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The investigational antiplatelet drug cangrelor outperformed clopidogrel during percutaneous coronary intervention, significantly reducing the risk of death, myocardial infarction, ischemic events, and stent thrombosis by 22%.
A 20% decrease in heart attack risk accounted for most of the benefit, which was achieved without an increased risk for bleeding. Cangrelor showed some treatment flexibility as well, maintaining its benefits whether given before, during, or after PCI.
The study – CHAMPION PHOENIX – was presented at the annual meeting of the American College of Cardiology and published simultaneously in the New England Journal of Medicine (2013; DOI:10.1056/NEJMoa1300815).
The findings shed a more positive light on cangrelor, which fared poorly in two discontinued phase III trials, CHAMPION-PLATFORM, and CHAMPION-PCI; both studies examined the drug’s use in PCI. In 2009, The Medicines Company, which manufactures cangrelor, pulled the plug on both trials after deciding that neither would provide enough positive evidence to pave the way for approval.
In 2012, however, the company published positive results from its BRIDGE trial, finding that cangrelor could effectively maintain anticoagulation for patients who needed to stop their regular antiplatelet therapy while waiting for a non-emergency coronary artery bypass graft.
While neither of the CHAMPION trials met their primary endpoints, both showed positive findings on some secondary endpoints, including stent thrombosis, according to Dr. Deepak L. Bhatt of the Veterans Administration Boston Healthcare System, and his coauthors.
CHAMPION PHOENIX comprised 11,145 patients undergoing either urgent or elective PCI. They were randomized to either a cangrelor/clopidogrel or clopidogrel-only protocol. Patients in the study arm received a cangrelor bolus and infusion, followed by placebo capsules before PCI, and either 300 mg or 600 mg of clopidogrel after (according to the site investigator’s preference). Patients in the comparator group received a placebo bolus and infusion, followed by clopidogrel before PCI and placebo capsules after.
The primary endpoint was a combination of death, myocardial infarction (MI), revascularization because of ischemia, or stent thrombosis at 48 hours after treatment. The secondary endpoint was stent thrombosis at 48 hours. Severe bleeding at 48 hours was the primary safety endpoint.
The patients’ average age was 64 years. Stable angina was the most common indication for PCI (56%). Other indications were non–ST-segment elevation acute coronary syndrome (26%) and ST-segment elevation MI (18%).
The median time from admission to PCI was just over 4 hours. Drug-eluting stents were placed in 56% of the group and bare-metal stents in 42%.
The combined primary endpoint occurred in 5% of the cangrelor group and 6% of the clopidogrel group – a significant 22% risk reduction. The number needed to treat to prevent 1 primary endpoint event was 84.
Stent thrombosis was also significantly less common in the cangrelor group, compared with the placebo group (0.8% vs. 1.4%; OR 0.62).
At 30 days, the incidence of the composite primary endpoint remained significantly lower in the cangrelor group, compared with the placebo group (6% vs. 7%; OR 0.85), as did the incidence of stent thrombosis (1.3% vs. 1.9%; OR 0.68).
The rate of intraprocedural stent thrombosis was also significantly lower in the cangrelor group, compared with the placebo group (0.6% vs. 1%; OR 0.65). Rescue therapy was employed in significantly fewer patients taking cangrelor (2.3% vs. 3.5%; OR 0.65). The rate of procedural complications was also significantly lower in patients taking cangrelor (3.4% vs. 4.5%; OR 0.74).
The rate of severe bleeding was 0.16% in the cangrelor group and 0.11% in the clopidogrel group – not significantly different. Overall, the rate of adverse events was similar, occurring in 20% of cangrelor patients, compared with 19% of clopidogrel patients. However, patients taking the study drug experienced significantly more dyspnea (1.2% vs. 0.3%).
Cangrelor was equally effective in all patient subgroups, the investigators noted.
