A Prospective, Randomized, Placebo-Controlled Study of Extended-Duration Post-Discharge Thromboprophylaxis with Enoxaparin Following Arthroscopic Reconstruction of the Anterior Cruciate Ligament.

Abstract

Introduction Deep-vein thrombosis (DVT) with subsequent pulmonary embolism (PE) is the most life-threatening complication that occurs after knee arthroscopy. Although the incidence of clinically diagnosed DVT is low, thromboprophylaxis with a low-molecular-weight heparin (LMWH) following arthroscopic reconstruction of the anterior cruciate ligament (ACL) is generally recommended until full weight bearing is achieved. The aim of this study was to compare the effect of extended-duration thromboprophylaxis using the LMWH enoxaparin with placebo on the incidence of DVT and PE during the 20-day post-discharge period after arthroscopic ACL reconstruction. Methods 175 patients, scheduled for arthroscopic ACL reconstruction with a middle-third patellar, bone-tendon-bone autograft, were randomized to two groups. Both groups received enoxaparin 40 mg s.c. once daily, initiated 12–18 hours before the start of surgery and continued 3–8 days during hospitalization. Following hospital discharge, the groups of patients self-administered either enoxaparin 40 mg (n=87) or placebo (n=88) s.c. once daily for a further 20 days in the outpatient setting. The primary endpoint was DVT or PE. DVT was confirmed by magnetic resonance (MR) venography performed on the operated leg in sagittal and coronal views. Filling defects of a deep vein were considered to be an indirect sign of DVT. PE was confirmed by lung scan. The intention-to-treat (ITT) population was all randomized patients who received at least one dose of study drug, underwent baseline examinations and one further examination for DVT. Results In accordance with predefined criteria, 35 patients were excluded from the ITT analysis as they did not undergo an evaluation for the primary endpoint of DVT because of medical reasons (arthroscopy, but no ACL reconstruction; n=16), non-compliance (n=11), MR venography not possible for technical reasons (n=4), lost to follow-up (n=2), withdrawal (n=1), and adverse events (n=1). The ITT analysis of 140 patients (enoxaparin group n=72; placebo group n=68) showed an overall DVT incidence of 21.4% (30/140). The total incidence of DVT was significantly lower in the enoxaparin group compared with the placebo group (relative risk reduction 93%; Table 1). The incidences of DVT in the popliteal and femoral regions were significantly lower in the enoxaparin group compared with the placebo group (Table 1). PE was not observed in either group. Enoxaparin was well tolerated and no major bleeding complications occurred in either group. Conclusion Enoxaparin, self-administered once daily subcutaneously in the outpatient setting, is feasible, safe and significantly reduces the incidence of DVT in patients with arthroscopic ACL reconstruction. Extended-duration thromboprophylaxis with enoxaparin for 20 days post-discharge should be considered for this patient group. Table 1. Incidence of DVT or PE in patients undergoing ACL reconstruction Enoxaparin 40 mg Placebo P value *DVT was detected in more than one location in some patients N 72 68 - Total DVT*, n (%) 2 (2.8) 28 (41.2) <0.0001 Lower leg DVT, n (%) 2 (2.8) 28 (41.2) <0.0001 Popliteal DVT, n (%) 2 (2.8) 12 (17.7) 0.0034 Upper leg DVT, n (%) 1 (1.4) 6 (8.8) 0.0437 PE, n (%) 0 (0) 0 (0) -