DEFINITE ICD Clinical Study Results Appearing In New England Journal of Medicine; St. Jude Medical-Sponsored Study to be Presented at Heart Rhythm Society Meeting.

Business Editors/Health/Medical Writers

ST. PAUL, Minn.--(BUSINESS WIRE)--May 19, 2004

Patients with heart failure not due to coronary artery disease (non-ischemic) who received an implantable cardioverter defibrillator (ICD) had a statistically significant reduction in their rate of sudden cardiac death compared to patients treated with standard drug therapy, according to new data from the DEFINITE (Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation) study, appearing in the May 20th edition of the New England Journal of Medicine.

In the study, participants were randomized into two groups - one receiving standard heart failure drug therapy (control group) and the other receiving drug therapy and a St. Jude Medical ICD. The study's primary endpoint was death from any cause, while sudden arrhythmic death was a secondary end point.

The DEFINITE results showed that ICD recipients had a statistically significant reduced risk of sudden cardiac death and a strong - although not statistically significant - trend toward reduction of overall mortality rates. In addition, the patients with the worst heart failure symptoms showed a statistically significant reduction in overall mortality.

DEFINITE is the first large-scale study to focus on potential mortality benefits of ICDs in "non-ischemic" heart failure patients - those people whose weakened heart muscle is caused by factors unrelated to coronary artery disease.

Initial study results were presented at the American Heart Association's Scientific Sessions in November 2003 by DEFINITE principal investigator Alan Kadish, M.D., Chester D. and Deborah M. Cooley Professor of Medicine from Feinberg School of Medicine at Northwestern University in Chicago, Illinois. Additional data analysis will be presented at the Heart Rhythm Society's annual meeting and is the basis for the New England Journal of Medicine article. N.A. Mark Estes III, M.D., Director, Cardiac Arrhythmia Service, New England Medical Center Hospital and Professor of Medicine, Tufts University School of Medicine, Boston, will present these results at a Late-Breaking Clinical Trials session on Saturday, May 22.

The DEFINITE study, which began in May 1998, followed 458 participants at 48 medical centers in the United States and Israel. Of the 68 deaths in the study, 40 came from the standard-therapy group, while 28 came from the ICD group, a result that approached but did not achieve statistical significance (hazard ratio, 0.65; 95% confidence interval, 0.40 to 1.06; p=0.08). Overall mortality rates at two years were 14.1% in the control group and 7.9% in the ICD group.

Of the total deaths, 17 resulted from sudden cardiac arrhythmias: 3 in the ICD group, compared to 14 in the standard therapy group (hazard ratio, 0.20; 95% confidence interval, 0.06 to 0.71; p=0.006).

Although the overall mortality results did not reach the level of statistical significance as defined in the study protocol, the subset of participants in the NYHA (New York Heart Association) Class III heart failure group who received an ICD showed a statistically significant reduction in risk of death from all causes. The NYHA rankings are a measure of patients' assessments of symptoms, ranging from Class I to Class IV (most severe).

"The DEFINITE study demonstrated that ICDs are highly effective in preventing sudden death from cardiac causes in non-ischemic heart failure patients," said Dr. Kadish. "The data also showed a 35 percent decrease in the relative risk of death from any cause among participants who received ICDs, similar to the MADIT II trial findings that reported a 31 percent decrease."

"DEFINITE is a significant contribution to the series of major multi-center trials showing that new patient populations can benefit from ICD therapy," said Eric S. Fain, M.D., Senior Vice President, Development and Clinical/Regulatory Affairs for St. Jude Medical's Cardiac Rhythm Management business. "These encouraging results will offer new hope to many patients suffering from heart failure due to causes other than coronary disease, who face serious risk of sudden cardiac death."

Participants in the DEFINITE trial ranged in age from 21 to 80 years and had a history of symptomatic heart failure, spontaneous ventricular arrhythmias, and a low left-ventricular ejection fraction (LVEF - a measure of the heart's ability to pump blood). The study's principal investigators were Dr. Kadish and Joseph H. Levine, M.D., Director of Arrhythmia Service at St. Francis Hospital & Medical Center in Rosyln, New York.

Heart failure patients are at significantly increased risk for life-threatening ventricular arrhythmias, including ventricular tachycardia (VT) and ventricular fibrillation (VF) - common contributors to sudden cardiac arrest and the number one cause of sudden cardiac death in the United States. More than 400,000 people die from sudden cardiac arrest in the U.S. every year. ICDs are small devices implanted near the collarbone and connected to the heart with leads, which can deliver shocks and other electrical therapies to stop these dangerous ventricular arrhythmias.

Any statements made regarding St. Jude Medical's anticipated future product launches, regulatory approvals, revenues, earnings, market shares, and potential clinical success are forward-looking statements which are subject to risks and uncertainties, such as those described in the Financial Section of the Company's Annual Report to Shareholders for the fiscal year ended December 31, 2003 (see pages 11-16). Actual results may differ materially from anticipated results.

St. Jude Medical, Inc. (www.sjm.com) is dedicated to the design, manufacture and distribution of innovative medical devices of the highest quality, offering physicians, patients and payers unmatched clinical performance and demonstrated economic value.