Ximelagatran versus warfarin for prophylaxis of venous thromboembolism in major orthopedic surgery: systematic review of randomized controlled trials

Abstract

BACKGROUND: Ximelagatran has been recently studied for prophylaxis in surgical orthopedic cases. PURPOSE: We proposed to establish whether interventions involving ximelagatran, as compared with warfarin, would increase thromboembolic prophylaxis in patients undergoing major orthopedic knee surgery. DATA SOURCE: Studies with random assignment were identified by an electronic search of the medical literature up to 2006. Data were double-entered into the Review Manager software, version 4.2.5. DATA SYNTHESIS: We included three well-conducted clinical trials involving 4,914 participants. Sub-groups with two dosages of ximelagatran (24 mg and 36 mg, b.i.d.), were defined. Ximelagatran showed significantly lower frequency of total venous thromboembolism (VTE) than warfarin, but only with the 36-mg dosage (risk relative, RR: 0.72; 95% confidence interval, CI: 0.64-0.81; p < 0.00001). For the 24-mg subgroup, total VTE frequency was similar (RR: 0.86; 95% CI: 0.73-1.01; p = 0.06). No significant differences were shown with either ximelagatran dosage for deep vein thrombosis (DVT), pulmonary embolism, any bleeding or severe bleeding. At the end of the treatment, alanine aminotransferase (ALT) elevation was less frequent in the 24-mg ximelagatran sub-group (RR: 0.33; 95% CI: 0.12-0.91; p = 0.03], but during the follow-up period, the ALT elevation rate was greater in the 36-mg ximelagatran group (RR: 6.97; 95% CI: 1.26-38.50; p = 0.03]. CONCLUSIONS: Ximelagatran appears to be more effective than warfarin when used in higher dosages (36 mg b.i.d.), but at the expense of increased frequency of ALT elevation during the follow-up period.

Apixaban Versus Enoxaparin in Elective Major Orthopedic Surgery

“…New oral anticoagulants (NOACs) have been developed to overcome these limitations and thereby improve patient care, especially after early hospital discharge and the need to manage the therapy by the patient himself. [3][4][5][6][7][8][9][10][11][12] Apixaban is an oral, direct, potent, and selective inhibitor of coagulation factor Xa (FXa) that reversibly binds directly to the active site of FXa and exerts anticoagulant and antithrombotic effects by diminishing the conversion of prothrombin to thrombin. 13 Apixaban has an high oral bioavailability (approximately 52%), reaching the peak concentrations in 3 to 4 hours after administration within an 8 to 15 hours for half-life.…”

Os novos anticoagulantes orais no Brasil

“…The already known pharmacodynamic and pharmacokinetic limitations of this class of drugs fostered research into the development of new anticoagulant molecules, with similar effectiveness but presenting the following "theoretically ideal" characteristics: single daily dose oral administration; wide therapeutic window; rapid onset of action; no need for regular laboratory monitoring; predictable pharmacokinetics and pharmacodynamics; fast reversibility in case of bleeding (with antidote); limited food and drug interactions; and a low cost 2 . Following the frustrated experience with ximelagatran, which was withdrawn from both Brazilian and international markets in 2006 for causing severe liver injury, 3,4 new, promising perspectives emerged in Brazil with the release, by the Brazilian Health Surveillance Agency (ANVISA), of orally administered dabigatran etexilate (Pradaxa ® , Boehringer Ingelheim), a direct thrombin inhibitor, for VTE prophylaxis, and rivaroxaban (Xarelto ® , Bayer Healthcare), a direct inhibitor of activated factor X, for VTE prophylaxis and treatment. The RE-Novate, RE-Model, and RE-Mobilize dabigatran studies showed safety and effectiveness profiles that were not inferior to those obtained with subcutaneous enoxaparin in VTE prophylaxis during major hip and knee surgeries, using both the European regimen (40 mg/day) and the American regimen (30 mg every 12 hours)…”

Propriedades de medida do "Morisky Medication Adherence Scale" e da Medida de Adesão aos Tratamentos

“…76 Essas novas moléculas começaram a ser estudadas e elaboradas a partir dos anos 90, nesse período, a primeira substância a ser implementada e testada para administração oral foi o ximelagatran, não obtendo bons resultados devido à ocorrência de casos de toxicidade hepática severa, sendo retirado do mercado em 2006. 77 As pesquisas foram evoluindo e outros anticoagulantes foram criados ao longo dos anos, desde então se estruturaram duas novas classes de NOACs: os inibidores diretos da trombina e os inibidores do fator Xa. Os inibidores diretos da trombina atuam exatamente sobre a trombina, inibindo tanto sua forma livre como a forma ligada à fibrina.…”