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. Henry R. Black, MD1,
  2. Barry Davis, MD, PHD2,
  3. Joshua Barzilay, MD3,
  4. Chuke Nwachuku, MA, MPH, DRPH4,
  5. Charles Baimbridge, MS2,
  6. Horia Marginean, MD, MS5,
  7. Jackson T. Wright, Jr., MD, PHD6,
  8. Jan Basile, MD7,
  9. Nathan D. Wong, PHD8,
  10. Paul Whelton, MD, MSC9,
  11. Richard A. Dart, MD10 and
  12. Udho Thadani, MD11
  1. 1New York University School of Medicine, New York, New York
  2. 2University of Texas Health Science Center at Houston School of Public Health, Houston, Texas
  3. 3Kaiser Permanente of Georgia, Tucker, Georgia
  4. 4National Heart, Lung, and Blood Institute, Bethesda, Maryland
  5. 5Ottawa Hospital, Ottawa, Ontario, Canada
  6. 6General Clinical Research Center, University Hospitals of Cleveland, Cleveland, Ohio
  7. 7VA Medical Center Charleston, Charleston, South Carolina
  8. 8University of Southern California Medical Center, Los Angeles, California
  9. 9Loyola University School of Medicine, Maywood, Illinois
  10. 10Marshfield Clinic, Marshfield, Wisconsin
  11. 11University of Oklahoma Health Sciences Center, VA Medical Center, Oklahoma City, Oklahoma
  1. 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

Abstract

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.

Footnotes

  • C.N. is currently affiliated with AstraZeneca, Wilmington, Delaware.

    Published ahead of print at http://care.diabetesjournals.org on 13 November 2007. DOI: 10.2337/dc07-1452. Clinical trial reg. no. NCT00000542, clinicaltrials.gov.

    Additional information for this article can be found in an online appendix at http://dx.doi.org/10.2337/dc07-1452.

    J.Bar. has received honoraria/consulting fees from Boehringer Ingelheim. J.Bas. has received honoraria/consulting fees from Astra-Zeneca, Novartis, Pfizer, and Sankyo. H.R.B. has received honoraria/consulting fees from Abbott Laboratories, Astra-Zeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daichi Sankyo, Forest Pharmaceuticals, Gilead (Myogen), GlaxoSmithKline, InterCure, Merck, Novartis, Pfizer, and sanofi aventis. B.D. has received honoraria/consulting fees from Biomarin, GlaxoSmithKline, Proctor and Gamble, and Takeda. C.N. is employed by Astra-Zeneca. U.T. holds stock in Bayer, has received financial support from Bristol-Myers Squib and Novartis, and has received honoraria/consulting fees from Pfizer and Sanofi Synthelabo. N.D.W. has received financial support from Merck and Pfizer and honoraria/consulting fees from Novartis, Pfizer, sanofi aventis, and Takeda. J.T.W. has received honoraria/consulting fees from GlaxoSmithKline, Novartis, Pfizer, and Sanofi Synthelabo and financial support from GlaxoSmithKline and Novartis.

    The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C Section 1734 solely to indicate this fact.

    • Accepted October 26, 2007.
    • Received July 26, 2007.
« Previous | Next Article »Table of Contents

This Article

  1. Published online before print November 13, 2007, doi: 10.2337/dc07-1452 Diabetes Care February 2008 vol. 31 no. 2 353-360
  1. » Abstract
  2. Full Text
  3. Full Text (PDF)
  4. Online-Only Appendix
  5. All Versions of this Article:
    1. dc07-1452v1
    2. 31/2/353 most recent

Current Issue

  1. November 2009, 32 (11)
  1. Current Issue
  1. Alert me to new issues of Diabetes Care