Meeting News CoveragePerspective

MATRIX: Event rates not different for bivalirudin, heparin after PCI for ACS

LONDON — In patients with ACS undergoing PCI, rates of major adverse cardiac events and net adverse clinical events were similar between patients assigned bivalirudin and those assigned heparin, according to new findings from the MATRIX study.

Among patients assigned bivalirudin (Angiomax, The Medicines Company), patients who had a post-PCI bivalirudin infusion did not have better rates of NACE, urgent target vessel revascularization or definite stent thrombosis compared with those who had no post-PCI infusion, Marco Valgimigli, MD, PhD, from Thoraxcenter, Erasmus Medical Center, Rotterdam, the Netherlands, said during a press conference at the European Society of Cardiology Congress.

Marco Valgimigli

Marco Valgimigli

 

Valgimigli presented the post-PCI bivalirudin results here. He previously presented the bivalirudin vs. heparin results at the American College of Cardiology 2015 Scientific Sessions. Both sets of results were published in The New England Journal of Medicine to coincide with the ESC Congress.  

In a secondary analysis, researchers determined that the bivalirudin group had lower numerical rates of all-cause mortality, CV mortality, bleeding, non–access-related bleeding and fatal bleeding compared with the heparin group.

In an exploratory analysis, patients in the post-PCI bivalirudin infusion group who received a full dose of 1.75 mg/kg/hour for up to 4 hours had better outcomes than those who received a reduced dose of 0.25 mg/kg/hour for at least 6 hours.

Bivalirudin vs. heparin

Valgimigli and colleagues randomly assigned 7,213 patients with ACS and an anticipated need for PCI to receive bivalirudin or unfractionated heparin. They then further randomized the bivalirudin group to receive or not receive a post-PCI bivalirudin infusion. Whether the patients who received a post-PCI bivalirudin infusion received a full or reduced dose was at the discretion of the physician performing the procedure, Valgimigli said.

For the comparison of bivalirudin and heparin, the primary outcome was MACE, defined as a composite of death, MI and stroke, and NACE, a composite of MACE and major bleeding, at 30 days. For the comparison of post-PCI bivalirudin or not, the primary outcome was a composite of NACE, urgent TVR and definite stent thrombosis at 30 days.

The researchers found no significant difference between the bivalirudin and heparin groups in MACE (bivalirudin, 10.3%; heparin, 10.9%; relative risk = 0.94; 95% CI, 0.81-1.09) or NACE (bivalirudin, 11.2%; heparin, 12.4%; RR = 0.89; 95% CI, 0.78-1.03) at 30 days.

Post-PCI infusion not a factor

In the bivalirudin group, those who received a post-PCI infusion and those who did not had similar rates of NACE/urgent TVR/definite stent thrombosis (bivalirudin, 11%; heparin, 11.9%; relative risk = 0.91; 95% CI, 0.74-1.11) at 30 days, Valgimigli said.

Major BARC 3 or 5 bleeding occurred less often in the bivalirudin group (1.4% vs. 2.5%; rate ratio = 0.55; 95% CI, 0.39-0.78), which the researchers determined was driven by non–access-related events. Rates of fatal bleeding, TIMI major/minor bleeding and GUSTO severe/moderate bleeding were also lower in the bivalirudin group.

The bivalirudin group also had a lower rate of all-cause death (1.7% vs. 2.3%; rate ratio = 0.71; 95% CI, 0.51-0.99) and cardiac death (1.5% vs. 2.2%; rate ratio = 0.68; 95% CI, 0.48-0.97), according to the researchers. However, the rate of definite stent thrombosis was higher in the bivalirudin group (1% vs. 0.6%, rate ratio = 1.71; 95% CI, 1-2.93).

MI, which accounted for approximately two-thirds of the events contributing to MACE and NACE, did not differ between the groups (bivalirudin, 8.6%; heparin, 8.5%; rate ratio = 1.01; 95% CI, 0.85-1.19).

Other analyses

Among the bivalirudin group, patients who received a post-PCI infusion had a higher rate of BARC 2 bleeding (P = .02), but a lower rate of BARC 3 or 5 non–access-related bleeding (P = .001) and GUSTO bleeding (P = .01) compared with those who did not receive an infusion, Valgimigli said.

