Evidence Based Snapshots

The Journal of Informed Pharmacotherapy 2002;9:151

Major Cardiovascular Events in Hypertensive Patients Randomized to Doxazosin or Chlorthalidone - The Antihypertensive and Lipid-lowering Treatment to Prevent Heart Attack Trial (ALLHAT)

Reviewer: James McCormack, B.Sc. (Pharm), Pharm. D.
Reviewer's email address:
Reviewer's profession/specialty:
Professor, Faculty of Pharmaceutical Sciences, University of British Columbia

Original Citation

Major cardiovascular events in hypertensive patients randomized to doxazosin vs chlorthalidone: the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT). ALLHAT Collaborative Research Group. JAMA 2000;283:1967-75. PubMed Citation

Overall Study Question

These investigators evaluated the differences in long-term outcomes when hypertensive patients were treated with either doxazosin or chlorthalidone.


24,335 patients mean age 67 (47% women) with hypertension (>140/90) and at least one other coronary heart disease risk factor.


Chlorthalidone 12.5 or 25 mg po daily versus doxazosin 2,4, and 8 mg po daily. 


The doxazosin arm was stopped early after 3.3 years. 


Fatal and nonfatal MI (%) All deaths (%) CHD death, non-fatal MI, revascularization, and angina (%) CHF (%) Strokes (%)
Chlorthalidone 6.3 9.1 12 4.5 3.6
Doxazosin 6.3 9.6 13.1 8.1 4.2
Relative Risk Reduction NSS 8 44 31
Absolute Risk Reduction 1.1 3.6 0.6
NNT/NNH over 3.3 years 91 28 167

NNT = numbers needed to treat, NNH = numbers needed to harm, NSS = not statistically significant 

Systolic blood pressure was approximately 2-3 mmHg lower in the chlorthalidone group, thre was no difference in the diastolic blood pressure between groups.  Cholesterol was 0.2 mmol/L lower, potassium was 0.4 mmol/L higher, and mean serum glucose was 0.2 mmol/L lower in the doxazosin group.

How does this study contribute to the drug therapy of patients with hypertension?

This study shows that despite similar changes in surrogate markers, chlorthalidone patients had fewer CHD death, non-fatal, MI, revascularization, and angina (1.1% absolute difference), CHF (3.6 % absolute difference) and strokes (0.6% absolute difference) than patients treated with doxazosin.

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