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AMBER: Patiromer enables persistent spironolactone treatment in patients with hypertension, CKD
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PHILADELPHIA — Concomitant use of the potassium binder patiromer enabled more patients with resistant hypertension and advanced chronic kidney disease to continue treatment with spironolactone, with less hyperkalemia, according to new data from the AMBER trial presented at the Heart Failure Society of America Scientific Meeting.
In the phase 2, randomized, double-blind, placebo-controlled trial, 295 patients with resistant hypertension and advanced CKD were randomly assigned receive placebo or patiromer 8.4 g once daily (Veltassa, Relypsa) in addition to open-label spironolactone, started at 25 mg once daily, and baseline BP medications.
At 12 weeks, the proportion of patients on spironolactone was 66% in the placebo group compared with 86% in the patiromer group (between-group difference, 19.5%; 95% CI, 10-29; P < .0001).
“This enablement was accompanied by a lower proportion of hyperkalemia and fewer discontinuations of spironolactone because of hyperkalemia, as well as a delay in the time to hyperkalemia in patients treated with patiromer,” the researchers wrote in The Lancet.
Discussing the findings with Healio, Bryan Williams, MD, FRCP, FESC, FAHA, chair of medicine and professor at University College London Institute of Cardiovascular Sciences, said “using the potassium-binding polymer enables the use of spironolactone in patients in whom it wouldn’t otherwise be possible to use spironolactone, because it reduces the likelihood that they’re going to develop hyperkalemia.”
Further, Williams, said, “the fascinating thing in this study is that hyperkalemia occurred in about two-thirds of the placebo group, and this was reduced by almost half by using patiromer. [The hyperkalemia] doesn’t go away completely, but [the addition of patriomer] reduces the risk, and therefor enables you to use a highly effective drug more commonly in a high-risk population.”
In other results, systolic automated BP was significantly reduced in both groups from baseline to 12 weeks: mean change, 10.8 mm Hg in the placebo group vs. 11.7 mm Hg in the patiromer group. The BP reductions observed in this study were similar to those in the PATHWAY-2 trial. In an exploratory analysis of patients who discontinued spironolactone before 12 weeks, the researchers observed a “rebound increase” in BP in 2 weeks.
“We found that patients could be given spironolactone to reduce their blood pressure effectively with resistant hypertension in patients with advanced chronic kidney disease,” Williams told Healio.
Adverse events occurred in 53% of the placebo group vs. 56% of the patiromer group and were generally mild to moderate in severity.
In addition, “in a subgroup of those patients with heart failure, we saw the same enablement of spironolactone use with patiromer in patients with advanced chronic kidney disease compared to those without such advanced chronic kidney disease,” Williams told Healio.
During the 12-week trial, more than two-thirds (69%) of patients assigned patiromer increased their dose to 50 mg of spironolactone vs. 51% of patients assigned placebo. The mean cumulative dose of spironolactone was higher by 384.7 mg compared with placebo.
Those enrolled completed a screening period that comprised four visits to ensure patients were on stable doses of medication and met the inclusion criteria. All patients enrolled had an estimated glomerular filtration rate of 25 to 45 mL/min/1.73 m2, serum potassium level of 4.3 mmol/L to 5.1 mmol/L, and resistant hypertension, defined as systolic automated office BP of 135 mm Hg to 160 mm Hg, despite use of three or more antihypertensive medications. About 40% of patients enrolled in AMBER had HF.
“We're going to see a lot more excitement and interest in this field over the next few years,” Williams said. – by Scott Buzby
References:
Williams B, et al. Late Breaking Clinical Trials. Presented at: Heart Failure Society of America Scientific Meeting; Sept. 13-16, 2019; Philadelphia.
Agarwal R, et al. Lancet. 2019;doi:10.1016/S0140-6736(19)32135-X.
Disclosures: The study was funded by Relypsa. Williams reports he is a member of the steering committee for the AMBER trial and received honoraria from Relypsa.