Favourable results in randomised trial to replace heparin

Clinical trial results comparing The Medicines Company's bivalirudin (Angiomax) to heparin in off-pump coronary artery bypass graft surgery (CABG) reported that bivalirudin anticoagulation was feasible in CABG 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, anesthesiologists and hematologists,' said Dr Theodore Warkentin, a leading hematology expert, in a commentary that accompanied the trial results.

The randomised, 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 with heparin. This was the first ever randomised comparison of a new anticoagulant with heparin and protamine reversal for anticoagulation during cardiac surgery.

Dr Warkentin stated: 'Bleeding rates were similar between the two study arms (bivalirudin: median, 793 mL, versus heparin plus protamine, 805 mL; P = 0.165). 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 (82% vs 67%; P = 0.03).'

About CABG

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, stabilise the heart by keeping certain areas immobile with various devices, and do not use a bypass machine.

About Heparin

Heparin has been the standard anticoagulant for CABG surgery since the 1950s. 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 characterised 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 significantly 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 program investigating Angiomax as a potential anticoagulant in both on-pump and off-pump CABG surgery.

About Angiomax

Angiomax is a synthetic product currently approved for use in unstable angina patients undergoing coronary angioplasty. Angiomax is a direct thrombin inhibitor with a naturally reversible mechanism of action. In clinical trials, Angiomax has shown a reduction in the incidence of death, myocardial infarction, and the need for revascularisation in patients undergoing coronary angioplasty, as well as significant reductions in bleeding complications compared to heparin, or heparin plus a glycoprotein IIb/IIIa inhibitor, in the contemporary catheterisation lab setting. These reductions in ischemic and bleeding complications remain evident even in high-risk patients. Reductions in these complications represent the opportunity not only for better patient care, and for cost savings. Angiomax is intended for use with aspirin.