Trail of research that led to discovery of aspirin's role in prevention of first heart attack

Charles H. Hennekens, M.D., DrPH, the first Sir Richard Doll Research Professor as well as first recipient of an endowed chair in the new Charles E. Schmidt College of Medicine at Florida Atlantic University, has published a Citation Classic in the current issue of Clinical Chemistry. Hennekens was the founding principal investigator (PI) of the landmark Physician's Health Study and was the first to demonstrate that aspirin prevents a first heart attack. He was also the first to demonstrate that aspirin prevents heart attacks, strokes, and cardiovascular deaths when given within 24 hours after onset of symptoms of a heart attack as well as to a wide variety of patients who have survived an event associated with a blockage in the heart, brain, or legs. In this Citation Classic in Clinical Chemistry, 24 years after his seminal publication in the New England Journal of Medicine, Hennekens discusses the trail of research to his first discovery that aspirin prevents a first heart attack when he was the first Eugene Braunwald Professor of Medicine at Harvard Medical School and first Chief of Preventive Medicine at Brigham and Women's Hospital, as well as all the subsequent research that has confirmed his initial landmark finding.

Hennekens points out that since his first discovery from the Physician's Health Study of 22,071 apparently healthy men funded by the U.S. National Institutes of Health (NIH), there have been five additional large scale randomized trials worldwide, which include more than 90,000 men and women to confirm the conclusive benefit of aspirin to reduce the risk of a first heart attack by approximately one third. He served as the founding PI of the largest of these trials, the Women's Health Study of 39,972 apparently healthy female health professionals, which also was funded by the NIH.

"Any decision to use aspirin to prevent a first heart attack should be an individual judgment by the health care provider that weighs the clear benefit of reducing the risk of a first heart attack against the side effects of increased bleeding," said Hennekens.

Hennekens believes aspirin has a net benefit for those with a 10-year risk of a first heart attack of 10 percent or more. In fact, the American Heart Association guidelines support his conclusions regarding the role of aspirin in the prevention of a first heart attack. He also points out that 40 percent of Americans have metabolic syndrome, a constellation of obesity, high blood pressure, abnormal blood lipids and insulin resistance, a precursor of diabetes. According to Hennekens, patients with metabolic syndrome have a 10-year risk of a first heart attack of 16 to18 percent.

"My chief motivation to pursue preventive cardiovascular medicine in my career was the premature death of my father from sudden cardiac death," said Hennekens. "While death is inevitable premature death is not."

According to Science Watch, Hennekens was the third most widely cited medical researcher in the world from 1995-2005, and five of the top 20 were his former trainees and/or fellows.

It has been estimated that the research of Hennekens, which includes, but is not limited to, his seminal contributions to randomized trials of aspirin as well as statins, angiotensin converting enzyme inhibitors and beta adrenergic blockers has contributed to the avoidance of 1,159,461 premature deaths worldwide.

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