AGGRASTAT(R), Lowers Incidence Of Heart Attack, In Patients Who Respond Poorly To Aspirin Or Clopidogrel, After Elective Coronary Angioplasty
Antiplatelet medicine, AGGRASTAT® (tirofiban HCL), a glycoprotein IIb/IIIa inhibitor, has been shown to significantly lower the incidence of heart attack after elective coronary angioplasty, in patients with coronary artery disease who have shown poor response to standard oral antiplatelet agents such as... aspirin and clopidogrel.1 These results were announced at the Annual European Society of Cardiology Congress in Munich, Germany.
"These findings are significant in that we demonstrate a proof of concept for a new treatment strategy in a patient segment whose needs have so far remained unaddressed - managing for the increased risk of thrombotic events due to non-responsiveness of patients to standard oral antiplatelets such as aspirin or clopidogrel," said Dr Marco Valgimigli, Chair of Cardiology, University of Ferrara, Italy and principal investigator of the 3T/2R Study (Tailoring Treatment with Tirofiban in patients showing Resistance to aspirin and/or Resistance to clopidogrel).
Inhibition of platelet aggregation following an intake of aspirin or clopidogrel varies greatly among patients, and previous studies have shown that poor response to oral antiplatelet agents increases the risk of thrombotic events, especially after coronary angioplasty.1 It was previously unknown if this reflected suboptimal platelet inhibition per se which might benefit from alternative or more potent antiplatelet agents.
Enrolled in the study were 263 patients who were poor responders to aspirin and/or clopidogrel, based upon a point-of-care assay, who underwent elective coronary angioplasty at ten European sites for stable or low-risk unstable coronary artery disease. Patients were randomly assigned in a double blind manner to receive either AGGRASTAT® or placebo on top of standard aspirin and clopidogrel therapy.1 The primary end point was the occurrence of periprocedural myocardial infarction, as defined by an increase in Troponin I or T within 48 hours, and was observed in 20.4 percent of patients treated with AGGRASTAT®, compared to 35.1 percent of patient treated with placebo.1 This resulted in a significant reduction of major adverse cardiovascular events within 30 days in the AGGRASTAT® group compared to the placebo group (21.2 percent versus 36.6 percent, respectively; p=0.0065).1 The incidence of bleeding was low and did not differ between the two groups.1
"Current treatment strategies for patients with coronary artery disease ignore the individual response to antiplatelet agents, and likewise fail to identify therapeutic targets for platelet reactivity necessary to intensify treatment," said Dr Paul Gurbel, Director of Cardiovascular Research, Centre for Thrombosis Research, Sinai Hospital, Baltimore, USA. "These findings illustrate the efficacy and safety of AGGRASTAT® in treating poor responders to aspirin or clopidogrel, as compared to standard care. This study shows that by assessing response to standard antiplatelet agents by a point-of-care assay, intensity of treatment can be modulated accordingly."
Dr Gurbel further commented, "These data are in accordance with our earlier results from the CLEAR PLATELETS studies that have demonstrated the strong association between high periprocedural platelet reactivity and the risk of in-hospital myocardial infarction in patients undergoing elective stenting. The use of glycoprotein IIb/IIIa inhibitors, in patients identified as poor responders to oral antiplatelet agents by objective measurements of platelet function, makes perfect sense and deserves greater attention in future studies."
"These data findings are extremely encouraging for this patient population and we believe it reinforces the potential benefits of high-dose bolus AGGRASTAT®," said John Vavricka, President and Chief Executive Officer of Iroko Pharmaceuticals. "Iroko is committed to furthering clinical research in this area, and exploring AGGRASTAT®'s potential for patients who do not respond to oral anti-platelet therapy."
In January of 2008, Iroko Pharmaceuticals acquired all non-US commercial rights to AGGRASTAT® from Merck & Co., Inc. The 3T/2R study was initiated and conducted by the University of Ferrara, Italy with an unrestricted grant from Merck & Co., Inc. and Iroko.
