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Hypertension. 2017 Jul;70(1):94-102. doi: 10.1161/HYPERTENSIONAHA.117.09221. Epub 2017 May 30.

Heterogeneity in Early Responses in ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial).

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1
From the Robert Wood Johnson Foundation Clinical Scholars Program (S.S.D., H.M.K.), Section of Cardiovascular Medicine (E.S.S., A.C.C., F.W., H.M.K.), Department of Internal Medicine, and Department of Obstetrics, Gynecology and Reproductive Sciences (X.X.), Yale School of Medicine, New Haven, CT; Department of Biostatistics (H.L.) and Section of Health Policy and Management (H.M.K.), Yale School of Public Health, New Haven, CT; Department of Mathematics, Yale University, New Haven, CT (R.R.C.); The Center for Outcomes Research and Evaluation, Yale New Haven Health, CT (C.H., E.S.S., A.C.C., F.W., S.-X.L., X.X., H.M.K.); Veterans Affairs Connecticut Healthcare System, West Haven (S.S.D.); Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC (C.D.F.); and University of Texas School of Public Health, Houston (B.R.D., S.L.P.).
2
From the Robert Wood Johnson Foundation Clinical Scholars Program (S.S.D., H.M.K.), Section of Cardiovascular Medicine (E.S.S., A.C.C., F.W., H.M.K.), Department of Internal Medicine, and Department of Obstetrics, Gynecology and Reproductive Sciences (X.X.), Yale School of Medicine, New Haven, CT; Department of Biostatistics (H.L.) and Section of Health Policy and Management (H.M.K.), Yale School of Public Health, New Haven, CT; Department of Mathematics, Yale University, New Haven, CT (R.R.C.); The Center for Outcomes Research and Evaluation, Yale New Haven Health, CT (C.H., E.S.S., A.C.C., F.W., S.-X.L., X.X., H.M.K.); Veterans Affairs Connecticut Healthcare System, West Haven (S.S.D.); Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC (C.D.F.); and University of Texas School of Public Health, Houston (B.R.D., S.L.P.). harlan.krumholz@yale.edu.

Abstract

Randomized trials of hypertension have seldom examined heterogeneity in response to treatments over time and the implications for cardiovascular outcomes. Understanding this heterogeneity, however, is a necessary step toward personalizing antihypertensive therapy. We applied trajectory-based modeling to data on 39 763 study participants of the ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) to identify distinct patterns of systolic blood pressure (SBP) response to randomized medications during the first 6 months of the trial. Two trajectory patterns were identified: immediate responders (85.5%), on average, had a decreasing SBP, whereas nonimmediate responders (14.5%), on average, had an initially increasing SBP followed by a decrease. Compared with those randomized to chlorthalidone, participants randomized to amlodipine (odds ratio, 1.20; 95% confidence interval [CI], 1.10-1.31), lisinopril (odds ratio, 1.88; 95% CI, 1.73-2.03), and doxazosin (odds ratio, 1.65; 95% CI, 1.52-1.78) had higher adjusted odds ratios associated with being a nonimmediate responder (versus immediate responder). After multivariable adjustment, nonimmediate responders had a higher hazard ratio of stroke (hazard ratio, 1.49; 95% CI, 1.21-1.84), combined cardiovascular disease (hazard ratio, 1.21; 95% CI, 1.11-1.31), and heart failure (hazard ratio, 1.48; 95% CI, 1.24-1.78) during follow-up between 6 months and 2 years. The SBP response trajectories provided superior discrimination for predicting downstream adverse cardiovascular events than classification based on difference in SBP between the first 2 measurements, SBP at 6 months, and average SBP during the first 6 months. Our findings demonstrate heterogeneity in response to antihypertensive therapies and show that chlorthalidone is associated with more favorable initial response than the other medications.

KEYWORDS:

antihypertensive agents; blood pressure; cardiovascular diseases; hypertension; precision medicine

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