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: Sripal Bangalore, Barry R Davis, William C Cushman, Sara L Pressel, Paul M Muntner, David A Calhoun, John B Kostis, Paul K Whelton, Jeffrey L Probstfield, Mahboob Rahman, Henry R Black, ALLHAT Collaborative Research Group
• Journal: The American journal of medicine (Am J Med) Vol. 130 Issue 4 Pg. 439-448.e9 (Apr 2017) ISSN: 1555-7162 [Electronic] United States
• PMID: 27984005 (Publication Type: Journal Article, Randomized Controlled Trial)
• Copyright: Copyright © 2016 Elsevier Inc. All rights reserved.

Chemical References

• Antihypertensive Agents
• Diuretics
• Amlodipine
• Lisinopril
• Chlorthalidone

Topics

• Aged
• Amlodipine (administration & dosage, therapeutic use)
• Antihypertensive Agents (administration & dosage, therapeutic use)
• Blood Pressure (drug effects)
• Cardiovascular Diseases (etiology)
• Chlorthalidone (administration & dosage, therapeutic use)
• Diuretics (administration & dosage, therapeutic use)
• Drug Therapy, Combination
• Female
• Humans
• Hypertension (complications, drug therapy)
• Lisinopril (administration & dosage, therapeutic use)
• Male
• Treatment Failure
• Treatment Outcome