PHILADELPHIA, PA, April 1, 2008 — Data from a randomized, double-blind, multi-national, placebo-control study showed that treatment with tirofiban (AGGRASTAT®), in addition to aspirin (ASA), heparin and clopidogrel (600mg), significantly reduced the incidence of residual ST-segment deviation after percutaneous coronary intervention (PCI) in ST-elevation myocardial infarction (STEMI) patients. These findings were reported today at the 57th Annual Scientific Session of the American College of Cardiology.
Data showed a significant reduction in the percentage of patients with more than 3 mm residual ST-segment deviation one hour post-PCI in the tirofiban versus placebo-treated group (33.6 percent versus 44.3 percent, respectively; P=0.026 [primary endpoint]). Additionally, a median of 60 minutes pre-PCI administration of tirofiban in the ambulance or referral center setting significantly reduced cumulative ST-segment deviation before PCI as compared to placebo (10.9 mm versus 12.1 mm, respectively; P=0.028). Cumulative ST-segment deviation as a continuous variable was also reduced with early tirofiban administration (3.3 mm versus 4.8 mm, respectively; P=0.002).
“These positive data underscore the importance of diagnosing STEMI patients early thereby having the possibility of initiating anti-thrombotic and triple anti-platelet therapy including high bolus dose tirofiban, as early as the ambulance setting,” said Arnoud van’t Hof, MD, PhD, Department of Cardiology, Isala Klinieken, Zwolle, the Netherlands and principal investigator of the On-TIME 2 study.
Study results also showed that the combined incidence of death, recurrent myocardial infarction (MI), urgent target vessel revascularization (uTVR), and thrombotic bailout were significantly reduced in the tirofiban group (26.0 percent) versus placebo (33.3 percent; P=0.013). Early intervention with tirofiban did not result in a significant increase of major bleeding when compared to placebo (4.0 percent versus 2.9 percent, respectively; P=0.363); results for minor bleeding were consistent with this trend (6.1 percent of tirofiban-treated patients versus 4.4%; P=0.233).
AGGRASTAT is not currently approved for use in STEMI patients or as adjunctive therapy in patients undergoing percutaneous coronary intervention (PCI).
“Adding early high-dose tirofiban to our current standard of care in primary PCI for AMI not only provides us with an efficacious treatment option, but also a safe one. The combined endpoint of death, MI, uTVR and thrombotic bailout was reduced without a significant increase in bleeding,” said Christian Hamm, MD, Director, Department of Cardiology, Kerckhoff Heart Center, Germany and co-principal study investigator.
In January of 2008, Iroko Pharmaceuticals acquired all non-US commercial rights to AGGRASTAT® (tirofiban HCl) from Merck & Co., Inc.
"We are pleased to announce these new data which reinforce the potential benefits of high-dose AGGRASTAT," said John Vavricka, President and Chief Executive Officer of Iroko Pharmaceuticals. "Iroko is committed to furthering its clinical research in this area, and exploring tirofiban’s potential as an early intervention strategy for patients with acute myocardial infarction."
Ongoing Tirofiban in Myocardial Infarction Evaluation (On-TIME) 2
The double-blind, European study of 984 patients was conducted at high-volume PCI centers in Germany, Belgium and the Netherlands. Patients were randomly assigned to pre-hospital treatment with tirofiban 25 µg/kg bolus and 0.15 µg/kg/min maintenance infusion for 18 hours post-PCI or placebo (patients treated with aspirin, unfractioned heparin and clopidogrel [600 mg]).
The study’s primary end points evaluated the benefit of pre-hospital initiation of high bolus tirofiban, administered in addition to aspirin, unfractioned heparin and 600 mg clopidogrel on the extent of residual ST-segment deviation (defined as percentage of patients with >3 mm deviation of ST segment) at one hour after PCI in patients with STEMI. Secondary endpoints evaluated the effect of this treatment regimen, as compare with placebo and in addition to aspirin, unfractioned heparin and clopidogrel, on the incidence of death, MI, uTVR or thrombotic bailout combined at 30 days. Additionally, major bleeding, as measured by the Thrombolysis in Myocardial Infarction (TIMI) criteria, was also assessed.
In the ambulance, all patients also received a bolus of unfractioned heparin (5000 IU) and aspirin intravenously, as well as 600 mg of clopidogrel orally. Following this, a bolus of tirofiban or placebo was injected, followed by an infusion of tirofiban or placebo. Before PCI, activated clotting time was assessed once; if it was <250 seconds, an additional bolus of 2500 IU of unfractioned heparin was administered.
AGGRASTAT is not currently approved for use in STEMI patients or as adjunctive therapy in patients undergoing percutaneous coronary intervention (PCI).
About GP IIb/IIIa Antagonists
Platelets are blood cells that provide an early defense from the potential complications of vascular injury. When a blood vessel is damaged, platelets adhere to the site and promote blood clot formation. Clot formation prevents bleeding and recruits other cells to help heal the damage. While usually a beneficial process, these effects can be harmful when a clot forms on a ruptured lipid plaque within the coronary vasculature.
GP IIb/IIIa antagonists block the ability of platelets to aggregate, inhibiting clot formation and reducing the potential for cardiac ischemia. Over the last 8-10 years, several large-scale, placebo-controlled clinical trials have established the efficacy of intravenous GP IIb/IIIa inhibitors for patients with acute coronary syndrome who are medically managed or go to the cath lab.
About AGGRASTAT
Important Information about AGGRASTAT® Injection.
AGGRASTAT® 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 Pharmaceuticals
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 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.
For more information about Aggrastat, visit www.iroko.com.