The ACUITY Trial suggests that bivalirudin may be superior to standard combinations of antithrombotic agents in patients with acute coronary syndrome, according to an article in the November 23 issue of the New England Journal of Medicine.

Researchers randomized 13,819 patients in 17 countries with acute coronary syndrome to one of three antithrombotic regimens: unfractionated heparin or enoxaparin plus a glycoprotein IIb/IIIa inhibitor, bivalirudin plus a glycoprotein IIb/IIIa inhibitor, or bivalirudin alone. Bivalirudin alone reduced the risk of major bleeding by 47 percent compared with the standard combination of injectable agents.

Study design for ACUITY (Acute Catheterization and Urgent Intervention Triage strategY) used an early invasive strategy, starting anticoagulant therapy at arrival to the emergency department and quickly moving patients to the cardiac catheterization laboratory for evaluation and, in most cases, percutaneous coronary intervention. Anticoagulant treatments were continued during procedures.

Bivalirudin is a direct thrombin inhibitor with a naturally reversible mechanism of action. In clinical trials, it has demonstrated efficacy plus reductions in bleeding complications compared with heparin as the foundation anticoagulant in the contemporary catheterization lab setting.

Bivalirudin plus a glycoprotein IIb/IIIa inhibitor compared with heparin plus a glycoprotein IIb/IIIa inhibitor was associated with noninferior 30-day rates of the composite ischemia end point (7.7 percent and 7.3 percent, respectively), major bleeding (5.3 percent and 5.7 percent), and the net clinical outcome end point (11.8 percent and 11.7 percent).

Bivalirudin alone compared with heparin plus a glycoprotein IIb/IIIa inhibitor was associated with a noninferior rate of composite ischemia (7.8 percent and 7.3 percent, respectively) and significantly reduced rates of major bleeding (3.0 percent versus 5.7 percent) and the net clinical outcome end point (10.1 percent versus 11.7 percent).

In summary, in patients with moderate- or high-risk acute coronary syndromes who were undergoing invasive treatment with glycoprotein IIb/IIIa inhibitors, bivalirudin was associated with rates of ischemia and bleeding that were similar to those with heparin. Bivalirudin alone was associated with similar rates of ischemia and significantly lower rates of bleeding.

"In ACUITY, we tested several different combinations of drug therapies and found that the simplest regimen was the best," said ACUITY's Principal Investigator, Gregg W. Stone, MD, Professor of Medicine and Director of Cardiovascular Research and Education at Columbia University Medical Center's Center for Interventional Vascular Therapy. "Previous acute coronary syndrome trials have added drug on top of drug to achieve better efficacy, sacrificing safety along the way. The ACUITY trial showed that bivalirudin alone is as effective as more complicated dual drug regimens, and results in significantly less bleeding, which means improved outcomes for patients."