A clinical trial by The Medicines Company showed results comparing bivalirudin (Angiomax) to heparin in off-pump coronary artery bypass graft surgery (CABG) were published in the Annals of Thoracic Surgery.

"Without question, heparin is not an ideal drug for anticoagulation during cardiac surgery, despite its near-monopoly status. As a 'designer drug' bivalirudin could be the 'holy grail' eagerly sought by cardiac surgeons and anesthesiologists (and hematologists)," said Theodore Warkentin, a leading hematology expert, in commentary that accompanied the trial results.

The randomized, blinded trial showed that anticoagulation for off-pump CABG surgery with bivalirudin was feasible, with similar bleeding but with better graft flow 90 days after surgery compared to heparin. The authors noted in the paper, "This was the first ever randomized comparison of a new anticoagulant with heparin and protamine reversal for anticoagulation during cardiac surgery."

"Bleeding rates were similar between the two study arms. Intriguingly, superior graft patency by several parameters was evident in the bivalirudin-treated patients, including a greater number of grafts with normal (grade 3) blood flow (82per cent vs 67per cent)."

CABG is a type of open vascular surgery commonly referred to as open-heart surgery. Surgeons bypass a blockage in the patient's artery by grafting a vein to the artery on both sides of the blockage to restore flow around the obstruction. On-pump CABG is conducted with the use of a cardiac pulmonary bypass machine, a device that pumps the patient's blood while the heart is stopped and the surgery is conducted. For off-pump CABG, physicians slow the heartbeat, stabilize the heart by keeping certain areas immobile with various devices, and do not use a bypass machine.

Heparin has been the standard anticoagulant for CABG surgery since the 1950's. Because heparin's duration of effect is variable and sometimes prolonged, surgeons often give protamine to reverse heparin at the end of surgery. Both heparin and protamine can cause immune reactions, which may compromise patient survival and treatment results, and may also result in greater procedure costs. Heparin is manufactured from by-products of cow lungs or pig intestines. Protamine is manufactured from by-products of salmon sperm.

The immune reactions caused by heparin may manifest as a clinical condition known as heparin-induced thrombocytopenia and thrombosis syndrome, or HIT/TS. HIT/TS is characterized by reduced platelet counts and potentially by widespread, life-threatening blood clots. Patients are particularly at risk of HIT/TS if they have had previous exposure to heparin and developed a heparin antibody. If they are administered heparin again, while antibody positive, they are at a higher risk of developing HIT/TS.

Because there is no approved alternative to heparin specifically for patients undergoing CABG surgery - even patients who are heparin antibody positive -- The Medicines Company is sponsoring a Phase III clinical study programme investigating Angiomax as a potential anticoagulant in both on-pump and off-pump CABG surgery. The programme includes the Choose studies, which are evaluating patients who are heparin antibody positive, and the Evolution studies conducted in the general CABG patient population. The studies include both on-pump and off-pump trials. Patient enrollment in the off-pump Evolution study has recently been completed.

The Medicines Company meets the demands of the world's most advanced medical practitioners by developing products that improve hospital acute care.