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WASHINGTON – Unfractionated heparin outperformed bivalirudin for 28-day outcomes in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention in a single-center randomized trial of more than 1,800 patients when use of a glycoprotein IIb/IIIa inhibitor was kept to a minimum.
Use of unfractionated heparin (UFH) compared with bivalirudin (Angiomax) led to a significant reduction in the rate of combined major adverse coronary events after 28 days compared with bivalirudin driven primarily by a significant cut in the rate of acute stent thrombosis and repeat myocardial infarctions with no increased risk for major bleeding events, consistent results across all subgroups examined, and the potential for substantial savings in drug costs, Dr. Adeel Shahzad said at the annual meeting of the American College of Cardiology.
The combined rate of major adverse coronary events was 6% in patients treated with UFH and 9% in those treated with bivalirudin, a statistically significant difference for the study’s primary efficacy endpoint. The rate of major bleeding events, the study’s primary safety endpoint, occurred in 3.5% of patients treated with bivalirudin and in 3.1% of those who received UFH, a difference that was not statistically significant.
The superior outcome with UFH in this study, which contrasted sharply with the results of several prior head-to-head comparisons of the two drugs in patients with a ST-segment elevation myocardial infarction (STEMI) or other acute coronary syndrome events undergoing primary percutaneous coronary intervention (PCI) seemed closely tied to the study’s protocol that restricted coadministration of a glycoprotein IIb/IIIa inhibitor (such as abciximab [ReoPro]) to only those patients experiencing thrombotic complications during PCI ("bailout" use).
"For the first time, unfractionated heparin was used like bivalirudin," with low use of a glycoprotein IIb/IIIa inhibitor, noted the study’s principal investigator, Dr. Rod Stables, director of the cardiac catheterization laboratory at Liverpool (England) Heart and Chest Hospital.
Current STEMI management guidelines from the American College of Cardiology and American Heart Association (J. Am. Coll. Cardiol. 2013;61:e78-140) and from the European Society of Cardiology (Eur. Heart J. 2012;33:2569-619) endorse use of either bivalirudin or UFH as an anticoagulant when patients undergo primary PCI. The European guidelines say that bivalirudin is preferred over UFH when a glycoprotein IIb/IIIa antagonist is administered along with UFH.
"It’s perfectly legitimate with the guidelines to use unfractionated heparin, but most people [in the United States] use bivalirudin or a glycoprotein IIb/IIIa inhibitor with heparin," said Dr. Spencer B. King III, an interventional cardiologist at St. Joseph’s Health System in Atlanta.
Based on the new results, "people will say it’s really interesting, and they may at least think about not using bivalirudin all the time," said Dr. David R. Holmes Jr., an interventional cardiologist and professor of medicine at the Mayo Clinic in Rochester, Minn. "Those who are believers in bivalirudin will continue to use it, but others will say that heparin did just fine [in this trial] and is less expensive.
Dr. Stables predicted that based on these results, interventionalists at his institution who can choose between bivalirudin and UFH will increasingly use heparin, a change that he estimated could save his hospital as much as 500,000 pounds per year (about $800,000).
The HEAT-PPCI (How Effective are Antithrombotic Therapies in Primary PCI) trial randomized 1,829 STEMI patients at Liverpool Heart and Chest Hospital during February 2012–November 2013. The data analysis included the 1,812 patients from the series who agreed to participate in the study, which had a delayed-consent design (see sidebar). A total of 1,917 patients with STEMI presented at Liverpool during this 22-month period, with about 5% of patients excluded because of prespecified exclusion criteria. This produced a highly representative, "real-world" population. "It’s the closest you can get to an all-comers trial," Dr. Stables said.
About 62% of the patients received ticagrelor (Brilinta) as an antiplatelet drug, about 27% received prasugrel (Effient), and the remaining 11% received clopidogrel. About 14% of the bivalirudin-treated patients and about 16% of those randomized to receive UFH were treated with a glycoprotein IIb/IIIa inhibitor. The door-to-balloon time for patients in the study averaged 29 minutes, and the average age of the patients was 63 years. About 81% of patients underwent coronary catheterization by radial-artery access, with the remainder undergoing femoral-artery access; about 82% of all patients had a PCI procedure actually performed. And of those who underwent primary PCI, about 92% of all patients received at least one coronary stent. The 907 consenting patients randomized to UFH received a dose of 70 units/kg prior to catheterization. The 905 consenting patients randomized to bivalirudin received a 0.75-mg/kg bolus and a 1.75-mg/kg/hour infusion during their procedure.
