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| |  AHA: Integrilin Combination Therapy Opens Clogged Arteries After Heart Attack ATLANTA, GA -- November 10, 1999 -- Results announced at the 72nd Annual Scientific Sessions of the American Heart Association from a study of patients with acute myocardial infarction (heart attack) showed that the anti-platelet agent Integrilin(R) combined with half-dose alteplase (tPA), restored blood flow through clogged arteries supplying oxygen-starved heart muscle in 78 percent of patients. Studies of full-dose accelerated alteplase, commonly referred to as a clot buster, have reported that 54 percent of heart attack patients achieved restoration of blood flow.
The findings were based on results from the first phase of the INTRO-AMI (Integrilin and Reduced Dose Of Thrombolytic in Acute Myocardial Infarction) study. This was a Phase II clinical trial involving over 340 patients presenting to the hospital with a heart attack confirmed by electrocardiogram. Various combination doses of Integrilin and alteplase were evaluated in a stepwise fashion to determine their effect on opening clogged coronary arteries within 60 and 90 minutes of initiation of drug therapy. Normal blood flow was determined using an angiographic assessment known as TIMI grade 3 blood flow. A combination of Integrilin dosed as a 180 microg/kg bolus followed by a 90 microg/kg bolus and 1.33 microg/kg/min infusion for up to 72 hours administered with an alteplase 15 mg bolus and 35 mg infusion for 60 minutes restored normal blood flow through clogged arteries at ninety minutes in 78 percent of patients. The most common adverse event reported was bleeding at the site of catheter insertion into the groin artery (used to determine TIMI grade 3 blood flow). The combination was not associated with an increase in major bleeding complications relative to that reported in other angiographic studies of full-dose accelerated alteplase therapy. Heart attack is the result of an occlusive clot in one of the coronary arteries depriving oxygenated blood to heart muscle. The clot consists of a clump or aggregate of small blood components, platelets, held together by strands, known as fibrin. Traditional therapies for heart attack known as fibrinolytics, such as alteplase, break up the fibrin strands that hold together the blood clot. These therapies, however, do not prevent continued platelet clumping and can indirectly stimulate platelet aggregation and clot reformation. GP IIb-IIIa inhibitors, such as Integrilin, help to prevent platelet clumping and potential complete occlusion of coronary arteries. INTRO-AMI was designed to determine whether the combination of a GP IIb-IIIa inhibitor with fibrinolytic therapy would achieve normal blood flow in clogged arteries in a larger percentage of heart attack patients than that reported for fibrinolytic therapy alone. "Clinically, these findings could translate into a major breakthrough in the management of heart attack patients, " said Dr. Eric J. Topol, Chairman of the Department of Cardiology at the Cleveland Clinic Foundation, the coordinating center for INTRO-AMI. "Fibrinolytic therapies restore blood flow to heart muscle in less than 60 percent of patients. The remaining patients continue to experience irreversible heart muscle damage. By combining low doses of fibrinolytic agents with GP IIb-IIIa inhibitor therapy, it is hoped that precious heart muscle might be saved." A second phase of INTRO-AMI is underway to compare the effects of two doses of Integrilin (eptifibatide) Injection combined with half-dose alteplase versus full-dose accelerated alteplase alone on coronary blood flow restoration. Integrilin is currently indicated for the treatment of patients with acute coronary syndrome (unstable angina and non-Q-wave myocardial infarction), including patients who are to be managed medically and those undergoing percutaneous coronary intervention (PCI). It is also indicated for the treatment of patients undergoing PCI. Integrilin is contraindicated in patients with a history of bleeding diathesis, or evidence of abnormal bleeding within the previous 30 days; severe hypertension (systolic blood pressure greater than 200 mm Hg or diastolic blood pressure greater than 110 mm Hg) not adequately controlled on antihypertensive therapy; major surgery within the preceding six weeks; history of stroke within 30 days, or any history of hemorrhagic stroke; current or planned administration of another parenteral GP IIb-IIIa inhibitor; platelet count less than 100,000/mm3; serum creatinine greater than or equal to 4.0 mg/dL (in patients with serum creatinine levels between 2.0 mg/dL and 4.0 mg/dL, a 135 ug/kg bolus and 0.5 ug/kg/min infusion should be administered); dependency on renal dialysis; or known hypersensitivity to any component of the product. Previous clinical trials have shown that bleeding is the most common complication encountered during Integrilin therapy. The majority of excess major bleeding events were localized at the femoral artery access site. Oropharyngeal, genitourinary, gastrointestinal and retroperitoneal bleeding were also seen more commonly with Integrilin compared to placebo.
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