About AGGRASTAT®
AGGRASTAT®, a glycoprotein IIb/IIIa inhibitor, is indicated for the prevention of early myocardial infarction in patients presenting with unstable angina or non-Q-wave myocardial infarction with the last episode of chest pain occurring within 12 hours and with ECG changes and/or elevated cardiac enzymes. Patients most likely to benefit from AGGRASTAT® treatment are those at high risk of developing myocardial infarction within the first 3-4 days after onset of acute angina symptoms including for instance those that are likely to undergo an early PTCA.
In most patients, AGGRASTAT® should be administered intravenously, at an initial rate of 0.4 mcg/kg/min for 30 minutes and then continued at 0.1 mcg/kg/min. For complete information, please refer to the product's prescribing information. AGGRASTAT® is intended for use with acetylsalicylic acid and unfractionated heparin.
AGGRASTAT® (tirofiban hydrochloride) is contraindicated in patients with known hypersensitivity to any component of the product; active internal bleeding or a history of bleeding diathesis within the previous 30 days; or a history of intracranial hemorrhage, intracranial neoplasm, arteriovenous malformation, or aneurysm. Other contraindications to AGGRASTAT® include: a history of thrombocytopenia following prior exposure to AGGRASTAT®; history of stroke within 30 days or any history of hemorrhagic stroke; major surgical procedure or severe physical trauma within the previous month; or history, symptoms, or findings suggestive of aortic dissection. AGGRASTAT® is also contraindicated in patients with: severe hypertension (systolic blood pressure >180 mmHg and/or diastolic blood pressure >110 mmHg); concomitant use of another parenteral GP IIb/IIIa inhibitor; or acute pericarditis.
Bleeding is the most common complication encountered during therapy with AGGRASTAT®. Administration of AGGRASTAT® is associated with an increase in bleeding events classified as both major and minor bleeding events, by criteria developed by the Thrombolysis in Myocardial Infarction Study group (TIMI). Most major bleeding associated with AGGRASTAT® occurs at the arterial access site for cardiac catheterization. Fatal bleedings have been reported. AGGRASTAT® should be used with caution in patients with platelet count <150,000/mm3, in patients with hemorrhagic retinopathy, and in chronic hemodialysis patients. Because AGGRASTAT® inhibits platelet aggregation; caution should be employed when it is used with other drugs that affect hemostasis. The safety of AGGRASTAT® when used in combination with thrombolytic agents has not been established. During therapy with AGGRASTAT®, patients should be monitored for potential bleeding. When bleeding cannot be controlled with pressure, infusion of AGGRASTAT® and heparin should be discontinued.
The following additional adverse reactions have been reported in post- marketing experience: bleeding, intracranial bleeding, retroperitoneal bleeding, hemopericardium, and pulmonary (alveolar) hemorrhage. Fatal bleedings have been reported; body as a whole: acute and/or severe decreases in platelet counts which may be associated with chills, low grade fever, or bleeding complications; hypersensitivity; rash and/or hives.
Please refer to the specific Prescribing Information for your country for complete warnings and precautions.
About Iroko
Iroko is a pharmaceutical company focused on acquiring, developing, and maximizing the potential of currently marketed pharmaceutical products on a worldwide basis. Iroko applies concentrated selling and marketing efforts and product life cycle management strategies focused on developing new and relevant formulations and indications that benefit patient health. For more information, visit http://www.iroko.com.