“The study leaves both options open,” he said. “There was no safety signal with respect to prolonging bivalirudin, which was of course a potential concern. However, I think our study clearly shows that prolonging bivalirudin does not mitigate the risk of acute stent thrombosis.”

Within the post-PCI bivalirudin infusion group, patients who received a reduced dose had a numerically higher rate of NACE, death, definite/acute/subacute stent thrombosis and BARC 3 or 5 bleeding, he said.

“Based on our study results, I do discourage use of the [lower-dose] regimen after PCI,” he said. – by Erik Swain

References:

Valgimigli M, et al. Hot Line VI: Coronary Artery Disease. Presented at: European Society of Cardiology Congress; Aug. 29-Sept. 2, 2015; London.

Valgimigli M, et al. N Engl J Med. 2015;doi:10.1056/NEJMoa1507854.

Disclosures: The study was funded by The Medicines Company and Terumo Medical. Valgimigli reports receiving grant support from The Medicines Company and Terumo; grant support and personal fees from AstraZeneca; personal fees from Abbott Vascular, Alvimedica, Correivo, St. Jude Vascular and Terumo; and personal fees and nonfinancial support from The Medicines Company.

LONDON — In patients with ACS undergoing PCI, rates of major adverse cardiac events and net adverse clinical events were similar between patients assigned bivalirudin and those assigned heparin, according to new findings from the MATRIX study.

Among patients assigned bivalirudin (Angiomax, The Medicines Company), patients who had a post-PCI bivalirudin infusion did not have better rates of NACE, urgent target vessel revascularization or definite stent thrombosis compared with those who had no post-PCI infusion, Marco Valgimigli, MD, PhD, from Thoraxcenter, Erasmus Medical Center, Rotterdam, the Netherlands, said during a press conference at the European Society of Cardiology Congress.

Marco Valgimigli

Marco Valgimigli

 

Valgimigli presented the post-PCI bivalirudin results here. He previously presented the bivalirudin vs. heparin results at the American College of Cardiology 2015 Scientific Sessions. Both sets of results were published in The New England Journal of Medicine to coincide with the ESC Congress.  

In a secondary analysis, researchers determined that the bivalirudin group had lower numerical rates of all-cause mortality, CV mortality, bleeding, non–access-related bleeding and fatal bleeding compared with the heparin group.

In an exploratory analysis, patients in the post-PCI bivalirudin infusion group who received a full dose of 1.75 mg/kg/hour for up to 4 hours had better outcomes than those who received a reduced dose of 0.25 mg/kg/hour for at least 6 hours.

Bivalirudin vs. heparin

Valgimigli and colleagues randomly assigned 7,213 patients with ACS and an anticipated need for PCI to receive bivalirudin or unfractionated heparin. They then further randomized the bivalirudin group to receive or not receive a post-PCI bivalirudin infusion. Whether the patients who received a post-PCI bivalirudin infusion received a full or reduced dose was at the discretion of the physician performing the procedure, Valgimigli said.

For the comparison of bivalirudin and heparin, the primary outcome was MACE, defined as a composite of death, MI and stroke, and NACE, a composite of MACE and major bleeding, at 30 days. For the comparison of post-PCI bivalirudin or not, the primary outcome was a composite of NACE, urgent TVR and definite stent thrombosis at 30 days.

The researchers found no significant difference between the bivalirudin and heparin groups in MACE (bivalirudin, 10.3%; heparin, 10.9%; relative risk = 0.94; 95% CI, 0.81-1.09) or NACE (bivalirudin, 11.2%; heparin, 12.4%; RR = 0.89; 95% CI, 0.78-1.03) at 30 days.

Post-PCI infusion not a factor

In the bivalirudin group, those who received a post-PCI infusion and those who did not had similar rates of NACE/urgent TVR/definite stent thrombosis (bivalirudin, 11%; heparin, 11.9%; relative risk = 0.91; 95% CI, 0.74-1.11) at 30 days, Valgimigli said.

