Timing of death and myocardial infarction in patients with non-ST elevation acute coronary syndromes: insights from randomized clinical trials.

BACKGROUND: Adverse events occur following non-ST elevation acute coronary syndromes (NSTE ACS). However, the timing of these events in relation to index event is less clear. METHODS: Accordingly, we evaluated 26,466 NSTE ACS patients from the Global Use of Strategies to Open Occluded Arteries in Acute Coronary Syndromes (GUSTO-IIb), Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT), and Platelet IIb/IIIa Antagonism for the Reduction of Acute Coronary Syndrome Events in a Global Organization Network (PARAGON) A and B trials to ascertain the timing of adverse events. Outcomes of interest were death, myocardial infarction (MI), and death or MI at 180 days. Logistic regression modeling for death was used to categorize patients into low-, medium-, and high-risk groups. RESULTS: At 6 months, 6.2% of patients died, 12.1% had MI, and 15.7% suffered death or MI. From 15% to 40% of these events occurred beyond 30 days. At 6 months, 3%, 4%, and 13% of patients died in low-, medium-, and high-risk groups, respectively. However, the proportion of patients dying beyond 30 days was similar in the three groups (44%, 43%, and 41% of death, respectively). Similarly, whereas death or MI increased with higher risk (11%, 14%, and 23%, respectively), the proportion of patients with this event beyond 30 days did not differ in the three strata (22%, 20%, and 25%, respectively). CONCLUSIONS: Our study provides important insights into the timing of adverse events and suggests that the substantial proportion of patients suffer subsequent adverse events after their index NSTE ACS. Thus, these data call for continuous surveillance for these events and efforts beyond the acute phase at increasing adherence to evidence-based therapies to improve the outcomes of these patients.

Treatment of hirudin overdosage in a dialysis patient with heparin-induced thrombocytopenia with mixed hemodialysis and hemofiltration treatment.

We report a patient who developed type II heparin-induced thrombocytopenia (HIT) and accidentally received a recombinant hirudin (r-hirudin) overdosage. Treatment with hemodialysis (HD) using high-flux polysulfone dialyzer and hemofiltration was performed. Length of treatment was adjusted, monitoring activated partial thromboplastin time (aPTT) to 1.5-2.5 times the mean of the normal range. She developed deep venous thrombosis and occlusion of vascular access. Only after cessation of heparin lock catheter, platelet count began to increase. After one year of treatment with acenocoumarol and additional low-dose r-hirudin, neither bleeding nor thrombotic episodes have been reported.

Bivalent direct thrombin inhibitors: hirudin and bivalirudin.

Hirudin derivatives (e.g. lepirudin, desirudin) and hirudin analogues (e.g. bivalirudin) are bivalent direct thrombin inhibitors; that is, they bind to two distinct sites on thrombin-its active (catalytic) site and its fibrinogen-binding site (exosite 1). These bivalent binding properties contribute to their high affinity and high specificity for thrombin. This review compares the pharmacological properties of these agents, and describes studies of their efficacy and safety in diverse clinical settings such as immune heparin-induced thrombocytopenia, postoperative antithrombotic prophylaxis, and treatment of acute coronary syndrome. Certain disadvantages of hirudin, such as its predominant renal excretion and immunogenicity, have been overcome through development of the hirudin analogue, bivalirudin. Compared with hirudin derivatives, bivalirudin exhibits a shorter half-life (25 vs 80 minutes), predominant non-renal (enzymic) metabolism, and low immunogenicity. Further work is required to define the scope of clinical thrombosis problems that could benefit from these novel agents.

Bivalirudin (Angiomax) use during intracoronary brachytherapy may predispose to acute closure.

We describe two cases of intracoronary vascular brachytherapy where bivalirudin (Angiomax), employed as an anticoagulant, led to abrupt vessel closure or threatened abrupt closure. Use of bivalirudin (Angiomax) during intracoronary brachytherapy may predispose to the formation of intracoronary thrombus, related to the reversible binding kinetics of the bivalirudin to thrombin, and resulting in recovery of thrombin functional activity during periods of prolonged stasis that occur during intracoronary brachytherapy. Intracoronary abciximab administration may be a useful strategy in resolving the acute closure, since abciximab administered early during the formation of thrombus has been shown to facilitate clot lysis.

Antihirudin antibodies following low-dose subcutaneous treatment with desirudin for thrombosis prophylaxis after hip-replacement surgery: incidence and clinical relevance.

Recombinant hirudin has been found to be immunogenic in patients treated with lepirudin following heparin-induced thrombocytopenia (HIT). We assessed the incidence of immunoglobulin G (IgG) antihirudin antibodies by enzyme-linked immunosorbent assay in 112 patients enrolled in a dose-finding study with desirudin. Patients received desirudin subcutaneously following orthopedic hip surgery at 10 mg twice a day (n = 17), 15 mg twice a day (n = 75), and 20 mg twice a day (n = 20). Of 112 patients, 11 (9.8%) developed antihirudin antibodies independently of the dose. The rate of immunization did not differ from that observed in HIT patients treated with lepirudin (P =.113). Plasma concentrations of desirudin did not differ between antihirudin antibody-positive and -negative patients. Antihirudin antibodies had no impact on incidences of deep vein thrombosis and/or pulmonary embolism, allergic reactions, and hemorrhage. However, the total number of immunized patients observed was low and so infrequent (but severe) effects of antihirudin antibodies cannot be excluded.