FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4293490437> ?p ?o ?g. }

• W4293490437 endingPage "720" @default.
• W4293490437 startingPage "718" @default.
• W4293490437 abstract "HomeCirculationVol. 146, No. 9Chlorthalidone for Resistant Hypertension in Advanced Chronic Kidney Disease Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBChlorthalidone for Resistant Hypertension in Advanced Chronic Kidney Disease Rajiv Agarwal, MD, MS, Arjun D. Sinha, MD, MS and Wanzhu Tu, PhD Rajiv AgarwalRajiv Agarwal Correspondence to: Rajiv Agarwal, MD, MS, Indiana University School of Medicine, 1481 West 10th St, 111N, Indianapolis, IN 46202. Email E-mail Address: [email protected] https://orcid.org/0000-0001-8355-7100 Division of Nephrology, Department of Medicine (R.A., A.D.S.), Indiana University School of Medicine, Indianapolis. Richard L. Roudebush Veterans Administration Medical Center, Indianapolis, IN (R.A., A.D.S.). Search for more papers by this author , Arjun D. SinhaArjun D. Sinha Division of Nephrology, Department of Medicine (R.A., A.D.S.), Indiana University School of Medicine, Indianapolis. Richard L. Roudebush Veterans Administration Medical Center, Indianapolis, IN (R.A., A.D.S.). Search for more papers by this author and Wanzhu TuWanzhu Tu Department of Biostatistics & Health Data Science, Richard M. Fairbanks School of Public Health, Indiana University Center for Aging Research (W.T.), Indiana University School of Medicine, Indianapolis. Regenstrief Institute, Indianapolis, IN (W.T.). Search for more papers by this author Originally published29 Aug 2022https://doi.org/10.1161/CIRCULATIONAHA.122.060167Circulation. 2022;146:718–720Resistant hypertension increases the risk for cardiovascular events and end-stage kidney disease.1 Few therapies exist for people with chronic kidney disease (CKD). In a double-blind randomized, controlled trial (CLICK [Chlorthalidone in Chronic Kidney Disease]; URL: https://www.clinicaltrials.gov; Unique identifier: NCT02841280), we demonstrated that chlorthalidone substantially reduced blood pressure (BP) in stage 4 CKD.2 Here, we examine the drug’s safety and efficacy in people with resistant hypertension and stage 4 CKD with or without a loop diuretic and whether chlorthalidone reduces albuminuria.After receiving study approval by an institutional review committee and obtaining informed consent, we randomly assigned patients with stage 4 CKD to either placebo or chlorthalidone 12.5 mg daily in a 1:1 ratio stratified by previous loop diuretic use. The primary end point was the change in 24-hour systolic ambulatory BP from baseline to 12 weeks. Of the 160 randomized patients, 113 (71%) had resistant hypertension, defined as having poorly controlled 24-hour ambulatory BP monitoring despite receiving ≥3 antihypertensive medications. Among the 90 participants (80%) on loop diuretics, 42 (78%) were in the placebo group and 48 (81%) were in the chlorthalidone group. Patients on average took 4.1 antihypertensive agents (SD 1.1). K-sparing diuretics were used in 14 (12%) patients (spironolactone 13, amiloride 1), of whom 9 (17%) were assigned placebo and 5 (8%) chlorthalidone. Mean 24-hour ambulatory BP at randomization was 140.7 (8.4)/71.8 (9.8) mm Hg in the placebo group and 142.7 (7.9)/73.3 (10.5) mm Hg in the chlorthalidone group. The statistical approach used in the current analysis mirrored that of the main analysis of the CLICK trial. All supporting data are available within the article and the original publication.2The adjusted change from baseline to 12 weeks in 24-hour systolic BP was 1.3 mm Hg (95% CI, −2.3 to 5.0) in the placebo group (n=54) and −12.6 mm Hg (95% CI, −16.4 to −8.8) in the chlorthalidone group (n=59). The between-group difference was −13.9 mm Hg (95% CI, −19.4 to −8.4; P<0.0001; Table). Improvement in clinic BP occurred rapidly within 4 weeks and was sustained over the 12 weeks of the trial. Seated clinic systolic BP was reduced by 13.2, 14.5, and 16.2 mm Hg with chlorthalidone in 4, 8, and 12 weeks, respectively. Thus, 