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Characteristics and Long-Term Follow-Up of Participants with Peripheral Arterial Disease During ALLHAT

Journal of General Internal Medicine volume 29, pages 1475–1483 (2014)Cite this article

A Capsule Commentary to this article was published on 05 August 2014

ABSTRACT

Background

Hypertension is a major risk factor for peripheral artery disease (PAD). Little is known about relative efficacy of antihypertensive treatments for preventing PAD.

Objectives

To compare, by randomized treatment groups, hospitalized or revascularized PAD rates and subsequent morbidity and mortality among participants in the Antihypertensive and Lipid-Lower Treatment to Prevent Heart Attack Trial (ALLHAT).

Design

Randomized, double-blind, active-control trial in high-risk hypertensive participants.

Participants

Eight hundred thirty participants with specified secondary outcome of lower extremity PAD events during the randomized phase of ALLHAT.

Interventions/events

In-trial PAD events were reported during ALLHAT (1994–2002). Post-trial mortality data through 2006 were obtained from administrative databases. Mean follow-up was 8.8 years.

Main Measures

Baseline characteristics and intermediate outcomes in three treatment groups, using the Kaplan-Meier method to calculate cumulative event rates and post-PAD mortality rates, Cox proportional hazards regression model for hazard ratios and 95 % confidence intervals, and multivariate Cox regression models to examine risk differences among treatment groups.

Key Results

Following adjustment for baseline characteristics, neither participants assigned to the calcium-channel antagonist amlodipine nor to the ACE-inhibitor lisinopril showed a difference in risk of clinically advanced PAD compared with those in the chlorthalidone arm (HR, 0.86; 95 % CI, 0.72–1.03 and HR, 0.98; 95 % CI, 0.83–1.17, respectively). Of the 830 participants with in-trial PAD events, 63 % died compared to 34 % of those without PAD; there were no significant treatment group differences for subsequent nonfatal myocardial infarction, coronary revascularizations, strokes, heart failure, or mortality.

Conclusions

Neither amlodipine nor lisinopril showed superiority over chlorthalidone in reducing clinically advanced PAD risk. These findings reinforce the compelling need for comparative outcome trials examining treatment of PAD in high-risk hypertensive patients. Once PAD develops, cardiovascular event and mortality risk is high, regardless of type of antihypertensive treatment.

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ACKNOWLEDGMENTS

The authors thank Dr. Ellen Breckenridge, The University of Texas School of Public Health, for editorial assistance in the preparation of this manuscript.

Funding

This research was supported by contracts NO1-HC-35130 and HHSN268201100036C from the National Heart, Lung, and Blood Institute. The ALLHAT investigators acknowledge contributions of study medications supplied by Pfizer, Inc. (amlodipine and doxazosin), AstraZeneca (atenolol and lisinopril), and Bristol-Myers Squibb (pravastatin) and financial support provided by Pfizer, Inc.

Prior Presentations

None

Conflict of Interest

Dr. Basil has received honoraria from Daiichi Sankyo and Takeda.

Dr. Probstfield has received research support from GlaxcoSmithKline and Sanofi Aventis.

Dr. Rahman has received honoraria from Boehringer Ingelheim.

Drs. Baraniuk, Dart, Davis, Ellsworth, Fendley, Habib, Piller, Simpson, and Whelton have no financial interests to disclose.

Author information

Affiliations

  1. The University of Texas School of Public Health, 1200 Herman Pressler St., W-906, Houston, TX, 77030, USA

    Linda B. Piller MD, MPH, Lara M. Simpson PhD, Sarah Baraniuk PhD & Barry R. Davis MD, PhD

  2. Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, USA

    Gabriel B. Habib MD

  3. University Hospitals Case Medical Center, Louis Stokes Cleveland VA Medical Center, Case Western Reserve University, Cleveland, OH, USA

    Mahboob Rahman MD

  4. Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC, USA

    Jan N. Basile MD

  5. Marshfield Clinic Research Foundation, Marshfield, WI, USA

    Richard A. Dart MD

  6. University of Washington, Seattle, WA, USA

    Allan J. Ellsworth PharmD

  7. AHEC Family Practice Center, Pine Bluff, AR, USA

    Herbert Fendley MD

  8. Division of Cardiology, University of Washington School of Medicine, Seattle, WA, USA

    Jeffrey L. Probstfield MD

  9. Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA

    Paul K. Whelton MB., MD, MSc.

Authors
  1. Linda B. Piller MD, MPH
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  2. Lara M. Simpson PhD
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  3. Sarah Baraniuk PhD
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  4. Gabriel B. Habib MD
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  5. Mahboob Rahman MD
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  6. Jan N. Basile MD
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  7. Richard A. Dart MD
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  8. Allan J. Ellsworth PharmD
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  9. Herbert Fendley MD
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  10. Jeffrey L. Probstfield MD
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  11. Paul K. Whelton MB., MD, MSc.
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  12. Barry R. Davis MD, PhD
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Consortia

for the ALLHAT Collaborative Research Group

Corresponding author

Correspondence to Linda B. Piller MD, MPH.

Additional information

Clinical Trial Registration

www.clinicaltrials.gov NCT00000542

For a complete list of members of the ALLHAT Collaborative Research Group, see JAMA 2002;288:2981–2997.

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Cite this article

Piller, L.B., Simpson, L.M., Baraniuk, S. et al. Characteristics and Long-Term Follow-Up of Participants with Peripheral Arterial Disease During ALLHAT. J GEN INTERN MED 29, 1475–1483 (2014). https://doi.org/10.1007/s11606-014-2947-1

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KEY WORDS

  • cardiovascular disease
  • hypertension
  • clinical trials