BOSTON — Combining spironolactone therapy with patiromer may allow patients with CKD and resistant hypertension to safely manage their blood pressure without increasing their risk for developing hyperkalemia, according to phase 2 results from the AMBER trial, presented at the National Kidney Foundation Spring Clinical Meetings.
“Based on the results from PATHWAY-2, spironolactone became the first-line treatment for patients with resistant hypertension,” Rajiv Agarwal, MD, MS, FAHA, FASN, FASH, professor of medicine at Indiana University, said during his presentation. “[However], the study excluded patients with advanced CKD [and, thus, who were] at high risk for hyperkalemia. AMBER wanted to enable persistent use of spironolactone in patients with advanced CKD and hypertension, while preventing hyperkalemia.”
To evaluate both the safety and efficacy of adding patiromer to spironolactone therapy, researchers conducted a multicenter, double-blind, placebo-controlled randomized trial of 295 patients with CKD (eGFR between 25 mL/min/1.73 m2 to 45 mL/min/1.73 m2) and resistant hypertension (systolic automated office BP, 135 mm Hg to 160 mm Hg). Patients were randomized to either spironolactone plus placebo (n = 148; mean age, 69 years; mean systolic BP, 145 mm Hg; 47% with history of heart failure; mean eGFR, 36 mL/min/1.73 m2) or spironolactone plus patiromer (n = 147; mean age, 68 years; mean systolic BP, 143 mm Hg; 43% with history of heart failure; mean eGFR 35 mL/min/1.73 m2).
The primary endpoint of the study was the between-group difference in the proportion of patients remaining on spironolactone at week 12. The between-group difference in change of systolic blood pressure was the secondary endpoint.
Although change in systolic BP between groups was similar, researchers found spironolactone use was associated with an 11 mm Hg to 12 mm Hg reduction overall.
At week 12, 66% of patients in the placebo group remained on spironolactone compared with 86% of patients in the patiromer group, with patiromer use also allowing patients to use 385 mg more of spironolactone during this time.
Finally, while two out of three patients treated with placebo developed hyperkalemia, researchers determined patiromer reduced this risk by half.
“Spironolactone has not previously been studied in this patient population due to the potential increased risk of developing hyperkalemia,” Agarwal said in a press release. “The results of the AMBER study suggest that patients treated with patiromer may be more likely to stay on spironolactone therapy, a life-saving medicine to control blood pressure.”
During the trial, patients were intensely monitored, according to Agarwal.
“We did not risk the lives of our patients,” he said in the presentation. “We knew it would be dangerous to do the trial without supervision. We wanted to be sure that we were not putting our patients in jeopardy.” – by Melissa J. Webb
Agarwal R. Late-breaking research presentations: The CREDENCE Trial and the AMBER Study. Presented at: National Kidney Foundation Spring Clinical Meetings; May 8-12, 2019; Boston.
Disclosure: Agarwal reports receiving personal fees from AbbVie, Akebia, Amgen, AstraZeneca and Bayer, among others. He also reports receiving research grants from the U.S. Veterans Administration and the NIH.