Major outcomes in high-risk hypertensive patients randomized to ACE inhibitor or calcium channel blocker vs diuretic

Original Citation

The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. 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;288:2981-97.

Overall Study Question

These investigators compared chlorthalidone, amlodipine and lisinopril for the treatment of hypertension. The primary outcome was combined fatal coronary heart disease (CHD) or non-fatal myocardial infarction. Secondary outcomes were all-cause mortality, stroke, combined CHD (primary outcome, coronary revascularization, or angina with hospitalization), and combined cardiovascular disease (combined CHD, stroke, treated angina without hospitalization, heart failure, and peripheral arterial disease).

Patients

33,357 patients with hypertension and 1 or more risk factors. Their mean age was 67.  47% were women, 36% had diabetes, 25% had a history of heart disease, 22% were smokers, and 12% had an HDL < 0.9 mmol/L.

Treatment

Patients were randomized in a blinded fashion to receive either chlorthalidone, amlodipine or lisinopril. Second line therapy was atenolol, clonidine or reserpine.

Duration

The mean duration of follow up was 4.9 years.

Results

Blood pressure differences at 5 years

Mean systolic blood pressures – amlodipine 0.8 mmHg higher than in the chlorthalidone group; lisinopril 2.0 mmHg higher than in the chlorthalidone group

Mean diastolic blood pressures – amlodipine 0.8 mmHg lower higher than in the chlorthalidone group, lisinopril no difference compared to the chlorthalidone group

* p <0.05 lisinopril vs. chlorthalidone

** p <0.05 lisinopril vs. amlodipine

*** p = 0.05 lisinopril vs. chlorthalidone, p = 0.06 amlodipine vs. chlorthalidone

# p = 0.06 amlodipine vs. chlorthalidone

Diabetic subset – Compared with chlorthalidone – Absolute numbers not provided
More stroke, more combined cardiovascular disease and more heart failure with lisinopril
More heart failure with amlodipine

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

This study suggests that, in terms of the the primary outcomes evaluated, there were no differences between chlorthalidone, amlodipine and lisinopril when used for the the treatment of hypertension.  However, chlorthalidone did produce a greater reduction in a number of secondary outcomes when compared to amlodipine and lisinopril.  This study confirms the abundance of previous other evidence that thiazide diuretics are the preferred first choice agents for hypertension in patients with hypertension including those patients with diabetes.

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