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Vial of heparin

LONDON—The latest results* of the MATRIX trial haven’t provided any cut-and-dried answers when it comes to anticoagulation in the context of percutaneous coronary intervention (PCI), according to articles published in NEJM and data presented at the ESC Congress 2015.

The trial suggested that, overall, bivalirudin and heparin produce comparable results in patients undergoing PCI.

The drugs produced similar rates of major adverse cardiovascular events (MACE) and net adverse clinical events (NACE).

In addition, among patients in the bivalirudin arm, there was no significant difference in a composite primary outcome between patients who received an additional infusion of bivalirudin after PCI and those who did not.

Results from this trial were published in NEJM alongside a related editorial. At the ESC Congress 2015, the bivalirudin dosing comparison was reported in abstract 6004.

MATRIX was sponsored by the Societa Italiana di Cardiologia Invasiva (GISE), with funding from The Medicines Company and Terumo.

The trial enrolled 7213 patients with acute coronary syndrome who were set to undergo PCI. Patients were randomized to receive bivalirudin (n=3610) or unfractionated heparin (n=3603). Patients in the bivalirudin arm were then randomized to either receive a post-PCI infusion of bivalirudin (n=1799) or not (n=1811).

Primary outcomes for the comparison between bivalirudin and heparin were the occurrence of MACE (a composite of death, myocardial infarction, or stroke) and NACE (a composite of major bleeding or a major adverse cardiovascular event).

The primary outcome for the comparison of post-PCI bivalirudin infusion with no infusion was a composite of urgent target-vessel revascularization, definite stent thrombosis, or NACE.

Heparin vs bivalirudin

There was no significant difference between the bivalirudin and heparin groups with regard to MACE—10.3% and 10.9%, respectively (P=0.44). And the same was true for NACE—11.2% and 12.4%, respectively (P=0.12).

Likewise, there was no significant difference between the bivalirudin arm and the heparin arm with regard to myocardial infarction—8.6% and 8.5%, respectively (P=0.93)—or stroke—0.4% and 0.5%, respectively (P=0.57).

However, bivalirudin was associated with a significantly lower rate of all-cause mortality than heparin—1.7% and 2.3%, respectively (P=0.04)—and a significantly lower rate of cardiac-related death—1.5% and 2.2%, respectively (P=0.03).

The rate of definite stent thrombosis was significantly higher in the bivalirudin group than the heparin group—1.0% and 0.6%, respectively (P=0.048). But there was no significant difference in the rate of definite or probable stent thrombosis—1.3% and 1.0% (P=0.27).

The rate of any bleeding was significantly lower with bivalirudin than with heparin—11.0% and 13.6%, respectively (P=0.001). And the same was true for major bleeding (BARC 3 or 5)—1.4% and 2.5%, respectively (P<0.001).

Bivalirudin duration

“Post-PCI bivalirudin did not reduce the composite outcome of ischemic and bleeding outcomes, including stent thrombosis risk, as compared to no post-PCI bivalirudin infusion,” said study investigator Marco Valgimigli, MD, PhD, of the Swiss Cardiovascular Center in Bern, Switzerland.

The proportion of patients who met the primary endpoint was 11.0% in the post-PCI infusion group and 11.9% in the no-infusion group (P=0.34).

Similarly, there was no significant difference between the infusion and no-infusion groups in the risk of definite stent thrombosis—1.3% and 0.7%, respectively (P=0.09)—or definite/probable stent thrombosis—1.5% and 1.1%, respectively (P=0.29).

And there was no significant difference in the rate of any bleeding—11.3% and 10.7%, respectively (P=0.62)—but the rate of BARC 3 or 5 bleeding was lower in the group that received the post-PCI infusion—1.0% vs 1.8% (P=0.03).

“Both treatment options are allowed per current European label and observational studies,” Dr Valgimigli said.

“Hence, I believe the option to prolong or stop bivalirudin infusion after PCI remains open for clinicians, who will have to decide based on the ischemic and bleeding risk of individual patients, as well as perhaps based on type of acute coronary syndrome, timing of loading dose, and type of oral P2Y12 inhibitors. This is in keeping with the current labeling of the drug in EU and USA.”

Cost concerns

In the NEJM editorial, Peter Berger, MD, of North Shore–Long Island Jewish Health System in Great Neck, New York, noted that bivalirudin costs more than 400 times the price of heparin.

“Many studies have shown that bivalirudin is safer than heparin—that it causes fewer bleeding complications,” Dr Berger said. “But other studies have shown that heparin is every bit as safe, especially when used in lower doses. And one recent, large study actually suggested that heparin is more effective than bivalirudin.”

Despite these conflicting results, Dr Berger said “nearly everyone” agrees that if the more expensive drug is not superior in some way, the less expensive one should be used.

“Many studies raise more questions than they answer,” he added. “It will be interesting to see whether doctors accept the results of the MATRIX trial or wait for more studies before deciding which blood thinner they prefer.” end hematology article

*MATRIX investigators previously compared vascular access sites and found that radial access outperformed femoral access. These results were published earlier this year in
The Lancet.

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