Meeting News

Experts make cases for heparin, bivalirudin

Roxana Mehran
Roxana Mehran

SAN DIEGO — Evidence exists to support heparin or bivalirudin as the anticoagulant of choice during primary PCI, two experts said during a debate at the Society for Cardiovascular Angiography and Interventions Scientific Sessions.

Roxana Mehran, MD, MSCAI, FACC, FAHA, FESC, associate medical editor of Cardiology Today’s Intervention and a cardiologist and professor of medicine at Icahn School of Medicine at Mount Sinai, argued in favor of bivalirudin, whereas Duane S. Pinto, MD, MPH, FACC, FSCAI, chief of interventional cardiology section and director of the cardiac ICU at Beth Israel Deaconess Medical Center, associate professor of medicine at Harvard Medical School and a Cardiology Today’s Intervention Editorial Board Member, argued in favor of heparin.

The case for bivalirudin

Mehran said the interventional cardiology community has been less enthusiastic about bivalirudin in recent years because “at the time that bivalirudin was being tested in ACS, the standard was heparin with a glycoprotein IIb/IIIa inhibitor. Now that we have better agents, we are questioning decades of data with bivalirudin.”

Duane S. Pinto

Much of the case against bivalirudin came as a result of the HEAT-PPCI trial, which found a “higher level of MACE for bivalirudin driven by more reinfarctions” compared with heparin, she said. However, HEAT-PPCI was a single-center study and its results have not been duplicated in multicenter studies, most recently in the VALIDATE-SWEDEHEART study.

Much of the case against bivalirudin came as a result of the HEAT-PPCI trial, which found a “higher level of MACE for bivalirudin driven by more reinfarctions” compared with heparin, she said. However, HEAT-PPCI was a single-center study and its results have not been duplicated in multicenter studies, most recently in the VALIDATE-SWEDEHEART study.

More obvious, Mehran said, is that bivalirudin is associated with less major bleeding than heparin in several large randomized trials.

“Throughout the debate over bivalirudin — I thought we were done with it — there’s been an important reduction in major bleeding that should not go understated,” she said. “Yes, the heparin arm usually did have glycoprotein IIb/IIIa inhibitors, especially in HORIZONS-AMI and EUROMAX, but in BRIGHT and MATRIX, where that was not the case, there still was a reduction in bleeding” with bivalirudin.

A soon-to-be-published meta-analysis indicates that net adverse clinical events favor bivalirudin if HEAT-PPCI is excluded, Mehran said.

“Bivalirudin hasn’t gone away. It can be used as an alternative to heparin. Let’s not push it aside, especially in those patients who can’t receive heparin, such as those with heparin-induced thrombocytopenia,” she said. “If you’re going to give a glycoprotein IIb/IIIa inhibitor [with heparin], please at least think about bivalirudin as an alternative. Because you will reduce non-access bleeding compared to heparin with a glycoprotein IIb/IIIa inhibitor. With the novel P2Y12 antagonists as well as IV P2Y12 inhibitors, and with full-dose bivalirudin and a good infusion rate, we should take care of any untoward ischemic complication that would have been an effect of bivalirudin alone.”

The case for heparin

Pinto said meta-analyses have shown, as was seen in HEAT-PPCI, that bivalirudin is associated with more than twice the risk for acute stent thrombosis compared with heparin.

“We do pay a penalty on the ischemic side with bivalirudin, especially when not appropriately treated with antiplatelet medications,” he said.

Another meta-analysis found bivalirudin was riskier than heparin for any ischemic event “and the benefit [of heparin] was evident whether it was planned glycoprotein IIb/IIIa inhibitors in both arms, planned glycoprotein IIb/IIIa inhibitors in the heparin-alone arm or provisional, which is how we utilize glycoprotein IIb/IIIa antagonists in current practice,” he said.

Although some trials have shown that heparin is associated with more bleeding risk vs. bivalirudin, “if glycoprotein IIb/IIIa antagonists aren’t used, heparin and bivalirudin have similar bleeding rates,” according to Pinto.

Pinto also argued that “in the contemporary era of radial access and potent P2Y12 inhibition, heparin is the best choice.”

Among patients with STEMI from the CATH-PCI registry undergoing PCI via transradial access, he said there was no difference in outcomes between bivalirudin and heparin, and VALIDATE-SWEDEHEART, “which now reflects contemporary practice: mainly radial approach, mainly ticagrelor (Brilinta, AstraZeneca),” showed no difference in mortality or MI at 180 days and no difference in bleeding events.

“The reality is, we shouldn’t be looking at a way to improve bivalirudin outcomes by giving heparin to mitigate the risk of stent thrombosis,” Pinto said. “But we also shouldn’t be prolonging an infusion just to get to the same place we started with heparin. That doesn’t seem to be a good strategy.”

As with all debates at meetings, the arguments made by the participants may not be reflective of their actual positions, Pinto said. – by Erik Swain

References:

Mehran R.

Pinto DS. Controversies in Interventional Pharmacology – Debate I: Heparin vs. Bivalirudin. Both presented at: Society for Cardiovascular Angiography and Interventions Scientific Sessions; April 25-28, 2018; San Diego.

Disclosures: Mehran reports she has financial ties with multiple pharmaceutical and device companies and her spouse received honoraria from The Medicines Company. Pinto reports he consults for Chiesi and Terumo and has served as an investigator for Chiesi, and in the past received honoraria, consultant fees and research grants from The Medicines Company.

