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Ideas and Opinions |

ALLHAT: Setting the Record Straight

Barry R. Davis, MD, PhD; Curt D. Furberg, MD, PhD; Jackson T. Wright Jr., MD, PhD; Jeffrey A. Cutler, MD, MPH; Paul Whelton, MD, MSc, the ALLHAT Collaborative Research Group
[+] Article and Author Information

From The University of Texas Health Science Center at Houston School of Public Health, Houston, Texas; Wake Forest University School of Medicine, Winston-Salem, North Carolina; Case Western Reserve University, Cleveland, Ohio; Division of Epidemiology and Clinical Applications, National Heart, Lung, and Blood Institute, Bethesda, Maryland; and Tulane University Health Sciences Center, New Orleans, Louisiana.


Grant Support: By the National Heart, Lung, and Blood Institute (contract N01-HC-35130). The ALLHAT investigators received study medications from Pfizer (amlodipine and doxazosin), AstraZeneca (atenolol and lisinopril), and Bristol-Myers Squibb (pravastatin) and financial support from Pfizer.

Potential Financial Conflicts of Interest:Consultancies: J.T. Wright Jr. (Astra, Aventis, Bayer, Bristol-Myers Squibb, Merck & Co., Novartis Pharma AG, Pfizer, Phoenix Pharmaceuticals, Searle & Co., SmithKline Beecham, Solvay/Unimed); Honoraria: B.R. Davis (Pfizer), J.T. Wright Jr. (Astra, Aventis, Bayer, Bristol-Myers Squibb, Merck & Co., Novartis Pharma AG, Pfizer, Phoenix Pharmaceuticals, Searle & Co., SmithKline Beecham, Solvay/Unimed), P. Whelton (Pfizer); Grants received: J.T. Wright Jr. (Astra, Aventis, Bayer, Bristol-Myers Squibb, Eli Lilly & Co., Merck & Co., Novartis Pharma AG, Pfizer, Searle & Co., SmithKline Beecham, Solvay/Unimed); J.A. Cutler (Pfizer, AstraZeneca, Bristol-Myers Squibb).

Requests for Single Reprints: Barry R. Davis, MD, PhD, The University of Texas Health Science Center at Houston School of Public Health, 1200 Herman Pressler Street, Suite E801, Houston, TX 77030; e-mail, bdavis@sph.uth.tmc.edu.

Current Author Addresses: Dr. Davis: The University of Texas Health Science Center at Houston School of Public Health, 1200 Herman Pressler Street, Suite E801, Houston, TX 77030.

Dr. Furberg: Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 57157-1063.

Dr. Wright: Case Western Reserve University, General Clinical Research Center, Horvitz Tower, Suite 7311, 11100 Euclid Avenue, Cleveland, OH 44106-5041.

Dr. Cutler: National Heart, Lung, and Blood Institute, Division of Epidemiology and Clinical Applications, 6701 Rockledge Drive, Room 8130, Bethesda, MD 20892-7936.

Dr. Whelton: Tulane University Health Sciences Center, 1440 Canal Street TW-5, Suite 2400, New Orleans, LA 70112.


Ann Intern Med. 2004;141(1):39-46. doi:10.7326/0003-4819-141-1-200407060-00013
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The findings of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) have generated worldwide reaction from clinicians and researchers, including a recent commentary in this journal. Such response was expected for a trial of ALLHAT's size and scope, especially since its results challenged some widely held beliefs. This paper reviews key aspects of the ALLHAT design, analyses, findings, and conclusions to provide a perspective on the commentary about the trial's results and implications for clinical practice. Several of the most frequent comments regarding the study's results are addressed, particularly with respect to heart failure and diabetes outcomes. Responses to these comments reinforce the investigators' original conclusion that thiazide-type diuretics should remain the preferred first-step drug class for treating hypertension and should generally be a part of any multidrug regimen.

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Response to Letter "ACE-Inhibitors and diuretics, optimal combination therapy"
Posted on September 15, 2004
Barry R. Davis
University of Texas - Houston, School of Public Health
Conflict of Interest: None Declared

We thank Dr. Krantz for his thoughtful letter (1). The proposed strategy of using a diuretic and ACE inhibitor simultaneously is supported by the effects of combined treatment in the PROGRESS trial (2), but that study could also be (and was) interpreted as showing that it's the blood pressure that matters, especially for stroke, and blood pressure reduction is much more effective with a diuretic in the regimen. Although, in theory, the use of ACE inhibitors could offset the metabolic effects (higher glucose, lower potassium) of thiazides, other potassium-sparing regimens may be just as or more effective, and a randomized trial to compare such regimens would be valuable. In addition, minimizing the metabolic effects would not necessarily translate into lower rates of important clinical outcomes, including coronary heart disease, stroke, and heart failure. Therefore, an events trial is also needed to test initiating treatment with different two-drug combinations wherein one of the medications is a thiazide diuretic.

References:

1. Krantz, Mori. ACE-Inhibitors and diuretics, optimal combination therapy [Letter]. Annals of Internal Medicine. 2004.

2. Chapman N, Huxley R, Anderson C, Bousser MG, Chalmers J, Colman S, et al. Effects of a perindopril-based blood pressure-lowering regimen on the risk of recurrent stroke according to stroke subtype and medical history: the PROGRESS Trial. Stroke. 2004;35:116-21. [PMID: 14671247]

Conflict of Interest:

Potential Financial Conflicts of Interest: Honoraria: PK Whelton (Pfizer), JT Wright (Astra, Aventis, Bayer, Bristol Myers Squibb, Merck & Co., Novartis Pharma AG, Pfizer, Phoenix Pharmaceuticals, Searle & Co., SmithKline Beechham, Solvay/Unimed); Grants received: JA Cutler (Pfizer, AstraZeneca, Bristol-Myers Squibb, JT Wright (AstraZeneca, Aventis, Bayer, Bristol-Myers Squibb, Eli Lilly & Co., Merck & Co., Novartis Pharma AG, Pfizer, Searle & Co., SmithKline Beechham, Solvay/Unimed); Consulting Fees: JT Wright (Astra, Aventis, Bayer, Bristol Myers Squibb, Merck & Co., Novartis Pharma AG, Pfizer, Phoenix Pharmaceuticals, Searle & Co., SmithKline Beechham, Solvay/Unimed)

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