No Differences Between Bivalirudin, Unfractionated Heparin in ACS Patients With or Without ST Elevation: MATRIX
(UPDATED) The MATRIX trial found no advantage to bivalirudin over unfractionated heparin in reducing major adverse cardiovascular events (MACE) or net adverse cardiovascular events (NACE) in ACS patients undergoing PCI. Now a new analysis confirms that this lack of difference in ischemic and thrombotic complications extends to patients both with and without persistent ST-segment elevation.
“Bivalirudin has been shown to be associated [with] a mortality difference only in STEMI, whereas in NSTE ACS, some studies have seen an excess of periprocedural events,” senior author on the study Marco Valgimigli, MD (Swiss Cardiovascular Centre, Bern, Switzerland), told TCTMD in an email. “So it was important to check the consistency of the MATRIX results across type of ACS.”
The MATRIX results were originally presented at the American College of Cardiology 2015 Scientific Sessions, as reported by TCTMD. This prespecified substudy, led by Sergio Leonardi, MD (Fondazione IRCCS Policlinico San Matteo, Pavia, Italy), was published earlier this week in the BMJ.
Leonardi et al compared outcomes between 4,010 patients presenting with persistent ST-segment elevation ACS and 3,203 presenting without ST elevation. The decision to add on glycoprotein IIb/IIIa inhibitors (GPIs) in heparin-treated patients was taken in 30.7% of those with ST-segment elevation ACS and in 10.9% of those with NSTE ACS.
Within the ST-segment elevation ACS group, MACE occurred in 5.9% of bivalirudin-treated as compared with 6.5% of heparin-treated patients, a nonsignificant difference. In those without ST-segment elevation, 15.9% of bivalirudin-treated and 16.4% of heparin-treated patients developed a MACE, again, with no significant differences between treatment groups.
For the endpoint of NACE, which included major bleeding in combination with MACE components (all-cause mortality, myocardial infarction, or stroke), investigators also saw no differences between bivalirudin and heparin stratified according to the presence or absence of ST-segment elevation.
As has been seen in other analyses, bivalirudin monotherapy was associated with reduced bleeding as compared with heparin plus provisional use of GPIs in patients both with and without ST-elevation ACS. An excess risk of stent thrombosis with bivalirudin—something also seen in earlier studies and added as a caution to drug labelling in the United States earlier this year—was not seen in this analysis, however, although the findings were “directionally similar” in MATRIX, investigators said. Of note, a full-dose bivalirudin infusion could be prolonged by up to 4 hours (and up to 6 hours at a reduced dose) among patients randomized to receive this, according to a second study aim of the original trial design. (A third randomization in MATRIX compared radial versus femoral access). Prolonged infusion is also now noted in the US labelling as a strategy to reduce the risk of stent thrombosis.
“The main finding of this analysis . . . is that a regimen of bivalirudin monotherapy, compared with unfractionated heparin with provisional glycoprotein IIb/IIIa inhibitors, did not result in reduced major adverse cardiovascular events or net adverse clinical events,” Leonardi et al conclude “These results are consistent with the findings from the overall population with acute coronary syndrome.”
They add: “The choice of the anticoagulant regimen thus requires a careful balance between the expected risk of bleeding and thrombotic complications with the expected benefits for each patient.”
To TCTMD, Valgimigli said he currently uses unfractionated heparin in the majority of his patients. But, he continued, “I think the most convincing message which now, thanks to MATRIX, extends also to patients treated with a radial approach, is the bleeding advantage [with bivalirudin]. So if you are concerned about bleeding, that [patient] is the right patient in whom to choose bivalirudin.”
- Leonardi S, Frigoli E, Rothenbühler M, et al. Bivalirudin or unfractionated heparin in patients with acute coronary syndromes managed invasively with and without ST elevation (MATRIX). BMJ. 2016;Epub ahead of print.
- Leonardi reports honorariums for advisory boards from The Medicines Company during the conduct of the study outside the submitted work.
- The MATRIX trial was sponsored by the Italian Society of Invasive Cardiology (GISE), and received grant support and study drug from The Medicines Company, and grant support from Terumo.
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