Roxana Mehran
Roxana Mehran

SAN DIEGO — Evidence exists to support heparin or bivalirudin as the anticoagulant of choice during primary PCI, two experts said during a debate at the Society for Cardiovascular Angiography and Interventions Scientific Sessions.

Roxana Mehran, MD, MSCAI, FACC, FAHA, FESC, associate medical editor of Cardiology Today’s Intervention and a cardiologist and professor of medicine at Icahn School of Medicine at Mount Sinai, argued in favor of bivalirudin, whereas Duane S. Pinto, MD, MPH, FACC, FSCAI, chief of interventional cardiology section and director of the cardiac ICU at Beth Israel Deaconess Medical Center, associate professor of medicine at Harvard Medical School and a Cardiology Today’s Intervention Editorial Board Member, argued in favor of heparin.

The case for bivalirudin

Mehran said the interventional cardiology community has been less enthusiastic about bivalirudin in recent years because “at the time that bivalirudin was being tested in ACS, the standard was heparin with a glycoprotein IIb/IIIa inhibitor. Now that we have better agents, we are questioning decades of data with bivalirudin.”

Duane S. Pinto

Much of the case against bivalirudin came as a result of the HEAT-PPCI trial, which found a “higher level of MACE for bivalirudin driven by more reinfarctions” compared with heparin, she said. However, HEAT-PPCI was a single-center study and its results have not been duplicated in multicenter studies, most recently in the VALIDATE-SWEDEHEART study.

Much of the case against bivalirudin came as a result of the HEAT-PPCI trial, which found a “higher level of MACE for bivalirudin driven by more reinfarctions” compared with heparin, she said. However, HEAT-PPCI was a single-center study and its results have not been duplicated in multicenter studies, most recently in the VALIDATE-SWEDEHEART study.

More obvious, Mehran said, is that bivalirudin is associated with less major bleeding than heparin in several large randomized trials.

“Throughout the debate over bivalirudin — I thought we were done with it — there’s been an important reduction in major bleeding that should not go understated,” she said. “Yes, the heparin arm usually did have glycoprotein IIb/IIIa inhibitors, especially in HORIZONS-AMI and EUROMAX, but in BRIGHT and MATRIX, where that was not the case, there still was a reduction in bleeding” with bivalirudin.

A soon-to-be-published meta-analysis indicates that net adverse clinical events favor bivalirudin if HEAT-PPCI is excluded, Mehran said.

“Bivalirudin hasn’t gone away. It can be used as an alternative to heparin. Let’s not push it aside, especially in those patients who can’t receive heparin, such as those with heparin-induced thrombocytopenia,” she said. “If you’re going to give a glycoprotein IIb/IIIa inhibitor [with heparin], please at least think about bivalirudin as an alternative. Because you will reduce non-access bleeding compared to heparin with a glycoprotein IIb/IIIa inhibitor. With the novel P2Y12 antagonists as well as IV P2Y12 inhibitors, and with full-dose bivalirudin and a good infusion rate, we should take care of any untoward ischemic complication that would have been an effect of bivalirudin alone.”

The case for heparin

Pinto said meta-analyses have shown, as was seen in HEAT-PPCI, that bivalirudin is associated with more than twice the risk for acute stent thrombosis compared with heparin.

“We do pay a penalty on the ischemic side with bivalirudin, especially when not appropriately treated with antiplatelet medications,” he said.

Another meta-analysis found bivalirudin was riskier than heparin for any ischemic event “and the benefit [of heparin] was evident whether it was planned glycoprotein IIb/IIIa inhibitors in both arms, planned glycoprotein IIb/IIIa inhibitors in the heparin-alone arm or provisional, which is how we utilize glycoprotein IIb/IIIa antagonists in current practice,” he said.

Although some trials have shown that heparin is associated with more bleeding risk vs. bivalirudin, “if glycoprotein IIb/IIIa antagonists aren’t used, heparin and bivalirudin have similar bleeding rates,” according to Pinto.

Pinto also argued that “in the contemporary era of radial access and potent P2Y12 inhibition, heparin is the best choice.”

Among patients with STEMI from the CATH-PCI registry undergoing PCI via transradial access, he said there was no difference in outcomes between bivalirudin and heparin, and VALIDATE-SWEDEHEART, “which now reflects contemporary practice: mainly radial approach, mainly ticagrelor (Brilinta, AstraZeneca),” showed no difference in mortality or MI at 180 days and no difference in bleeding events.

“The reality is, we shouldn’t be looking at a way to improve bivalirudin outcomes by giving heparin to mitigate the risk of stent thrombosis,” Pinto said. “But we also shouldn’t be prolonging an infusion just to get to the same place we started with heparin. That doesn’t seem to be a good strategy.”

As with all debates at meetings, the arguments made by the participants may not be reflective of their actual positions, Pinto said. – by Erik Swain

References:

Mehran R.

Pinto DS. Controversies in Interventional Pharmacology – Debate I: Heparin vs. Bivalirudin. Both presented at: Society for Cardiovascular Angiography and Interventions Scientific Sessions; April 25-28, 2018; San Diego.

Disclosures: Mehran reports she has financial ties with multiple pharmaceutical and device companies and her spouse received honoraria from The Medicines Company. Pinto reports he consults for Chiesi and Terumo and has served as an investigator for Chiesi, and in the past received honoraria, consultant fees and research grants from The Medicines Company.

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