Major BARC 3 or 5 bleeding occurred less often in the bivalirudin group (1.4% vs. 2.5%; rate ratio = 0.55; 95% CI, 0.39-0.78), which the researchers determined was driven by non–access-related events. Rates of fatal bleeding, TIMI major/minor bleeding and GUSTO severe/moderate bleeding were also lower in the bivalirudin group.

The bivalirudin group also had a lower rate of all-cause death (1.7% vs. 2.3%; rate ratio = 0.71; 95% CI, 0.51-0.99) and cardiac death (1.5% vs. 2.2%; rate ratio = 0.68; 95% CI, 0.48-0.97), according to the researchers. However, the rate of definite stent thrombosis was higher in the bivalirudin group (1% vs. 0.6%, rate ratio = 1.71; 95% CI, 1-2.93).

MI, which accounted for approximately two-thirds of the events contributing to MACE and NACE, did not differ between the groups (bivalirudin, 8.6%; heparin, 8.5%; rate ratio = 1.01; 95% CI, 0.85-1.19).

Other analyses

Among the bivalirudin group, patients who received a post-PCI infusion had a higher rate of BARC 2 bleeding (P = .02), but a lower rate of BARC 3 or 5 non–access-related bleeding (P = .001) and GUSTO bleeding (P = .01) compared with those who did not receive an infusion, Valgimigli said.

“The study leaves both options open,” he said. “There was no safety signal with respect to prolonging bivalirudin, which was of course a potential concern. However, I think our study clearly shows that prolonging bivalirudin does not mitigate the risk of acute stent thrombosis.”

Within the post-PCI bivalirudin infusion group, patients who received a reduced dose had a numerically higher rate of NACE, death, definite/acute/subacute stent thrombosis and BARC 3 or 5 bleeding, he said.

“Based on our study results, I do discourage use of the [lower-dose] regimen after PCI,” he said. – by Erik Swain

References:

Valgimigli M, et al. Hot Line VI: Coronary Artery Disease. Presented at: European Society of Cardiology Congress; Aug. 29-Sept. 2, 2015; London.

Valgimigli M, et al. N Engl J Med. 2015;doi:10.1056/NEJMoa1507854.

Disclosures: The study was funded by The Medicines Company and Terumo Medical. Valgimigli reports receiving grant support from The Medicines Company and Terumo; grant support and personal fees from AstraZeneca; personal fees from Abbott Vascular, Alvimedica, Correivo, St. Jude Vascular and Terumo; and personal fees and nonfinancial support from The Medicines Company.

    Perspective
    Johanne Silvain

    Johanne Silvain

    Based on the data presented at this meeting, I don’t see much reason to continue the infusion of bivalirudin in patients with ACS. If I ever have to use bivalirudin, I will stick to the normal protocol. It was a good question to ask because of the increase in stent thrombosis associated with bivalirudin despite its benefit in bleeding, and we want to avoid that. Since prolonging infusion didn’t work, we will have to go to other solutions, such as higher use of ticagrelor (Brilinta, AstraZeneca) and prasugrel (Effient, Daiichi Sankyo/Eli Lilly) or maybe using new, faster drugs such as cangrelor (Kengreal, The Medicines Company).

    The main contribution of the MATRIX study was the superiority of the radial approach over the femoral approach. If you still use the femoral approach, then maybe you need to use a drug like bivalirudin to lower bleeding events.

    With regard to bivalirudin vs. heparin, people in the cath lab have their habits based on what has worked well for them. The main result was neutral, as was the other main endpoint including bleeding. There was no benefit for one over the other, so I’m not sure this will prompt people to change their minds. My personal view is, if you were using unfractionated heparin before, combined with the radial approach, why move to bivalirudin?

    • Johanne Silvain, MD
    • Associate professor of cardiology, University of Paris VI Director, Coronary Care Unit, Pitié-Salpêtrière University Hospital Member, ACTION Study Group, Institut de Cardiologie, Paris

    Disclosures: Silvain reports receiving research grants via his institution from Boehringer Ingelheim, BRAHMS, Daiichi Sankyo, Eli Lilly, and Sanofi Aventis; consultant fees from AstraZeneca, Daiichi Sankyo, Eli Lilly and The Medicines Company; and lecture fees from AstraZeneca, Cordis, Daiichi Sankyo, Eli Lilly, Iroko Cardio International and STENTYS.

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