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Therapeutics

Review: Low-molecular-weight heparin is at least as effective as unfractionated heparin for preventing thrombosis and embolism after surgery

ACP J Club. 1998 Jan-Feb;128:5. doi:10.7326/ACPJC-1998-128-1-005


Source Citation

Koch A, Bouges S, Ziegler S, et al. Low molecular weight heparin and unfractionated heparin in thrombosis prophylaxis after major surgical intervention: update of previous meta-analyses. Br J Surg. 1997 Jun 7; 84:750-9.


Abstract

Objective

To compare, using meta-analysis, the efficacy and safety of low-molecular-weight heparin (LMWH) and unfractionated heparin (UFH) for the prevention of deep venous thrombosis (DVT) after surgery.

Data sources

Studies were identified through MEDLINE (1988 to March 1996) and Embase (1990 to March 1996) using the terms low molecular weight heparin, trade and generic names of the LMWH products, postoperative complications, thromboembolism, and thrombophlebitis. Bibliographies of relevant studies were checked, and pharmaceutical companies were contacted.

Study selection

Studies were selected if they were randomized, double-blind, controlled trials comparing LMWH with UFH for prophylaxis against thromboembolic events after either general or orthopedic surgery. Studies that added dihydroergotamine were included only if the drug was given to both treatment groups. Studies of danaparoid, a heparinoid, were excluded.

Data extraction

Major end points were DVT detected by any method (efficacy) and wound hematoma (safety). Data were also extracted on type of surgery; dose of LMWH; and the secondary outcomes of death, pulmonary embolism, injection site hematoma, and bleeding episodes.

Main results

36 trials that studied 16 583 patients were included. The groups did not differ for the incidence of DVT for all studies combined. Subgroup analyses involving orthopedic surgery, general surgery, and low- or high-dose LMWH in general surgery also did not show differences for incidence of DVT. For orthopedic surgery, a trend favoring LMWH was seen (P = 0.07). The groups did not differ for wound hematomas for all the surgery trials (P = 0.1) or general (P = 0.09) or orthopedic surgery trials (P = 0.8). General surgery studies that assessed high-dose LMWH showed more wound hematomas with LMWH than with UFH (P = 0.02), whereas general surgery trials of low-dose LMWH showed more wound hematomas with UFH (P < 0.01). The secondary outcomes of pulmonary embolism (P = 0.01) and injection site hematomas (P < 0.01) were lower in the LMWH group than in the UFH group. The groups did not differ for death or bleeding after surgery that required withdrawal, intervention, or transfusion. Strong heterogeneity was seen among the trials.

Conclusions

Low-molecular-weight heparin is as effective and safe as unfractionated heparin for reducing the rate of deep venous thrombosis after surgery. In the general surgery trials, low-dose low-molecular-weight heparin causes fewer wound hematomas, whereas high-dose low-molecular-weight heparin causes more wound hematomas than unfractionated heparin. The incidence of pulmonary embolism and injection site hematoma is lower with low-molecular-weight heparin than with unfractionated heparin.

Source of funding: In part, Deutsche Forschungsgemeinschaft.

For article reprint: Dr. A. Koch, Abteilung Medizinische Biometrie, Universit├Ąt Heidelberg, Im Neuenheimer Feld 305, 69 120 Heidelberg, Germany. FAX 49-6221-56-4195.


Commentary

Among the meta-analyses that have compared the efficacy and safety of UFH and LMWH, only the review by Koch and colleagues (1-4) restricted study selection to randomized, double-blind, controlled trials. The analysis combined trials in which the thromboembolic outcome was based on sensitive outcome assessment measures with those in which relatively insensitive screening measures were used.

Although the various meta-analyses used different criteria for study selection and analysis, the conclusions are consistent. In general surgery, because UFH and LMWH provide similar efficacy and safety, the advantages of LMWH (reduced risk for heparin-induced thrombocytopenia and convenience of once-a-day dosing vs 2 or 3 daily injections for UFH) must be balanced against the greater cost of these medications.

For the higher risk hip and knee surgery patients, Koch and colleagues found a trend favoring greater efficacy with LMWH without increased bleeding. When only orthopedic studies that used routine venography were assessed, the difference in efficacy is highly significant (rates of DVT were 23.2% vs 17.9% in the low-dose UFH and LMWH groups, respectively [ P = 0.01, NNT 19]). The superiority of LMWH in other high-risk patients, including those with spinal cord injury and major trauma, has also been shown (5). Use of LMWH compared with UFH results in even greater risk reduction for proximal DVT than for total DVT and, therefore, should be considered the prophylactic agent of choice in these high-risk groups (3-5).

William H. Geerts, MD
Sunnybrook Health Science CentreToronto, Ontario, Canada


References

1. Leizorovicz A, Haugh MC, Chapuis FR, Samama MM, Boissel JP. Low molecular weight heparin in prevention of perioperative thrombosis. BMJ. 1992; 305:913-20.

2. Nurmohamed MT, Rosendaal FR, Buller HR, et al. Low-molecular-weight heparin versus standard heparin in general and orthopaedic surgery: a meta-analysis. Lancet. 1992;340:152-6.

3. Jorgensen LN, Wille-Jorgensen P, Hauch O. Whole body and regional soft tissue changes in growth hormone deficient adults after one year of growth hormone treatment: a double-blind, randomized, placebo-controlled study. Br J Surg. 1993;80:689-704.

4. Palmer AJ, Koppenhagen K, Kirchhof B, Weber U, Bergemann R. Efficacy and safety of low molecular weight heparin, unfractionated heparin and warfarin for thrombo-embolism prophylaxis in orthopaedic surgery: a meta-analysis of randomised clinical trials. Haemostasis. 1997;27:75-84.

5. Geerts WH, Jay RM, Code KI, et al. A comparison of low-dose heparin with low-molecular-weight heparin as prophylaxis against venous thromboembolism after major trauma. N Engl J Med. 1996;335:701-7.