Argatroban Provides Anticoagulation In Heparin-Induced Thrombocytopenia Patients

SAN FRANCISCO, CA — October 25, 2000 — Treatment with Argatroban injection provided adequate anticoagulation in patients with heparin-induced thrombocytopenia (HIT) who underwent percutaneous coronary intervention (PCI), most frequently balloon angioplasty, according to clinical trial results presented at the annual meeting of the American College of Chest Physicians (ACCP.

This finding complements data recently presented at the Transcatheter Cardiovascular Therapeutics Scientific Sessions, which showed repeated Argatroban exposure is well tolerated without increasing the dose or safety risk.

HIT is a serious immune disorder caused by heparin, a common anticoagulant used to prevent blood clots. Each year, nearly 12 million Americans are treated with heparin for conditions such as blood clots in the legs or lungs, heart attacks, or angioplasty. Of these 12 million people, as many as 360,000 will develop HIT, of which an estimated 120,000 will develop a thrombotic complication (stroke, limb amputation, or death), and up to 36,000 will die.

Heparin is commonly used in coronary procedures such as balloon angioplasty. According to the American Heart Association, approximately 447,000 angioplasty procedures were performed in the United States in 1997 (the most recent year for which data were available).

“We are pleased with the results of this study as they support the use of Argatroban as an anticoagulant for patients with coronary heart disease who develop complications after prior exposure to heparin,” said Bruce Lewis, M.D., Associate Professor of Medicine, Loyola University Medical Center, Loyola University, Chicago, Illinois. “Effective anticoagulation is one of the key factors in determining the success of a cardiac procedure such as angioplasty. These results also underscore the importance of selecting an appropriate anticoagulant for these patients.”

In this combined analysis of three studies, HIT patients on Argatroban who underwent PCI were assessed for investigator-rated primary efficacy outcomes and acute procedural success (i.e., lack of death, emergent bypass surgery or Q-wave myocardial infarction). Acute procedural success and major bleeding rates were compared with data obtained from the Cleveland Clinic Registry and the heparin arm of the EPILOG trial, respectively.

Results from the trials indicate that of the 91 patients treated with Argatroban, 97.8 percent had adequate anticoagulation, while 94.5 percent achieved satisfactory procedural outcomes. In patients who received Argatroban, acute procedural success was 98.9 percent versus 94.3 percent in the control group. Similarly, major bleeding rates for Argatroban patients compared favorably with historical controls (2.2 percent versus 3.1 percent, respectively).

“Minimal bleeding rates were observed in these studies,” commented Dr. Lewis. “Because of these low rates, I believe Argatroban can play an important role in anticoagulation treatment in HIT patients undergoing PCI.”

In this analysis, unsatisfactory procedural outcomes occurred in 5 of 91 patients and were coronary artery dissection, emergent bypass surgery, acute hypotension, failure to revascularize and failure of the stent. No death or Q-wave myocardial infarction occurred. Major bleeding events, which occurred in 2 patients, were retroperitoneal and gastrointestinal.

Data evaluating the efficacy of Argatroban in HIT patients who required PCI on multiple occasions were also reported in additional presentations at the Society for Cardiac Angiography and Interventions’ Transcatheter Cardiovascular Therapeutics Scientific Sessions. In this analysis, outcomes from the 91 patients who received initial treatment with Argatroban during PCI were compared with outcomes from patients who had multiple procedures and multiple exposure to Argatroban therapy.

Results from this comparative analysis demonstrated that 100 percent of the 21 patients achieved satisfactory procedural outcomes and acute procedural success. All of these patients also experienced adequate anticoagulation upon re-exposure to Argatroban, without major bleeding.

“Many PCI patients will undergo a second coronary intervention, so physicians should choose an anticoagulant that will continue to be as well tolerated when used in re-exposure, as it is the first time,” said Dr. Lewis. “Unlike some other anticoagulants, Argatroban does not cross-react with heparin-dependent antibodies that cause HIT or form antibodies to itself. It is, therefore, considered a safe option for these patients requiring anticoagulation.”

Argatroban is a synthetic direct thrombin inhibitor that blocks the activity of thrombin, a key factor in blood clotting. It is currently indicated for the prophylaxis or treatment of thrombosis (abnormal blood clotting) in patients with HIT. Major bleeding events observed with Argatroban in HIT patients included gastrointestinal and genitourinary. The most common nonhemorrhagic side effects, regardless of relationship to treatment, include dyspnea, hypotension, and fever.