Speaker: Maria Cappellini, MD, Professor of Internal Medicine, Centro Anemia Congenite, Institute of Internal Medicine and Pathophysiologic Medicine, University of Milan, Milan, Italy
Deferasirox (ICL 670) (Exjade®, Novartis), an investiga-tional once-daily oral iron chelator, induced a long-term, sustained, clinically relevant reduction in liver iron concentration in heavily transfused patients with beta-thalassemia and iron overload. The non-inferiority of the agent, at doses of 20 and 30 mg/kg per day, was demonstrated in a comparison with deferoxamine (Desferal®, Novartis), the current standard iron chelation therapy. This latter approach typically requires a slow infusion by pump over eight to 12 hours for at least five days a week.
A total of 586 patients with beta-thalassemia and transfusion-related iron overload were enrolled into an international, open-label, randomized phase 3 clinical trial. The patients were assigned, in a 1:1 ratio, to receive oral deferasirox once daily in doses of 5, 10, 20, or 30 mg/kg, respectively, or subcutaneous deferoxamine in doses of 20 to 60 mg/kg daily for five days a week.
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Treatment initially was given for one year, to be followed by an extension phase, during which patients who had been randomly selected to receive deferoxamine could switch to deferasirox. The primary endpoint was achievement of a specified reduction in liver iron concentration after one year. Patients with lower initial liver iron levels at the baseline evaluation in the deferoxamine group were allowed to continue their pre-study doses. They were compared with patients receiving the lower doses of deferasirox 5 or 10 mg/kg per day. Many of these individuals, therefore, received significantly higher doses of deferoxamine relative to deferasirox.
Because of the disproportionately low dosing with deferasirox 5 and 10 mg/kg per day, compared with deferoxamine, non-inferiority was not shown in the overall patient population; however, it was demonstrated in patients receiving deferasirox 20 and 30 mg/kg per day.
At the one-year follow-up, there was a statistically significant absolute reduction of liver iron concentration in the overall patient population. The mean overall change from the baseline was -5.3 ± 8.0 mg of iron per gram dry weight for patients taking deferasirox 20 and 30 mg/kg per day. Patients taking comparable doses of deferoxamine achieved a reduction in liver iron levels of -4.3 ± 5.8 mg of iron per gram dry weight.
Enoxaparin as a Bridging Anticoagulation Agent in Mechanical Prosthetic Heart Valve Patients
Speaker: Alexander G. Turpie, MD, Professor, Department of Medicine, McMaster University, Hamilton, Ontario, Canada
Enoxaparin (Lovenox®, Sanofi-Aventis), a well-known low-molecular-weight heparin (LMWH), appears to be effective and safe as a bridging anticoagulation therapeutic agent; however, there has been concern about its use in patients with mechanical prosthetic heart valves because of reports of fatal thromboemboli in pregnant women with mechanical heart valves.
A prospective cohort study was conducted to assess the efficacy and safety of enoxaparin for bridging anticoagulation in 174 consecutive patients with a mechanical prosthetic heart valve who required temporary interruption of warfarin therapy because of elective surgery or other invasive procedures. Warfarin therapy was discontinued, and bridging anticoagulation therapy was given according to a standardized perioperative protocol. The patients underwent a clinical follow-up for three months after surgery.
Study outcomes included (1) the incidence and an associated 95% conference interval during follow-up for major bleeding; (2) arterial thromboembolism, including stroke, transient ischemia attack (TIA), systemic embolism, or valve thrombosis; and (3) all-cause mortality. erectalis 20
No patients were lost to follow-up. After three months’ follow-up, only four patients experienced nonfatal bleeding, one patient had a nonfatal stroke, and four patients died as a result of non-drug-related serious adverse events. There were no episodes of valve thrombosis or systemic embolism. The results suggested that patients needing anticoagulation bridging therapy will now have a safe option.