Enoxaparin plus Compression Stockings Compared with Compression Stockings Alone in the Prevention of Venous Thromboembolism after Elective Neurosurgery
Giancarlo Agnelli, M.D., Franco Piovella, M.D., Pio Buoncristiani, M.D., Paolo Severi, M.D., Mario Pini, M.D., Armando D'Angelo, M.D., Chiara Beltrametti, M.D., Marcello Damiani, M.D., Gian Carlo Andrioli, M.D., Raffaelino Pugliese, M.D., Alfonso Iorio, M.D., and Gianluigi Brambilla, M.D.
Background Compression stockings are recommended for prophylaxisagainst venous thromboembolism in patients undergoing neurosurgery,but anticoagulant agents have not gained wide acceptance becauseof concern about intracranial bleeding.
Methods In a multicenter, randomized, double-blind trial, weassessed the efficacy and safety of enoxaparin in conjunctionwith the use of compression stockings in the prevention of venousthromboembolism in patients undergoing elective neurosurgery.Enoxaparin (40 mg once daily) or placebo was given subcutaneouslyfor not less than seven days beginning within 24 hours aftersurgery. The primary end point was symptomatic, objectivelyconfirmed venous thromboembolism or deep-vein thrombosis assessedby bilateral venography, which was performed in all patientson day 8±1. Bleeding side effects were carefully assessed.
Results Among the 307 patients assigned to treatment groups,129 of the 154 patients receiving placebo (84 percent) and 130of the 153 patients receiving enoxaparin (85 percent) had venographicstudies adequate for analysis. An additional patient in theplacebo group died before venography of autopsy-confirmed pulmonaryembolism. In this analysis, 42 patients given placebo (32 percent)and 22 patients given enoxaparin (17 percent) had deep-veinthrombosis (relative risk in the enoxaparin group, 0.52; 95percent confidence interval, 0.33 to 0.82; P=0.004). The ratesof proximal deep-vein thrombosis were 13 percent in patientsreceiving placebo and 5 percent in patients receiving enoxaparin(relative risk in the enoxaparin group, 0.41; 95 percent confidenceinterval, 0.17 to 0.95; P=0.04). Two patients in the placebogroup died of autopsy-confirmed pulmonary embolism on days 9and 16. Major bleeding occurred in four patients receiving placebo(intracranial bleeding in all four) and four patients (intracranialbleeding in three) receiving enoxaparin (3 percent of each group).
Conclusions Enoxaparin combined with compression stockings ismore effective than compression stockings alone for the preventionof venous thromboembolism after elective neurosurgery and doesnot cause excessive bleeding.
Source Information
From the Istituto di Medicina Interna e Medicina Vascolare, Università di Perugia, and Divisione di Neurochirurgia, Ospedale Silvestrini, Perugia (G.A., P.B., M.D., A.I.); the Clinica Neurochirurgica and Clinica Medica II, Università di Pavia, Pavia (F.P., C.B., R.P., G.B.); the Divisione di Neurochirurgia, Ospedale Galliera, Genoa (P.S., G.C.A.); V Divisione Medica, Azienda Ospedaliera, Parma (M.P.); and the Divisione di Neurochirurgia and Servizio di Coagulazione, Ospedale S. Raffaele, Milan (A.D.) all in Italy.
Address reprint requests to Professor Agnelli at the Istituto di Medicina Interna e Medicina Vascolare, Università di Perugia, Via Enrico dal Pozzo, 06123 Perugia, Italy.
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