@entity24772 and XXXX compared with @entity16960 for prevention of @entity1211 after total hip or knee replacement: the METHRO II randomised trial.

@entity1 @entity556 @entity548 @entity16960 @entity1151 @entity1150 @entity1031 @entity954 @entity18422 @entity1211 @entity24772
BACKGROUND: Heparins substantially reduce the risk of @entity1031 after total hip or knee replacement. However, they can be given only by injection and have several other drawbacks. We did a multicentre, randomised, double-blind study to examine the dose-response relation of subcutaneous @entity18422 , a direct @entity556 inhibitor, followed by oral @entity24772 as thromboprophylaxis after total hip or knee replacement. We aimed to compare the efficacy and safety with that of @entity16960 . METHODS: Of 1900 @entity1 , 1495 were assigned to four dose categories of subcutaneous @entity18422 from just before surgery (1.00 mg, 1.50 mg, 2.25 mg, or 3.00 mg twice daily) followed from the day after surgery by oral @entity24772 (8 mg, 12 mg, 18 mg, or 24 mg twice daily). 381 @entity1 were assigned subcutaneous @entity16960 5000 IU once daily, from the evening before surgery. Bilateral venography was done at 7-10 days, and clinically suspected @entity1211 ( @entity1211 ) was confirmed radiologically. The primary endpoint was the rate of @entity1150 and @entity1151 ( @entity1151 ). Analyses were by intention to treat. FINDINGS: 1876 @entity1 underwent total replacement of hip (n=1270) or knee (n=606); evaluable venograms were obtained in 1473 (79%). Four @entity1 without evaluable venograms had @entity1151 . Overall, a significant dose-dependent decrease in @entity1211 was seen with @entity18422 / @entity24772 (lowest to highest group: 111 [37.8%], 70 [24.1%], 71 [23.7%], and 43 [15.1%]; p=0.0001); there were also significant relations for both total hip and total knee replacement individually. The frequency of @entity1211 was significantly lower with the highest dose of @entity18422 / @entity24772 than with @entity16960 (15.1% vs 28.2%, p<0.0001). There were no reoperations due to @entity548 and no critical @entity548 . @entity954 was uncommon but more frequent in the highest dose group. INTERPRETATION: This sequential therapy was effective and safe in @entity1 undergoing major joint replacement surgery. The findings should be confirmed in a large phase III trial.