Cangrelor demonstrated some treatment flexibility. The drug was equally effective in preventing the primary composite endpoint when given before PCI (OR 0.80), during PCI (OR 0.79), or after PCI (OR 0.79). It also worked equally as well for the 75% of patients who received the 600-mg clopidogrel loading dose, as it did for the 25% who received the 300-mg loading dose (OR 0.77 and 0.84, respectively).
The study design specified at least 2 hours of cangrelor infusion; the median infusion time was 129 minutes. But the drug was just as effective in those who had less than 129 minutes, as for those who had more (OR 0.85 and 0.72, respectively).
Cangrelor is a fast-acting ADP P2Y12 inhibitor, achieving an immediate antiplatelet effect, which is maintained as long as the drug is infused. However, its half-life is extremely short – just 3-5 minutes after discontinuation; platelet function normalizes within 1 hour. Because of this, the drug could benefit those who need a short-acting anticoagulant, the authors noted.
“For example, in patients waiting to undergo open-heart surgery, cangrelor (at a lower dose than that used in this study) has been shown to result in consistent platelet inhibition without a significant increase in bleeding,” they reported.
The Medicines Company funded the study. Dr. Bhatt reported that he has received grant money from numerous pharmaceutical companies. He has also received remuneration for lectures, manuscripts and manuscript preparation, and that he holds patents and receives royalties; however, he did not provide details about any of these disclosures.
The need for a rapid-acting anticoagulant is real –
but is cangrelor the answer?
Not necessarily, according to Dr. Richard A. Lange and Dr. L. David Hills. At face value, the CHAMPION PHOENIX trial data look
good – certainly better than the past two CHAMPION studies, in which the drug
failed to achieve its primary endpoints. PHOENIX
investigators concluded that this study succeeded where its predecessors failed.
But PHOENIX
is riddled with methodological flaws that taint the findings, they wrote.
Unlike patients who took clopidogrel, those who took
the study drug did experience a maximal antiplatelet effect before and during percutaneous
coronary intervention (PCI). But 25% of the clopidogrel group received a 300 mg
loading dose – an amount inferior to the 600 mg dose the rest of the patients
received.
"Furthermore, 37% of the patients in the clopidogrel
group received the drug during or after PCI; as a result, the antiplatelet
effects of clopidogrel were suboptimal at the time of PCI. In the case of the
63% of the patients who received clopidogrel before PCI, information on the
time from the administration of clopidogrel to PCI is not provided, thereby making
it difficult to ascertain whether the antiplatelet effects of the drug were
maximal at the time of PCI," they wrote.
And, Dr. Lange and Dr. Hills noted, "in many centers, patients with
an acute coronary syndrome (which was the diagnosis at presentation in 44% of
the patients in this study) receive ticagrelor or prasugrel, since these drugs
are superior to clopidogrel at reducing PCI-related complications."
There are no studies comparing cangrelor to those drugs.
They also pointed out that a composite primary
endpoint of reduction in periprocedural myocardial infarction and stent
thrombosis drove the positive findings in CHAPMION PHOENIX. But the investigators
didn’t provide enough detail to really break the findings down.
"It is often difficult to distinguish a myocardial
infarction that occurs before randomization from one that occurs after
randomization, especially when the time from hospitalization to PCI is brief,"
Dr. Lange and Dr. Hills noted.
The PHOENIX
study findings didn’t describe how stent thromboses were identified, nor did the findings mention whether all
coronary angiograms were interpreted by a core lab.
"On the basis of these concerns, it would seem that
although some patients undergoing PCI may benefit from intravenous ADP-receptor
antagonist, such as cangrelor, the routine use of this therapy for all patients
undergoing PCI is not yet justified," they wrote.
Dr. Lange and Dr. Hills are from the University of Texas Health Sciences Center, San Antonio. They made these comments in an editorial accompanying the study (N. Engl. J. Med. 2013; DOI:10.1056/NEJMe1302504). They did not disclose having any conflicts of interest.
The need for a rapid-acting anticoagulant is real –
but is cangrelor the answer?
