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Patiromer (Veltassa) works as an adjunctive therapy enabling persistent spironolactone (Aldactone) use among patients with uncontrolled resistant hypertension and chronic kidney disease (CKD), according to a study in nearly 300 people.

Twelve weeks after randomization, use of spironolactone was confirmed in 66% of the placebo arm and 86% with the potassium binder group (P<0.0001), according to Rajiv Agarwal, MD, of Indiana University, Richard L Roudebush VA Medical Center, both in Indianapolis, and colleagues.

"Two-thirds of patients in the placebo group developed hyperkalemia, and this risk was reduced by half in patients in the patiromer group," the AMBER investigators wrote in the.

Agarwal previously reported the main findings at the 2019 National Kidney Foundation Spring Clinical Meeting.

"Use of the K+ binder patiromer enabled more persistent use of spironolactone in patients with uncontrolled resistant hypertension and advanced CKD. 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," Agarwal's group concluded.

Greater use of spironolactone in this population would be of clinical relevance given that the major spironolactone studies excluded CKD patients due to the risk of spironolactone-induced hyperkalemia, and that patiromer is already approved in the U.S. to lower serum K+ in patients with hyperkalemia.

"These are significant findings in that we now have tolerable therapy that attenuates the risk of hyperkalemia associated with drugs that are known to be antihypertensive and cardiorenal protective," commented George Bakris, MD, of University of Chicago Medicine. "Drugs like patiromer act as 'enablers' of life-saving therapies in a subset of people that normally couldn't take these medications because of hyperkalemia."

"When used together, drugs like patiromer help bind potassium in the gut when the kidney, which is responsible for 90% of the potassium excretion, is unable to handle the load in part as a result of agents like spironolactone and drugs that inhibit the renin angiotensin system like ACE inhibitors and angiotensin receptor blockers," said Bakris, who was not involved in the study.

The ongoing phase III is enrolling approximately 2,4o0 people (heart failure patients who are hyperkalemic on renin angiotensin aldosterone system inhibitors such as spironolactone) to compare patiromer and placebo in time to first occurrence of cardiovascular death or hospitalization.

In AMBER, adverse events occurred at similar rates between groups (53% for placebo vs 56% for patiromer). Mild or moderate gastrointestinal disorders such as diarrhea comprised the most frequent events (16% in both arms).

The extent of automatic office blood pressure (BP) reduction was similar between groups by study's end (-10.8 vs -11.7 mm Hg). Among patients who had BP measured at spironolactone discontinuation and again during a follow-up visit 2 weeks later, the mean increase in systolic BP was 6 mm Hg for an average persistent BP reduction from baseline of 7.1 mm Hg.

"Thus, 54% of the systolic BP effect remained despite discontinuation of spironolactone 2 weeks earlier," Agarwal and colleagues noted, adding that 2 weeks may not be long enough to see a difference in automatic office BP.

The blinded phase II randomized trial screened 574 adults with CKD and uncontrolled resistant hypertension for enrollment. Participants had to have an estimated glomerular filtration rate of 25-45 mL/min per 1.73 m² and serum K+ between 4.3 and 5.1 mmol/L. Screening took place at 62 centers in 10 countries.

After each candidate had four visits to ensure that they were on stable doses of medication and had true treatment-resistant hypertension, 295 people were selected and randomized to get patiromer (8.4 g once daily) or placebo in addition to open-label spironolactone (starting at 25 mg once daily) and baseline BP medications.

The average patient age was 68, and roughly half were women, while another half had diabetes; nearly half a history of heart failure.

Resistant-treatment hypertension meant systolic automatic office BP of 135-160 mm Hg while the patient was taking three or more classes of antihypertensive medications (or any BP with four or more classes of these drugs).

Dose titrations of patiromer and spironolactone were permitted at 1 week and 3 weeks, respectively.

The diuretic was uptitrated to 50 mg for 69% of the patiromer group (versus 51% of placebo). Consequently, the mean cumulative dose of spironolactone administered over 12 weeks was nearly 400 mg higher per person in the former group.

Adherence to spironolactone consistently exceeded 90% over the study period among those who should have stayed on the drug.

"Our study did not include a placebo for spironolactone control group; hence, we cannot definitively conclude that spironolactone reduced BP in patients with resistant hypertension with CKD," Agarwal and colleagues cautioned. Furthermore, theirs was a predominantly white study cohort.

The AMBER study appears to be well done, according to Lee Green, MD, MPH, of University of Alberta in Edmonton, Canada.

"These results only apply to a very small number of patients that the typical family physician will manage, but it's a useful option to have for those few patients," Green, who was not involved in the study, told 乌鸦传媒.

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