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Cost-effectiveness of Chlorthalidone, Amlodipine, and Lisinopril as First-step Treatment for Patients with Hypertension: An Analysis of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)

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Abstract

Objective

To evaluate the cost-effectiveness of first-line treatments for hypertension.

Background

The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) found that first-line treatment with lisinopril or amlodipine was not significantly superior to chlorthalidone in terms of the primary endpoint, so differences in costs may be critical for optimizing decision-making.

Methods

Cost-effectiveness analysis was performed using bootstrap resampling to evaluate uncertainty.

Results

Over a patient’s lifetime, chlorthalidone was always least expensive (mean $4,802 less than amlodipine, $3,700 less than lisinopril). Amlodipine provided more life-years (LYs) than chlorthalidone in 84% of bootstrap samples (mean 37 days) at an incremental cost-effectiveness ratio of $48,400 per LY gained. Lisinopril provided fewer LYs than chlorthalidone in 55% of bootstrap samples (mean 7-day loss) despite a higher cost. At a threshold of $50,000 per LY gained, amlodipine was preferred in 50%, chlorthalidone in 40%, and lisinopril in 10% of bootstrap samples, but these findings were highly sensitive to the cost of amlodipine and the cost-effectiveness threshold chosen. Incorporating quality of life did not appreciably alter the results. Overall, no reasonable combination of assumptions led to 1 treatment being preferred in over 90% of bootstrap samples.

Conclusions

Initial treatment with chlorthalidone is less expensive than lisinopril or amlodipine, but amlodipine provided a nonsignificantly greater survival benefit and may be a cost-effective alternative. A randomized trial with power to exclude “clinically important” differences in survival will often have inadequate power to determine the most cost-effective treatment.

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Acknowledgement

This study was supported by contract NO1-HC-35130 with the National Heart, Lung, and Blood Institute (NHLBI). ALLHAT investigators received contributions of study medications supplied by Pfizer (amlodipine and doxazosin), AstraZeneca (atenolol and lisinopril), and Bristol-Myers Squibb (pravastatin), and financial support provided by Pfizer.

Conflict of Interest

Dr. Davis has worked as a consultant for Takeda, Merck, and Glaxo Smith Kline. Dr. Furberg has received honoraria from Berlex and Wyeth and worked on a research grant funded by Glaxo Smith Kline. Dr. Nwachuku is presently employed by AstraZeneca. The other authors report no conflicts.

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Authors and Affiliations

  1. VA Palo Alto Health Care System, Palo Alto, CA, USA

    Paul A. Heidenreich MD, MS

  2. Coordinating Center for Clinical Trials, University of Texas Houston School of Public Health, Houston, TX, USA

    Barry R. Davis MD, PhD, David R. Lairson PhD & Sara L. Pressel MS

  3. National Heart, Lung, and Blood Institute, Bethesda, MD, USA

    Jeffrey A. Cutler MD, MPH & Chuke Nwachuku MA, MPH, DrPH

  4. Wake Forest University, Winston-Salem, NC, USA

    Curt D. Furberg MD, PhD

  5. University of California at San Francisco, San Francisco, CA, USA

    Michael G. Shlipak MD, MPH

  6. College of Physicians and Surgeons, Columbia University, New York, NY, USA

    Lee Goldman MD

Authors
  1. Paul A. Heidenreich MD, MS
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  2. Barry R. Davis MD, PhD
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  3. Jeffrey A. Cutler MD, MPH
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  4. Curt D. Furberg MD, PhD
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  5. David R. Lairson PhD
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  6. Michael G. Shlipak MD, MPH
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  7. Sara L. Pressel MS
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  8. Chuke Nwachuku MA, MPH, DrPH
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  9. Lee Goldman MD
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Corresponding author

Correspondence to Sara L. Pressel MS.

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Heidenreich, P.A., Davis, B.R., Cutler, J.A. et al. Cost-effectiveness of Chlorthalidone, Amlodipine, and Lisinopril as First-step Treatment for Patients with Hypertension: An Analysis of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). J GEN INTERN MED 23, 509–516 (2008). https://doi.org/10.1007/s11606-008-0515-2

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  • DOI: https://doi.org/10.1007/s11606-008-0515-2

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