The difference in rates of major adverse coronary events during the 28-day follow-up seemed driven primarily by a difference in the rate of myocardial infarctions, which occurred in 2.3% of the bivalirudin patients and in 0.8% of the UFH patients, Dr. Shahzad said. The rate of acute stent thrombosis was 2.9% in the bivalirudin arm and 0.9% in patients on UFH.
Several prior trials that compared UFH and bivalirudin in STEMI or acute coronary syndrome patients undergoing PCI or other invasive procedures used either mandatory coadministration of a glycoprotein IIb/IIIa inhibitor along with UHF, or a much higher rate of discretionary use, such as in the ACUITY (N. Engl. J. Med. 2006;355:2203-16), HORIZONS (N. Engl. J. Med. 2008;358:2218-30), and EUROMAX (N. Engl. J. Med. 2013;369:2207-17) studies. In all these trials, the rates of major bleeding events were significantly higher in the UFH arm, and this appeared to lead to an increased number of adverse coronary events during the first month following intervention.
"What we’ve seen in every trial before was a reduction in bleeding complications of about 40% to 50%. The National Cardiovascular Data Registry shows a tremendous decrease [in bleeding] when you change from heparin to bivalirudin," said Dr. Roxana Mehran, an interventional cardiologist and professor of medicine at Mount Sinai Hospital in New York.
"All the trials had differential use of glycoprotein IIb/IIIa inhibitors" in the UFH and bivalirudin arms, noted Dr. Shahzad, an interventional cardiologist at Liverpool Heart and Chest Hospital.
Dr. Stables said that the low bleeding rates with UFH in the new study seemed largely dependent on the relatively low rate at which patients received a glycoprotein IIb/IIIa inhibitor and did not correlate with radial-artery access. "We did a prespecified subgroup analysis of patients who underwent radial or femoral access and the outcomes were the same in both groups," he said.
Dr. Gregg W. Stone, who served as lead investigator for ACUITY and HORIZONS, contended that the trialists in HEAT-PPCI underdosed bivalirudin based on the average activated clotting time (ACT) of 270 seconds in the bivalirudin-treated patients in the study. Most patients properly treated with bivalirudin achieve ACTs of 350-450 seconds, said Dr. Stone, professor of medicine and director of cardiovascular research and education at Columbia University in New York. Dr. Stone also noted that the "results of this single-center study were markedly different from three randomized, controlled trials done at 250 centers and involving more than 8,000 patients."
Dr. Shahzad countered that the ACT-measuring device used at his institution was consistently accurate but measures ACT levels that are typically 50 seconds below values obtained with most other devices.
HEAT-PPCI did not receive any commercial funding. Dr. Shahzad, Dr. Stables, Dr. King, and Dr. Holmes had no disclosures. Dr. Mehran has received consultant fees, honoraria, and/or research grants from 10 drug and device companies, but not from The Medicines Company, which markets Angiomax. Dr. Stone has grants or fees from, or has an ownership position in, several drug or device companies, but not The Medicines Company.
On Twitter @mitchelzoler
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Mitchel L. Zoler/Frontline Medical News
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This was an extremely well-conducted trial with a very large patient population and meticulous oversight and exceptionally complete follow-up.
There has been a signal of increased stent thrombosis early on with bivalirudin, as was seen in the EUROMAX trial (N. Engl. J. Med. 2013;369:2207-17), but over the longer term these differences in event rates have been mitigated. A surprise in the current study was the absence of a difference in major bleeding complications between the two drug arms. The trial used radial access in 80% of patients, and radial access has been associated with significant decreases in access-site bleeding compared with transfemoral access. Future studies should examine the role of transradial access in leading to reduced bleeding in this setting.
David Kandzari, M.D., is an interventional cardiologist with Piedmont Healthcare in Atlanta. He has been a consultant to, and has received honoraria from, Micell Technologies, Biotronik, Boston Scientific, Thoratec, and Medtronic. He made these comments as a discussant for the trial.
