Argatroban Found Safe and Effective in Patients With Heparin-Induced Thrombocytopenia (HIT) Undergoing Percutaneous Coronary Interventions (PCI) (i.e. Angioplasty, Stent Placement or Atherectomy)
Wednesday September 25, 9:15 am ET
WASHINGTON, Sept. 25 /PRNewswire/ -- GlaxoSmithKline's (NYSE: GSK - News) Argatroban provides safe and effective anticoagulation for patients who have heparin-induced thrombocytopenia (HIT), a limb- and life-threatening reaction to heparin that causes blood clots, during cardiac interventional procedures. This conclusion from the largest clinical trial of direct thrombin inhibitors in patients with HIT who are undergoing PCI (percutaneous coronary interventions such as coronary angioplasty, stent placement or atherectomy), was reported during the Transcatheter Cardiovascular Therapeutics, an international symposium for physicians in the field of vascular medicine. The study will be published in the October issue of Catheterization and Cardiovascular Interventions.
There were no approved alternative anticoagulant agents for patients with HIT undergoing PCI at the time the study was performed. Last April, Argatroban became the first anticoagulant approved by the Food and Drug Administration for use in patients who have, or are at risk for, HIT undergoing PCI. Argatroban is also the only anticoagulant approved for both the prophylaxis (prevention) and treatment of thrombosis associated with HIT.
"Maintaining adequate anticoagulation during PCI is essential, and HIT poses an additional threat of thrombosis to patients who develop an adverse immune reaction to heparin. HIT puts them at risk for limb amputation, and death occurs in approximately 20-30 percent of patients who develop thrombosis," said study investigator Bruce Lewis, M.D., professor of medicine at Loyola University Medical Center, and a presenter at the symposium. "Prior to the availability of the direct thrombin inhibitor Argatroban, clinicians had no alternative anticoagulant to offer HIT patients during PCI."
The prospective, multi-center open-label study of 91 patients who had a previous or current case of HIT and required PCI, found that 98 percent of those who received intravenous Argatroban for an initial PCI procedure achieved adequate anticoagulation, and 100 percent of those (21 patients) who required subsequent admissions for PCI with Argatroban achieved successful anticoagulation. The study also found that Argatroban was safe for administration in this population -- 98 percent of patients remained free from major complications of death, emergent coronary artery bypass graft surgery and Q-wave myocardial infarction; and only one patient experienced periprocedural major bleeding. The study outcomes compare favorably with historical data reported for heparin anticoagulation during PCI.
"This is the first study to show that we can treat patients during PCI with an alternative anticoagulant and produce outcomes which appear equivalent to those seen with heparin in patients who don't have HIT," Dr. Lewis said.
HIT: Potential Catastrophic Drug Reaction
HIT is a potentially severe adverse reaction to heparin, and may occur with any heparin type including unfractionated heparins and low-molecular weight heparins. This immune-driven condition causes a decrease in the number of platelets and the development of life-threatening blood clots. Between 360,000 and 600,000 individuals a year are potentially affected, a number nearly twice that of new breast cancer cases diagnosed annually and nearly equal to the number of new cases of angina uncovered in the United States each year.
"The condition is not widely recognized and is often easy to overlook, therefore physicians do not usually expect to find it," explained investigator Marc Cohen, M.D., professor of medicine at Drexel University College of Medicine and director of clinical research at Hahnemann University Hospital. "You might call HIT a counterintuitive disease because heparin, a medicine that is supposed to be a blood thinner itself, actually participates in the formation of blood clots."
Argatroban: Offering New Treatment Opportunities
Argatroban is a synthetic direct thrombin inhibitor which acts to prevent the activity of thrombin, a protein involved in the production of clots. Efficacy and safety trials of Argatroban have found significant reductions in the rates of new clot and death in comparison to historical groups.
"One of the important highlights of Argatroban is that it gives the clinician a treatment option for patients who are suspected of having HIT ... due to a decrease in platelet levels but for whom a definitive diagnosis has not yet been made based on laboratory testing," said study investigator William H. Matthai, Jr., M.D., clinical associate professor of medicine at the University of Pennsylvania Medical School.
Important Safety Information
Caution should be exercised when administering Argatroban to patients with liver disease by starting with a lower dose and raising that dose carefully until the desired level of anticoagulation is achieved.
The safety and effectiveness of Argatroban for cardiac indications outside of patients with or at risk for HIT undergoing percutaneous interventions have not been established.
No interactions between Argatroban and other commonly used drugs have been identified. All oral anticoagulants should be discontinued before administration of Argatroban due to an increased risk of bleeding.
Comparison between Argatroban and historical groups further showed no important differences in bleeding events.
As with all anticoagulants, bleeding is a serious concern. Hemorrhage can occur at any site in the body in patients receiving Argatroban. An unexpected fall in hematocrit, fall in blood pressure, or any unexplained symptom should lead to consideration of a hemorrhagic event. Argatroban should be used with extreme caution in disease states or other circumstances in which there is an increased danger of hemorrhage. These include severe hypertension; immediately following lumbar puncture; spinal anesthesia; major surgery, especially involving the brain, spinal cord, or eye; hematologic conditions associated with increased bleeding tendencies such as congenital or acquired bleeding disorders and gastrointestinal lesions such as ulcerations. |
