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.
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).
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
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.