Eugene Braunwald: Maestro Of American Cardiology pg. 6
But his devotion to cardiovascular research never wavered.
The next frontier
By the end of the 1970s, the injection by catheter of a thrombolytic (clot-busting) agent, streptokinase, into blocked coronary arteries was just beginning to take hold. In 1981, Braunwald’s team showed for the first time that when streptokinase was used in this manner to open blocked arteries, myocardial tissue threatened during an AMI could be salvaged by restoring the supply of oxygen-laden blood.
The question then became how to administer these thrombolytic drugs intravenously, so that patients could receive medication as quickly as possible, even away from the hospital—in an ambulance, if possible. Streptokinase worked fine when given through an intracoronary catheter, but it performed poorly as an intravenous therapy.
In the early 1980s, a new class of recombinant-DNA drugs was developed, including the thrombolytic agent, tissue plasminogen activator (tPA), which was effective when delivered intravenously. Braunwald was certain that tPA and the concept of on-site, immediate treatment of evolving AMI was the next frontier, and he prevailed on the NIH to let him set up a clinical trials network to test this theory.
In 1984, he established the first TIMI (Thrombolysis in Myocardial Infarction) study, which found that intravenous tPA was indeed superior to streptokinase in opening occluded arteries. With more than 800 sites in 46 countries participating in subsequent TIMI studies, today Braunwald is viewed as one of the world’s masters of the clinical trial.
“Ask anybody who’s ever worked for Dr. Braunwald. The best work you’ll ever do is when he is standing behind you, looking over your shoulder,” says Marc Pfeffer, M.D., Ph.D., professor of Medicine at Brigham and Women’s Hospital. “He sets high standards, but he lives by those standards, too.”
Pfeffer and his late wife, Janice Pfeffer, Ph.D., came to Boston in the mid-1970s to pursue studies of left ventricular enlargement (also called hypertrophy), associated with systemic hypertension and by AMI with Braunwald.
By the early 1980s, they had established that captopril, an angiotensin converting enzyme (ACE) inhibitor, developed to control hypertension, also reversed hypertrophy and improved cardiac performance and survival in rats with MI. Their findings led to the Survival and Ventricular Enlargement (SAVE) clinical trial, which in 1992 showed that ACE inhibitors improved the left ventricular function and reduced mortality in patients who’d suffered a major heart attack.
Today, ACE inhibition is routinely recommended for patients following an MI, and is given to millions of such patients worldwide each year.
By 1988, doctors knew that patients with elevated low-density lipoprotein (LDL) cholesterol tended to be at risk for recurrent MI. In another study, the Cholesterol and Recurrent Events (CARE) trial, Braunwald and his colleagues studied whether heart attack patients with “average” cholesterol levels (at the time, 210 milligrams per deciliter of blood), also would benefit from taking cholesterol-lowering drugs.
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