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Metabolic and Clinical Outcomes in Nondiabetic Individuals With the Metabolic Syndrome Assigned to Chlorthalidone, Amlodipine, or Lisinopril as Initial Treatment for Hypertension

A report from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)

¹ 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
³ Kaiser Permanente of Georgia, Tucker, Georgia
⁴ National Heart, Lung, and Blood Institute, Bethesda, Maryland
⁵ Ottawa Hospital, Ottawa, Ontario, Canada
⁶ General Clinical Research Center, University Hospitals of Cleveland, Cleveland, Ohio
⁷ VA Medical Center Charleston, Charleston, South Carolina
⁸ University of Southern California Medical Center, Los Angeles, California
⁹ Loyola University School of Medicine, Maywood, Illinois
¹⁰ Marshfield Clinic, Marshfield, Wisconsin
¹¹ University of Oklahoma Health Sciences Center, VA Medical Center, Oklahoma City, Oklahoma

Address correspondence and reprint requests to Joshua Barzilay, MD, Kaiser Permanente of Georgia, 200 Crescent Centre Pkwy, Tucker, GA 30084. E-mail: joshua.barzilay{at}kp.org

OBJECTIVE—Optimal initial antihypertensive drug therapy in people with the metabolic syndrome 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, and renal outcomes in individuals assigned to initial hypertension treatment with a thiazide-like diuretic (chlorthalidone), a calcium channel blocker (CCB; amlodipine), or an ACE inhibitor (lisinopril) in nondiabetic individuals with or without metabolic syndrome.

RESULTS—In participants with metabolic syndrome, at 4 years of follow-up, the incidence of newly diagnosed diabetes (fasting glucose 126 mg/dl) was 17.1% for chlorthalidone, 16.0% for amlodipine (P = 0.49, chlorthalidone vs. amlodipine) and 12.6% for lisinopril (P < 0.05, lisinopril vs. chlorthalidone). For those without metabolic syndrome, the rate of newly diagnosed diabetes was 7.7% for chlorthalidone, 4.2% for amlodipine, and 4.7% for lisinopril (P < 0.05 for both comparisons). There were no differences in relative risks (RRs) for outcomes with amlodipine compared with chlorthalidone in those with metabolic syndrome; in those without metabolic syndrome, there was a higher risk for heart failure (RR 1.55 [95% CI 1.25–1.35]). In comparison with lisinopril, chlorthalidone was superior in those with metabolic syndrome with respect to heart failure (1.31 [1.04–1.64]) and combined cardiovascular disease (CVD) (1.19 [1.07–1.32]). No significant treatment group–metabolic syndrome interaction was noted.

CONCLUSIONS—Despite a less favorable metabolic profile, thiazide-like diuretic initial therapy for hypertension offers similar, and in some instances possibly superior, CVD outcomes in older hypertensive adults with metabolic syndrome, as compared with treatment with CCBs and ACE inhibitors.

Abbreviations: ALLHAT, Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial • ARB, angiotensin receptor blocker • CCB, calcium channel blocker • CHD, coronary heart disease • CVD, cardiovascular disease • DBP, diastolic blood pressure • GFR, glomerular filtration rate • MI, myocardial infarction • SBP, systolic blood pressure

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