About Merck
Merck & Co., Inc. is a global research-driven pharmaceutical company dedicated to putting patients first. Established in 1891, Merck currently discovers, develops, manufactures and markets vaccines and medicines to address unmet medical needs. The company devotes extensive efforts to increase access to medicines through far-reaching programs that not only donate Merck medicines but help deliver them to the people who need them. Merck also publishes unbiased health information as a not-for-profit service. http://www.merck.com
References
1 Valgimigli M, Campo Gianluca, de Cesare N, Meliga E et al. A double-blind randomised multicentre trial of tailored infusion of tirofiban in poor aspirin and/or clopidogrel responders undergoing elective percutaneous coronary intervention. Presented at ESC, 2 September 2008
Merck & Co., Inc
"These findings are significant in that we demonstrate a proof of concept for a new treatment strategy in a patient segment whose needs have so far remained unaddressed - managing for the increased risk of thrombotic events due to non-responsiveness of patients to standard oral antiplatelets such as aspirin or clopidogrel," said Dr Marco Valgimigli, Chair of Cardiology, University of Ferrara, Italy and principal investigator of the 3T/2R Study (Tailoring Treatment with Tirofiban in patients showing Resistance to aspirin and/or Resistance to clopidogrel).
Inhibition of platelet aggregation following an intake of aspirin or clopidogrel varies greatly among patients, and previous studies have shown that poor response to oral antiplatelet agents increases the risk of thrombotic events, especially after coronary angioplasty.1 It was previously unknown if this reflected suboptimal platelet inhibition per se which might benefit from alternative or more potent antiplatelet agents.
Enrolled in the study were 263 patients who were poor responders to aspirin and/or clopidogrel, based upon a point-of-care assay, who underwent elective coronary angioplasty at ten European sites for stable or low-risk unstable coronary artery disease. Patients were randomly assigned in a double blind manner to receive either AGGRASTAT® or placebo on top of standard aspirin and clopidogrel therapy.1 The primary end point was the occurrence of periprocedural myocardial infarction, as defined by an increase in Troponin I or T within 48 hours, and was observed in 20.4 percent of patients treated with AGGRASTAT®, compared to 35.1 percent of patient treated with placebo.1 This resulted in a significant reduction of major adverse cardiovascular events within 30 days in the AGGRASTAT® group compared to the placebo group (21.2 percent versus 36.6 percent, respectively; p=0.0065).1 The incidence of bleeding was low and did not differ between the two groups.1
"Current treatment strategies for patients with coronary artery disease ignore the individual response to antiplatelet agents, and likewise fail to identify therapeutic targets for platelet reactivity necessary to intensify treatment," said Dr Paul Gurbel, Director of Cardiovascular Research, Centre for Thrombosis Research, Sinai Hospital, Baltimore, USA. "These findings illustrate the efficacy and safety of AGGRASTAT® in treating poor responders to aspirin or clopidogrel, as compared to standard care. This study shows that by assessing response to standard antiplatelet agents by a point-of-care assay, intensity of treatment can be modulated accordingly."
Dr Gurbel further commented, "These data are in accordance with our earlier results from the CLEAR PLATELETS studies that have demonstrated the strong association between high periprocedural platelet reactivity and the risk of in-hospital myocardial infarction in patients undergoing elective stenting. The use of glycoprotein IIb/IIIa inhibitors, in patients identified as poor responders to oral antiplatelet agents by objective measurements of platelet function, makes perfect sense and deserves greater attention in future studies."
"These data findings are extremely encouraging for this patient population and we believe it reinforces the potential benefits of high-dose bolus AGGRASTAT®," said John Vavricka, President and Chief Executive Officer of Iroko Pharmaceuticals. "Iroko is committed to furthering clinical research in this area, and exploring AGGRASTAT®'s potential for patients who do not respond to oral anti-platelet therapy."
In January of 2008, Iroko Pharmaceuticals acquired all non-US commercial rights to AGGRASTAT® from Merck & Co., Inc. The 3T/2R study was initiated and conducted by the University of Ferrara, Italy with an unrestricted grant from Merck & Co., Inc. and Iroko.
