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Evevident
Original paper
2002JAMACardiology

ALLHAT

Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)

RCTHypertension

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Overview

Chlorthalidone was at least as good as amlodipine or lisinopril for major CHD outcomes and better for several HF/stroke-related outcomes.

Clinical takeaway

ALLHAT supports thiazide-type diuretics, especially chlorthalidone, as a durable first-line option for uncomplicated hypertension, particularly when cost and outcomes matter.

Key result

No superiority of amlodipine or lisinopril over chlorthalidone for the primary CHD outcome.

Practice impact

Thiazide-type diuretics remain first-line antihypertensives for many patients.

Evidence

Study design

Randomized, double-blind, active-controlled trial.

Enrollment

33,357

Follow-up

Mean 4.9 years.

Geography

United States, Canada, Puerto Rico

Clinical question

Among high-risk patients with hypertension, are amlodipine or lisinopril superior to chlorthalidone for preventing fatal CHD or nonfatal MI?

Population

  • High-risk adults with hypertension and at least one additional CHD risk factor.

Intervention

Amlodipine or lisinopril.

Comparator

Chlorthalidone.

Primary outcome

Fatal CHD or nonfatal myocardial infarction.

Neither amlodipine nor lisinopril was superior to chlorthalidone for the primary coronary outcome, and chlorthalidone was better for several heart-failure and stroke outcomes.

Relative risk / 0.98 / CI 95% CI 0.90-1.07 (amlodipine vs chlorthalidone) / p=0.65

Key results

  • Primary outcome (fatal CHD or nonfatal MI): no difference. Amlodipine vs chlorthalidone RR 0.98 (95% CI 0.90-1.07); lisinopril vs chlorthalidone RR 0.99 (95% CI 0.91-1.08).
  • All-cause mortality did not differ between groups.
  • Heart failure was more frequent with amlodipine (6-year rate 10.2% vs 7.7%; RR 1.38; 95% CI 1.25-1.52).
  • Lisinopril had higher rates of combined CVD (RR 1.10), stroke (RR 1.15), and heart failure (RR 1.19) than chlorthalidone.

Harms

  • Heart failure was more frequent with amlodipine than chlorthalidone (RR 1.38; 95% CI 1.25-1.52).
  • Lisinopril was associated with more stroke, combined cardiovascular disease, and heart failure than chlorthalidone.
  • The doxazosin arm was stopped early for excess heart failure versus chlorthalidone.

Clinical Use

When to cite

  • When choosing initial drug therapy for uncomplicated hypertension, especially when explaining the outcome evidence behind thiazide-type diuretics.

Practice impact

  • Thiazide-type diuretics remain first-line antihypertensives for many patients.

Applicability

  • Most applicable to high-risk adults with hypertension and at least one additional CHD risk factor.
  • Supports thiazide-type diuretics as first-line therapy for uncomplicated hypertension.

Limitations

  • Doxazosin arm was stopped early and is often discussed separately.
  • Older high-risk population; results may not map perfectly to individualized modern comorbidity profiles.
  • Compared chlorthalidone specifically, whereas hydrochlorothiazide is more commonly prescribed.

Common misinterpretations

  • The alpha-blocker (doxazosin) finding is separate from the main three-drug comparison and should not be conflated with it.
  • ALLHAT does not mean thiazides are best for every patient; compelling indications such as CKD or heart failure may favor other agents.

Citation

ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA. 2002;288(23):2981-2997. doi:10.1001/jama.288.23.2981

Thiazide-type diuretics are superior in preventing 1 or more major forms of CVD and are less expensive. They should be preferred for first-step antihypertensive therapy.