ORIGINAL ARTICLES   

International Angiology 1998 September;17(3):135-45

Copyright © 2000 EDIZIONI MINERVA MEDICA

lingua: Inglese

Efficacy of a low molecular weight heparin administered intravenously or subcutaneously in comparison with intravenous unfractionated heparin in the treatment of deep venous thrombosis

Kirchmaier C. M., Wolf H., Schafer H., Ehlers B., Breddin H. K.

for the Certoparin-Study group

Background. The main objec­tive of the study pre­sent­ed was to test if throm­bus regres­sion can be ­improved by treat­ment with an intra­ve­nous­ly or sub­cu­ta­ne­ous­ly admin­is­tered low molec­u­lar ­weight hep­ar­in (LMWH). Patients with acute deep vein throm­bo­sis were ran­dom­ly ­assigned to ­receive ­either intra­ve­nous UFH (131 ­patients), intra­ve­nous (i.v.) LMWH (128 ­patients), or 8000 IU of the same LMWH bid sub­cu­ta­ne­ous­ly (s.c.) (128 ­patients). All ­patients were treat­ed with hep­ar­in for 14 to 16 days. Vitamin-K-antag­o­nist pro­phy­lax­is was start­ed ­between Day 12 and Day 14 after enroll­ment into the study.
Methods. Phlebographies and per­fu­sion/ven­ti­la­tion lung scans were per­formed at base­line and on Days 12 to 16. Primary end­point of the study was a reduc­tion of the phleb­o­graph­ic Marder score. Secondary end­points were recur­rent throm­bo­sis and pul­mo­nary embo­lism (PE), major and minor bleed­ings and the rate of PE at inclu­sion and at the end of the study ­assessed by ven­ti­la­tion/per­fu­sion scans.
Results. The Marder score ­improved by at least 30% in 32.4% (95% CI: 22.6...42.2) of the ­patients receiv­ing UFH, in 34.0% (95% CI: 24.9...44.0) receiv­ing LMWH i.v. and in 42.6% (95% CI: 32.8...52.8) treat­ed with the low molec­u­lar ­weight hep­ar­in s.c.. The dif­fer­ence ­between LMWH s.c. and UFH was 10.2% (95% CI: -3.7% ...+24.5%) (p=0.11). PE with clin­i­cal signs con­firmed by objec­tive meth­ods ­occured in three ­patients of the UFH group, one of whom died and was not ­observed in ­patients of the i.v. or s.c. LMWH-­groups. During the first 15 days no ­patient receiv­ing UFH or i.v. LMWH, and one ­patient on s.c. LMWH had a recur­rent throm­bo­sis. Major bleed­ings were ­observed in four ­patients receiv­ing i.v. UFH com­pared to nine ­patients on i.v. LMWH (one of these ­patients died) and one ­patient on s.c. LMWH. Perfusion ven­ti­la­tion lung scans were ­obtained from 287 ­patients at base­line and from 246 ­patients on Days 12-16. PE, ­defined accord­ing to ­PIOPED-cri­te­ria as inter­me­di­ate or high prob­abil­ity scans, was ­observed in 38.0% of the ­patients enter­ing the study and in 18.3% on Days 12 to 16. New asymp­to­mat­ic PE ­occurred less fre­quent­ly in the ­groups on LMWH (7.1%, 7.5%, respec­tive­ly) than in the UFH-group (12.6%) (not sig­nif­i­cant).
Conclusions. S.c. treat­ment with a LMWH (certoparin) (b.i.d.) is at least as effec­tive as UFH i.v. The hypoth­e­sis of ­increased effi­ca­cy of sub­cu­ta­ne­ous LMWH in resolv­ing ­venous throm­bi will have to be con­firmed by an inde­pen­dent study com­par­ing s.c. LMWH with UFH. The i.v. con­tin­u­ous infu­sion of the LMWH for 12 to 16 days does not ­result in a high­er ­venous re-open­ing rate than intra­ve­nous stan­dard hep­ar­in.