Dataset Information

Management of hypertension in advanced kidney disease.

ABSTRACT:

Purpose of review

The aim of this study was to present recent developments in pharmacotherapy of hypertension in patients with advanced chronic kidney disease (CKD).

Recent findings

In the AMBER trial, compared with placebo, the potassium-binder patiromer mitigated the risk of hyperkalaemia and enabled more patients with uncontrolled resistant hypertension and stage 3b/4 CKD to tolerate and continue spironolactone treatment; add-on therapy with spironolactone provoked a clinically meaningful reduction of 11-12 mmHg in unattended automated office SBP over 12 weeks of follow-up. In the BLOCK-CKD trial, the investigational nonsteroidal mineralocorticoid-receptor-antagonist (MRA) KBP-5074 lowered office SBP by 7-10 mmHg relative to placebo at 84 days with a minimal risk of hyperkalaemia in patients with advanced CKD and uncontrolled hypertension. The CLICK trial showed that the thiazide-like diuretic chlorthalidone provoked a placebo-subtracted reduction of 10.5 mmHg in 24-h ambulatory SBP at 12 weeks in patients with stage 4 CKD and poorly controlled hypertension.

Summary

Enablement of more persistent spironolactone use with newer potassium-binding agents, the clinical development of novel nonsteroidal MRAs with a more favourable benefit-risk profile and the recently proven blood pressure lowering action of chlorthalidone are three therapeutic opportunities for more effective management of hypertension in high-risk patients with advanced CKD.

SUBMITTER: Georgianos PI

PROVIDER: S-EPMC9728619 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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Publications

Management of hypertension in advanced kidney disease.

Georgianos Panagiotis I PI Agarwal Rajiv R

Current opinion in nephrology and hypertension 20220701 4

<h4>Purpose of review</h4>The aim of this study was to present recent developments in pharmacotherapy of hypertension in patients with advanced chronic kidney disease (CKD).<h4>Recent findings</h4>In the AMBER trial, compared with placebo, the potassium-binder patiromer mitigated the risk of hyperkalaemia and enabled more patients with uncontrolled resistant hypertension and stage 3b/4 CKD to tolerate and continue spironolactone treatment; add-on therapy with spironolactone provoked a clinically ...[more]

PMID: 35727171

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Project description:BackgroundLittle evidence has been available to support the use of thiazide diuretics to treat hypertension in patients with advanced chronic kidney disease.MethodsWe randomly assigned patients with stage 4 chronic kidney disease and poorly controlled hypertension, as confirmed by 24-hour ambulatory blood-pressure monitoring, in a 1:1 ratio to receive chlorthalidone at an initial dose of 12.5 mg per day, with increases every 4 weeks if needed to a maximum dose of 50 mg per day, or placebo; randomization was stratified according to previous use of loop diuretics. The primary outcome was the change in 24-hour ambulatory systolic blood pressure from baseline to 12 weeks. Secondary outcomes were the change from baseline to 12 weeks in the urinary albumin-to-creatinine ratio, N-terminal pro-B-type natriuretic peptide level, plasma renin and aldosterone levels, and total body volume. Safety was also assessed.ResultsA total of 160 patients underwent randomization, of whom 121 (76%) had diabetes mellitus and 96 (60%) were receiving loop diuretics. At baseline, the mean (±SD) estimated glomerular filtration rate was 23.2±4.2 ml per minute per 1.73 m2 of body-surface area and the mean number of antihypertensive medications prescribed was 3.4±1.4. At randomization, the mean 24-hour ambulatory systolic blood pressure was 142.6±8.1 mm Hg in the chlorthalidone group and 140.1±8.1 mm Hg in the placebo group and the mean 24-hour ambulatory diastolic blood pressure was 74.6±10.1 mm Hg and 72.8±9.3 mm Hg, respectively. The adjusted change in 24-hour systolic blood pressure from baseline to 12 weeks was -11.0 mm Hg (95% confidence interval [CI], -13.9 to -8.1) in the chlorthalidone group and -0.5 mm Hg (95% CI, -3.5 to 2.5) in the placebo group. The between-group difference was -10.5 mm Hg (95% CI, -14.6 to -6.4) (P<0.001). The percent change in the urinary albumin-to-creatinine ratio from baseline to 12 weeks was lower in the chlorthalidone group than in the placebo group by 50 percentage points (95% CI, 37 to 60). Hypokalemia, reversible increases in serum creatinine level, hyperglycemia, dizziness, and hyperuricemia occurred more frequently in the chlorthalidone group than in the placebo group.ConclusionsAmong patients with advanced chronic kidney disease and poorly controlled hypertension, chlorthalidone therapy improved blood-pressure control at 12 weeks as compared with placebo. (Funded by the National Heart, Lung, and Blood Institute and the Indiana Institute of Medical Research; CLICK ClinicalTrials.gov number, NCT02841280.).

