Studies make case for choosing bivalirudin over heparin

Research presented at the ACC conference has shown that the antithrombin agent bivalirudin has certain advantages over heparin in various situations and patient populations. These studies have emerged as hospitals try to deal with the recall of contaminated lots of heparin.

The mechanism of directly blocking thrombin behind bivalirudin (Angiomax, The Medicines Company) differs from that of heparin, an indirect thrombin inhibitor.  Unlike heparin, bivalirudin essentially shuts down a master switch of thrombosis by deactivating circulating and clot-bound thrombin and thrombin-mediated platelet activation. Bivalirudin’s makers say this difference may explain the improved outcomes.

Steven V. Manoukian, MD, from Emory University School of Medicine in Atlanta, reported that an analysis of the ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trial showed that major bleeding is an independent predictor of one-year mortality and is associated with increased rates of ischemic events at one year in patients with acute coronary syndromes (ACS). He also reported that patients receiving bivalirudin alone had lower rates of major bleeding compared to heparin plus glycoprotein IIb/IIIa inhibitor (GPI).

A further analysis of ACUITY found blood transfusion to be an independent predictor of one-year mortality and associated with increased one-year ischemic event rates in patients with ACS. Manoukian reported that transfusion rates were lower in patients treated with bivalirudin compared to those treated with heparin plus GPI.

Duane S. Pinto, MD, from Beth Israel Deaconess Medical Center in Boston and colleagues sought to determine the economic impact of bivalirudin therapy versus heparin plus GPI. They performed a prospective economic analysis of the nearly 8,000 U.S. patients enrolled in ACUITY who were randomized to receive heparin plus GPI, bivalirudin plus GPI or bivalirudin alone.

Although anticoagulant costs were lowest for heparin plus cath lab GPI, initial hospital costs were lowest with bivalirudin alone compared to either heparin plus upstream GPI or heparin plus cath lab GPI. Similar results were found at 30 days. Regression modeling demonstrated that savings with bivalirudin were primarily due to less major and minor bleeding.

In the HORIZONS AMI trial (Harmonizing Outcomes with RevascularIZatiON and Stents in Acute Myocardial Infarction), a total of 3,602 patients at 123 centers in 11 countries with STEMI undergoing primary PCI were randomized to bivalirudin or heparin plus GPI and followed for 30 days. Researchers led by Gregg W. Stone, MD, from Columbia University Medical Center found that the bivalirudin monotherapy significantly reduced major bleeding and net adverse clinical events, including cardiac mortality.

Various HORIZONS AMI researchers further parsed the data and found that the beneficial effects of bivalirudin were independent of:

  • age
  • diabetic status
  • baseline renal function
  • clopiodgrel loading dose of either 300 mg or 600 mg, and
  • whether the GPI used was abciximab or double-bolus eptifibatide.

They also found that bivalirudin monotherapy results were consistent in women, as well as men.

In a separate study, Pramod Krishnamurthy, MD, and colleagues at Mount Sinai Medical Center in New York found that bivalirudin was safer and had less ischemic/bleeding events after PCI in patients with end stage renal disease requiring hemodialysis compared to heparin plus GPI. The researchers concluded that bivalirudin should be the standard antithrombotic monotherapy in patients with end stage renal disease requiring PCI.

Researchers from Massachusetts General Hospital found that the use of bivalirudin in patients undergoing PCI had better outcomes regarding vascular access site complications, as well as earlier ambulation.

Aloke V. Finn, MD, and colleagues at MGH randomized 110 patients to bivalirudin or heparin plus GPI. They found that time to ambulation was less in the bivalirudin group by 90 minutes and that the occurrence of hematoma was significantly less in the bivalirudin group (20 percent) compared with the heparin plus GPI group (45 percent). The bivalirudin group also exhibited smaller hematomas: 2.3 cm vs. 3.6 cm.

And finally, David E. Allie, MD, and colleagues at Cardiovascular Institute of the South, Lafayette, La., studied the efficacy of a bivalirudin regimen in patients with critical limb ischemia. These patients typically have a high incidence of diabetes, small vessel disease, hypercoagulability, platelet dysfunction, thrombus, distal macro-/microembolization and overall complications.

Researchers wanted to determine if an effective PCI regimen of a single dose high bolus GPI with limited infusions combined with bivalirudin would be as effective in peripheral vascular interventions.

They divided patients into two groups:

  • Group A – single high dose bolus GPI (Aggrastat, Medicure, Inc.) with a limited six-hour infusion plus a bivalirudin bolus and periprocedural infusion
  • Group B – unfractionated heparin plus GPI

They found a trend for better outcomes in Group A, but no findings were significant. They concluded that the GPI-bivalirudin combination is safe and feasible during peripheral vascular interventions in critical limb ischemia.