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Cardiologist Tests Theory that DNA Can Determine Drug Effects

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Posted: 5/10/2004

COLUMBUS, Ohio – An Ohio State University Medical Center cardiologist is poised to take the final step in testing his theory that the presence of a particular gene makes the difference in how patients with coronary artery disease respond to anti-platelet medication.

The results could lead to the ability to personalize patient-care strategies in the roughly 30 percent of Americans with heart disease who carry the gene, a goal of the burgeoning field of pharmacogenomics.

Dr. Glen Cooke, a cardiologist and researcher in the Davis Heart and Lung Research Institute at OSU Medical Center, is leading a clinical trial of 2,500 patients to determine which of two medication options produces the best response in patients who have undergone stent placement to open narrowed vessels caused by disease.

Patients will be randomized to receive one of two accepted anti-platelet drugs – aspirin or clopidogrel – and monitored for a year to see how they respond to the medication.

“We already know people with this gene don’t do well without medication and are at risk for complications after the placement of a stent,” Cooke said. “By monitoring how patients do in this trial, we can demonstrate the link between genetics and response to medication, advancing the concept of tailoring therapies more specifically and identifying patients at risk for disease, all based on their DNA.

“I think this approach, pharmacogenomics, represents the future of medicine.”

People with stents receive drugs to reduce the clumping action of platelets in the blood to avoid the risk for more clots. Aspirin has emerged as one of the most effective anti-platelet drugs in protecting people from developing heart attacks and reducing death rates in patients who develop heart attacks, and in preventing excessive tissue growth, or restenosis, when used in combination with clopidogrel in arteries in which stents have been placed.

But other drugs also have anti-platelet qualities, and patients’ genetics likely influence which drugs work best in which patients.

Cooke linked the existence of the altered gene in question, called the PlA2 polymorphism, to aspirin’s beneficial effects on the heart in 1998, when he was a postdoctoral researcher at Ohio State. He and colleagues later associated the gene with complications following stent placement in people with coronary artery disease. This study will complete the process of devising the best anti-platelet strategies in heart patients carrying the PlA2 gene, Cooke said.

Enrollment for the study is expected to begin this spring. Cooke’s trial is funded by a $650,000 career development grant from the National Institutes of Health.

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Emily Caldwell
Medical Center Communications

Basic Research; Clinical/Translational Research; Heart Disease; Ross Heart Hospital; Stroke