Novastan (brand of argatroban): a small-molecule, direct thrombin inhibitor.

Because of the unsatisfactory options available for safe and effective antithrombotic therapy, recent, intense research and development efforts have focused on direct, or site-directed, thrombin inhibitors. Argatroban is a small-molecule, reversible, direct thrombin inhibitor selective for the catalytic site of the thrombin molecule. Argatroban's molecular properties (small molecule; fast, selective, and reversible inhibition of the thrombin catalytic site; and similar in vitro potency for inhibiting both clot-bound and soluble thrombin) offer the potential for significant antithrombotic efficacy with minimal systemic anticoagulant effects. Its clinical pharmacologic properties offer the potential for minimal risk of bleeding, very rapid achievement of therapeutic antithrombotic efficacy, predictable dose response, and rapid restoration of the hemostatic systems to baseline on termination of intravenous infusion. The intravenous agent Novastan (brand of argatroban) is currently approved for clinical use in Japan for the treatment of peripheral arterial occlusive disease. Novastan is in advanced clinical development in North and South America for several indications, including (1) anticoagulant/antithrombotic therapy in heparin-induced thrombocytopenia (HIT) and heparin-induced thrombocytopenia, and thrombosis syndrome (HITTS); and (2) adjunctive therapy to thrombolytic agents in acute myocardial infarction. Results from these trials are projected to be available by early 1997.

Results of a national survey on anticoagulation for PTCA.

In order to assess the current practice patterns in the United States for anticoagulation during PTCA, a survey was sent to the ACC membership. A total of 377 surveys from physicians performing PTCA were tabulated; 5 (1.3%) respondents performed < 20 PTCAs/year, 128 (34.0%) performed 20-75 PTCAs/year, 141 (37.4%) performed 75-150 PTCAs/year, 98 (26.0%) performed > 150 PTCAs/year and 5 (1.3%) did not report their volume. Seventy-eight (20.7%) were at university hospitals 153 (40.6%) were at other teaching hospitals, 142 (37.7%) were at non-teaching hospitals and 4 (1.1%) did not report their institutional affiliation. A total of 76.8% of respondents routinely started with a 10,000 U bolus of heparin, while only 3.2% of respondents used only a weight-adjusted heparin bolus. Fifty-nine percent of respondents routinely used intra-procedure heparin infusions, usually 1000 U/hr. Anticoagulation monitoring was used by 92.6% of respondents during PTCA, almost always activated clotting times (ACTs). Of the 335 physicians who used ACTs to guide heparin therapy during PTCA, 59.1% used the Hemochron device, 16.7% used the HemoTec device, and 24.2% did not know which machine they used. Lower volume operators and operators at non-teaching hospitals were more likely not to know the type of ACT machine used. Post-procedure heparin infusions (usually titrated to an aPTT > 2 x control) were used by 70.3% of respondents. Lower volume operators were more likely to use post-procedure heparin infusions. Thus, heparin therapy for PTCA continues to be largely empiric, although the vast majority of cardiologists surveyed use ACT-guided heparin therapy for the procedure.(ABSTRACT TRUNCATED AT 250 WORDS)