Not necessarily, according to Dr. Richard A. Lange and Dr. L. David Hills. At face value, the CHAMPION PHOENIX trial data look
good – certainly better than the past two CHAMPION studies, in which the drug
failed to achieve its primary endpoints. PHOENIX
investigators concluded that this study succeeded where its predecessors failed.
But PHOENIX
is riddled with methodological flaws that taint the findings, they wrote.
Unlike patients who took clopidogrel, those who took
the study drug did experience a maximal antiplatelet effect before and during percutaneous
coronary intervention (PCI). But 25% of the clopidogrel group received a 300 mg
loading dose – an amount inferior to the 600 mg dose the rest of the patients
received.
"Furthermore, 37% of the patients in the clopidogrel
group received the drug during or after PCI; as a result, the antiplatelet
effects of clopidogrel were suboptimal at the time of PCI. In the case of the
63% of the patients who received clopidogrel before PCI, information on the
time from the administration of clopidogrel to PCI is not provided, thereby making
it difficult to ascertain whether the antiplatelet effects of the drug were
maximal at the time of PCI," they wrote.
And, Dr. Lange and Dr. Hills noted, "in many centers, patients with
an acute coronary syndrome (which was the diagnosis at presentation in 44% of
the patients in this study) receive ticagrelor or prasugrel, since these drugs
are superior to clopidogrel at reducing PCI-related complications."
There are no studies comparing cangrelor to those drugs.
They also pointed out that a composite primary
endpoint of reduction in periprocedural myocardial infarction and stent
thrombosis drove the positive findings in CHAPMION PHOENIX. But the investigators
didn’t provide enough detail to really break the findings down.
"It is often difficult to distinguish a myocardial
infarction that occurs before randomization from one that occurs after
randomization, especially when the time from hospitalization to PCI is brief,"
Dr. Lange and Dr. Hills noted.
The PHOENIX
study findings didn’t describe how stent thromboses were identified, nor did the findings mention whether all
coronary angiograms were interpreted by a core lab.
"On the basis of these concerns, it would seem that
although some patients undergoing PCI may benefit from intravenous ADP-receptor
antagonist, such as cangrelor, the routine use of this therapy for all patients
undergoing PCI is not yet justified," they wrote.
Dr. Lange and Dr. Hills are from the University of Texas Health Sciences Center, San Antonio. They made these comments in an editorial accompanying the study (N. Engl. J. Med. 2013; DOI:10.1056/NEJMe1302504). They did not disclose having any conflicts of interest.
The need for a rapid-acting anticoagulant is real –
but is cangrelor the answer?
Not necessarily, according to Dr. Richard A. Lange and Dr. L. David Hills. At face value, the CHAMPION PHOENIX trial data look
good – certainly better than the past two CHAMPION studies, in which the drug
failed to achieve its primary endpoints. PHOENIX
investigators concluded that this study succeeded where its predecessors failed.
But PHOENIX
is riddled with methodological flaws that taint the findings, they wrote.
Unlike patients who took clopidogrel, those who took
the study drug did experience a maximal antiplatelet effect before and during percutaneous
coronary intervention (PCI). But 25% of the clopidogrel group received a 300 mg
loading dose – an amount inferior to the 600 mg dose the rest of the patients
received.
"Furthermore, 37% of the patients in the clopidogrel
group received the drug during or after PCI; as a result, the antiplatelet
effects of clopidogrel were suboptimal at the time of PCI. In the case of the
63% of the patients who received clopidogrel before PCI, information on the
time from the administration of clopidogrel to PCI is not provided, thereby making
it difficult to ascertain whether the antiplatelet effects of the drug were
maximal at the time of PCI," they wrote.
And, Dr. Lange and Dr. Hills noted, "in many centers, patients with
an acute coronary syndrome (which was the diagnosis at presentation in 44% of
the patients in this study) receive ticagrelor or prasugrel, since these drugs
are superior to clopidogrel at reducing PCI-related complications."
There are no studies comparing cangrelor to those drugs.
They also pointed out that a composite primary
endpoint of reduction in periprocedural myocardial infarction and stent
thrombosis drove the positive findings in CHAPMION PHOENIX. But the investigators
didn’t provide enough detail to really break the findings down.
