Hypertension Online Slides - VA Cooperative Study, reserpine, hydralazine

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Browsing Talk: The Veterans Administration Cooperative Study on Antihypertensive Agents
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The Veterans Administration Cooperative Study on Antihypertensive Agents

The Veterans Administration Cooperative Study on Antihypertensive Agents

VA Cooperative Study

The VA Cooperative Study, 1967

The Veterans Administration Cooperative Study on Antihypertensive Agents

hydralazine | antihypertensive therapy | diastolic blood pressure | diuretic | hydrochlorothiazide | reserpine | VA Cooperative Study

The VA Cooperative Study was begun at a time when it was not know whether hypertension therapy was beneficial, of no value, or possibly even harmful. Freis and his VA Cooperative Study Group colleagues designed the first adequately powered placebo-controlled, randomized clinical trial of drug treatment in patients with hypertension. Understandably, they selected patients with fairly severe hypertension—diastolic blood pressures of 115-129 mmHg—for this landmark demonstration study. Active treatment included hydrochlorothiazide, reserpine, and hydralazine hydrochloride. The study was terminated prematurely after only one and a half years because of clear evidence of benefit of treatment and excessive, rapid mortality in the placebo group. This landmark finding precluded any future placebo controlled trials in patients with severe hypertension.

The VA Cooperative Study, 1967: Change in Systolic and Diastolic Blood Pressure

The Veterans Administration Cooperative Study on Antihypertensive Agents

hydralazine | antihypertensive therapy | blood pressure | diuretic | hydrochlorothiazide | reserpine | VA Cooperative Study

Changes in blood pressure during treatment in the two study arms of the VA Cooperative Study are depicted above. Patients receiving placebo were far more likely to experience a rise in blood pressure and far less likely to have a reduction in blood pressure than those receiving active treatment. In those assigned to active therapy, blood pressure fell on average by 43/30 mmHg.

The VA Cooperative Study, 1967: Assessable Morbid/Fatal Events

The Veterans Administration Cooperative Study on Antihypertensive Agents

hydralazine | antihypertensive therapy | diuretic | hydrochlorothiazide | hypertension | reserpine | VA Cooperative Study

During an average of 11 months of follow-up (2–16 months), far more hypertension-related events occurred in the placebo treated group than in those assigned to active therapy in the VA Cooperative Study. Most notable was the reduction in incidence of accelerated hypertension (12 vs 0).

The VA Cooperative Study, 1967: Conclusions

The Veterans Administration Cooperative Study on Antihypertensive Agents

hydralazine | antihypertensive therapy | diastolic blood pressure | diuretic | hydrochlorothiazide | reserpine | VA Cooperative Study

The VA Cooperative Study documented that treatment of severe diastolic hypertension could reduce risk for hypertension-related complications. Although the sample size was small and the follow-up was short, the risk for complications was exquisitely high and the design of the study was sufficiently rigorous to provide a definitive answer.

The VA Cooperative Study, 1970

The Veterans Administration Cooperative Study on Antihypertensive Agents

hydralazine | diabetes mellitus | diuretic | hydrochlorothiazide | hypertension | reserpine | VA Cooperative Study

The second VA Cooperative Study* involved longer-term follow-up of men with mild-to-moderate hypertension (diastolic blood pressure 90–114 mmHg). As anticipated, because of the lower risks associated with mild-to-moderate hypertension, the study sample was larger (n=380) and the follow-up far longer (mean 3.8 years) than in the earlier VA trial.

*this cohort and the severe hypertension cohort reported in 1967 were actually recruited simultaneously and subsequently separated.

The VA Cooperative Study, 1970: Assessable Morbid/Fatal Events

The Veterans Administration Cooperative Study on Antihypertensive Agents

hydralazine | antihypertensive therapy | congestive heart failure | diuretic | hydrochlorothiazide | reserpine | stroke | VA Cooperative Study

In the second VA Cooperative Study* of patients with mild-to-moderate hypertension, those randomized to active therapy experienced fewer morbid and fatal events than those receiving placebo. Most remarkable was the reduction in those on active therapy compared to placebo in stroke (5 vs 20 events, respectively) and congestive heart failure (0 vs 11 events, respectively).

*this cohort and the severe hypertension cohort reported in 1967 were actually recruited simultaneously and subsequently separated.

The VA Cooperative Study, 1970: Conclusions

The Veterans Administration Cooperative Study on Antihypertensive Agents

hydralazine | antihypertensive therapy | diastolic blood pressure | diuretic | hydrochlorothiazide | reserpine | VA Cooperative Study

In the second VA Cooperative Study* of patients with mild-to-moderate hypertension, Freis and colleagues once again demonstrated the benefits of hypertension treatment. They extended the results of the first VA Cooperative Study to patients with less severe diastolic hypertension.

*this cohort and the severe hypertension cohort reported in 1967 were actually recruited simultaneously and subsequently separated.

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