Drug combo safe, effective for patients with resistant high BP and kidney failure
High blood pressure (BP) may lead to chronic kidney failure an chronic kidney failure contributes to increase of blood pressure, BP. It is therefore a challenge to control resistant hypertension in CKD.This challenge is further enhanced as the potassium sparing drugs used to control high blood pressure raise risk of increased blood potassium levels.
A combo of spironolactone (Aldactone) and potassium-binding polymer patiromer (Veltassa) may help in the management of blood pressure (BP) without increasing the risk for hyperkalemia, in patients with resistant hypertension (RHTN) and chronic kidney disease (CKD).
Results of the study were reported at the National Kidney Foundation Spring Clinical Meeting and subsequently published in the American Journal of Nephrology.
While chronic kidney disease (CKD) is common in resistant high blood pressure (resistant hypertension), prior studies evaluating mineralocorticoid receptor antagonists excluded patients with reduced kidney function due to the risk of hyperkalemia
Resistant hypertension is defined as unattended systolic automated office blood pressure (AOBP) of 135–160 mm Hg during screening despite taking ≥3 antihypertensives, including a diuretic, and an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker (unless not tolerated or contraindicated).
CKD is a common manifestation of resistant hypertension. Prior studies evaluating mineralocorticoid receptor antagonists did not include patients with reduced kidney function due to the risk of hyperkalemia. Rajiv Agarwal, Department of Medicine, Division of Nephrology, Indiana University, Indianapolis, and colleagues in this phase, II AMBER trial, determined if patiromer treatment in CKD patients receiving spironolactone for the treatment of RHTN leads to hypertension management and hypertension management. In short, they determined whether patiromer treatment facilitated the use of spironolactone in patients with CKD and RHTN.
The PATHWAY-2 trial 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."
The researchers in this double-blind, placebo-controlled study 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 a 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.
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- Patients who continued to take spironolactone at week 12 had a least squares mean difference between groups of 20%.
- 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.
- Although a 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.
- Two out of three patients treated with placebo developed hyperkalemia, but the researchers determined patiromer reduced the risk by half.
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"AMBER will define the ability of patiromer to facilitate the use of spironolactone, an effective antihypertensive therapy for patients with RHTN and CKD," concluded the authors.
For detailed study follow the link: https://doi.org/10.1159/000492622