VA Cooperative Study on Hypertension

Background:

Cohort studies of cardiovascular disease epidemiology demonstrated conclusively in the 1950’s that elevated blood pressure was associated with cardiovascular risk, as had been known in clinical medicine for many years. Drugs that could effectively reduce blood pressure with adequate safety and tolerable side effects were not available, however, until the 1960’s. Ed Freis was a pioneer in developing and testing antihypertensive medications and utilized Veterans Administration facilities to lead a collaborative group in a pioneer series of trials.

The first VA Cooperative Study addressed hypertension at the severe level of diastolic pressure:115 through 129, and demonstrated a clear treatment effect. More relevant, however, to cardiovascular disease epidemiology and to mass prevention of hypertensive complications was a trial carried out in the late 1960’s with patients having diastolic blood pressure averaging 90 through 114 millimeters mercury, “mild to moderate hypertension.”

Methods and Design:

380 male hypertensive patients with diastolic pressures averaging 90 to 114 mm. Hg were randomly assigned to anti-hypertensive agents versus placebos and followed for an average of slightly more than three years, with a dropout rate of 15% due to developing more severe hypertension or intolerance to therapy. Design and randomization were appropriate and adherence to protocol was tested by fluorescence in the medications and by pill counts.

Results:

The estimated risk of developing a morbid event over a five-year period was reduced from 55% in the control group to 18% by treatment with combined thiazide diuretics and reserpine. Deaths were reduced from 35 in the control group to 9 in the treated group. 20 control patients developed serious hypertension of 125 mm Hg or higher compared to none in the treatment group. Treatment was more effective in preventing heart failure and stroke than coronary events and benefit was related to the level of pre-randomization blood pressure.

Conclusions:

The study for the first time demonstrated conclusively that anti-hypertensive therapy was effective and that side effects were generally tolerable. The higher the level of blood pressure the greater the benefit of therapy. Hypertensive complications of heart failure, stroke and renal failure were virtually eliminated by treatment, as was progression of hypertension. This study influenced the clinical and public health management of hypertension worldwide and initiated studies of systolic hypertension and studies in younger and older groups and throughout the range of hypertension, which have occupied cardiovascular disease epidemiology in recent decades. (HB)