Bivalirudin Angioplasty Study - BAT

Description:

The BAT trial was a multicenter, randomized, double-blinded trial to evaluate the efficacy and safety of bivalirudin versus heparin in patients undergoing coronary angioplasty for unstable or postinfarction angina.

Hypothesis:

To determine whether treatment with bivalirudin results in a lower incidence of ischemic complications than heparin among patients undergoing coronary angioplasty for unstable or postinfarction angina.

Study Design

Study Design:

Patients Screened: 16,584
Patients Enrolled: 4,312
Mean Follow Up: Six months
Mean Patient Age: Median 63
Female: 33

Patient Populations:

Chest pain with age >21 years and urgently scheduled to undergo angioplasty for unstable angina or for postinfarction angina less than two weeks after myocardial infarction

Exclusions:

Serum creatinine concentrations >3.0 mg/dl; fibrinolytic therapy within the previous 24 hours; patients scheduled to undergo coronary atherectomy, stenting, or laser angioplasty or scheduled for a staged angioplasty procedure; possible pregnancy; or intolerance to aspirin or heparin

Primary Endpoints:

Composite of death, myocardial infarction, abrupt closure of the dilated vessel, or rapid clinical deterioration of cardiac origin requiring bypass surgery, intra-aortic balloon counterpulsation, or repeated coronary angioplasty

Secondary Endpoints:

Major hemorrhage (overt bleeding with a decrease in the hemoglobin concentration of at least 3 g/dl, a need for transfusion, intracranial hemorrhage, or retroperitoneal bleeding), and individual components of the primary endpoint

Drug/Procedures Used:

Therapy with either bivalirudin or heparin was initiated immediately before angioplasty.

  • Bivalirudin: Bolus dose of 1.0 mg/kg, followed by a four-hour infusion at a rate of 2.5 mg/kg/h and a 14-20-hour infusion at a rate of 0.2 mg/kg/h.
  • Heparin: Bolus dose of 175 U/kg followed by an 18-24-hour infusion at a rate of 15 U/kg/h.
The activated clotting time (ACT) was measured five minutes and 45 minutes after the administration of the bolus dose. If the ACT was <350 seconds, saline placebo was given to bivalirudin-treated patients, and a bolus dose of 60 U/kg of additional heparin was given to heparin-treated patients.

Concomitant Medications:

Aspirin (300-325 mg) was given to all patients.

Principal Findings:

A total of 4,312 patients were enrolled and among these, 4,098 patients underwent angioplasty. There were minor differences between the two treatment groups, with patients randomized to bivalirudin having slightly more complex lesions. The median ACT was 346 seconds in the bivalirudin arm versus 383 seconds in the heparin arm (p<0.001).

The incidence of the primary composite endpoint was similar in both treatment groups (11.4% for bivalirudin vs. 12.2% for heparin, p=0.44), as was the rate of death, myocardial infarction, and repeat revascularization at six months (25.7% vs. 26.6%, p=0.54). Rates of in-hospital death (0.4% vs. 0.2%), myocardial infarction (3.2% vs. 3.9%), emergency bypass surgery (1.7% in both groups), and other ischemic complications were similar in both treatment groups. Additionally, the incidence of the primary endpoint (11.8% for bivalirudin vs. 12.9% for heparin, p=0.26) was similar in both groups in an intention-to-treat analysis (including patients not receiving angioplasty).

In the subgroup of patients undergoing angioplasty for postinfarction angina, bivalirudin was associated with a lower incidence of the primary endpoint (9.1% vs. 14.2%, p=0.04) as well as myocardial infarction (2.0% vs. 5.1%, p=0.04) when compared to heparin, but these observations were not paralleled among patients with unstable angina.

Rates of bleeding were lower among patients treated with bivalirudin: 3.8% versus 9.8%, p<0.001 for major hemorrhage; 3.7% versus 8.6%, p<0.001 for transfusions; and 0.2% versus 0.7%, p=0.02 for retroperitoneal hemorrhage.

Interpretation:

Among patients undergoing angioplasty for unstable or postinfarction angina, treatment with bivalirudin versus heparin was associated with similar rates of ischemic complications and a lower incidence of bleeding complications. In the prespecified subgroup of patients with postinfarction angina, treatment with bivalirudin was associated with reduced short-term ischemic complications, with no significant differences in six-month death, myocardial infarction, or repeat revascularization.

In a secondary post-hoc analysis conducted by the study investigators using the original intent-to-treat cohort (all patients regardless of whether they underwent angioplasty) with different definitions of myocardial infarction and a combined clinical endpoint, treatment with bivalirudin appeared to be associated with a reduction in short-term but not long-term ischemic complications. Consistent with the original report, treatment with bivalirudin also appeared to be associated with less bleeding when compared to high-dose heparin.

Overall, these results point to a potential use for bivalirudin in reducing bleeding complications compared to heparin monotherapy during angioplasty of moderate- to high-risk patients. However, this trial was conducted prior to widespread use of lower dose heparin, thienopyridines, glycoprotein IIb/IIIa inhibitors, and coronary stenting procedures, making it difficult to directly extrapolate this study's results to current clinical practice.

References:

  1. Bittl JA, Strony J, Brinker JA, et al. Treatment with bivalirudin (Hirulog) as compared with heparin during coronary angioplasty for unstable or postinfarction angina. Hirulog Angioplasty Study Investigators. N Engl J Med 1995;333:764-9.
  2. Bittl JA, Chaitman BR, Feit F, Kimball W, Topol EJ. Bivalirudin versus heparin during coronary angioplasty for unstable or postinfarction angina: Final report reanalysis of the Bivalirudin Angioplasty Study. Am Heart J 2001;142:952-9.

Clinical Topics: Anticoagulation Management, Invasive Cardiovascular Angiography and Intervention

Keywords: Hirudin Therapy, Myocardial Infarction, Heparin, Recombinant Proteins, Peptide Fragments, Angioplasty, Thienopyridines


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