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Patients with ST-segment elevation myocardial infarction (STEMI) who receive early emergency heparin can be safely switched to bivalirudin before undergoing percutaneous coronary intervention (PCI). In a substudy of the HORIZONS-AMI trial published in the June 7, 2011, issue of the Journal of the American College of Cardiology, researchers found that the strategy reduced rates of major bleeding and improved early and late cardiac survival.

In the original HORIZONS-AMI trial, 3,602 STEMI patients undergoing primary PCI were randomized to bivalirudin monotherapy or unfractionated heparin plus a glycoprotein IIb/IIIa inhibitor (GPI). Bivalirudin therapy reduced rates of major and minor bleeding, thrombocytopenia, and the need for transfusion. As a result, both all-cause and cardiac mortality over the short and long term were significantly reduced among patients who received the antithrombin agent.

Randomization Within a Randomization

However, there has been lingering concern about the safety of administering bivalirudin in the cath lab to patients already treated with heparin by emergency personnel, especially if their activated clotting time remained high.

To address this concern, Gregg W. Stone, MD, of Columbia University Medical Center (New York, NY), and the HORIZONS-AMI trial investigators analyzed the outcomes of the 2,357 patients from the study who were treated with unfractionated heparin before being randomized to receive bivalirudin (n = 1,178) or continued unfractionated heparin plus a GPI (n = 1,179). This was a separate stratified randomization that occurred within the overall trial randomization.

Both short- and long-term follow-up results highlighted the benefits of bivalirudin. After 30 days, the rate of major bleeding was 7.6% in the bivalirudin group, compared with 12.3% in the control group (P = 0.0001). Similarly, cardiac mortality was 1.6% among those who received bivalirudin vs. 2.9% for those who received heparin and a GPI (P = 0.04).

After 2 years, rates of major bleeding, cardiac mortality, and reinfarction all were lower in the bivalirudin group, while rates of definite or probable stent thrombosis remained similar in both groups (table 1).

Table 1. Two-Year Follow-up

^a Received heparin followed by bivalirudin.
^b Received heparin plus a glycoprotein IIb/IIIa inhibitor.

“We found that the reduction in bleeding was evident regardless of what the activated clotting time was from the unfractionated heparin,” Dr. Stone told TCTMD in a telephone interview. “So, even in patients who had a high activated clotting time from the unfractionated heparin, they still benefited from bivalirudin, and they did not have an excess of bleeding from adding the bivalirudin on top.”

Reflects a Common Treatment Practice

The analysis is important, said Sunil V. Rao, MD, of Duke University Medical Center (Durham, NC), in an e-mail correspondence with TCTMD, because, “it is very common for patients to receive an antithrombin in the [emergency department] which may not necessarily be the antithrombin that is desired in the cath lab. There is some suggestion that adding [bivalirudin on top of heparin] may be associated with increased bleeding risk. We need to know what the effect of adding bivalirudin is, especially given the mortality benefit seen in HORIZONS-AMI.”

Dr. Rao added that “from this paper, it appears that switching from heparin to bivalirudin in the primary PCI setting is quite safe and preserves the mortality benefit of bivalirudin. . . . So, interventionalists can feel very secure in using bivalirudin for primary PCI if that is their antithrombin of choice.”

Dr. Stone agreed, saying, “there [are] now 2 ways to use bivalirudin in primary angioplasty for STEMI. Number 1, it could be started upfront in the emergency room and then continued to the cath lab. That’s what was done in about 35% of patients in HORIZONS. Or 2, [unfractionated heparin] could be given early, either in the emergency room or in an ambulance or transfer hospital, and then once the patient comes to the cath lab . . . the patient can be switched to bivalirudin. And that latter approach is practical because it’s easier for emergency rooms to just give a bolus of heparin than it is to start bivalirudin, which requires a weight-adjusted bolus plus an infusion.”

Eric R. Bates, MD, of the University of Michigan Medical Center (Ann Arbor, MI), said the finding that bivalirudin was effective with either unfractionated heparin or clopidogrel pretreatment is interesting since both ACUITY and HORIZONS-AMI seem to suggest that bivalirudin monotherapy is inadequate in the first few hours without an extra boost.

“The best antithrombotic strategy might be prasugrel and bivalirudin, but it hasn't been tested yet,” he added.

Note: Dr. Stone and several coauthors of the study are faculty members of the Cardiovascular Research Foundation, which owns and operates TCTMD.

Related Stories:

• High-Risk Primary PCI Patients Benefit Most from Bivalirudin
• HORIZONS-AMI Substudies: Bivalirudin Benefits Vary Among Patient Subgroups