Australian National Blood Pressure Study Group - ANBP2


The goal of the trial was to compare outcomes with use of ACE inhibitors vs diuretics among elderly hypertensive patients.

Study Design

Study Design:

Patients Screened: 54,288
Patients Enrolled: 6,083
Mean Follow Up: median 4.1 years
Mean Patient Age: 65-84 years
Female: 51

Patient Populations:

Average SBP of at least 160 mm Hg or average DBP of at least 90 mm Hg (if SBP was at least 140 mm Hg); absence of recent cardiovascular events in prior 6 months


Life-threatening illness, contraindication to an ACE inhibitor or diuretic, a plasma creatinine concentration of > 2.5 mg/dL, malignant hypertension, or dementia

Primary Endpoints:

All cardiovascular events or death from any cause. All cardiovascular events defined as MI, coronary events associated with therapeutic procedures involving the coronary arteries, heart failure, acute occlusion of a major feeding artery in any vascular bed other than cerebral or coronary, dissecting or ruptured aortic aneurysm, stroke or TIA

Secondary Endpoints:

First cardiovascular event; individual components of composite

Drug/Procedures Used:

Patients were randomized to either open-label ACE inhibitor therapy (n=3,044) or diuretic therapy (n=3,039). The ACE inhibitor enalapril and the diuretic hydrochlorothiazide were recommended as initial therapy; however, the choice of the specific agent and dose was made by the family practitioner. The goal the reduction was SBP by at least 20 mm Hg to less than 160 mm Hg, with a further reduction to less than 140 mm Hg if tolerated, and a reduction of DBP by at least 10 mm Hg to less than 90 mm Hg, with a further reduction to less than 80 mm Hg.

Concomitant Medications:

Calcium-channel blockers (22.9% in ACE arm and 24.9% in diuretic arm), beta-blockers (10.8% and 13.7%, respectively), and angiotensin-receptor blockers (14.0% and 12.4%, respectively).

Principal Findings:

At the end of the study, 58% of subjects randomized to the ACE-inhibitor arm and 62% randomized to the diuretic arm were still receiving the assigned treatment. Blood pressure decreased by 20/9 mm Hg in the ACE arm and 22/9 mm Hg in the diuretic arm by year 1; by 23/10 mm Hg in the ACE arm and 24/10 mm Hg in the diuretic arm by year 2; and by 26/12 mm Hg in both groups by year 5. The primary endpoint, all cardiovascular events or death from any cause, was lower in the ACE-inhibitor group vs the diuretic group (Hazard ratio 0.89, 95% CI 0.79 to 1.00, p=0.05). The benefit was observed in the male subset of patients (HR 0.83, 95% CI 0.71 to 0.97, p=0.02) but was not evident in female patients (HR 1.00, 95% CI 0.83 to 1.21, p=0.98). Similar results were observed for the secondary endpoint of first cardiovascular events, with a benefit in the ACE arm vs the diuretic arm (HR 0.88, 95% CI 0.77 to 1.01, p=0.07) as well as with the first MI endpoint (HR 0.68, 95% CI 0.47 to 0.98, p=0.04). Mortality did not differ between the arms (HR 0.90, 95% CI 0.75–1.09, p=0.27).


Among elderly patients with hypertension, treatment with ACE inhibitors was associated with a benefit in the composite of all-cause death or cardiovascular events at 4 year follow-up. Substudy analysis showed the benefit was only observed in male patients; no benefit occurred in female patients. However, this was a post-hoc analysis and should be interpreted as such. The results of the ANBP2 trial differ from the recently published ALLHAT trial, which reported no difference in the primary endpoint between the diuretic arm and the ACE inhibitor arm. However, there were several differences in both the agents studied (enalapril vs lisinopril and hydrochlorothiazide vs chlorthalidone) and the primary and secondary endpoints. Patients in the ANBP2 trial, while older, had lower baseline risk factors compared with other trials of the elderly: 8% had prior coronary event, 5% had previous cerebrovascular disease, and 7% had diabetes. While randomized, the ANBP2 trial was open label, a limitation of the trial.


N Engl J Med 2003;348:583-592.

Clinical Topics: Prevention, Vascular Medicine, Statins, Hypertension

Keywords: Lisinopril, Enalapril, Chlorthalidone, Cerebrovascular Disorders, Diuretics, Blood Pressure, Hydrochlorothiazide, Hypertension, Diabetes Mellitus

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