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Mitchel L. Zoler/Frontline Medical News
|
This was an extremely well-conducted trial with a very large patient population and meticulous oversight and exceptionally complete follow-up.
There has been a signal of increased stent thrombosis early on with bivalirudin, as was seen in the EUROMAX trial (N. Engl. J. Med. 2013;369:2207-17), but over the longer term these differences in event rates have been mitigated. A surprise in the current study was the absence of a difference in major bleeding complications between the two drug arms. The trial used radial access in 80% of patients, and radial access has been associated with significant decreases in access-site bleeding compared with transfemoral access. Future studies should examine the role of transradial access in leading to reduced bleeding in this setting.
David Kandzari, M.D., is an interventional cardiologist with Piedmont Healthcare in Atlanta. He has been a consultant to, and has received honoraria from, Micell Technologies, Biotronik, Boston Scientific, Thoratec, and Medtronic. He made these comments as a discussant for the trial.
|
Mitchel L. Zoler/Frontline Medical News
|
This was an extremely well-conducted trial with a very large patient population and meticulous oversight and exceptionally complete follow-up.
There has been a signal of increased stent thrombosis early on with bivalirudin, as was seen in the EUROMAX trial (N. Engl. J. Med. 2013;369:2207-17), but over the longer term these differences in event rates have been mitigated. A surprise in the current study was the absence of a difference in major bleeding complications between the two drug arms. The trial used radial access in 80% of patients, and radial access has been associated with significant decreases in access-site bleeding compared with transfemoral access. Future studies should examine the role of transradial access in leading to reduced bleeding in this setting.
David Kandzari, M.D., is an interventional cardiologist with Piedmont Healthcare in Atlanta. He has been a consultant to, and has received honoraria from, Micell Technologies, Biotronik, Boston Scientific, Thoratec, and Medtronic. He made these comments as a discussant for the trial.
WASHINGTON – Unfractionated heparin outperformed bivalirudin for 28-day outcomes in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention in a single-center randomized trial of more than 1,800 patients when use of a glycoprotein IIb/IIIa inhibitor was kept to a minimum.
Use of unfractionated heparin (UFH) compared with bivalirudin (Angiomax) led to a significant reduction in the rate of combined major adverse coronary events after 28 days compared with bivalirudin driven primarily by a significant cut in the rate of acute stent thrombosis and repeat myocardial infarctions with no increased risk for major bleeding events, consistent results across all subgroups examined, and the potential for substantial savings in drug costs, Dr. Adeel Shahzad said at the annual meeting of the American College of Cardiology.
The combined rate of major adverse coronary events was 6% in patients treated with UFH and 9% in those treated with bivalirudin, a statistically significant difference for the study’s primary efficacy endpoint. The rate of major bleeding events, the study’s primary safety endpoint, occurred in 3.5% of patients treated with bivalirudin and in 3.1% of those who received UFH, a difference that was not statistically significant.
The superior outcome with UFH in this study, which contrasted sharply with the results of several prior head-to-head comparisons of the two drugs in patients with a ST-segment elevation myocardial infarction (STEMI) or other acute coronary syndrome events undergoing primary percutaneous coronary intervention (PCI) seemed closely tied to the study’s protocol that restricted coadministration of a glycoprotein IIb/IIIa inhibitor (such as abciximab [ReoPro]) to only those patients experiencing thrombotic complications during PCI ("bailout" use).
"For the first time, unfractionated heparin was used like bivalirudin," with low use of a glycoprotein IIb/IIIa inhibitor, noted the study’s principal investigator, Dr. Rod Stables, director of the cardiac catheterization laboratory at Liverpool (England) Heart and Chest Hospital.
Current STEMI management guidelines from the American College of Cardiology and American Heart Association (J. Am. Coll. Cardiol. 2013;61:e78-140) and from the European Society of Cardiology (Eur. Heart J. 2012;33:2569-619) endorse use of either bivalirudin or UFH as an anticoagulant when patients undergo primary PCI. The European guidelines say that bivalirudin is preferred over UFH when a glycoprotein IIb/IIIa antagonist is administered along with UFH.
"It’s perfectly legitimate with the guidelines to use unfractionated heparin, but most people [in the United States] use bivalirudin or a glycoprotein IIb/IIIa inhibitor with heparin," said Dr. Spencer B. King III, an interventional cardiologist at St. Joseph’s Health System in Atlanta.
