Prevention of fatal pulmonary embolism and mortality in surgical patients

Abstract

The incidences of fatal pulmonary embolism and death in surgical patients receiving low-molecular-weight heparin thromboprophylaxis have not been previously determined in large, adequately designed clinical trials and information on the relative efficacy and safety of unfractionated and low-molecular-weight heparin in preventing these clinical endpoints is not available. In a double-blind study, 23078 surgical patients randomly received the low-molecular-weight heparin, certoparin (3000 anti Xa IU) subcutaneously once-daily, or unfractionated heparin (5000 IU) subcutaneously three-times daily, for a minimum of 5 days. The primary outcome measure, autopsy-proven fatal pulmonary embolism recorded up to 14 days after the end of prophylaxis, occurred in 0.152% (95% confidence interval (CI) 0.10, 0.20%; 35 of 23078 patients) of cases, with no significant difference between the certoparin-treated patients (0.147% (95% CI 0.077, 0.217%; 17 of 11542 patients) and patients treated with unfractionated heparin (0.156% (95% CI 0.084, 0.228%; 18 of 11,536 patients, P=0.868). The autopsy rate was 70.2%. Comparing mortality, there was no significant difference between the groups (1 .44% [166 of 11542 certoparin patients] versus 1.27% [146 of 11536 unfractionated heparin patients]; P=0.279). The safety profiles of both treatment groups were similar. Once-daily certoparin and three-times daily unfractionated heparin are equally effective and safe in reducing fatal pulmonary embolism and death to low levels in surgical patients and mirror the findings of comparative efficacy studies using surrogate endpoints.

Tromboembolismo pulmonar en pacientes hospitalizados entre 1994-2000: serie de autopsia

“…Mientras que la introducción de tromboprofilaxis farmacológica, si ha modificado la incidencia de ETE en los pacientes quirúrgicos (18,19), no parece que el efecto haya sido similar en los pacientes "médicos" (20). Así en las series recientes de autopsia donde se objetivó tromboembolismo pulmonar, solo una cuarta parte de los pacientes tenían antecedentes quirúrgicos, dato que se mantiene también en nuestro estudio (22,5%).…”

The long path to NOAC

“…Our research group was involved in many detailed investigations concerning the preclinical research and development of several LMWH preparations for the prophylaxis of venous thromboembolism (9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26). For example, in the first thrombosis treatment study with the LMWH certoparin, we investigated whether it should be administered subcutaneously or intravenously.…”

Perioperative Thromboprophylaxis

“…In this double-blind study, some 23,000 surgical patients received either low-dose UFH (3 × 5,000 IU per day) or the LMWH, certoparin, at a daily dose of 3,000 IU anti-Xa. The incidence of the primary efficacy endpoint of autopsy-proven fatal PE was similar between the two groups [11]. Based on their overall safety and efficacy profile, the significantly reduced risk of heparin-induced thrombocytopenia (and probably also of osteopenia), and the convenience of once daily injections, national guidelines favor LMWH over low-dose UFH for pharmacological thromboprophylaxis in surgical patients [1].…”