Project description:ImportanceChronic kidney disease (CKD) affects 37 million adults in the United States, and for patients with CKD, hypertension is a key risk factor for adverse outcomes, such as kidney failure, cardiovascular events, and death.ObjectiveTo evaluate a computerized clinical decision support (CDS) system for the management of uncontrolled hypertension in patients with CKD.Design, setting, and participantsThis multiclinic, randomized clinical trial randomized primary care practitioners (PCPs) at a primary care network, including 15 hospital-based, ambulatory, and community health center-based clinics, through a stratified, matched-pair randomization approach February 2021 to February 2022. All adult patients with a visit to a PCP in the last 2 years were eligible and those with evidence of CKD and hypertension were included.InterventionThe intervention consisted of a CDS system based on behavioral economic principles and human-centered design methods that delivered tailored, evidence-based recommendations, including initiation or titration of renin-angiotensin-aldosterone system inhibitors. The patients in the control group received usual care from PCPs with the CDS system operating in silent mode.Main outcomes and measuresThe primary outcome was the change in mean systolic blood pressure (SBP) between baseline and 180 days compared between groups. The primary analysis was a repeated measures linear mixed model, using SBP at baseline, 90 days, and 180 days in an intention-to-treat repeated measures model to account for missing data. Secondary outcomes included blood pressure (BP) control and outcomes such as percentage of patients who received an action that aligned with the CDS recommendations.ResultsThe study included 174 PCPs and 2026 patients (mean [SD] age, 75.3 [0.3] years; 1223 [60.4%] female; mean [SD] SBP at baseline, 154.0 [14.3] mm Hg), with 87 PCPs and 1029 patients randomized to the intervention and 87 PCPs and 997 patients randomized to usual care. Overall, 1714 patients (84.6%) were treated for hypertension at baseline. There were 1623 patients (80.1%) with an SBP measurement at 180 days. From the linear mixed model, there was a statistically significant difference in mean SBP change in the intervention group compared with the usual care group (change, -14.6 [95% CI, -13.1 to -16.0] mm Hg vs -11.7 [-10.2 to -13.1] mm Hg; P = .005). There was no difference in the percentage of patients who achieved BP control in the intervention group compared with the control group (50.4% [95% CI, 46.5% to 54.3%] vs 47.1% [95% CI, 43.3% to 51.0%]). More patients received an action aligned with the CDS recommendations in the intervention group than in the usual care group (49.9% [95% CI, 45.1% to 54.8%] vs 34.6% [95% CI, 29.8% to 39.4%]; P < .001).Conclusions and relevanceThese findings suggest that implementing this computerized CDS system could lead to improved management of uncontrolled hypertension and potentially improved clinical outcomes at the population level for patients with CKD.Trial registrationClinicalTrials.gov Identifier: NCT03679247.

Dataset Information

Management of hypertension in advanced kidney disease.

Purpose of review

Recent findings

Summary

Publications

Management of hypertension in advanced kidney disease.

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