Meta-analysis Delves Into Bivalirudin Versus Heparin Debate in Primary PCI

CHICAGO, IL—A new meta-analysis of contemporary trials comparing the efficacy and safety of bivalirudin and heparin during PCI reveals no differences in mortality rates between the two drugs. And, consistent with other trials, it shows bivalirudin is associated with an increased risk of stent thrombosis.

The debate over which antithrombin to use and when is a storied one. MATRIX—the most recent trial comparing the two therapies—made a splash last spring when it was presented at the American College of Cardiology (ACC) 2015 Scientific Sessions and failed to show an overall benefit with bivalirudin over unfractionated heparin in patients with ACS, but did show a reduction in all-cause mortality. Neither HEAT-PPCI nor EUROMAX showed a mortality benefit with bivalirudin, but the latter did demonstrate lower bleeding with the newer drug in STEMI patients.

Now, “the trend seems to be [towards thinking] that heparin is just as good as bivalirudin,” clinical pharmacist Samuel Akinyele, PharmD (Memorial Hermann Southwest Hospital, Richmond, TX), who was not part of the study, commented to TCTMD. “It seems like the trend is going toward provisional use of GPI, which is what we do in my cath lab. . . . My thought is, if stent thrombosis is increased with bivalirudin and there’s no benefit for major bleeding, why not go back to heparin? It’s more economically viable.”

Presenting results of the 18-study meta-analysis that included more than 40,000 patients in a poster session at the ACC 2016 Scientific Sessions, Ashish Correa, MD (Mount Sinai St. Luke’s Hospital, New York, NY), said there were no differences between bivalirudin and heparin with regards to mortality, MI, or stroke. However, bivalirudin was linked with more TVR, less major bleeding, and a trend toward more stent thrombosis compared with heparin.

When the studies were stratified according to routine or provisional use of GPIs for patients receiving heparin, bivalirudin was still associated with higher TVR (P = 0.02) and lower major bleeding (P < 0.00001) in the studies that mandated routine GPI use.

It has been “anecdotally known” that bivalirudin is associated with a greater risk of stent thrombosis, Correa told TCTMD, and this analysis bolsters that belief. “The presumption was that the mandated GPIs in the heparin arm make heparin a more potent blood thinner, and so by comparison bivalirudin would be less so, and would be associated with greater stent thrombosis risk. Now that more and more studies are coming out where GPIs are not mandated, because that’s no longer standard practice, this effect would not be seen,” since heparin alone was predicted to lose its edge as a stand-alone agent. Instead, he continued, heparin’s benefits in terms of reducing stent thrombosis held up, even when used in isolation.

“You could make the argument that bivalirudin is indeed associated with greater stent thrombosis and this has nothing to do with GPIs in the heparin arm,” Correa said.                                                                                                                              

Correa acknowledged that the results were largely driven by the 8,400-patient MATRIX trial. “While it is a study where GPIs were only provisional, as many as 25% of patients ultimately did get GPIs routinely in the heparin arm,” he said. “So perhaps the greater stent thrombosis that we’ve seen with bivalirudin is because of a very large group of patients in the MATRIX study who did get GPIs.”

Commenting on current practice at his institution, Correa said they use intra-arterial bivalirudin, but added, “I think perhaps it’s more sensible and more economical to go back to using heparin.”

In agreement, Akinyele said using risk calculators to better determine patient bleeding risk and then deciding which drug to use would be beneficial, “but getting physician buy-in is very difficult.”

• Correa A. Bivalirudin versus heparin with or without glycoprotein IIb/IIIa inhibitors in patients undergoing percutaneous coronary intervention: a meta-analysis of greater than 40,000 patients. Presented at: American College Cardiology 2016 Scientific Sessions. April 2, 2016. Chicago, IL.

Related Stories:

• MATRIX Antithrombin: Bivalirudin Fails to Reduce Net Adverse Events vs Heparin in ACS Patients Undergoing PCI
• BRAVO 3: Bivalirudin Similar to Heparin in Transfemoral TAVR
• HEAT-PPCI Published: Discrepant Finding of Heparin’s Superiority over Bivalirudin in Primary PCI Still Puzzles