Direct thrombin inhibitor urged for PCI patients

January 23, 2006

Percutaneous coronary intervention (PCI) encompasses a variety of procedures, including percutaneous transluminal coronary angioplasty (PTCA), intracoronary stenting, and atheroablative technologies used to diagnose and treat patients with coronary artery syndromes such as heart attacks and angina. In the United States, more than one million PCI procedures are performed annually, and it is estimated that about two million procedures are performed annually worldwide. Patients undergoing PCIs are at risk for developing blood clots in the coronary artery, which can result in a variety of complications including heart attack, emergency surgery, and even death.

The American College of Cardiology (ACC) and the American Heart Association (AHA) Task Force on Practice Guidelines is responsible for gathering information to develop and revise practice guidelines concerning the appropriate use of technologies for the diagnosis and treatment of patients with cardiovascular diseases. Percutaneous coronary interventions are an important group of technologies in this regard. The PCI guidelines were last revised in 2001. However, over the past four years, there have been dramatic advances in PCI techniques, devices, and pharmacological treatments with platelet glycoprotein (GP) IIb/IIIa receptor antagonists-e.g., abciximab (ReoPro, Centocor), tirofiban (Aggrastat, Merck), eptifibatide (Integrilin, Millennium Pharmaceuticals)-drug-eluting stents; and direct thrombin inhibitors. Due to these advances, ACC, AHA, and the Society for Cardiovascular Angiography and Interventions (SCAI) have recently updated the 2001 Guidelines for PCI to include the recommendation for the use of Angiomax (bivalirudin, Biogen Idec/The Medicines Co.), a direct thrombin inhibitor in patients undergoing PCI.

Bivalirudin is a specific and reversible direct thrombin inhibitor that is approved in the United States and the European Union. It is indicated for use as an anticoagulant in patients with unstable angina undergoing PTCA and for patients with or at risk of heparin-induced thrombocytopenia (HIT) undergoing PCI. Bivalirudin is intended for use with aspirin and has been studied only in patients receiving concomitant aspirin.

Dan Fintel, M.D., director of the Coronary Care Unit at Northwestern Memorial Hospital and associate professor at the Feinberg School of Medicine, Northwestern University in Chicago, believes that the clinical data regarding bivalirudin are encouraging and its inclusion in the ACC/AHA/SCAI guidelines will accelerate its use in the clinical setting.

The updated ACC/AHA/ SCAI guidelines include a review of the data from the Randomized Evaluation of PCI Linking Angiomax to Reduced Clinical Events (REPLACE)-2 trial. The REPLACE-2 was a randomized, double-blind trial conducted in the United States, Canada, Western Europe, and Israel that included more than 6,000 patients. The study was designed to evaluate whether patients receiving bivalirudin plus provisional GP IIb/IIIa inhibitors would have outcomes that were the same as, or "non-inferior" to, patients in the trial receiving heparin plus GP IIb/IIIa inhibitors.

The REPLACE-2 trial demonstrated that in patients undergoing elective or urgent PCI, intraprocedural administration with bivalirudin, with provisional GP IIb/IIIa receptor inhibition provides similar protection from acute ischemic events compared with a regimen of heparin plus planned GP IIb/IIIa inhibition. The results established that bivalirudin is not superior to standard therapy, but it is an alternative in non-high-risk patients undergoing PCI.

With the more frequent use of potent antithrombin and antiplatelet agents in people undergoing PCI, bleeding is a complication of increasing concern. The REPLACE-2 trial demonstrated that patients who received bivalirudin, with provisional GP IIb/IIIa receptor inhibition experienced significantly fewer hemorrhagic complications compared with patients who received heparin plus planned GP IIb/IIIa inhibition. Additional findings from the study demonstrated that bivalirudin is easier to use and safer and less costly than heparin given with GP IIb/IIIa inhibitors.