Based on the new results, "people will say it’s really interesting, and they may at least think about not using bivalirudin all the time," said Dr. David R. Holmes Jr., an interventional cardiologist and professor of medicine at the Mayo Clinic in Rochester, Minn. "Those who are believers in bivalirudin will continue to use it, but others will say that heparin did just fine [in this trial] and is less expensive.
Dr. Stables predicted that based on these results, interventionalists at his institution who can choose between bivalirudin and UFH will increasingly use heparin, a change that he estimated could save his hospital as much as 500,000 pounds per year (about $800,000).
The HEAT-PPCI (How Effective are Antithrombotic Therapies in Primary PCI) trial randomized 1,829 STEMI patients at Liverpool Heart and Chest Hospital during February 2012–November 2013. The data analysis included the 1,812 patients from the series who agreed to participate in the study, which had a delayed-consent design (see sidebar). A total of 1,917 patients with STEMI presented at Liverpool during this 22-month period, with about 5% of patients excluded because of prespecified exclusion criteria. This produced a highly representative, "real-world" population. "It’s the closest you can get to an all-comers trial," Dr. Stables said.
About 62% of the patients received ticagrelor (Brilinta) as an antiplatelet drug, about 27% received prasugrel (Effient), and the remaining 11% received clopidogrel. About 14% of the bivalirudin-treated patients and about 16% of those randomized to receive UFH were treated with a glycoprotein IIb/IIIa inhibitor. The door-to-balloon time for patients in the study averaged 29 minutes, and the average age of the patients was 63 years. About 81% of patients underwent coronary catheterization by radial-artery access, with the remainder undergoing femoral-artery access; about 82% of all patients had a PCI procedure actually performed. And of those who underwent primary PCI, about 92% of all patients received at least one coronary stent. The 907 consenting patients randomized to UFH received a dose of 70 units/kg prior to catheterization. The 905 consenting patients randomized to bivalirudin received a 0.75-mg/kg bolus and a 1.75-mg/kg/hour infusion during their procedure.
The difference in rates of major adverse coronary events during the 28-day follow-up seemed driven primarily by a difference in the rate of myocardial infarctions, which occurred in 2.3% of the bivalirudin patients and in 0.8% of the UFH patients, Dr. Shahzad said. The rate of acute stent thrombosis was 2.9% in the bivalirudin arm and 0.9% in patients on UFH.
Several prior trials that compared UFH and bivalirudin in STEMI or acute coronary syndrome patients undergoing PCI or other invasive procedures used either mandatory coadministration of a glycoprotein IIb/IIIa inhibitor along with UHF, or a much higher rate of discretionary use, such as in the ACUITY (N. Engl. J. Med. 2006;355:2203-16), HORIZONS (N. Engl. J. Med. 2008;358:2218-30), and EUROMAX (N. Engl. J. Med. 2013;369:2207-17) studies. In all these trials, the rates of major bleeding events were significantly higher in the UFH arm, and this appeared to lead to an increased number of adverse coronary events during the first month following intervention.
"What we’ve seen in every trial before was a reduction in bleeding complications of about 40% to 50%. The National Cardiovascular Data Registry shows a tremendous decrease [in bleeding] when you change from heparin to bivalirudin," said Dr. Roxana Mehran, an interventional cardiologist and professor of medicine at Mount Sinai Hospital in New York.
"All the trials had differential use of glycoprotein IIb/IIIa inhibitors" in the UFH and bivalirudin arms, noted Dr. Shahzad, an interventional cardiologist at Liverpool Heart and Chest Hospital.
Dr. Stables said that the low bleeding rates with UFH in the new study seemed largely dependent on the relatively low rate at which patients received a glycoprotein IIb/IIIa inhibitor and did not correlate with radial-artery access. "We did a prespecified subgroup analysis of patients who underwent radial or femoral access and the outcomes were the same in both groups," he said.
