Oral direct thrombin inhibitor versus low molecular weight heparin in the prevention of proximal deep vein thrombosis after major orthopedic surgery (DTI-ORTHO): A meta-analysis.

BACKGROUND: Venous thromboembolism (VTE), which consists of deep vein thrombosis (DVT) and pulmonary embolism, is a common complication after total knee replacement surgery. It is also considered to be the most common preventable cause of hospital-related death. Hence, prophylaxis is recommended following major orthopedic surgery. Thromboprophylaxis with heparin and low-molecular weight heparins (LMWH) has significantly decreased the risk of thromboembolic complications after total knee or total hip replacement. Heparins are only given by injections and many patients are hesitant to use it. With the advent of direct thrombin inhibitors (DTI) which can be taken orally, patient may adhere more with the therapy and reduce the incidence of proximal DVT. The objective of this study was to determine if oral DTIs are comparable with LMWHs in preventing DVT after major orthopedic surgery.

METHODS: Computer search was conducted using the MEDLINE, National Library of Medicine, COCHRANE, NCBI, Embase, and PubMed for articles published from year 2000 up to 2010. Search was restricted to meta-analyses and randomized controlled trials comparing oral DTIs and LMWHs. Search terms used were "venous thromboembolism", "deep vein thrombosis", "arthroplasty", "knee surgery", "hip surgery", "oral thrombin inhibitor", and "low molecular weight heparin". The primary author and another independent reviewer reviewed and screened titles and trial abstracts identified through the search strategy.  The reviewers used Cochrane Quality Score to evaluate the quality of the study. Results were analyzed using RevMan version 5software.  Chi2 test was used to analyze heterogeneity.

RESULTS: Eight trials were analyzed for proximal DVT events, with 4234 patients randomized to oral DTI and 4189 patients randomized to LMWH. Overall, the risk of proximal DVT was not significantly different for LMWH compared with the oral DTI [OR 0.87 (95% C.I. 0.69, 1.09; P=0.22). Nine trials were analyzed for major bleeding events, with 7302 patients randomized to oral DTI and 7309 patients randomized to LMWH. The combined studies revealed that oral DTIs had significantly more major bleeding events than LMWHs [OR 1.33 (95% C.I. 1.10, 1.61; P=0.003)].

CONCLUSIONS: This review demonstrated no overall advantage for either LMWH or oral DTI in thromboprophylaxis following major orthopedic surgery.   The benefits of oral DTIs in the prevention of proximal DVT are at the expense of higher risk of major bleeding events as compared with LMWH.