GLFD Guilford Pharmaceuticals (MM)

Guilford Pharmaceuticals: AGGRASTAT(R) Injection Clinical Data Presented at American College of Cardiology Annual Meeting BALTIMORE, March 8 /PRNewswire-FirstCall/ -- Guilford Pharmaceuticals Inc. (NASDAQ:GLFD) today announced the presentation of additional data from the ADVANCE trial (The Additive Value of Tirofiban Administered With the High-Dose Bolus in the Prevention of Ischemic Complications During High-Risk Coronary Artery Angioplasty) at the 2005 Scientific Sessions of the American College of Cardiology Annual Meeting in Orlando. The data presented today by Dr. Marco Valgimigli showed that in this study a single high dose bolus (SHDB) regimen of AGGRASTAT(R) Injection (tirofiban hydrochloride) improved outcomes in diabetic patients undergoing percutaneous coronary intervention (PCI) when compared to placebo. AGGRASTAT(R), in combination with heparin and aspirin, is indicated for the treatment of acute coronary syndrome (ACS) including patients who are to be managed medically and those undergoing PTCA or atherectomy. Marco Valgimigli, M.D., Chair of Cardiology, University of Ferrara, Italy, and principal investigator for the ADVANCE trial, commented, "Diabetic patients are known to experience a higher rate of adverse ischemic events during and after PCI. One hypothesis is that this is a result of the differences in platelet physiology between diabetic and non-diabetic patients. Diabetic platelets are larger and demonstrate enhanced aggregation compared to non-diabetic platelets. We sought to determine whether AGGRASTAT(R), administered as a SHDB regimen could reduce ischemic events in diabetic patients referred for elective or urgent PCI." ADVANCE Methodology and Results: The ADVANCE study was a double-blind, placebo-controlled, randomized trial that included 202 high-risk patients undergoing PCI. Patients in the placebo group were eligible to receive bail-out GP IIb/IIIa inhibitor therapy during PCI if deemed necessary by the investigator. In this PCI trial, 98% of patients underwent intracoronary stenting. The data presented today were based on a prespecified subgroup analysis of 99 patients with diabetes who participated in the ADVANCE trial. On background therapy of heparin, aspirin and a thienopyridine (ticlopidine or clopidogrel), patients were randomized to receive the SHDB regimen of AGGRASTAT(R) (N=54; bolus of 25 mcg/Kg/3-min, followed by an infusion of 0.15 mcg/Kg/min for 24-48 h), or placebo (N=45). The primary endpoint was a composite of death, nonfatal myocardial infarction (MI), urgent target vessel revascularization and thrombotic bailout GP IIb/IIIa inhibitor therapy occurring within six months of PCI. After a median follow-up of 262 days (range: 143-398) the results yielded a significantly reduced primary composite endpoint with the SHDB regimen of AGGRASTAT(R) when compared to placebo (17% vs. 40%; HR 0.37 [95% CI: 0.11- 0.58]; p=0.003), with a relative risk reduction of 58%. The incidence of major and minor bleeding was not statistically different between the two groups. However, this lack of difference in adverse events could be due to the fact that the study was underpowered. The difference in the incidence of adverse ischemic events was mainly due to a lower rate of periprocedural MI in the AGGRASTAT(R) versus the placebo group (4% vs. 18%, p=0.048). In this study, the Investigators concluded that "the SHDB regimen of AGGRASTAT(R), by decreasing the incidence of ischemic complications, was both safe and effective, supporting the notion that diabetic patients, irrespective of their clinical status, would probably benefit from a tailored drug regimen during PCI." These findings were based on a limited and selected sample size, and thus should be viewed as preliminary. Important Information About AGGRASTAT(R) Injection AGGRASTAT(R) Injection (tirofiban hydrochloride) was approved by the Food and Drug Administration (FDA) on May 14, 1998. AGGRASTAT(R), in combination with heparin, and aspirin, if not contraindicated, is indicated for the treatment of ACS including patients who are to be managed medically and those undergoing PTCA or atherectomy. In this setting, AGGRASTAT(R), has been shown to decrease the rate of a combined endpoint of death, new myocardial infarction or refractory ischemia/repeat cardiac procedure. In most patients, AGGRASTAT(R) 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(R) 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(R) include: a history of thrombocytopenia following prior exposure to AGGRASTAT(R); 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(R) 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(R). Administration of AGGRASTAT(R) 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(R) occurs at the arterial access site for cardiac catheterization. Fatal bleedings have been reported. AGGRASTAT(R) should be used with caution in patients with platelet count