Argatroban

Bruce E Lewis, MD(*); Marc Cohen, MD; Fred Leya, MD; William Matthai, Jr, MD and the ARG-216/310/311 Investigators, Cardiology, Loyola University Medical Center, Maywood, IL; Cardiology, Hahneman Hospital, Philadelphia, PA and Cardiology, Presbyterian Medical Center, Philadelphia, PA.

PURPOSE: Anticoagulation is required for percutaneous coronary intervention (PCI), but heparin is contraindicated for patients with heparin-induced thrombocytopenia (HIT) due to increased thrombotic risk. Argatroban, a direct thrombin inhibitor, has been used during PCI for HIT patients in 3 multicenter , similarly-designed trials . We performed a combined analysis of these trials to assess clinical outcomes for HIT patients undergoing PCI with argatroban.

METHODS: HIT patients who underwent PCI on intravenous argatroban (350 [micro]g/kg bolus plus 25 [15-40] [micro]g/kg/min titrated to achieve an activated clotting time [ACT] of 300-450 seconds) in any 1 of 3 multicenter trials conducted between 1995-1998 were included for analysis. For patients with multiple entries, outcomes from the first entry only were used. Endpoints assessed were the primary efficacy outcomes (investigators' assessments of procedural satisfaction and adequate anticoagulation), acute procedural success (defined as lack of death, emergent bypass surgery or Q-wave myocardial infarction [MI]) and major bleeding. Acute procedural success and major bleeding rates were compared with those reported historically (Cleveland Clinic Registry [1991-1993] and the heparin arm of the EPILOG trial [[italic]NEJM 1997;24:1689-96], respectively) for PCI with heparin.

RESULTS: Ninety-one patients (64% male, 36% female; 95% Caucasian, 3% black, 2% other) underwent PCI using argatroban on one or more occasions. Mean (range) patient age and weight were 67.4 (44-85) years and 81.9 (45-141) kg. Procedural satisfaction occurred in 86 patients (94.5% [95% CI: 87.6-98.2%]), and adequate anticoagulation in 89 patients (97.8% [92.3-99.7%]). Acute procedural success and bleeding rates compared favorably with those reported historically (see Table).

Unsatisfactory procedural outcomes (per investigator) were coronary artery dissection, emergent bypass surgery, acute hypotension, failure to revascularize and failure of the stent (1 patient each). No death or Q-wave MI occurred. Inadequate anticoagulation was noted in the patient with coronary artery dissection and in 1 patient for whom the ACT remained [less than] 300 seconds. The major bleeding events were retroperitoneal and gastrointestinal (1 patient each).

CONCLUSION: Argatroban provides adequate anticoagulation with minimal bleeding risk while enabling procedural success in HIT patients undergoing PCI. Procedural outcomes and bleeding rates are similar to those reported historically for heparin use during PCI.

CLINICAL IMPLICATIONS: Argatroban offers effective anticoagulation with minimal bleeding risk for HIT patients during PCI.

COPYRIGHT 2000 American College of Chest Physicians
COPYRIGHT 2001 Gale Group