Safety After Fifty Evaluation - SAFE


Safety and tolerability of metoprolol and hydrochorothiazide in elderly.


To determine the short-term efficacy and tolerability of once-daily therapy with metoprolol alone or in combination with hydrochlorothiazide in the treatment of mild hypertension in patients 50 to 75 years of age.

Study Design

Patients Screened: 24,816
Patients Enrolled: 21,692
Mean Follow Up: 8 weeks
Mean Patient Age: 60
Female: 55.5

Patient Populations:

50 to 75 years of age
Newly diagnosed hypertension: diastolic BP between 90 and 104 mmHg and systolic BP ≤ 200 mmHg
Previously treated hypertension if therapy withdrawn before study entry


Angina requiring beta blocker therapy
Heart rate < 55 bpm
Heart block greater than first degree
Congestive heart failure
Bronchospastic disease
Cardiac pacemakers
Intolerance to beta blockers or sulfonamide therapy

Primary Endpoints:

Blood pressure

Secondary Endpoints:

Safety and tolerability

Drug/Procedures Used:

Metoprolol 100 mg qd; hydrochlorothiazide 25 mg qd added if necessary after 4 weeks.

Principal Findings:

Patients had a mean duration of 4.8 years of hypertension; 40.3% were newly diagnosed and 59.7% were previously treated.

At 4 weeks, mean systolic and diastolic blood pressures decreased from 162/95 to 148/87 mmHg (p < 0.001)

At 8 weeks, the mean blood pressure was 143/84 mmHg.

At the termination of the study, 50% of patients continued metoprolol monotherapy and 27% continued combined therapy with hydrochlorothiazide.

Forty patients died during the study; 25 of these deaths were due to cardiovascular or cerebrovascular causes.


Metoprolol, alone or in combination with hydrochlorothiazide, reduced blood pressure in elderly patients. Although declines in blood pressure have traditionally been the regulatory basis for approval for most antihypertensive agents, long-term clinical outcomes remain highly important.


1. Am Heart J 1988;116:301-4. Study design
2. J Am Geriatr Soc 1992;40:354-58. Final results

Clinical Topics: Heart Failure and Cardiomyopathies, Prevention, Statins, Hypertension

Keywords: Diuretics, Hydrochlorothiazide, Metoprolol, Hypertension, Systole

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