Use of patiromer results in more patients remaining on spironolactone in resistant hypertension and CKD, with and without HF
Patiromer to Enable Spironolactone in Patients with Resistant Hypertension and Chronic Kidney Disease (AMBER): Results in the Prespecified Subgroup with Heart Failure
Presented at ESC Heart Failure 2019 in Athens, Greece, by Patrick Rossignol Vandoeuvre Les Nancy, France
Introduction and methods
The PATHWAY-2 trial demonstrated that spironolactone was the most effective add-on drug in patients with resistant hypertension. However, patients with eGFR <45 mL/min/1.73m² were excluded in the PATHWAY-2 study, as in other studies. As there are no data on use of spironolactone in patients with resistant hypertension and eGFR <45 mL/min/1.73m², the 2018 ESC/ESH Guidelines for the management of arterial hypertension suggest not to use spironolactone in these patients.
The AMBER trial therefore examined whether patiromer, by preventing hyperkalemia, could result in a persistent use of spironolactone in patients with advanced CKD and resistant hypertension.
The AMBER trial included CKD patients (eGFR 25-45 mL/min/1.73m²) with resistant hypertension (systolic AOBP 135-160 mmHg) and potassium levels 4.3-5.1 mmol/L, who were randomized to spironolactone plus patiromer (n=147) or spironolactone plus placebo (n=148) for 12 weeks after a screening/run-in period of 4 weeks. Safety was followed for another 2 weeks. Primary endpoint was percentage patients who remained on spironolactone at week 12. Analysis of subgroups of patients with and without heart failure (HF) was prespecified. There were 65 HF patients in the placebo group and 63 HF patients in the patiromer group.
- At 12 week, a higher number of patients remained on spironolactone in the patiromer group compared to the placebo group (86% vs. 66%, difference of 20%, 95%CI: 10-29%, P<0.0001).
- Percentage of patients that reached potassium level ≥5.5 mmol/L was lower in the patiromer group compared to placebo group (in time, log-rank P<0.0001).
- Systolic AOBP decreased over time in a similar way in both groups.
- There was no difference in percentage of patients who stayed on spironolactone with patiromer vs. placebo at week 12 between those with HF and without HF.
- There were no differences in adverse events between groups.
In patients with advanced CKD and resistant hypertension, use of patiromer resulted in higher percentage of patients remaining of spironolactone at week 12 compared to placebo. In addition, percentage of patients that developed hyperkalemia was reduced in the patiromer group vs. placebo group. There were no differences in findings for patients with HF vs. those without. Addition of patiromer to spironolactone appeared to be safe, also in the subgroup of HF patients.
The discussant Javed Butler (Atlanta, USA) said that this study is valuable for HF patients, as most HF patients have CKD or reduced eGFR. He was impressed with the potency of this approach, as it was achieved in only 12 weeks. He did raise some concerns about the characterization of HF. 44% of the study population had HF, but some had missing data on EF and should perhaps not have been classified as HF. The patients in this study had low eGFR and hypertension, yet 90% had NYHA class I or II, which raises the question whether they truly had HF.
He concluded that it is very important to target these patients, but one should keep in mind that characterization of HF is important if you plan to do a study like this.
Our reporting is based on the information provided at the ESC Heart Failure 2019 congress