title: Treatment-Resistant Hypertension and Outcomes Based on Randomized Treatment Group in ALLHAT.
abstract: BACKGROUND
  Although hypertension guidelines define treatment-resistant hypertension as blood pressure uncontrolled by ≥3 antihypertensive medications, including a diuretic, it is unknown whether patient prognosis differs when a diuretic is included.
  
  
  METHODS
  Participants in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) were randomly assigned to first-step therapy with chlorthalidone, amlodipine, or lisinopril. At a Year 2 follow-up visit, those with average blood pressure ≥140 mm Hg systolic or ≥90 mm Hg diastolic on ≥3 antihypertensive medications, or blood pressure <140/90 mm Hg on ≥4 antihypertensive medications were identified as having apparent treatment-resistant hypertension. The prevalence of treatment-resistant hypertension and its association with ALLHAT primary (combined fatal coronary heart disease or nonfatal myocardial infarction) and secondary (all-cause mortality, stroke, heart failure, combined coronary heart disease, and combined cardiovascular disease) outcomes were identified for each treatment group.
  
  
  RESULTS
  Of participants assigned to chlorthalidone, amlodipine, or lisinopril, 9.6%, 11.4%, and 19.7%, respectively, had treatment-resistant hypertension. During mean follow-up of 2.9 years, primary outcome incidence was similar for those assigned to chlorthalidone compared with amlodipine or lisinopril (amlodipine- vs chlorthalidone-adjusted hazard ratio [HR] 0.86; 95% confidence interval [CI], 0.53-1.39; P = .53; lisinopril- vs chlorthalidone-adjusted HR = 1.06; 95% CI, 0.70-1.60; P = .78). Secondary outcome risks were similar for most comparisons except coronary revascularization, which was higher with amlodipine than with chlorthalidone (HR 1.86; 95% CI, 1.11-3.11; P = .02). An as-treated analysis based on diuretic use produced similar results.
  
  
  CONCLUSIONS
  In this study, which titrated medications to a goal, participants assigned to chlorthalidone were less likely to develop treatment-resistant hypertension. However, prognoses in those with treatment-resistant hypertension were similar across treatment groups.
authors.affiliation: Department of Medicine, New York University School of Medicine.
authors.forename: Sripal
authors.initials: S
authors.lastname: Bangalore
authors.affiliation: Coordinating Center for Clinical Trials, The University of Texas School of Public Health, Houston. Electronic address: barry.r.davis@uth.tmc.edu.
authors.forename: Barry R
authors.initials: BR
authors.lastname: Davis
authors.affiliation: Memphis Veterans Affairs Medical Center, University of Tennessee College of Medicine.
authors.forename: William C
authors.initials: WC
authors.lastname: Cushman
authors.affiliation: Coordinating Center for Clinical Trials, The University of Texas School of Public Health, Houston.
authors.forename: Sara L
authors.initials: SL
authors.lastname: Pressel
authors.affiliation: Vascular Biology and Hypertension Program, University of Alabama, Birmingham.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Muntner
authors.affiliation: Vascular Biology and Hypertension Program, University of Alabama, Birmingham.
authors.forename: David A
authors.initials: DA
authors.lastname: Calhoun
authors.affiliation: Cardiovascular Institute, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ.
authors.forename: John B
authors.initials: JB
authors.lastname: Kostis
authors.affiliation: Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, La.
authors.forename: Paul K
authors.initials: PK
authors.lastname: Whelton
authors.affiliation: Department of Medicine, The University of Washington Medical Center, Seattle.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Probstfield
authors.affiliation: Department of Medicine, University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, Ohio.
authors.forename: Mahboob
authors.initials: M
authors.lastname: Rahman
authors.affiliation: Department of Medicine, New York University School of Medicine.
authors.forename: Henry R
authors.initials: HR
authors.lastname: Black
mesh_terms: D000368:Aged; D017311:Amlodipine / Q000008:administration & dosage / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000209:etiology; D002752:Chlorthalidone / Q000008:administration & dosage / Q000627:therapeutic use; D004232:Diuretics / Q000008:administration & dosage / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy*; D017706:Lisinopril / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents; D004232:Diuretics; D017311:Amlodipine; D017706:Lisinopril; D002752:Chlorthalidone
keywords: Angiotensin-converting enzyme inhibitor; Calcium channel blocker; Diuretics; Hypertension; Resistance