81% of the treatment effect was evident with the lowest dose of chlorthalidone (12.5 mg per day) in 4 weeks. Two weeks after stopping the drug, 76% of the treatment effect persisted, suggesting that the treatment effect is long-acting. Previous diuretic use did not modify the primary end point (change from baseline −14.4 mm Hg [95% CI, −25.5 to −3.3] in loop diuretic nonusers [n=23] versus −14.0 mm Hg [95% CI, −19.6 to −8.3] in loop diuretic users [n=90]).Table. Ambulatory Blood Pressure at Randomization and at 12 Weeks (End of Assigned Regimen)VariablePlacebo (n=54)Chlorthalidone (n=59)Treatment effect (95% CI)Systolic BP, mm Hg 24-hour BP At randomization140.7 (8.4)142.7 (7.9) Adjusted change at 12 weeks1.3 (−2.3 to 5.0)−12.6 (−16.4 to −8.8)−13.9 (−19.4 to −8.4) Daytime BP At randomization142.9 (8.9)145 (8.4) Adjusted change at 12 weeks1.4 (−2.4 to 5.3)−13.1 (−17.1 to −9.1)−14.5 (−20.3 to −8.8) Nighttime BP At randomization136.4 (10.7)138.7 (9.8) Adjusted change at 12 weeks1.5 (−2.8 to 5.8)−10.4 (−14.5 to −6.3)−11.9 (−17.7 to −6.1)Diastolic BP, mm Hg 24-hour BP At randomization71.8 (9.8)73.3 (10.5) Adjusted change at 12 weeks0.4 (−1.8 to 2.6)−5.4 (−7.7 to −3.2)−5.8 (−9.0 to −2.6) Daytime BP At randomization73.6 (9.6)75.8 (10.9) Adjusted change at 12 weeks0.5 (−1.9 to 2.8)−6.2 (−8.6 to −3.9)−6.7 (−10.2 to −3.2) Nighttime BP At randomization68.2 (11.1)69.1 (11) Adjusted change at 12 weeks−0.1 (−2.7 to 2.5)−3.7 (−6.2 to −1.3)−3.7 (−7.2 to −0.1)Patients with a nocturnal dip in systolic BP, n/total n (%) At randomization13/54 (24)10/58 (17) At 12 weeks11/49 (22)10/48 (21)0.64 (0.22 to 1.86)Data at randomization are mean (SD). Data on final 24-hour and daytime ambulatory blood pressure (BP) were imputed for 13 patients (4 placebo, 9 chlorthalidone) who had missing values for ambulatory BP. Data on nighttime BP were missing in 18 patients (6 placebo, 12 chlorthalidone), of which 17 were imputed because 1 was missing nighttime BP at baseline. The treatment effect is expressed as the mean difference with a 95% CI for all the variables except nocturnal dip in systolic BP, for which the effect is expressed as an odds ratio with a 95% CI. A nocturnal dip in systolic BP indicates a decrease >10% from the daytime value.Compared with placebo, the urine albumin-to-creatinine ratio in the chlorthalidone group at 12 weeks was −54% (95% CI, −65% to −40%). Two weeks after the assigned regimen was discontinued, the percent change in urinary albumin-to-creatinine ratio remained at −33% in the chlorthalidone group and −9% in the placebo group (between-group difference, −33% points [95% CI, −51% to −8%]).After randomization, hypokalemia (13.6% versus 0%), reversible increases in serum creatinine (51.8% versus 14.8%), hyperglycemia (18.6% versus 5.6%), dizziness (27.1% versus 20.4%), orthostatic hypotension (11.9% versus 3.7%), and hyperuricemia (23.7% versus 11.1%) occurred more frequently in the chlorthalidone group. From the time of randomization to the end of the trial, increases in the serum creatinine level >25% from baseline were strongly influenced by baseline loop diuretic use. The odds ratio associated with a 25% or greater increase in creatinine was 1.1 (95% CI, 0.1 to 18.3) among patients not on loop diuretics at baseline as compared with 8.5 (95% CI, 2.7 to 29.2) among those who were on loop diuretics at baseline. The difference did not reach the nominal level of statistical significance (P=0.078 for the treatment × loop diuretic interaction).In the general population, spironolactone is the standard of care for treating resistant hypertension.3 However, in a meta-analysis, spironolactone doubled the risk of hyperkalemia and quintupled the risk of gynecomastia compared with angiotensin-converting enzyme inhibitor or angiotensin receptor blockers (or both).4 In a randomized trial of patients with resistant hypertension and estimated glomerular filtration rate between 25 and ≤45 mL/min/1.73 m2, patiromer, a potassium binding polymer, enabled the use of spironolactone.5 