The Medicines Company Plans More Research in Emerging Field of Catheter-Based Valve Procedures

SAN FRANCISCO, CA (MARKETWIRE via COMTEX) --Clinical researchers here reported the first results of a pilot study with the anticoagulant Angiomax (R) (bivalirudin) as an adjunct to catheter-based procedures in patients with severely defective aortic heart valves in whom surgery was not possible. The results showed a 60% reduction in major bleeding events (from 13% to 5%, p = 0.003) in patients treated with Angiomax compared to patients treated with heparin. This investigational use of Angiomax is not approved in these procedures, collectively known as transcatheter aortic valve interventions. Angiomax is approved for patients undergoing percutaneous coronary interventions (PCI) with provisional glycoprotein IIb/IIIa inhibitor (GPI).

George D. Dangas, MD, PhD, of Mount Sinai Medical Center New York, NY led this study, which was also conducted at the University of Miami Health System (Drs. Annapoorna S. Kini and Mauricio Cohen were the respective team leaders) in a program called BRAVO (BivaliRudin to improve Aortic Valve intervention Outcomes), which is sponsored by The Medicines Company (NASDAQ: MDCO). The data were reported here at the Cardiovascular Research Foundation (CRF) annual Transcatheter Cardiovascular Therapeutics (TCT) conference.

The data reported by Dr. Dangas were the results from a two-center retrospective registry of 428 patients with severe aortic stenosis undergoing balloon valvuloplasty (BAV) via transfemoral access and the use of bivalirudin. BAV involves the insertion of a compressed balloon into a catheter, a long, thin, tube-like device. The catheter and balloon are inserted into the femoral artery through a small cut in the leg and threaded to the site of the diseased valve. The balloon is then inflated in an effort to increase the opening size of the valve and improve blood flow.

The study met its two objectives, demonstrating patients treated with bivalirudin versus unfractionated heparin experienced:

--  Reduced rates of in-hospital major bleeding
--  Reduced rates of in-hospital net adverse clinical events (major
    bleeding, all-cause mortality, myocardial infarction or stroke)

Dr. Dangas noted, "Technologies to enable heart valve replacement or repair without cracking open a patient's chest are emerging rapidly. Last week's US approval of the Sapien(TM) valve is the most recent example."

Anticoagulants are needed peri-procedurally to prevent clotting on the treated area and clotting in other organs such as the brain, which can result in a stroke; however, anticoagulants carry a risk of vascular and bleeding complications. Dr. Dangas said, "Advances in procedures such as PCI, valvuloplasty and TAVI may require improvements in anticoagulation to yield improved patient outcomes."

Clive Meanwell, MD, PhD, Chairman and Chief Executive Officer of The Medicines Company, said, "These results validate the commitment we made to study Angiomax once our patent rights were supported. I look forward to seeing the BRAVO program move ahead with a planned study in more patients next year. With continued certainty, we will be positioned to explore the potential of Angiomax to deliver clinical and economic advantages in other uses."

About Angiomax(R) (bivalirudin) for Injection

Angiomax is a direct thrombin inhibitor with a naturally reversible mechanism of action and a 25 minute half-life.

In the United States, Angiomax with provisional GPI is indicated in patients undergoing angioplasty, also called PCI, and in patients with, or at risk of, heparin-induced thrombocytopenia and thrombosis syndrome (HIT/HITTS) undergoing PCI. In addition, Angiomax is indicated for use as an anticoagulant in patients with UA undergoing percutaneous transluminal coronary angioplasty (PTCA). Angiomax is intended for use with aspirin. The most common adverse events for Angiomax in clinical trials comparing Angiomax and heparin were back pain, pain, nausea, headache and hypotension. The incidence of these adverse events was comparable in both the Angiomax and heparin groups in these trials. An unexplained fall in blood pressure or hematocrit, or any unexplained symptom, should lead to serious consideration of a hemorrhagic event and cessation of Angiomax administration. Angiomax is contraindicated in patients with active major bleeding or hypersensitivity to Angiomax or its components. Angiomax is not approved for use in ACS patients not undergoing PCI. Please see full prescribing information available at http://www.angiomax.com.

Source: The Medicines Company