Bivalirudin Shows Mixed Results in Antithrombin Evaluation of MATRIX

March 16, 2015—Results from the antithrombin program of the MATRIX study of minimizing adverse hemorrhagic events by transradial access site and systemic implementation of bivalirudin (Angiox, The Medicines Company) were presented at the American College of Cardiology’s 64^th annual scientific session in San Diego, California.

The study’s lead investigator is Marco Valgimigli, MD, Associate Professor of Cardiology and senior interventional cardiologist at the Erasmus University Medical Center in Rotterdam the Netherlands.

According to the ACC summary of the trial, patients with acute coronary syndrome (ACS) undergoing angioplasty who received the anticoagulant drug bivalirudin did not show significant improvements in either of two coprimary endpoints—a composite of rate of death, heart attack, or stroke at 30 days, or a composite of those events plus major bleeding—compared to patients receiving standard anticoagulation therapy. However, bivalirudin was associated with significantly lower rates of bleeding complications and death, two of the study’s secondary endpoints. Patients in the control group were given unfractionated heparin, as well as glycoprotein IIb/IIIa inhibitors, at the physician’s discretion.

In the ACC press release, Dr. Valgimigli commented, “We saw an impressive reduction in bleeding with bivalirudin compared to the control, which likely contributed to the reduced mortality in this group. I believe the study shows bivalirudin can provide additional benefits to patients as compared to unfractionated heparin in current medical practice.”

Additionally, the MATRIX investigators advised that the reason the study did not meet its coprimary composite endpoints is likely related to the high prevalence of heart attacks, which occurred in approximately 8.5% of patients in both groups and likely diluted the benefits reflected in the rates of death and bleeding. In addition, the study had a higher-than-usual bar for statistical significance due to its inclusion of two coprimary endpoints instead of only one.

The MATRIX study randomized more than 7,200 patients undergoing angioplasty at 78 hospitals in four European countries to bivalirudin or standard coagulation therapy. All participants had ACS or unstable angina.

Dr. Valgimigli reported that the significantly lower rate of death in the bivalirudin group compared to the control group (1.7% vs 2.3%) is likely the result of a significantly lower rate of bleeding complications (1.4% vs 2.5%). The difference in bleeding complications was especially pronounced for bleeding beyond that near the catheter insertion site.

As noted in the ACC summary, the study comes after a series of controversial and inconsistent bivalirudin trials. In a key departure from its predecessors, the MATRIX trial allowed interventional cardiologists to decide whether to give glycoprotein IIb/IIIa inhibitors as a complement to unfractionated heparin in control patients, whereas previous studies either required or forbade the use of these drugs. Glycoprotein IIb/IIIa inhibitors are widely used by surgeons in the United States, and rarely used in Europe, so neither requiring nor forbidding the use of these drugs is an accurate reflection of a real-world setting in which these drugs are used part of the time. For patients randomized to receive bivalirudin, glycoprotein IIb/IIIa inhibitors were allowed only as a backup strategy, noted the ACC.

Additionally, the trial randomized patients to receive angioplasty via transradial and transfemoral access, which accounts for the potential effects different catheter access points may have had on the results of previous studies. The effects of bivalirudin were consistent regardless of the access site that was used.

Another important aspect of the study is that participants had a higher-than-expected rate of adverse events because of their high-risk profile. Unlike many other studies, high-risk patients were not excluded from participating in the study. The study is limited in that it relied on a composite endpoint and it was not powered for mortality or major bleeding alone.

In the ACC press release, Dr. Valgimigli commented, “Our study really comes at the right moment to re-evaluate the role of bivalirudin. Glycoprotein IIb/IIIa inhibitors were used in about one-quarter of the control patients in our study, at the operator’s discretion, which is a better reflection of current practice than the control protocol used in previous studies.”