Early, inâambulance treatment with antiplatelet medicine AGGRASTATÂ® (tirofiban HCL), in addition to the standard combined treatment of aspirin, heparin and clopidogrel, significantly improves the results of primary coronary angioplasty (PCI) in patients with STâelevated myocardial infarction (STEMI).1 These study findings were presented today at the Annual European Society of Cardiology Congress in Munich, Germany.
Data from the combined open label and doubleâblind, placeboâcontrol, multinational, "Ongoing Tirofiban in Myocardial Infarction Evaluation (OnâTIME) 2" trial in 1398 randomised showed that treatment with AGGRASTATÂ®, a glycoprotein IIb/IIIa inhibitor, in addition to the standard triple treatment package, significantly reduced the incidence of residual STâsegment deviation versus placebo or no AGGRASTATÂ® after PCI in STEMI patients (3.7 Â± 5.2 mm versus 4.8 Â± 6.0 mm, p<0.005).1 The ST segment in the ECG is a good marker of vessel occlusion and closely linked to the outcome of the patients with myocardial infarction.
"These results are significant in that they address the two key unknowns in this area - firstly, the value of early intervention with glycoprotein IIb/IIIa inhibitors on top of the standard treatment of aspirin, heparin and clopidogrel in STEMI patients; and secondly, the most effective timing of that intervention," said Dr Arnoud vanÂ´t Hof, Department of Cardiology, Isala Klinieken, Zwolle, Netherlands and principal investigator. "The data from OnâTIME 2 shows the importance of diagnosing STEMI at the earliest possible point in the cascade of events that lead to a heart attack, thereby allowing for the initiation of antiâthrombotic and triple antiplatelet therapy including AGGRASTATÂ® , as early as the ambulance setting, thereby fully optimising the outcome for the patient."
The data from the doubleâblind placebo control trial was published recently in The Lancet, with an accompanying commentary from independent expert, Dr Gilles Montalescot, Institute of Cardiology PitiÃ©âSalpÃªtriÃ¨re Hospital, stating, "OnâTIME 2 tells us more than the benefit of AGGRASTATÂ® in preâPCI. The study reveals that highâdose clopidogrel is not effective enough and confirms the need for fast and strong platelet inhibition."2
OnâTIME 2 is the firstâever study to investigate the efficacy and safety of AGGRASTATÂ® , which belongs to the glycoprotein IIb/IIIa inhibitors (GPI) class of anticlotting medicines, in STEMI patients in the preâhospital setting.1
The data showed:
"Adding early AGGRASTATÂ® 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, recurrent myocardial infarction (MI) or urgent target vessel revascularization (uTVR), was reduced without a significant increase in bleeding," said Professor Christian Hamm, Department of Cardiology, KerckhoffâKlinik GmbH, Bad Nauheim, Germany and coâprincipal investigator. Study results showed that:
Professor Hamm continued, "Our finding that routine preâhospital initiation of AGGRASTATÂ® improved STâsegment resolution and clinical outcome after PCI, emphasises that early and intensive platelet aggregation inhibition is mandated in patients with STEMI undergoing PCI."
"We are pleased to announce these new data which reinforce the potential benefits of AGGRASTATÂ® in this critically ill patient population," said John Vavricka, President and Chief Executive Officer of Iroko Pharmaceuticals. "Iroko is committed to furthering its clinical research in this area, and exploring AGGRASTATÂ®Â´s potential as an early intervention strategy for patients with acute myocardial infarction."
In January of 2008, Iroko Pharmaceuticals acquired all nonâUS commercial rights to AGGRASTATÂ® (tirofiban HCl) from Merck & Co., Inc.
OnâTIME 2 Study (Ongoing Tirofiban in Myocardial Infarction Evaluation 2 Trial) 1
The European study was conducted at highâvolume PCI centers in Germany, Belgium and the Netherlands. The trial consisted of two consecutive phases:
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, AGGRASTATÂ® or placebo was injected, followed by an infusion of AGGRASTATÂ® 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.
The studyÂ´s primary end point evaluated the benefit of preâhospital initiation of high bolus tirofiban, administered in addition to aspirin, heparin and clopidogrel, on the extent of residual STâsegment deviation (defined as percentage of patients with >3 mm deviation of ST segment) at one hour after PCI. The key secondary endpoint of the pooled analysis for the open label and doubleâblind phase was the incidence of MACE: major adverse cardiac events (death, reâinfarction, urgent target vessel revascularization) at 30 days follow up. Additionally, major bleeding, as measured by the Thrombolysis in Myocardial Infarction (TIMI) criteria, was also assessed.
AGGRASTATÂ® is not currently approved for use in STEMI patients or as adjunctive therapy in patients undergoing percutaneous coronary intervention (PCI).
AGGRASTATÂ®, a glycoprotein IIb/IIIa inhibitor, is indicated for the prevention of early myocardial infarction in patients presenting with unstable angina or nonâQâwave 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 AGGRASTATÂ® treatment are those at high risk of developing myocardial infarction within the first 3â4 days after onset of acute angina symptoms including for instance those that are likely to undergo an early PTCA.
In most patients, AGGRASTATÂ® 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 productÂ´s prescribing information. AGGRASTATÂ® is intended for use with acetylsalicylic acid and unfractionated heparin.
AGGRASTATÂ® (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 AGGRASTATÂ® include: a history of thrombocytopenia following prior exposure to AGGRASTATÂ®; 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. AGGRASTATÂ® 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 AGGRASTATÂ®. Administration of AGGRASTATÂ® 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 AGGRASTATÂ® occurs at the arterial access site for cardiac catheterization. Fatal bleedings have been reported. AGGRASTATÂ® should be used with caution in patients with platelet count <150,000/mm3, in patients with hemorrhagic retinopathy, and in chronic hemodialysis patients. Because AGGRASTATÂ® inhibits platelet aggregation; caution should be employed when it is used with other drugs that affect hemostasis. The safety of AGGRASTATÂ® when used in combination with thrombolytic agents has not been established. During therapy with AGGRASTATÂ®, patients should be monitored for potential bleeding. When bleeding cannot be controlled with pressure, infusion of AGGRASTATÂ® and heparin should be discontinued.
The following additional adverse reactions have been reported in postâ 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.
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.
Merck & Co., Inc. is a global researchâdriven 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 farâreaching 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 notâforâprofit service.
1 VanÂ´t Hof A, ten Berg J, Heestermans T, Dill T et al. Prehospital initiation of tirofiban in patients with STâelevation myocardial infarction undergoing primary angioplasty (OnâTIME 2): a multicentre, doubleâblind, randomised controlled trial. Presented at ESC 31 August 2008
2 Montalescot G. Mechanical reperfusion: treat well, treat on time too. The Lancet; 372:509â10