Bivalirudin Lowers Bleeding in NSTEMI Patients Undergoing PCI

The direct thrombin inhibitor bivalirudin is superior to heparin plus a glycoprotein IIb/IIIa inhibitor (GPI) at reducing bleeding in patients with non-ST-segment elevation myocardial infarction (NSTEMI) who are undergoing percutaneous coronary intervention (PCI), though the agent does not reduce ischemic events. According to the authors of the study, published online October 9, 2012, in Circulation: Cardiovascular Interventions, the results are sufficient to recommend bivalirudin’s regular use in such patients.

Researchers led by Adnan Kastrati, MD, of the Deutsches Herzzentrum (Munich, Germany), pooled results from the ACUITY and ISAR-REACT 4 trials, which randomized a total of 3,798 NSTEMI patients undergoing PCI to bivalirudin or heparin (unfractionated or enoxaparin) plus a GPI (eptifibatide, tirofiban, or abciximab). All patients received clopidogrel loading prior to PCI.

Baseline characteristics were similar between the bivalirudin and heparin plus GPI groups. DES were used in 70% of the patients, BMS in 24%, and balloon angioplasty alone in 6%.

At 30 days, MACE as well as the individual component endpoints of death, MI, and urgent TVR were similar between the bivalirudin and heparin plus GPI groups, as were net adverse clinical events (NACE), defined as MACE plus bleeding (table 1).

Table 1. Thirty-Day Outcomes

 

Bivalirudin
(n = 1,928)

Heparin + GPI
(n = 1,870)

OR (95% CI)

MACE

10.6%

10.2%

1.04 (0.85-1.27)

NACE

13.4%

14.7%

0.90 (0.76-1.06)

Mortality

1.3%

1.1%

1.26 (0.70-2.25)

MI

8.7%

8.7%

1.00 (0.80-1.24)

TVR

1.7%

1.9%

0.91 (0.57-1.47)


Definite stent thrombosis within 30 days was also similar between the bivalirudin group and the heparin plus GPI group (0.5% vs. 0.7%; P = 0.47).

Several bleeding endpoints were lower in the bivalirudin group at 30 days, including protocol-defined major bleeding (46% risk reduction), TIMI major bleeding, and TIMI minor bleeding (table 2).

Table 2. Bleeding Outcomes at 30 Days

 

Bivalirudin
(n = 1,928)

Heparin + GPI
(n = 1,870)

P Value

Major Bleeding

3.4%

6.3%

< 0.001

TIMI Major Bleeding

1.3%

2.4%

0.02

TIMI Minor Bleeding

4.8%

7.5%

< 0.001


The 3 major endpoints of MACE, NACE, and major bleeding remained consistent across numerous subgroups defined by age, eGFR, specific trial, type of intervention, and LVEF. The only exception was in diabetics, who showed a trend toward greater relative benefit with bivalirudin with regard to NACE (P = 0.07).

“Although no significant difference in efficacy was seen in terms of suppression of adverse ischemic events, bivalirudin was superior to heparin plus a GPI in terms of reducing bleeding events,” the authors conclude. “Therefore, the use of bivalirudin in patients with high-risk ACS undergoing PCI (rather than heparin and a GPI) may be strongly recommended.”

The authors noted that the pooled analysis achieves a level of evidence supporting bivalirudin in NSTEMI patients comparable with that supporting the agent’s use in patients with STEMI. They acknowledge, though, that as opposed to the HORIZONS-AMI trial, which showed a mortality benefit with bivalirudin in STEMI patients, no such difference was shown with the direct thrombin inhibitor in the current study.

Key Question Answered

According to Sripal Bangalore, MD, MHA, of New York University School of Medicine (New York, NY), the study answers a key concern of clinicians. “The question has always been, if you have a patient with clopidogrel pretreatment, is the benefit of bivalirudin still seen?” he told TCTMD in a telephone interview. “In that sense and especially in the high-risk patients who are troponin positive with NSTEMI, this article clearly shows that the benefit in reducing the risk of bleeding is still preserved.”

Patients enrolled in ACUITY and ISAR-REACT 4 had elevated cardiac biomarker levels (troponin or CK-MB).

Dr. Bangalore noted that the lower mortality rate with bivalirudin in the HORIZONS-AMI trial is still somewhat puzzling. “We think that bleeding is not a benign thing and that patients who bleed are going to die, but we can only speculate,” he said. “We still don’t know why there was a mortality benefit.”

A reason this did not show up in the current analysis may have been the shorter 30-day follow-up, Dr. Bangalore noted. “HORIZONS data showed a 1-year reduction in mortality,” he said, adding that with longer follow-up, such a reduction may be observed in the current study.

Regardless, the benefits in terms of bleeding are enough to recommend bivalirudin for routine use in NSTEMI patients, he stressed. “At least in our practice, and in many practices across the nation, that’s how it’s been used,” Dr. Bangalore said. “I would say the use of IIb/IIIa’s has been extremely reduced in patients with NSTEMI.”

This, though, leads to another question. “If most practices do not use IIb/IIIa, you start wondering if you still see benefit if bivalirudin is compared to heparin alone, which has been used fairly often in NSTEMI patients. That’s the real question.”

Note: Study coauthors Gregg W. Stone, MD, and Roxana Mehran, MD, are faculty members of the Cardiovascular Research Foundation, which owns and operates TCTMD.

 


Source:
Ndrepepa G, Neumann F-J, Deliargyris EN, et al. Bivalirudin versus heparin plus a glycoprotein IIb/IIIa inhibitor in patients with non-ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention after clopidogrel pretreatment: Pooled analysis from the ACUITY and ISAR-REACT 4 trials. Circ Cardiovasc Interv. 2012;Epub ahead of print.

 

 

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Disclosures
  • Dr. Kastrati reports having received lecture fees from Daiichi-Sankyo, Eli Lilly, and The Medicines Company.
  • Dr. Bangalore reports no relevant conflicts of interest.

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