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BRIGHT: Bivalirudin outperformed heparin alone, heparin plus tirofiban in PCI
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WASHINGTON — Bivalirudin was superior to both heparin alone and heparin plus tirofiban in patients with acute MI undergoing coronary intervention, concluded continued follow-up and new analyses of the BRIGHT study presented at TCT 2014.
Lead investigator Yaling Han, MD, of General Hospital of Shenyang Military Region, Shenyang, China, presented findings from the BRIGHT trial, which was the first large-scale, prospective three-arm trial to compare bivalirudin (Angiomax, The Medicines Company), heparin monotherapy and heparin plus tirofiban (Aggrastat) in acute MI patients undergoing PCI.
The issue of determining the most favorable anticoagulant regimen for acute MI patients has been a matter of some controversy. Although the recent HORIZONS-AMI and EUROMAX trials reported that bivalirudin is superior to heparin plus a glycoprotein IIb/IIIa inhibitor in decreasing net adverse clinical events (NACE) in acute MI patients undergoing primary PCI, this benefit was offset by an increased rate of acute stent thrombosis in the bivalirudin group. Moreover, another recent trial, HEAT-PPCI, showed heparin monotherapy to be superior to bivalirudin alone.
In the BRIGHT trial, the researchers evaluated 2,194 patients with acute MI suitable for emergency PCI at 82 Chinese sites. They randomly assigned the patients to one of three regimens: bivalirudin alone (n=735); heparin alone (n=729); or heparin plus tirofiban (n=730). The primary endpoint was 30-day NACE, which was a composite of MACCE or BARC bleeding. Secondary endpoints included 1-year NACE, bleeding and MACCE at 30-day and 1-year follow-up.
Han discussed some of the clinical and procedural differences of the BRIGHT trial from other pivotal trials, including enrollment of both STEMI and non-STEMI patients, longer mean symptom to hospital times, and a very low proportion of bailout tirofiban use in the heparin monotherapy and bivalirudin groups. Notably, she said, the study used a prolonged infusion of bivalirudin.
“I’d like to emphasize that the mean duration of post-PCI bivalirudin infusion was about 4 hours; it was longer than that of other prior studies,” Han said in the press conference.
Han and colleagues found that at 30-days, the incidence of NACE was lower in the bivalirudin group (8.8%) than in the heparin group (13.2%) or the heparin plus tirofiban group (17%; P<.001).
These results persisted at 1 year, with the bivalirudin group yielding a 12.8% incidence of NACE events vs. 16.5% in the heparin monotherapy group and 20.5% in the heparin plus tirofiban group (P<.001). One-year rates of MACCE were 6.7% in the bivalirudin group vs. 7.3% in the heparin monotherapy group and 6.8% in the heparin plus tirofiban group (P=.9).
Furthermore, bivalirudin was associated with a decrease in major and minor bleeding, and had rates of adverse ischemic events comparable to both of the heparin groups. With the use of the post-procedure bivalirudin infusion, the researchers found that there were comparably low rates of stent thrombosis in the three arms.
Ph. Gabriel Steg
“This is a great trial,” said panel discussant Ph. Gabriel Steg, MD, of the Hôpital Bichat in Paris. “It’s a great advance to have these comparisons in a randomized fashion. That hasn’t been available anywhere else.”
When asked about whether the comparable bleeding results could be attributed to the higher heparin dose, Steg pointed out that the dosage used in the trial is the guideline-recommended dose.
“If the authors had used another dose, they might have been criticized for not following the guidelines,” he said.
The most compelling finding, according to Steg, was the fact that the bivalirudin group did not have an excess of stent thrombosis.
“The only explanation I have seen is the prolonged infusion, and that has been consistent with our own observations in post-hoc analysis of the EUROMAX trial, in which the subgroup of patients who got a prolonged infusion did not have an excess in stent thrombosis,” he said. “But that was not allocated in a randomized fashion in EUROMAX; here, it is part of the design of the trial, so that makes it very strong. So again, everything seems to fit into place now — we are seeing the data come together, and it is showing us where we should be going.” – by Jennifer Byrne
For more information:
Han Y. Plenary Session XIX: Late-Breaking Clinical Trials No. 3. Presented at: TCT 2014; Sept. 13-17, 2014; Washington, D.C.
Disclosure: Han reports no relevant disclosures. Steg reports receiving grant/research support from Sanofi Aventis and Servier, and consultant’s fees/honoraria/speaker’s fees from AstraZeneca, Bayer AG, Bristol-Myers Squibb, Daiichi Sankyo/Eli Lilly, GlaxoSmithKline, Medtronic, Merck/Schering Plough, Novartis, Pfizer and The Medicines Company.
Perspective
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Timothy D. Henry, MD
The BRIGHT trial was a very well-designed study; I am impressed with the fact that it had three different arms studying bivalirudin, heparin alone and heparin with tirofiban. A lot of the data have compared bivalirudin with heparin plus a glycoprotein IIb/IIIa inhibitor, and there has been so much controversy on which is better. This trial adds to the evidence that bivalirudin decreases bleeding in patients with STEMI. This is consistent with HORIZONS-AMI and EUROMAX, and the three-arm comparison really added to the evidence. In addition to showing that there is less bleeding with bivalirudin, the BRIGHT trial showed that there was no difference in ischemic events. So, we now have American, European and Chinese trials that show this; it’s encouraging when you get consistent results.Perspective
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Dominick J. Angiolillo, MD, PhD
This is a very important trial, because it follows a lot of recent debate after the HEAT-PPCI trial, in which there were no differences in terms of safety between bivalirudin and unfractionated heparin, but there was an increased risk for stent thrombosis. In the BRIGHT trial, there was no signal of increased risk for stent thrombosis in the bivalirudin arm. One thing to keep in mind is that in this trial there was a prolonged infusion of bivalirudin, and this made the difference. So overall, we are probably going to hear a lot about this trial. In my opinion, the BRIGHT trial is more aligned with previous bivalirudin studies, which support the safety of the drug in terms of reduced bleeding without a trade-off in ischemic events. Additionally, we can now show that with prolonged infusion, we can overcome the problem of early stent thrombosis.
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