About AGGRASTAT®
AGGRASTAT®, a glycoprotein IIb/IIIa inhibitor, is indicated for the prevention of early myocardial infarction in patients presenting with unstable angina or non-Q-wave myocardial infarction with the last episode of chest pain occurring within 12 hours and with ECG changes and/or elevated cardiac enzymes. Patients most likely to benefit from AGGRASTAT® treatment are those at high risk of developing myocardial infarction within the first 3-4 days after onset of acute angina symptoms including for instance those that are likely to undergo an early PTCA.
In most patients, AGGRASTAT® should be administered intravenously, at an initial rate of 0.4 mcg/kg/min for 30 minutes and then continued at 0.1 mcg/kg/min. For complete information, please refer to the product's prescribing information. AGGRASTAT® is intended for use with acetylsalicylic acid and unfractionated heparin.
AGGRASTAT® (tirofiban hydrochloride) is contraindicated in patients with known hypersensitivity to any component of the product; active internal bleeding or a history of bleeding diathesis within the previous 30 days; or a history of intracranial hemorrhage, intracranial neoplasm, arteriovenous malformation, or aneurysm. Other contraindications to AGGRASTAT® include: a history of thrombocytopenia following prior exposure to AGGRASTAT®; history of stroke within 30 days or any history of hemorrhagic stroke; major surgical procedure or severe physical trauma within the previous month; or history, symptoms, or findings suggestive of aortic dissection. AGGRASTAT® is also contraindicated in patients with: severe hypertension (systolic blood pressure >180 mmHg and/or diastolic blood pressure >110 mmHg); concomitant use of another parenteral GP IIb/IIIa inhibitor; or acute pericarditis.
Bleeding is the most common complication encountered during therapy with AGGRASTAT®. Administration of AGGRASTAT® is associated with an increase in bleeding events classified as both major and minor bleeding events, by criteria developed by the Thrombolysis in Myocardial Infarction Study group (TIMI). Most major bleeding associated with AGGRASTAT® occurs at the arterial access site for cardiac catheterization. Fatal bleedings have been reported. AGGRASTAT® should be used with caution in patients with platelet count <150,000/mm3, in patients with hemorrhagic retinopathy, and in chronic hemodialysis patients. Because AGGRASTAT® inhibits platelet aggregation; caution should be employed when it is used with other drugs that affect hemostasis. The safety of AGGRASTAT® when used in combination with thrombolytic agents has not been established. During therapy with AGGRASTAT®, patients should be monitored for potential bleeding. When bleeding cannot be controlled with pressure, infusion of AGGRASTAT® and heparin should be discontinued.
The following additional adverse reactions have been reported in post- marketing experience: bleeding, intracranial bleeding, retroperitoneal bleeding, hemopericardium, and pulmonary (alveolar) hemorrhage. Fatal bleedings have been reported; body as a whole: acute and/or severe decreases in platelet counts which may be associated with chills, low grade fever, or bleeding complications; hypersensitivity; rash and/or hives.
Please refer to the specific Prescribing Information for your country for complete warnings and precautions.
About Iroko
Iroko is a pharmaceutical company focused on acquiring, developing, and maximizing the potential of currently marketed pharmaceutical products on a worldwide basis. Iroko applies concentrated selling and marketing efforts and product life cycle management strategies focused on developing new and relevant formulations and indications that benefit patient health. For more information, visit http://www.iroko.com.
About Merck
Merck & Co., Inc. is a global research-driven pharmaceutical company dedicated to putting patients first. Established in 1891, Merck currently discovers, develops, manufactures and markets vaccines and medicines to address unmet medical needs. The company devotes extensive efforts to increase access to medicines through far-reaching programs that not only donate Merck medicines but help deliver them to the people who need them. Merck also publishes unbiased health information as a not-for-profit service. http://www.merck.com
References
1 Valgimigli M, Campo Gianluca, de Cesare N, Meliga E et al. A double-blind randomised multicentre trial of tailored infusion of tirofiban in poor aspirin and/or clopidogrel responders undergoing elective percutaneous coronary intervention. Presented at ESC, 2 September 2008
Merck & Co., Inc