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

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.