"It is often difficult to distinguish a myocardial
infarction that occurs before randomization from one that occurs after
randomization, especially when the time from hospitalization to PCI is brief,"
Dr. Lange and Dr. Hills noted.
The PHOENIX
study findings didn’t describe how stent thromboses were identified, nor did the findings mention whether all
coronary angiograms were interpreted by a core lab.
"On the basis of these concerns, it would seem that
although some patients undergoing PCI may benefit from intravenous ADP-receptor
antagonist, such as cangrelor, the routine use of this therapy for all patients
undergoing PCI is not yet justified," they wrote.
Dr. Lange and Dr. Hills are from the University of Texas Health Sciences Center, San Antonio. They made these comments in an editorial accompanying the study (N. Engl. J. Med. 2013; DOI:10.1056/NEJMe1302504). They did not disclose having any conflicts of interest.
The investigational antiplatelet drug cangrelor outperformed clopidogrel during percutaneous coronary intervention, significantly reducing the risk of death, myocardial infarction, ischemic events, and stent thrombosis by 22%.
A 20% decrease in heart attack risk accounted for most of the benefit, which was achieved without an increased risk for bleeding. Cangrelor showed some treatment flexibility as well, maintaining its benefits whether given before, during, or after PCI.
The study – CHAMPION PHOENIX – was presented at the annual meeting of the American College of Cardiology and published simultaneously in the New England Journal of Medicine (2013; DOI:10.1056/NEJMoa1300815).
The findings shed a more positive light on cangrelor, which fared poorly in two discontinued phase III trials, CHAMPION-PLATFORM, and CHAMPION-PCI; both studies examined the drug’s use in PCI. In 2009, The Medicines Company, which manufactures cangrelor, pulled the plug on both trials after deciding that neither would provide enough positive evidence to pave the way for approval.
In 2012, however, the company published positive results from its BRIDGE trial, finding that cangrelor could effectively maintain anticoagulation for patients who needed to stop their regular antiplatelet therapy while waiting for a non-emergency coronary artery bypass graft.
While neither of the CHAMPION trials met their primary endpoints, both showed positive findings on some secondary endpoints, including stent thrombosis, according to Dr. Deepak L. Bhatt of the Veterans Administration Boston Healthcare System, and his coauthors.
CHAMPION PHOENIX comprised 11,145 patients undergoing either urgent or elective PCI. They were randomized to either a cangrelor/clopidogrel or clopidogrel-only protocol. Patients in the study arm received a cangrelor bolus and infusion, followed by placebo capsules before PCI, and either 300 mg or 600 mg of clopidogrel after (according to the site investigator’s preference). Patients in the comparator group received a placebo bolus and infusion, followed by clopidogrel before PCI and placebo capsules after.
The primary endpoint was a combination of death, myocardial infarction (MI), revascularization because of ischemia, or stent thrombosis at 48 hours after treatment. The secondary endpoint was stent thrombosis at 48 hours. Severe bleeding at 48 hours was the primary safety endpoint.
The patients’ average age was 64 years. Stable angina was the most common indication for PCI (56%). Other indications were non–ST-segment elevation acute coronary syndrome (26%) and ST-segment elevation MI (18%).
The median time from admission to PCI was just over 4 hours. Drug-eluting stents were placed in 56% of the group and bare-metal stents in 42%.
The combined primary endpoint occurred in 5% of the cangrelor group and 6% of the clopidogrel group – a significant 22% risk reduction. The number needed to treat to prevent 1 primary endpoint event was 84.
Stent thrombosis was also significantly less common in the cangrelor group, compared with the placebo group (0.8% vs. 1.4%; OR 0.62).
At 30 days, the incidence of the composite primary endpoint remained significantly lower in the cangrelor group, compared with the placebo group (6% vs. 7%; OR 0.85), as did the incidence of stent thrombosis (1.3% vs. 1.9%; OR 0.68).
