Major Cardiovascular Events in Hypertensive Patients Randomized to Doxazosin vs Chlorthalidone: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)
Bibliographic record
Abstract
ContextHypertension is associated with a significantly increased risk of morbidity and mortality. Only diuretics and β-blockers have been shown to reduce this risk in long-term clinical trials. Whether newer antihypertensive agents reduce the incidence of cardiovascular disease (CVD) is unknown.ObjectiveTo compare the effect of doxazosin, an α-blocker, with chlorthalidone, a diuretic, on incidence of CVD in patients with hypertension as part of a study of 4 types of antihypertensive drugs: chlorthalidone, doxazosin, amlodipine, and lisinopril.DesignRandomized, double-blind, active-controlled clinical trial, the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial, initiated in February 1994. In January 2000, after an interim analysis, an independent data review committee recommended discontinuing the doxazosin treatment arm based on comparisons with chlorthalidone. Therefore, outcomes data presented herein reflect follow-up through December 1999.SettingA total of 625 centers in the United States and Canada.ParticipantsA total of 24,335 patients (aged ≥55 years) with hypertension and at least 1 other coronary heart disease (CHD) risk factor who received either doxazosin or chlorthalidone.InterventionsParticipants were randomly assigned to receive chlorthalidone, 12.5 to 25 mg/d (n=15,268), or doxazosin, 2 to 8 mg/d (n=9067), for a planned follow-up of 4 to 8 years.Main Outcome MeasuresThe primary outcome measure was fatal CHD or nonfatal myocardial infarction (MI), analyzed by intent to treat; secondary outcome measures included all-cause mortality, stroke, and combined CVD (CHD death, nonfatal MI, stroke, angina, coronary revascularization, congestive heart failure [CHF], and peripheral arterial disease); compared by the chlorthalidone group vs the doxazosin group.ResultsMedian follow-up was 3.3 years. A total of 365 patients in the doxazosin group and 608 in the chlorthalidone group had fatal CHD or nonfatal MI, with no difference in risk between the groups (relative risk [RR], 1.03; 95% confidence interval [CI], 0.90-1.17; P=.71). Total mortality did not differ between the doxazosin and chlorthalidone arms (4-year rates, 9.62% and 9.08%, respectively; RR, 1.03; 95% CI, 0.90-1.15; P=.56.) The doxazosin arm, compared with the chlorthalidone arm, had a higher risk of stroke (RR, 1.19; 95% CI, 1.01-1.40; P=.04) and combined CVD (4-year rates, 25.45% vs 21.76%; RR, 1.25; 95% CI, 1.17-1.33; P<.001). Considered separately, CHF risk was doubled (4-year rates, 8.13% vs 4.45%; RR, 2.04; 95% CI, 1.79-2.32; P<.001); RRs for angina, coronary revascularization, and peripheral arterial disease were 1.16 (P<.001), 1.15 (P=.05), and 1.07 (P=.50), respectively.ConclusionOur data indicate that compared with doxazosin, chlorthalidone yields essentially equal risk of CHD death/nonfatal MI but significantly reduces the risk of combined CVD events, particularly CHF, in high-risk hypertensive patients.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.002 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.007 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".