麻豆传媒

Heparin remains the anticoagulant of choice in percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS). Nevertheless, some operators are open to using bivalirudin (Angiomax) amid unanswered questions about its safety and effectiveness in contemporary practice.

Unfractionated heparin (UFH) already had a long clinical history and was the standard of care when bivalirudin became popular in the late 2000s due to a targeted effect allowing for a purportedly lower risk of bleeding. Another selling point: greater ease of use. The intravenous direct thrombin inhibitor could help patients achieve continuous therapeutic anticoagulation, while avoiding the frequent monitoring of activated clotting time required for heparin use during PCI.

Yet the clinical evidence for bivalirudin has been mixed, as positive data from the 2000s gave way to newer studies that were neutral at best.

In 2013, bivalirudin still edged out heparin with reduced bleeds and deaths in the EUROMAX trial, at the cost of a greater risk of stent thrombosis. With 2014's HEAT-PPCI and 2017's trials, however, bivalirudin outright lost its advantage over heparin in terms of ischemic events and bleeding.

What changed during this era was that adjunctive glycoprotein IIb/IIIa inhibitors were falling out of favor, potent antiplatelets became available, and operators were increasingly trading transfemoral access for the transradial access associated with lower bleeding risk.

The newest data comparing bivalirudin against heparin with radial access showed no clear benefit, and an early risk of stent thrombosis, with the former, said Eric Secemsky, MD, of Beth Israel Deaconess Medical Center and Harvard Medical School in Boston.

Secemsky noted that bivalirudin was previously available only as a brand medication with a price tag that was sometimes prohibitive for cath labs. The drug only became available as a generic .

Thus, "unfractionated heparin is preferred for most patients receiving PCI ... bivalirudin has a very limited role in the management of patients with acute MI," said Sanket Dhruva, MD, MHS, of the University of California San Francisco School of Medicine and San Francisco Veterans Affairs Medical Center.

"With current potent antiplatelet regimens available, and the bleeding avoidance strategies by using radial access, UFH seems to be the drug of choice in most cases," agreed Roxana Mehran, MD, of Mount Sinai School of Medicine in New York City.

In 2017, Secemsky and colleagues reported that bivalirudin use rose from 2009 to 2013, but .

Proponents of the direct thrombin inhibitor continue to argue that it can be useful in periprocedural anticoagulation.

Recently, a meta-analysis linked bivalirudin to reductions in cardiac death and serious bleeding in people undergoing PCI for ST-segment elevation MI (STEMI). Non-STEMI patients saw a reduction only in serious bleeding -- rates of mortality, MI, and stent thrombosis were unchanged -- on bivalirudin versus heparin in this pooled analysis.

As such, the anticoagulant is still being used in patients with high bleeding risk undergoing PCI, especially those presenting with ACS, Mehran noted.

For Secemsky's group, the most common uses of bivalirudin are for treatment of heparin-induced thrombocytopenia and in cases when the patient is not responding to heparin, he said.

"In some centers where they're still using femoral access, bivalirudin would be used more frequently," he added. "That's probably a small number of centers in the U.S., not the majority."

He said one of the biggest unanswered questions is whether bivalirudin can hold an advantage over heparin in modern PCI with radial access and no glycoprotein IIb/IIIa inhibitors.

Also of interest is the idea that a longer high-dose infusion of bivalirudin after PCI might mitigate the risk of stent thrombosis, the rationale being that an abrupt termination in anticoagulation at the end of the procedure could lead to clotting, according to Secemsky.

In the MATRIX trial from 2015, however, there seemed to be no benefit of a post-PCI bivalirudin infusion.

Nevertheless, some still administer these 2-hour infusions in current practice, Secemsky said.

Finally, it is unknown how bivalirudin would fare against heparin plus a newer P2Y12 inhibitor such as cangrelor (Kengreal), which offers early platelet inactivation.

"Given that there are no randomized clinical trial data comparing cangrelor to P2Y12 inhibitors that are both more potent than clopidogrel [Plavix] and increasingly used in recent years -- ticagrelor [Brilinta] and prasugrel [Effient] -- there is limited insight into cangrelor's role," Dhruva said.

He noted that cangrelor has had very limited clinical adoption since receiving FDA approval in June 2015. "In my own clinical practice, I have personally never seen it used."

Antithrombotic strategies in the cath lab continue to evolve. In PCI, blood thinners are used so that the equipment doesn't cause any clotting, and platelets also need to be deactivated so they don't stick to any stents and cause stent thrombosis. Yet innovation has been uneven between these two areas, according to Secemsky.

He noted that there is a lot of early-stage investment in novel antiplatelets, one goal being the development of one that can be subcutaneously administered at first medical contact in acute MI patients. Among the investigational agents boasting the fast absorption and easy administration needed in this setting are the P2Y12 inhibitor and the glycoprotein IIb/IIIa inhibitor .

On the anticoagulation side, however, there is not much interest beyond heparin and bivalirudin.

"It's been a bit boring in our field," Secemsky said. "Most of the focus on blood thinners has been in the antiplatelet space ... not so much in procedural anticoagulation prior to PCI."

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