The rate of intraprocedural stent thrombosis was also significantly lower in the cangrelor group, compared with the placebo group (0.6% vs. 1%; OR 0.65). Rescue therapy was employed in significantly fewer patients taking cangrelor (2.3% vs. 3.5%; OR 0.65). The rate of procedural complications was also significantly lower in patients taking cangrelor (3.4% vs. 4.5%; OR 0.74).
The rate of severe bleeding was 0.16% in the cangrelor group and 0.11% in the clopidogrel group – not significantly different. Overall, the rate of adverse events was similar, occurring in 20% of cangrelor patients, compared with 19% of clopidogrel patients. However, patients taking the study drug experienced significantly more dyspnea (1.2% vs. 0.3%).
Cangrelor was equally effective in all patient subgroups, the investigators noted.
Cangrelor demonstrated some treatment flexibility. The drug was equally effective in preventing the primary composite endpoint when given before PCI (OR 0.80), during PCI (OR 0.79), or after PCI (OR 0.79). It also worked equally as well for the 75% of patients who received the 600-mg clopidogrel loading dose, as it did for the 25% who received the 300-mg loading dose (OR 0.77 and 0.84, respectively).
The study design specified at least 2 hours of cangrelor infusion; the median infusion time was 129 minutes. But the drug was just as effective in those who had less than 129 minutes, as for those who had more (OR 0.85 and 0.72, respectively).
Cangrelor is a fast-acting ADP P2Y12 inhibitor, achieving an immediate antiplatelet effect, which is maintained as long as the drug is infused. However, its half-life is extremely short – just 3-5 minutes after discontinuation; platelet function normalizes within 1 hour. Because of this, the drug could benefit those who need a short-acting anticoagulant, the authors noted.
“For example, in patients waiting to undergo open-heart surgery, cangrelor (at a lower dose than that used in this study) has been shown to result in consistent platelet inhibition without a significant increase in bleeding,” they reported.
The Medicines Company funded the study. Dr. Bhatt reported that he has received grant money from numerous pharmaceutical companies. He has also received remuneration for lectures, manuscripts and manuscript preparation, and that he holds patents and receives royalties; however, he did not provide details about any of these disclosures.
The investigational antiplatelet drug cangrelor outperformed clopidogrel during percutaneous coronary intervention, significantly reducing the risk of death, myocardial infarction, ischemic events, and stent thrombosis by 22%.
A 20% decrease in heart attack risk accounted for most of the benefit, which was achieved without an increased risk for bleeding. Cangrelor showed some treatment flexibility as well, maintaining its benefits whether given before, during, or after PCI.
The study – CHAMPION PHOENIX – was presented at the annual meeting of the American College of Cardiology and published simultaneously in the New England Journal of Medicine (2013; DOI:10.1056/NEJMoa1300815).
The findings shed a more positive light on cangrelor, which fared poorly in two discontinued phase III trials, CHAMPION-PLATFORM, and CHAMPION-PCI; both studies examined the drug’s use in PCI. In 2009, The Medicines Company, which manufactures cangrelor, pulled the plug on both trials after deciding that neither would provide enough positive evidence to pave the way for approval.
In 2012, however, the company published positive results from its BRIDGE trial, finding that cangrelor could effectively maintain anticoagulation for patients who needed to stop their regular antiplatelet therapy while waiting for a non-emergency coronary artery bypass graft.
While neither of the CHAMPION trials met their primary endpoints, both showed positive findings on some secondary endpoints, including stent thrombosis, according to Dr. Deepak L. Bhatt of the Veterans Administration Boston Healthcare System, and his coauthors.
CHAMPION PHOENIX comprised 11,145 patients undergoing either urgent or elective PCI. They were randomized to either a cangrelor/clopidogrel or clopidogrel-only protocol. Patients in the study arm received a cangrelor bolus and infusion, followed by placebo capsules before PCI, and either 300 mg or 600 mg of clopidogrel after (according to the site investigator’s preference). Patients in the comparator group received a placebo bolus and infusion, followed by clopidogrel before PCI and placebo capsules after.
