Study Indicates Adenosine Reduces Postoperative Complications In Patients Undergoing Coronary Artery Bypass Surgery.

RESEARCH TRIANGLE PARK, N.C.--(BUSINESS WIRE)--April 28, 1999--

Medco Research, Inc.(NYSE:MRE) announced that clinical research results published today in the Annals of Surgery indicate that the addition of adenosine to cold blood cardioplegia - the solution used to bathe the heart during coronary artery bypass graft (CABG) surgery - resulted in fewer deaths and myocardial infarctions. This finding supports further investigation of adenosine as a potential life-saving therapy in the over 750,000 open-heart procedures performed each year worldwide.

Dr. Robert M. Mentzer, Jr., Department of Surgery, University of Kentucky, was the Principal Investigator of this multicenter, double-blind, placebo-controlled trial sponsored by Medco Research, Inc. The 253 participants were divided into three cohorts: (A) standard cold blood cardioplegia, (B) low-dose adenosine - standard cold blood cardioplegia containing 500 uM adenosine, and (C) high-dose adenosine - standard cold blood cardioplegia containing 2mM adenosine. Patients who received adenosine cardioplegia also were exposed to an adenosine infusion (200 mcg/kg/min) immediately preceding the application of and immediately following the removal of the aortic crossclamp. Patients were monitored from the time of enrollment to follow-up 60 days after discharge.

Data from this clinical trial indicate that adenosine treatment is safe, well tolerated and associated with a decrease in morbidity and mortality rates. The results showed a dose-related reduction in the incidence of postoperative myocardial infarction - with 9.5% in the placebo group compared to 4.8% in the low-dose adenosine group and 1.2% in the high-dose adenosine group (p=0.016). There was also a dose-related trend toward a reduction in the incidence of postoperative mortality rates - with 6.0% in the placebo group compared to 3.6% in the low-dose adenosine group and 1.2% in the high-dose adenosine group. When a composite endpoint of high-dose dopamine use, epinephrine use, insertion of an intraaortic balloon pump, myocardial infarction, or death was analyzed, the percentage of patients experiencing one of these postoperative complications was significantly lower in the high-dose adenosine group (p=0.006). In this study of patients undergoing CABG surgery, 50% of the patients in the placebo cohort experienced one of the negative outcomes listed above, compared to 37% and 29% in the low- and high-dose adenosine cohorts, respectively.

"Despite marked improvements in surgical techniques and the development of various protective strategies designed to protect the heart during intraoperative cardiac arrest, myocardial stunning continues to be a common problem following open-heart surgery," commented Dr. Nils Johannesson, Vice President, Research and Development, Medco Research, Inc. "Based upon what is known about the numerous cardioprotective effects of adenosine, we undertook this program to explore the possibility of modifying existing cardioplegic solutions with the addition of adenosine in an attempt to potentially reduce myocardial stunning and improve patient outcomes. The favorable results reported by Dr. Mentzer provide us with yet another late-stage patent-protected opportunity for adenosine - which compliments our ongoing Phase-III trial in the setting of acute myocardial infarction. With an estimated worldwide market potential over $700 million for this indication, we are now discussing the feasibility of conducting a pivotal Phase-III clinical trial for adenosine -- as an additive to cold blood cardioplegia - together with a corporate partner."

Medco Research is an emerging pharmaceutical company engaged in the global commercialization of cardiovascular medicines and adenosine-based products. Two adenosine-based products successfully developed by the Company - Adenocard(R) and Adenoscan (R) -- are currently marketed and have established the value of adenosine-receptor technology in cardiovascular medicine.

Statements contained in this release which are not historical facts are forward looking statements under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Although the Company believes the expectations reflected in such forward looking statements are based upon reasonable assumptions, it can give no assurance that its expectations will be attained. Forward looking statements involve known and unknown risks that could cause the Company's actual results to differ materially from expected results. Factors that could cause actual results to differ materially include, among others, the high cost and uncertainty of the research, clinical trials and other development activities involving pharmaceutical products; the Company's ability to fund its activities internally or through corporate partnerships or other additional financing; the unpredictability of the duration and results of the U.S. FDA's review of New Drug Applications and/or the review of other regulatory agencies worldwide; the possible impairment of, or inability to obtain, intellectual property rights; intense competition; the uncertainty of obtaining, and the Company's dependence on third parties to manufacture and sell its products; results of pending or future litigation and other risk factors detailed from time to time in the Company's SEC filings.

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