Low-molecular-weight heparin in arterial reconstructive surgery: a double-blind, randomized dose-finding trial.

Periprocedural and postprocedural anticoagulation during arterial reconstructive surgery (ARS) with intravenous heparin is standard of care. The general use and correct dosage of low-molecular-weight heparin, however, are still under debate. A prospective, randomized, double-blind trial was performed with a parallel group comparison of four dose regimen of a low-molecular-weight heparin, reviparin sodium, in patients undergoing major ARS. Sixty-five patients were randomly allocated to receive twice-daily subcutaneous injections of reviparin, 3500 (group A, n=17), 4200 (group B, n=16), 5950 (group C, n=16), and 7000 (group D, n=16) anti-Xa IU per day. Patients were eligible for the trial if they had angiographically proven peripheral arterial obstructive disease with a planned arterial reconstruction of the infrarenal aorta, iliaca artery, or femoralis artery. Fifty-nine patients completed the trial. The goal was to determine the optimal dose of the low-molecular-weight heparin to achieve a minimum of early vascular events (less than 12%) with a minimum of major bleeding events (less than 10%) during a short-term follow-up of up to 8 postoperative days. There was no reocclusion in the entire population. Patients randomized into the two lower dose groups (A and B), however, experienced a relatively high incidence of restenosis, whereas patients enrolled in group D, receiving the highest dose of reviparin, experienced an unacceptably high rate of bleeding events (all bleeds, 43%; major bleeding, 14.3%). Thus, the optimal dose of reviparin sodium to be administered in patients undergoing major ARS is half the therapeutic dose: 5950 to 6300 anti Xa IU (75-85 anti Xa IU/kg body weight per day). Patients included in group C had no major bleeding event (95% confidence interval, 0% to 6.6%), a significant improvement of the doppler ankle-brachial systolic pressure index (difference of 0.46 +/- 0.29, P=.017), and a higher rate of responders with regard to the puls status measured at the tibialis posterior arteries (66.7%) compared to groups A and B (46.7% and 54.5%, respectively, P=.086). The efficacy and safety of this dosage regimen in comparison to standard of care should be further substantiated in larger trials.

RCT Entities:   Population Interventions Outcomes