patiromer mitigated the risk of hyperkalemia and enabled more patients with uncontrolled resistant hypertension and stage 3b/4 CKD to tolerate and continue spironolactone treatment; add-on therapy with spironolactone provoked a clinically meaningful reduction of 11–12 mmHg in unattended automated office systolic blood pressure (SBP) over 12 weeks of follow-up.”
“The addition of patiromer did not improve the most meaningful clinical endpoint, namely mean blood pressure between groups. When performing cost–benefit analysis of patiromer in this setting, the only remaining benefit is thus reducing the risk of hyperkalaemia associated with spironolactone.”
“The primary endpoint of AMBER was met with a very small probability (<1:10 000) that this could happen by chance alone in nearly 300 patients randomized equally to the patiromer or placebo groups. Retention of subjects in the clinical trial was excellent in both groups with <10% of study participants prematurely discontinuing the study.”
Enables greater spironolactone persistence in resistant hypertension with CKD; extends evidence for potassium binders in hyperkalemia-prone patients.
BACKGROUND: Spironolactone is effective at reducing blood pressure in patients with uncontrolled resistant hypertension. However, the use of spironolactone in patients with chronic kidney disease can be restricted by hyperkalaemia. We evaluated use of the potassium binder patiromer to allow more persistent use of spironolactone in patients with chronic kidney disease and resistant hypertension. METHODS: In this phase 2 multicentre, randomised, double-blind, placebo-controlled study, we enrolled participants aged 18 years and older with chronic kidney disease (estimated glomerular filtration rate 25 to ≤45 mL/min per 1·73 m FINDINGS: Between Feb 13, 2017, and Aug 20, 2018, we screened 574 patients. 295 (51%) of 574 patients met all inclusion criteria and were randomly assigned to spironolactone in addition to double-blind treatment with either placebo (n=148) or patiromer (n=147). At week 12, 98 (66%) of 148 patients in the placebo group and 126 (86%) of 147 patients in the patiromer group remained on spironolactone (between-group difference 19·5%, 95% CI 10·0-29·0; p<0·0001). Adverse events were mostly mild or moderate in severity and occurred in 79 (53%) of 148 patients in the placebo group and 82 (56%) of 147 patients in the patiromer group. INTERPRETATION: In patients with resistant hypertension and chronic kidney disease, patiromer enabled more patients to continue treatment with spironolactone with less hyperkalaemia. Persistent spironolactone enablement in this population of patients has clinical relevance for the treatment of resistant hypertension.
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Agarwal et al. (2019) conducted an RCT in Resistant hypertension and chronic kidney disease (n=295). Patiromer plus spironolactone vs. Placebo plus open-label spironolactone was evaluated on Proportion of patients remaining on spironolactone at week 12 (ARR 19.5%, 95% CI 10.0, 29.0, p=<0.0001). Patiromer significantly increased the proportion of patients with resistant hypertension and CKD remaining on spironolactone at 12 weeks compared to placebo (85.7% vs 66.2%, difference 19.5%, p<0.0001).
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