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SummaryA multicenter, randomized double-blind study compared in two parallel groups the efficacy and safety of a low molecular weight heparin (LMWH) enoxaparin 20 mg once daily, with unfractionated heparin (UFH) 5000 IU twice daily, administered subcutaneously for 10 days, in the prevention of venous thrombosis disease in 442 hospitalized elderly patients bedridden for an acute medical illness. The main efficacy endpoint was defined as the occurrence of venous thrombosis, diagnosed by a daily fibrinogen uptake test, and/or documented clinical pulmonary embolism.Intention-to-treat analysis of efficacy showed that the incidence of venous thromboembolic events was low: 4.8% (10/207) in the LMWH group (9 episodes of isotopic venous thrombosis and one of scintigraphic pulmonary embolism), and 4.6% (10/216) in the UFH group (10 episodes of isotopic venous thrombosis). The two treatments were equivalent, where equivalence was defined as a maximum difference of 7% between the two groups (p = 0.0005).There were no significant differences in terms of safety between the 216 patients in the LMWH group and the 223 patients in the UFH group who received at least one injection of the randomized treatment. During the study period, 15 patients (3.4%) died (7 in the LMWH group and 8 in the UFH group): 2 sudden deaths, one in each group, including one case in which pulmonary embolism could not be excluded since no autopsy was performed, and 13 others deaths unrelated to the study treatments. Six patients (1.4%) presented a bleeding complication: 2 (0.9%) in the enoxaparin group (one major and one minor hemorrhage), and 4 (1.8%) in the UFH group (2 major and 2 minor hemorrhages).These results indicate that subcutaneous enoxaparin 20 mg once daily for 10 days is as effective and well tolerated as subcutaneous UFH 5000 IU twice daily in the prevention of venous thromboembolic disease in bedridden elderly in-patients presenting an acute medical illness.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Increased INR was previously observed in patients treated with warfarin and amoxicillin/clavulanic acid (amoxiclav) combination. To date, no prospective study has yet evaluated the effect of amoxiclav on INR in patients on warfarin therapy and consequently, there are no clear-cut conclusions or clear recommendations for clinicians. WHAT THIS PAPER ADDS• We provided the first systematic prospective evaluation of the interaction between amoxiclav and warfarin and found that amoxiclav did not modify INR in patients treated with stable warfarin therapy in the absence of any infectious or inflammatory syndrome, suggesting that the previously observed INR increase in these patients may not be attributable to a drug-drug interaction. AIMSTo investigate whether an interaction exists between amoxicillin/clavulanic acid (amoxiclav) and warfarin in patients treated with stable oral anticoagulant therapy. METHODSIn a double-blind, cross-over, placebo-controlled study, 12 patients on stable warfarin therapy, received a 7 day amoxiclav regimen or placebo. RESULTSThe mean maximum increase in INR observed was 0.22 Ϯ 0.3 with amoxiclav vs. 0.24 Ϯ 0.6 with placebo (P = 0.94). The day 7-day 1 factor II, R(-) and S(-) warfarin plasma concentrations were similar during the amoxiclav and placebo study periods (P = 0.81, P = 0.45, P = 0.75, respectively). CONCLUSIONAmoxiclav did not modify anticoagulation in patients treated with stable warfarin therapy and without infection.