If this is not your name, click here.
| | If this is not your name, click here. | | |
| | Contact Us | Order Now | Journals | Bookstore | Register a colleague | | |
| |  AHA: Lovenox (Enoxaparin) And Aggrastat (Tirofiban) Well-Tolerated, Bleeding Rate Comparable To Heparin NEW ORLEANS, LA -- November 15, 2000 -- Treatment with the low-molecular-weight heparin Lovenox® (enoxaparin sodium) Injection in combination with the platelet blocker Aggrastat™ (tirofiban) is well-tolerated in patients with acute coronary syndromes, according to results of an international study. Data from a clinical trial of 525 patients in 27 countries were presented at the 73rd Scientific Sessions of the American Heart Association. ACUTE II (Antithrombotic Combination Using Tirofiban and Enoxaparin) is the first large study to investigate the safety profile of tirofiban, enoxaparin and aspirin in patients experiencing acute coronary syndromes, as compared to tirofiban plus unfractionated heparin and aspirin. Tirofiban, a potent, small-molecule, non-peptide drug in a class of intravenous medicines known as glycoprotein (GP) IIb/IIIa receptor antagonists, works quickly by blocking platelet aggregation, a step in the formation of the blood clots that may ultimately halt the flow in coronary arteries. Enoxaparin, a low-molecular-weight heparin, is a blood-thinning agent that plays a key role in inhibiting thrombin, an enzyme present throughout the circulatory system that, when activated by injury to a blood vessel, facilitates the formation of a blood clot. The study found that treatment with tirofiban and enoxaparin as compared to treatment with tirofiban and unfractionated heparin resulted in similar rates of major and minor bleeding, using criteria from the trials of TIMI (Thrombolysis In Myocardial Infarction), up to 24 hours after study drug cessation. Findings were that 3.5 percent (11 of 315) patients receiving tirofiban and enoxaparin experienced TIMI bleeding incidents, as compared to 3.8 percent (8 of 210) patients in the tirofiban and heparin group, a non-significant difference (p=1.000). "The combination of tirofiban and enoxaparin was found to be well-tolerated and resulted in low bleeding rates, comparable to that of standard unfractionated heparin," said Marc Cohen, MD, Professor of Medicine, MCP Hahnemann University School of Medicine; Director, Clinical Research, Hahnemann University Hospital; and principal investigator of ACUTE II. "These findings are important and exciting, as this is the first comparative trial to show that a GP IIb/IIIa blocker and enoxaparin may be used in a complementary way to treat patients with acute coronary syndromes." Currently, acute coronary syndrome patients may receive tirofiban in combination with unfractionated heparin. However, unlike unfractionated heparin, low-molecular-weight heparins such as enoxaparin are easier to administer and do not require laboratory monitoring and frequent dose adjustments. A number of studies have shown the superiority of enoxaparin to unfractionated heparin in acute coronary syndromes. "If enoxaparin can be added to tirofiban and result in similar safety profiles to that of standard heparin, while offering such added benefits as simpler administration and eliminating the need for monitoring, this combination will have great appeal to the medical community," added Dr. Cohen. ACUTE II was a multicenter, parallel, double-blinded trial that enrolled 525 patients with unstable angina or non-Q-wave myocardial infarction. Patients were randomized to receive either tirofiban plus enoxaparin or tirofiban plus unfractionated heparin, in a ratio of three to two, within 24 hours of their last episode of chest pain. All patients received aspirin. In addition to TIMI bleeding incidents, secondary safety parameters and clinical events, including myocardial infarction, death and rehospitalization for unstable angina, also were assessed. Researchers had the following -- No differences were noted between the tirofiban/enoxaparin and tirofiban/heparin arms in the incidence of cutaneous bleeds (19.4 percent vs. 21.0 percent, p=0.658), transfusion (2.2 percent vs. 2.9 percent, p=0.776), and thrombocytopenia, or decreased platelet counts (0.3 percent vs. 0.5 percent, p=1.000) through 24 hours after study drug cessation; -- At 30 days, tirofiban performed equally well in terms of mortality, with a 2.2 percent rate observed in the enoxaparin arm, as compared to a 2.4 percent rate in the heparin arm, a non-significant difference (p=1.000); -- In terms of myocardial infarction, similar findings were observed between patients in the tirofiban/enoxaparin arm as compared to those in the tirofiban/heparin arm (7 percent vs. 7.6 percent, p=0.864) and stroke (0.3 percent vs. 1.4 percent, p=0.307) at 30 days; -- At 30 days, patients receiving tirofiban/enoxaparin had a lower rate of recurrent angina or rehospitalization for unstable angina compared with the tirofiban/heparin arm (2.5 percent vs. 6.6 percent, p=0.026), a statistically significant difference. Additionally, patients in the tirofiban/enoxaparin arm were less likely to undergo angiography and revascularization, as needed, as compared to the tirofiban/heparin group (12.1 percent versus 18.1 percent, p=0.058). Tirofiban was administered as a 30-minute loading infusion of 0.4 mcg/kg/min, followed by a 47.5 to 107.5-hour maintenance infusion of 0.1 mcg/kg/min. Enoxaparin was given subcutaneously at 1.0 mg/kg every 12 hours for 24 to 96 hours. Unfractionated heparin was administered as a 5,000-unit bolus, with an adjusted maintenance infusion of 1,000-unit per hour. Coronary angiography followed by percutaneous intervention was permitted after 24 hours and eight hours after the last dose of enoxaparin. Larger clinical trials (A2Z and TETAMI) are currently underway that will further evaluate the safety and efficacy of tirofiban and enoxaparin in the treatment of acute coronary syndromes. Tirofiban, the only non-peptide platelet glycoprotein IIb/IIIa receptor antagonist, was discovered and developed by Merck, Sharp & Dohme (MSD). Enoxaparin sodium, a unique chemical entity in a distinct class of antithrombotic agents known as low-molecular-weight heparins, is obtained by alkaline degradation of heparin benzyl ester and is about one-third the molecular size of standard heparin. Enoxaparin sodium is marketed by Aventis Pharmaceuticals in the United States under the tradename Lovenox and in other parts of the world as Clexane® or Klexane®. Acute coronary syndromes involve the formation of blood clots in the blood vessels that supply the heart, resulting in the reduction of blood flow to the heart. These conditions include acute myocardial infarction (AMI), non-Q-wave myocardial infarction (NQMI) and unstable angina (UA). Current management of acute coronary syndromes includes a combination of treatments that work to block clot formation and restore blood flow through the blocked artery and surgical and mechanical interventions (angioplasty, for example) aimed at re-opening clogged arteries. According to the World Health Organization, in 1999, ischemic heart disease was responsible for the deaths of 7 million people worldwide. Likewise, cardiovascular diseases in general accounted for almost 17 million deaths. Related Links: Lovenox® (enoxaparin sodium) and Aggrastat™ (tirofiban).
|
