Randomized, Double-Blind Multicenter Comparison of Hydrochlorothiazide, Atenolol, Nitrendipine, and Enalapril in Antihypertensive Treatment - HANE


HANE was a multicenter, randomized, double-blind comparison of four different antihypertensive medications for single-agent control of blood pressure.


The antihypertensive medications hydrochlorothiazide, atenolol, nitrendipine, and enalapril will have different effects on blood pressure when used as single agents.

Study Design

Study Design:

Patients Screened: 1,218
Patients Enrolled: 868
Mean Follow Up: 48 weeks
Mean Patient Age: 21-70
Female: 45

Patient Populations:

Outpatients from 21 to 70 years of age with resting diastolic blood pressure of 95-120 mm Hg


Contraindication to any study drug, congestive heart failure, atrioventricular block, sick sinus syndrome, sinus bradycardia (<50 bpm), pregnancy, known renovascular hypertension, known intolerance to a study drug, myocardial infarction in the last six months, concomitant use of any other drug with antihypertensive potency, hyperuricemia, hyperlipidemia, or diabetes requiring drug therapy, use of oral contraceptives, creatinine ≥150 μmol/l, hypokalemia <3.6 mmol/l, history or evidence of malignancy, or >30% overweight

Primary Endpoints:

Ability to reduce diastolic blood pressure below 90 mm Hg and the incidence of premature termination of treatment for medical reasons

Secondary Endpoints:

Effects of patient characteristics of age, gender, and blood pressure before treatment on outcomes

Drug/Procedures Used:

Patients were randomized to four groups: hydrochlorothiazide, atenolol, nitrendipine, and enalapril. The first eight weeks of the trial were a dose titration phase. Patients were initially treated with hydrochlorothiazide 12.5 mg qd, atenolol 25 mg qd, nitrendipine 10 mg qd, or enalapril 5 mg qd.

If diastolic blood pressure was not reduced below 90 mm Hg within four weeks, doses were doubled to hydrochlorothiazide 25 mg qd, atenolol 50 mg qd, nitrendipine 20 mg qd, or enalapril 10 mg qd. If another two weeks failed to reduce diastolic blood pressure below 90 mm Hg, the drugs were doubled another time to hydrochlorothiazide 25 mg bid, atenolol 50 mg bid, nitrendipine 20 mg bid, or enalapril 10 mg bid. Patients who reached target blood pressure by the end of the eight-week titration phase were followed for an additional 40 weeks.

Concomitant Medications:

Any hypertensive medication used before the trial was discontinued.

Principal Findings:

The four treatment groups were well matched at baseline in terms of blood pressure, heart rate, age, gender, weight, and previous treatment. Of the initial 868 patients, 440 (50.7%) achieved goal blood pressure at the end of the eight-week titration phase. During this period, atenolol achieved goal blood pressure in significantly more patients than enalapril, hydrochlorothiazide, or nitrendipine (63.7% of patients vs. 50% vs. 44.7% vs 44.5%).

The 440 patients who achieved goal blood pressure at eight weeks were followed for an additional 40 weeks. After this period, only 324 patients were still below goal diastolic blood pressure of 90 mm Hg. Atenolol achieved goal blood pressure at 48 weeks in 48% of patients compared to 42.7% for enalapril, 35.4% for hydrochlorothiazide, and 32.9% for nitrendipine. At 48 weeks, atenolol was significantly better than hydrochlorothiazide and nitrendipine, but not enalapril.

Nitrendipine had a significantly increased dropout rate for adverse events (28 patients) at 48 weeks compared to atenolol (11 patients), enalapril (12 patients), and hydrochlorothiazide (9 patients).


Among hypertensive patients, treatment with atenolol was associated with improved diastolic blood pressure control at eight weeks compared to hydrochlorothiazide, enalapril, and nitrendipine. At 48 weeks, atenolol was associated with improved diastolic blood pressure control compared to hydrochlorothiazide and nitrendipine, but did not differ from enalapril. Nitrendipine had a higher incidence of adverse events compared to atenolol, hydrochlorothiazide, or enalapril.


Philipp T, Anlauf M, Distler A, Holzgreve H, Michaelis J, Wellek S. Randomised, double blind, multicentre comparison of hydrochlorothiazide, atenolol, nitrendipine, and enalapril in antihypertensive treatment: results of the HANE study. HANE Trial Research Group. BMJ 1997;315:154-9.

Clinical Topics: Prevention, Statins, Hypertension

Keywords: Nitrendipine, Enalapril, Diuretics, Blood Pressure, Hydrochlorothiazide, Heart Rate, Hypertension, Calcium Channel Blockers

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