Treatment-Resistant Hypertension and Outcomes Based on Randomized Treatment Group in ALLHAT.

Academic Article


  • 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.
  • Published In


  • Angiotensin-converting enzyme inhibitor, Calcium channel blocker, Diuretics, Hypertension, Resistance, Aged, Amlodipine, Antihypertensive Agents, Blood Pressure, Cardiovascular Diseases, Chlorthalidone, Diuretics, Drug Therapy, Combination, Female, Humans, Hypertension, Lisinopril, Male, Treatment Failure, Treatment Outcome
  • Digital Object Identifier (doi)

    Pubmed Id

  • 8087521
  • Author List

  • Bangalore S; Davis BR; Cushman WC; Pressel SL; Muntner PM; Calhoun DA; Kostis JB; Whelton PK; Probstfield JL; Rahman M
  • Start Page

  • 439
  • End Page

  • 448.e9
  • Volume

  • 130
  • Issue

  • 4