Self-managed long-term low-molecular-weight heparin therapy: the balance of benefits and harms.
OBJECTIVE
A substantial clinical need exists for an alternate to vitamin K antagonists for treating deep vein thrombosis in many patients. Long-term low-molecular-weight heparin (LMWH), body-weight adjusted, avoids anticoagulant monitoring and may be associated with less bleeding. We evaluated the effectiveness and safety of long-term LMWH compared with vitamin K antagonist therapy in a broad spectrum of patients with proximal vein thrombosis.


METHODS
We performed a multicenter, randomized, open-label clinical trial using objective outcome measures comparing therapy for 3 months. Outcomes were assessed at 3 and 12 months.


RESULTS
Of 737 patients, 18 of 369 receiving tinzaparin (4.9%) had recurrent venous thromboembolism at 3 months compared with 21 of 368 (5.7%) receiving usual care (absolute difference, -0.8%, 95% confidence interval -4.1-2.4). Hemorrhagic complications occurred less frequently in the LMWH group largely because of less minor bleeding: 48 of 369 patients (13.0%) versus 73 of 368 patients (19.8%) receiving usual-care anticoagulation (absolute difference -6.8%; P = .011; risk ratio = 0.66). New major bleeding events ceased early (by day 23, P = .034) for patients receiving LMWH but persisted throughout the study treatment interval for patients receiving vitamin K antagonist therapy. No mortality advantage was shown for LMWH.


CONCLUSIONS
Our study shows that LMWH is similar in effectiveness to the usual-care vitamin K antagonist treatment for preventing recurrent venous thromboembolism in a broad spectrum of patients. It causes less harm and enhances the clinicians' therapeutic options for patients with proximal deep vein thrombosis. Our findings reported here suggest the possibility of a broader role for long-term LMWH in selected patients.
Hull
Russell D
RD
University of Calgary, Calgary, AB, Canada. Jeanne.Sheldon@calgaryhealthregion.ca
Pineo
Graham F
GF
Brant
Rollin F
RF
Mah
Andrew F
AF
Burke
Natasha
N
Dear
Richard
R
Wong
Turnly
T
Cook
Roy
R
Solymoss
Susan
S
Poon
Man-Chiu
MC
Raskob
Gary
G
D000925:Anticoagulants / Q000008:administration & dosage / Q000627:therapeutic use; D002423:Cause of Death; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006470:Hemorrhage / Q000453:epidemiology; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D012646:Self Administration; D000078222:Tinzaparin; D016896:Treatment Outcome; D020246:Venous Thrombosis / Q000188:drug therapy*; D014812:Vitamin K / Q000037:antagonists & inhibitors*; D014859:Warfarin / Q000008:administration & dosage / Q000627:therapeutic use
D000925:Anticoagulants; D005343:Fibrinolytic Agents; D006495:Heparin, Low-Molecular-Weight; D014812:Vitamin K; D014859:Warfarin; D000078222:Tinzaparin