The primary endpoint was a combination of death, myocardial infarction (MI), revascularization because of ischemia, or stent thrombosis at 48 hours after treatment. The secondary endpoint was stent thrombosis at 48 hours. Severe bleeding at 48 hours was the primary safety endpoint.
The patients’ average age was 64 years. Stable angina was the most common indication for PCI (56%). Other indications were non–ST-segment elevation acute coronary syndrome (26%) and ST-segment elevation MI (18%).
The median time from admission to PCI was just over 4 hours. Drug-eluting stents were placed in 56% of the group and bare-metal stents in 42%.
The combined primary endpoint occurred in 5% of the cangrelor group and 6% of the clopidogrel group – a significant 22% risk reduction. The number needed to treat to prevent 1 primary endpoint event was 84.
Stent thrombosis was also significantly less common in the cangrelor group, compared with the placebo group (0.8% vs. 1.4%; OR 0.62).
At 30 days, the incidence of the composite primary endpoint remained significantly lower in the cangrelor group, compared with the placebo group (6% vs. 7%; OR 0.85), as did the incidence of stent thrombosis (1.3% vs. 1.9%; OR 0.68).
The rate of intraprocedural stent thrombosis was also significantly lower in the cangrelor group, compared with the placebo group (0.6% vs. 1%; OR 0.65). Rescue therapy was employed in significantly fewer patients taking cangrelor (2.3% vs. 3.5%; OR 0.65). The rate of procedural complications was also significantly lower in patients taking cangrelor (3.4% vs. 4.5%; OR 0.74).
The rate of severe bleeding was 0.16% in the cangrelor group and 0.11% in the clopidogrel group – not significantly different. Overall, the rate of adverse events was similar, occurring in 20% of cangrelor patients, compared with 19% of clopidogrel patients. However, patients taking the study drug experienced significantly more dyspnea (1.2% vs. 0.3%).
Cangrelor was equally effective in all patient subgroups, the investigators noted.
Cangrelor demonstrated some treatment flexibility. The drug was equally effective in preventing the primary composite endpoint when given before PCI (OR 0.80), during PCI (OR 0.79), or after PCI (OR 0.79). It also worked equally as well for the 75% of patients who received the 600-mg clopidogrel loading dose, as it did for the 25% who received the 300-mg loading dose (OR 0.77 and 0.84, respectively).
The study design specified at least 2 hours of cangrelor infusion; the median infusion time was 129 minutes. But the drug was just as effective in those who had less than 129 minutes, as for those who had more (OR 0.85 and 0.72, respectively).
Cangrelor is a fast-acting ADP P2Y12 inhibitor, achieving an immediate antiplatelet effect, which is maintained as long as the drug is infused. However, its half-life is extremely short – just 3-5 minutes after discontinuation; platelet function normalizes within 1 hour. Because of this, the drug could benefit those who need a short-acting anticoagulant, the authors noted.
“For example, in patients waiting to undergo open-heart surgery, cangrelor (at a lower dose than that used in this study) has been shown to result in consistent platelet inhibition without a significant increase in bleeding,” they reported.
The Medicines Company funded the study. Dr. Bhatt reported that he has received grant money from numerous pharmaceutical companies. He has also received remuneration for lectures, manuscripts and manuscript preparation, and that he holds patents and receives royalties; however, he did not provide details about any of these disclosures.
FROM ACC 13
Major finding: Compared
to clopidogrel, cangrelor reduced the risk of death, myocardial infarction,
ischemic events, and stent thrombosis by 22% in patients undergoing percutaneous
coronary intervention.
Data source: CHAMPION PHOENIX,
a phase III, randomized controlled trial of 11,145 patients undergoing PCI.
Disclosures: The Medicines Company funded the
study. Dr. Bhatt reported that he has received grant money from numerous pharmaceutical
companies. He also declared that he has received remuneration for lectures,
manuscripts and manuscript preparation, and that he holds patents and receives
royalties; however, he did not provide details about any of these disclosures.