Dr. Gregg W. Stone, who served as lead investigator for ACUITY and HORIZONS, contended that the trialists in HEAT-PPCI underdosed bivalirudin based on the average activated clotting time (ACT) of 270 seconds in the bivalirudin-treated patients in the study. Most patients properly treated with bivalirudin achieve ACTs of 350-450 seconds, said Dr. Stone, professor of medicine and director of cardiovascular research and education at Columbia University in New York. Dr. Stone also noted that the "results of this single-center study were markedly different from three randomized, controlled trials done at 250 centers and involving more than 8,000 patients."
Dr. Shahzad countered that the ACT-measuring device used at his institution was consistently accurate but measures ACT levels that are typically 50 seconds below values obtained with most other devices.
HEAT-PPCI did not receive any commercial funding. Dr. Shahzad, Dr. Stables, Dr. King, and Dr. Holmes had no disclosures. Dr. Mehran has received consultant fees, honoraria, and/or research grants from 10 drug and device companies, but not from The Medicines Company, which markets Angiomax. Dr. Stone has grants or fees from, or has an ownership position in, several drug or device companies, but not The Medicines Company.
On Twitter @mitchelzoler
WASHINGTON – Unfractionated heparin outperformed bivalirudin for 28-day outcomes in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention in a single-center randomized trial of more than 1,800 patients when use of a glycoprotein IIb/IIIa inhibitor was kept to a minimum.
Use of unfractionated heparin (UFH) compared with bivalirudin (Angiomax) led to a significant reduction in the rate of combined major adverse coronary events after 28 days compared with bivalirudin driven primarily by a significant cut in the rate of acute stent thrombosis and repeat myocardial infarctions with no increased risk for major bleeding events, consistent results across all subgroups examined, and the potential for substantial savings in drug costs, Dr. Adeel Shahzad said at the annual meeting of the American College of Cardiology.
The combined rate of major adverse coronary events was 6% in patients treated with UFH and 9% in those treated with bivalirudin, a statistically significant difference for the study’s primary efficacy endpoint. The rate of major bleeding events, the study’s primary safety endpoint, occurred in 3.5% of patients treated with bivalirudin and in 3.1% of those who received UFH, a difference that was not statistically significant.
The superior outcome with UFH in this study, which contrasted sharply with the results of several prior head-to-head comparisons of the two drugs in patients with a ST-segment elevation myocardial infarction (STEMI) or other acute coronary syndrome events undergoing primary percutaneous coronary intervention (PCI) seemed closely tied to the study’s protocol that restricted coadministration of a glycoprotein IIb/IIIa inhibitor (such as abciximab [ReoPro]) to only those patients experiencing thrombotic complications during PCI ("bailout" use).
"For the first time, unfractionated heparin was used like bivalirudin," with low use of a glycoprotein IIb/IIIa inhibitor, noted the study’s principal investigator, Dr. Rod Stables, director of the cardiac catheterization laboratory at Liverpool (England) Heart and Chest Hospital.
Current STEMI management guidelines from the American College of Cardiology and American Heart Association (J. Am. Coll. Cardiol. 2013;61:e78-140) and from the European Society of Cardiology (Eur. Heart J. 2012;33:2569-619) endorse use of either bivalirudin or UFH as an anticoagulant when patients undergo primary PCI. The European guidelines say that bivalirudin is preferred over UFH when a glycoprotein IIb/IIIa antagonist is administered along with UFH.
"It’s perfectly legitimate with the guidelines to use unfractionated heparin, but most people [in the United States] use bivalirudin or a glycoprotein IIb/IIIa inhibitor with heparin," said Dr. Spencer B. King III, an interventional cardiologist at St. Joseph’s Health System in Atlanta.
Based on the new results, "people will say it’s really interesting, and they may at least think about not using bivalirudin all the time," said Dr. David R. Holmes Jr., an interventional cardiologist and professor of medicine at the Mayo Clinic in Rochester, Minn. "Those who are believers in bivalirudin will continue to use it, but others will say that heparin did just fine [in this trial] and is less expensive.
Dr. Stables predicted that based on these results, interventionalists at his institution who can choose between bivalirudin and UFH will increasingly use heparin, a change that he estimated could save his hospital as much as 500,000 pounds per year (about $800,000).
