Walter Ageno

Exaggerated initial response to warfarin following heart valve replacement

The response to initiation of oral anticoagulants at a usual dose of 5 mg of warfarin has been retrospectively evaluated in patients following heart valve replacement (HVR). Patients starting oral anticoagulants after HVR have a lower target International Normalized Ratio (INR) (1.5 to 2.6) until the pacing wires are removed after operation. The mean daily doses and INR responses after HVR and nonsurgical patients were retrospectively compared during the first 5 days of warfarin treatment. In a subset from both groups, the mean dose of warfarin was correlated with age, body weight, and albumin levels. Eighty-four HVR and 32 nonsurgical patients were studied. The mean daily warfarin dosage was 3.29 +/- 1.29 mg after HVR and 4.96 +/- 1.76 mg in controls (p <0.001), and the mean INRs 2.08 +/- 0.60 and 1.60 +/- 0.54, respectively (p <0.001). Of the HVR patients and controls, 48.8% and 21.8%, respectively, exceeded the upper level of the targeted range (p = 0.014), 86.9% and 40.6% had the dose reduced after the first 5 mg (p <0.001), and 54.7% and 28.1%, respectively, had warfarin withheld for at least 1 day (p = 0.015). Thirty-nine patients were included in the subset analysis. Patients with serum albumin levels <35 g/L required significantly less warfarin (3.84 mg/day) than patients with levels > or =35 g/L (5.37 mg/day; p <0.05). Thus, patients starting oral anticoagulation after HVR are significantly more sensitive to warfarin than nonsurgical patients. Patients with serum albumin levels below the normal values require less warfarin than patients with normal values during the initial phase of treatment.

Role of new anticoagulants for the prevention of venous thromboembolism after major orthopaedic surgery and in hospitalised acutely ill medical patients.

Anticoagulation therapy for the prevention of venous thromboembolic events is indicated in patients after major orthopaedic surgery and in hospitalised acutely ill medical patients, who have a high or moderate risk of venous thromboembolism (VTE), respectively. Clinical trials have clearly demonstrated that short-term anticoagulation reduces the risk of VTE in these patient groups and that longer-term anticoagulation is beneficial for some indications. Evidence-based guidelines for thromboprophylaxis have been developed based on these studies. However, despite these guidelines, thromboprophylaxis is still underused, or used suboptimally, in many patients. This is, in part, because of the limitations of traditional anticoagulants such as unfractionated heparin, low- molecular-weight heparin, synthetic pentasaccharides, and vitamin K antagonists. Newer oral anticoagulants, such as rivaroxaban, apixaban, and dabigatran etexilate, have certain advantages over traditional agents. They can be administered orally at a fixed dose without routine coagulation monitoring and have minimal food and drug interactions. These characteristics may result in better adherence to guidelines and improved patient outcomes. This review provides an overview of phase III clinical trial data for these newer anticoagulants in major orthopaedic surgery and in hospitalised acutely ill medical patients, and discusses their potential for extended use in the post-hospital discharge setting. All three newer oral anticoagulants are approved in many countries for the prevention of VTE after hip replacement or knee replacement surgery in adult patients, and it is likely that these drugs will contribute considerably towards reducing the substantial healthcare burden associated with VTE.