However, even with patiromer, approximately one-third of patients administered spironolactone experienced hyperkalemia (K ≥5.5 mEq/L) over 12 weeks. Given the difficulty of using spironolactone, chlorthalidone is an attractive alternative to treat resistant hypertension in advanced CKD. An important advantage of chlorthalidone over spironolactone is that the risk of hyperkalemia is essentially nonexistent. However, hypokalemia becomes a concern. Serum creatinine, BP, blood glucose, and serum sodium would require careful monitoring.Data from patients with resistant hypertension in CLICK demonstrated that chlorthalidone effectively reduced both systolic and diastolic 24-hour ambulatory BP in stage 4 CKD independent of loop diuretic use. Chlorthalidone represents an attractive option for managing resistant hypertension in patients with advanced CKD.Article InformationREGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02841280.Sources of FundingSupported by National Heart, Lung, and Blood Institute grant R01 HL126903 and the Indiana Institute for Medical Research.Nonstandard Abbreviations and AcronymsBPblood pressureCKDchronic kidney diseaseDisclosures Dr Agarwal reports personal fees and nonfinancial support from Bayer Healthcare Pharmaceuticals Inc, Akebia Therapeutics, Boehringer Ingelheim, Eli Lilly, and Vifor Pharma; has received personal fees from Lexicon and Reata; is a member of data safety monitoring committees for Vertex and Chinook, steering committees of randomized trials for Akebia Therapeutics, Bayer, and Relypsa, and adjudication committees for Bayer; has served as Associate Editor of the American Journal of Nephrology and Nephrology Dialysis Transplantation and has been an author for UpToDate; and has received research grants from the National Institutes of Health and the US Veterans Administration. Dr Sinha is an end point adjudication consultant for George Clinical. Dr Tu reports no conflicts.FootnotesCirculation is available at www.ahajournals.org/journal/circFor Sources of Funding and Disclosures, see page 720.Correspondence to: Rajiv Agarwal, MD, MS, Indiana University School of Medicine, 1481 West 10th St, 111N, Indianapolis, IN 46202. Email [email protected]eduReferences1. De Nicola L, Gabbai FB, Agarwal R, Chiodini P, Borrelli S, Bellizzi V, Nappi F, Conte G, Minutolo R. Prevalence and prognostic role of resistant hypertension in chronic kidney disease patients.J Am Coll Cardiol. 2013; 61:2461–2467. doi: 10.1016/j.jacc.2012.12.061CrossrefMedlineGoogle Scholar2. Agarwal R, Sinha AD, Cramer AE, Balmes-Fenwick M, Dickinson JH, Ouyang F, Tu W. Chlorthalidone for hypertension in advanced chronic kidney disease.N Engl J Med. 2021; 385:2507–2519. doi: 10.1056/NEJMoa2110730CrossrefMedlineGoogle Scholar3. Nishizaka MK, Zaman M, Calhoun DA. Efficacy of low-dose spironolactone in subjects with resistant hypertension.Am J Hypertens. 2003; 16:925–930. doi: 10.1016/s0895-7061(03)01032-xCrossrefMedlineGoogle Scholar4. Bolignano D, Palmer SC, Navaneethan SD, Strippoli GF. Aldosterone antagonists for preventing the progression of chronic kidney disease.Cochrane Database Syst Rev. 2014;CD007004. doi: 10.1002/14651858.CD007004.pub3MedlineGoogle Scholar5. Agarwal R, Rossignol P, Romero A, Garza D, Mayo MR, Warren S, Ma J, White WB, Williams B. Patiromer versus placebo to enable spironolactone use in patients with resistant hypertension and chronic kidney disease (AMBER): a phase 2, randomised, double-blind, placebo-controlled trial.Lancet. 2019; 394:1540–1550. doi: 10.1016/S0140-6736(19)32135-XCrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By de la Espriella R, Cobo M and Núñez J (2022) Thiazides in chronic kidney disease: “back to the future”, Clinical Kidney Journal, 10.1093/ckj/sfac228 August 30, 2022Vol 146, Issue 9 Advertisement Article InformationMetrics © 2022 American Heart Association, Inc.https://doi.org/10.1161/CIRCULATIONAHA.122.060167PMID: 36037270 Originally publishedAugust 29, 2022 PDF download Advertisement SubjectsHigh Blood Pressure" @default.