The HEAT-PPCI (How Effective are Antithrombotic Therapies in Primary PCI) trial randomized 1,829 STEMI patients at Liverpool Heart and Chest Hospital during February 2012–November 2013. The data analysis included the 1,812 patients from the series who agreed to participate in the study, which had a delayed-consent design (see sidebar). A total of 1,917 patients with STEMI presented at Liverpool during this 22-month period, with about 5% of patients excluded because of prespecified exclusion criteria. This produced a highly representative, "real-world" population. "It’s the closest you can get to an all-comers trial," Dr. Stables said.
About 62% of the patients received ticagrelor (Brilinta) as an antiplatelet drug, about 27% received prasugrel (Effient), and the remaining 11% received clopidogrel. About 14% of the bivalirudin-treated patients and about 16% of those randomized to receive UFH were treated with a glycoprotein IIb/IIIa inhibitor. The door-to-balloon time for patients in the study averaged 29 minutes, and the average age of the patients was 63 years. About 81% of patients underwent coronary catheterization by radial-artery access, with the remainder undergoing femoral-artery access; about 82% of all patients had a PCI procedure actually performed. And of those who underwent primary PCI, about 92% of all patients received at least one coronary stent. The 907 consenting patients randomized to UFH received a dose of 70 units/kg prior to catheterization. The 905 consenting patients randomized to bivalirudin received a 0.75-mg/kg bolus and a 1.75-mg/kg/hour infusion during their procedure.
The difference in rates of major adverse coronary events during the 28-day follow-up seemed driven primarily by a difference in the rate of myocardial infarctions, which occurred in 2.3% of the bivalirudin patients and in 0.8% of the UFH patients, Dr. Shahzad said. The rate of acute stent thrombosis was 2.9% in the bivalirudin arm and 0.9% in patients on UFH.
Several prior trials that compared UFH and bivalirudin in STEMI or acute coronary syndrome patients undergoing PCI or other invasive procedures used either mandatory coadministration of a glycoprotein IIb/IIIa inhibitor along with UHF, or a much higher rate of discretionary use, such as in the ACUITY (N. Engl. J. Med. 2006;355:2203-16), HORIZONS (N. Engl. J. Med. 2008;358:2218-30), and EUROMAX (N. Engl. J. Med. 2013;369:2207-17) studies. In all these trials, the rates of major bleeding events were significantly higher in the UFH arm, and this appeared to lead to an increased number of adverse coronary events during the first month following intervention.
"What we’ve seen in every trial before was a reduction in bleeding complications of about 40% to 50%. The National Cardiovascular Data Registry shows a tremendous decrease [in bleeding] when you change from heparin to bivalirudin," said Dr. Roxana Mehran, an interventional cardiologist and professor of medicine at Mount Sinai Hospital in New York.
"All the trials had differential use of glycoprotein IIb/IIIa inhibitors" in the UFH and bivalirudin arms, noted Dr. Shahzad, an interventional cardiologist at Liverpool Heart and Chest Hospital.
Dr. Stables said that the low bleeding rates with UFH in the new study seemed largely dependent on the relatively low rate at which patients received a glycoprotein IIb/IIIa inhibitor and did not correlate with radial-artery access. "We did a prespecified subgroup analysis of patients who underwent radial or femoral access and the outcomes were the same in both groups," he said.
Dr. Gregg W. Stone, who served as lead investigator for ACUITY and HORIZONS, contended that the trialists in HEAT-PPCI underdosed bivalirudin based on the average activated clotting time (ACT) of 270 seconds in the bivalirudin-treated patients in the study. Most patients properly treated with bivalirudin achieve ACTs of 350-450 seconds, said Dr. Stone, professor of medicine and director of cardiovascular research and education at Columbia University in New York. Dr. Stone also noted that the "results of this single-center study were markedly different from three randomized, controlled trials done at 250 centers and involving more than 8,000 patients."
Dr. Shahzad countered that the ACT-measuring device used at his institution was consistently accurate but measures ACT levels that are typically 50 seconds below values obtained with most other devices.
HEAT-PPCI did not receive any commercial funding. Dr. Shahzad, Dr. Stables, Dr. King, and Dr. Holmes had no disclosures. Dr. Mehran has received consultant fees, honoraria, and/or research grants from 10 drug and device companies, but not from The Medicines Company, which markets Angiomax. Dr. Stone has grants or fees from, or has an ownership position in, several drug or device companies, but not The Medicines Company.
On Twitter @mitchelzoler
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