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BOSTON -- Spironolactone (Aldactone, CaroSpir) combined with patiromer (Veltassa) may help patients with resistant hypertension and chronic kidney disease (CKD) manage their blood pressure without increasing the risk for hyperkalemia, researchers reported here.

In the phase II AMBER trial, patients who continued to take spironolactone at week 12 had a least squares mean difference between groups of 20% (P<0.0001), reported Rajiv Agarwal, MBBS, MD, of the Indiana University School of Medicine in Indianapolis, and colleagues.

From baseline to week 12, the least squares mean between-group difference in systolic blood pressure (BP) based on automated office BP (AOBP) measures was -1.0 mmHg (P=0.58), Agarwal reported at National Kidney Foundation Spring Clinical Meeting.

The safety profile for patiromer was consistent with the findings in prior investigations, he added.

The showed that spironolactone was effective in resistant hypertension. However, it did not assess patients with advanced CKD, Agarwal said, adding that "The guidelines recommend that, in resistant hypertension, we use spironolactone, [which] is a key step in managing resistant hypertension, but it is restricted to patients at low risk for hyperkalemia."

These are patients who have [estimated glomerular filtration rate] eGFR ≥45 mL/min/1.73m² and a plasma K⁺ ≤4.5 mEq/L," Agarwal said.

Agarwal's group randomized 147 adult patients to the spironolactone and patiromer group and 148 patients to the spironolactone and placebo group at 62 centers in 10 countries. The patients had a mean age of about 69 and were 52% male. The cohort was evaluated over a 4-week screening or run-in period and a 12-week treatment period.

Inclusion criteria were uncontrolled hypertension as documented by systolic BP between 135 to 160 mm Hg measured by unwitnessed, AOBP at screening events, eGFR of 25 to 45 mL/min/1.73m², local lab K⁺ level of 4.3-5.1 mEq/L, and taking a minimum of three antihypertensive prescriptions for a minimum of 28 days at a stable dose.

Exclusion criteria were severe gastrointestinal disorder, recent cardiovascular event <3 months, current use of mineralocorticoid receptor antagonist (MRA), renal transplantation, and secondary hypertension.

The primary endpoint was the between-group difference in the proportion of patients remaining on spironolactone at week 12. The between-group difference in change of systolic BP was the secondary endpoint.

Although change in systolic BP between groups was similar, 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 versus 86% of patients in the patiromer group. Patients in the latter group were allowed patients to use 385 mg more of spironolactone during this time.

Finally, two out of three patients treated with placebo developed hyperkalemia, but the researchers determined patiromer reduced the risk by half.

Study limitations included the fact that patients did not have eGFR <25, K⁺ >4.5, and there were few black participants.

"The study for the first time shows that patiromer can enable the use of spironolactone in those patients who were denied this life-saving drug for the treatment of resistant hypertension due to eGFR <45 or k >4.5 mEq/l. Thus, it has the potential to change guidelines," Agarwal told 乌鸦传媒視頻.

"The challenge has been the significant incidence of hyperkalemia when one not only adds an MRA, but pushes the dose to give the beneficial effects for BP, commented Pablo Pergola, MD, PhD, of Renal Associates, in San Antonio.

"So knowing that hyperkalemia is almost an inevitable problem for these patients, proactively adding drugs like patiromer that can help you prevent that complication, and more importantly, maintain the patient in the MRA intervention is very important," said Pergola, who was not involved in the study.

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