• W4293490437 created "2022-08-29" @default.
• W4293490437 creator A5051708137 @default.
• W4293490437 creator A5053293986 @default.
• W4293490437 creator A5066416133 @default.
• W4293490437 date "2022-08-30" @default.
• W4293490437 modified "2023-10-13" @default.
• W4293490437 title "Chlorthalidone for Resistant Hypertension in Advanced Chronic Kidney Disease" @default.
• W4293490437 cites W2034121292 @default.
• W4293490437 cites W2064532153 @default.
• W4293490437 cites W2972966903 @default.
• W4293490437 cites W3210606186 @default.
• W4293490437 cites W4237773453 @default.
• W4293490437 doi "https://doi.org/10.1161/circulationaha.122.060167" @default.
• W4293490437 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36037270" @default.
• W4293490437 hasPublicationYear "2022" @default.
• W4293490437 type Work @default.
• W4293490437 citedByCount "4" @default.
• W4293490437 countsByYear W42934904372022 @default.
• W4293490437 countsByYear W42934904372023 @default.
• W4293490437 crossrefType "journal-article" @default.
• W4293490437 hasAuthorship W4293490437A5051708137 @default.
• W4293490437 hasAuthorship W4293490437A5053293986 @default.
• W4293490437 hasAuthorship W4293490437A5066416133 @default.
• W4293490437 hasBestOaLocation W42934904371 @default.
• W4293490437 hasConcept C126322002 @default.
• W4293490437 hasConcept C164705383 @default.
• W4293490437 hasConcept C177713679 @default.
• W4293490437 hasConcept C2778653478 @default.
• W4293490437 hasConcept C2779918671 @default.
• W4293490437 hasConcept C2780091579 @default.
• W4293490437 hasConcept C2780427769 @default.
• W4293490437 hasConcept C3019558611 @default.
• W4293490437 hasConcept C71924100 @default.
• W4293490437 hasConcept C84393581 @default.
• W4293490437 hasConceptScore W4293490437C126322002 @default.
• W4293490437 hasConceptScore W4293490437C164705383 @default.
• W4293490437 hasConceptScore W4293490437C177713679 @default.
• W4293490437 hasConceptScore W4293490437C2778653478 @default.
• W4293490437 hasConceptScore W4293490437C2779918671 @default.
• W4293490437 hasConceptScore W4293490437C2780091579 @default.
• W4293490437 hasConceptScore W4293490437C2780427769 @default.
• W4293490437 hasConceptScore W4293490437C3019558611 @default.
• W4293490437 hasConceptScore W4293490437C71924100 @default.
• W4293490437 hasConceptScore W4293490437C84393581 @default.
• W4293490437 hasIssue "9" @default.
• W4293490437 hasLocation W42934904371 @default.
• W4293490437 hasLocation W42934904372 @default.
• W4293490437 hasOpenAccess W4293490437 @default.
• W4293490437 hasPrimaryLocation W42934904371 @default.
• W4293490437 hasRelatedWork W115922469 @default.
• W4293490437 hasRelatedWork W2050943580 @default.
• W4293490437 hasRelatedWork W2080644573 @default.
• W4293490437 hasRelatedWork W2289647078 @default.
• W4293490437 hasRelatedWork W2313058495 @default.
• W4293490437 hasRelatedWork W2411331453 @default.
• W4293490437 hasRelatedWork W2542179394 @default.
• W4293490437 hasRelatedWork W3003144780 @default.
• W4293490437 hasRelatedWork W3042462394 @default.
• W4293490437 hasRelatedWork W3167123467 @default.
• W4293490437 hasVolume "146" @default.
• W4293490437 isParatext "false" @default.
• W4293490437 isRetracted "false" @default.
• W4293490437 workType "article" @default.