VA Cooperative Study of antihypertensive treatment

Through the 1960s doctors argued over whether ordinary essential hypertension needed treating at all. The Framingham studies had tied high blood pressure to stroke, heart failure and heart attack, and the new thiazide diuretics, first chlorothiazide, then hydrochlorothiazide and chlorthalidone, lowered pressure in small studies. No trial had yet shown that lowering it prevented harm.

The Veterans Administration had added research to the work of its hospitals, and its cooperative program made a multicenter trial possible. Recruitment began in 1964. In the first phase, 143 veterans with severe hypertension, diastolic pressures of 115 to 129 mm Hg, received either placebo or a combination of hydrochlorothiazide, reserpine and hydralazine. Pressure in the treated men fell by an average of 43/30 mm Hg, and follow-up averaged about a year and a half.

The results appeared in JAMA on December 11, 1967. Four men in the placebo group died, against none on treatment. There were 27 serious complications in the placebo group and 2 in the treated group. They included progression to malignant hypertension with bleeding in the retina, strokes, heart attacks, heart failure and dissecting aneurysm, and the largest difference was in progression to accelerated or malignant hypertension. A 2016 history of hypertension treatment describes the study as the first adequately powered placebo-controlled trial of antihypertensive therapy and the first multicenter trial of hypertension treatment.

A second phase, begun at the same time, enrolled men with moderate hypertension, diastolic pressures of 90 to 115 mm Hg. Because the disease was milder it needed more patients and a longer follow-up, a mean of 3.8 years. Reported in 1970, it found fewer strokes and less heart failure in the treated group.