Acute Catheterization And Urgent Intervention Triage Strategy Trial Research Articles

Safety and Efficacy of Bivalirudin Monotherapy in Patients With Diabetes Mellitus and Acute Coronary Syndromes: A Report From the ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) Trial

We sought to evaluate clinical outcomes of patients with diabetes mellitus in the ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trial, overall and by treatment arm. In the ACUITY trial, 13,819 patients with moderate- or high-risk acute coronary syndromes (ACS) were randomized to heparin (unfractionated or enoxaparin) plus glycoprotein IIb/IIIa inhibition (GPI), bivalirudin plus GPI, or bivalirudin monotherapy. Compared with heparin plus GPI, bivalirudin monotherapy resulted in similar protection from ischemic events with less major bleeding. Whether these results apply to patients with diabetes is unknown. We evaluated the impact of diabetes on 30-day net adverse clinical outcomes (composite ischemia [death, myocardial infarction, or unplanned ischemic revascularization] or major bleeding), overall and by antithrombotic strategy. Diabetes was present in 3,852 randomized patients (27.9%). Compared with nondiabetic patients, diabetic patients had higher 30-day rates of net adverse clinical outcomes (12.9% vs. 10.6%; p < 0.001), composite ischemia (8.7% vs. 7.2%; p = 0.003), and major bleeding (5.7% vs. 4.2%; p < 0.001). Among diabetic patients, compared with heparin plus GPI, bivalirudin plus GPI resulted in similar rates of net adverse clinical outcomes (14.0% vs. 13.8%; p = 0.89), while bivalirudin monotherapy resulted in a similar rate of composite ischemia (7.9% vs. 8.9%; p = 0.39) and less major bleeding (3.7% vs. 7.1%; p < 0.001), yielding fewer net adverse clinical outcomes (10.9% vs. 13.8%; p = 0.02). Diabetic patients with ACS managed invasively have higher rates of composite ischemia and major bleeding. Compared with treatment with heparin plus GPI, bivalirudin monotherapy provides similar protection from ischemic events with less major bleeding, resulting in a significant reduction in net adverse clinical outcomes.

Antithrombotic Strategies in non-ST Elevation Acute Coronary Syndromes: Focus On Bivalirudin

Acute coronary syndromes (ACS) are a common presentation of coronary artery disease, accounting for more than one million hospital admissions in the US annually. Owing to high rates of mortality and reinfarction, ACS represent a major public health concern. The following review discusses the pathogenesis of ACS and optimal approaches for the management of patients with ACS, with special focus on new antithrombotic strategies, including the direct thrombin inhibitor bivalirudin. Bivalirudin has several notable mechanistic advantages compared with unfractionated heparin, including activity against clot-bound thrombin, inhibition of thrombin-induced platelet activation, short plasma half-life in patients with normal or mildly impaired renal function (25 minutes), and linear pharmacokinetics less affected by plasma proteins and renal insufficiency. These properties provide a more predictable inhibition of coagulant activity than unfractionated heparin, with less degree of inter-patient variability in anticoagulation response. The findings from the several clinical trials assessing safety and efficacy of bivalirudin are analyzed in detail, including the recent randomized controlled Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trial. Based on the results of the ACUITY trial, a newer streamlined strategy for the invasive treatment of moderate- and high-risk patients with ACS is discussed.

Acute Catheterization and Urgent Intervention Triage strategY (ACUITY) trial: Study design and rationale

Background Patients with acute coronary syndromes (ACS; unstable angina and non–ST-segment elevation myocardial infarction) are at significant risk for death and myocardial infarction. Early angiography followed by revascularization is considered the treatment of choice for moderate- to high-risk patients with ACS. However, despite the integration of newer therapies including stents, glycoprotein IIb/IIIa inhibitors, and thienopyridines, the rate of adverse ischemic events still remains unacceptably high, and the intensive pharmacologic regimens used to stabilize the disrupted atherosclerotic plaque and support angioplasty and surgical revascularization procedures elicit a high rate of bleeding complications. Pilot trials suggest that the thrombin-specific anticoagulant bivalirudin may improve clinical outcomes in ACS. Study design In the Acute Catheterization and Urgent Intervention Triage strategY (ACUITY) trial, 13,800 patients with moderate- to high-risk ACS are being prospectively randomly assigned at up to 600 centers to unfractionated heparin or enoxaparin + IIb/IIIa inhibition, versus bivalirudin + IIb/IIIa inhibition, versus bivalirudin + provisional IIb/IIIa inhibition. All patients undergo cardiac catheterization within 72 hours, followed by percutaneous or surgical revascularization when appropriate. In a second random assignment, patients assigned to receive IIb/IIIa inhibitors are subrandomized to upstream drug initiation, versus IIb/IIIa inhibitor administration during angioplasty only. The primary study end point is the composite of death, myocardial infarction, unplanned revascularization for ischemia, and major bleeding at 30 days. Clinical follow-up will continue for 1 year. Conclusions The ACUITY trial is the largest study yet performed in patients with ACS undergoing an invasive strategy. In addition to evaluating the utility of bivalirudin in ACS, this study will also provide important guidance regarding the necessity for and timing of IIb/IIIa inhibitor administration.