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Metabolic and Clinical Outcomes in Non-Diabetic Individuals with the Metabolic Syndrome Assigned to Chlorthalidone, Amlodipine, or Lisinopril as Initial Treatment for Hypertension: A Report from the ALLHAT Study

¹ Rush Presbyterian-St. Luke's Medical Center, Chicago, Illinois (former); New York University School of Medicine, New York, New York
² University of Texas Health Science Center at Houston School of Public Health, Houston, Texas (former); Amgen, Thousand Oaks, California
³ Kaiser Permanente of Georgia, Tucker, Georgia
⁴ National Heart, Lung, and Blood Institute, Bethesda, Maryland (former); AstraZeneca, Wilmington, Delaware
⁵ University of Texas Health Science Center at Houston School of Public Health, Houston, Texas
⁶ University of Texas Health Science Center at Houston School of Public Health, Houston, Texas (former); Ottawa Hospital, Ottawa, Ontario, Canada
⁷ General Clinical Research Center, University Hospitals of Cleveland, Cleveland, Ohio
⁸ VAMC Charleston, Charleston, South Carolina
⁹ University of Southern California Medical Center, Los Angeles, California
¹⁰Loyola University School of Medicine, Maywood, Illinois
¹¹Marshfield Clinic, Marshfield, Wisconsin
¹²University of Oklahoma Health Sciences Center, VAMC, Oklahoma City, Oklahoma

Joshua.barzilay{at}kp.org

ABSTRACT

Objective: Optimal initial antihypertensive drug therapy in persons with the metabolic syndrome (MetS) is unknown.

Research Design and Methods: We conducted a subgroup analysis of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) to compare metabolic, cardiovascular (CV), and renal outcomes in individuals assigned to initial hypertension treatment with a thiazide-like diuretic (chlorthalidone [C]), a calcium channel blocker (amlodipine [A]), or an angiotensin converting enzyme inhibitor (lisinopril [L]), in non-diabetic persons with or without MetS.

Results: In participants with MetS, at 4 years of follow up, the incidence of new DM (FG 126 mg/dl) was 17.1% for C, 16.0% for A (p= 0.49, C vs. A) and 12.6% for L (p<0.05, L vs. C). For those without MetS, the rate of new DM was 7.7% for C, 4.2% for A and 4.7% for L (p<0.05 for both comparisons). There were no differences in relative risks (RR) for outcomes for A compared with C in those with MetS; in those without MetS there was a higher risk for heart failure (HF) (RR 1.55, 95% CI 1.25–1.35). For L compared with C, C was superior to L in those with MetS with respect to HF (1.31, 1.04–1.64) and combined CV disease (1.19, 1.07–1.32). No significant treatment group-MetS interactions were noted.

Conclusions: Despite a less favorable metabolic profile, thiazide-like diuretic initial therapy for hypertension offers similar, and in some instances possibly superior, CV disease outcomes in older hypertensive adults with MetS, as compared to treatment with CCBs and ACEI.

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