Low molecular weight heparins and heparinoids
Most randomised trials examining the efficacy of LMW heparins for the prevention of venous thromboembolism have used asymptomatic deep vein thrombosis as their primary outcome, as these events are much more common than symptomatic events. No thromboprophylaxis studies have shown a differential benefit of LMW heparin on fatal thromboembolism, or have examined an effect of LMW heparins on the incidence of postphlebitic syndrome.
General surgery: Meta-analyses of randomised controlled trials (RCTs) of heparin in patients undergoing general surgery indicate that heparins reduce the risk of venous thromboembolism and fatal pulmonary embolism by 50%–70% compared with controls (E1)7,8 (for an explanation of level-of-evidence codes, see Box 3). Direct comparisons of daily LMW heparin therapy versus unfractionated heparin therapy indicate that once-daily LMW heparins are at least as effective and safe as low-dose (eg, 5000 IU, three times daily) unfractionated heparin (E1).7,8
Orthopaedic surgery: Among patients undergoing surgery for hip fracture or elective hip or knee replacement, LMW heparins reduce the risk of venous thromboembolism by about 50% compared with placebo7,10-12 (E1). However, LMW heparins should be used with caution in surgical patients undergoing regional anaesthesia with an epidural catheter because of the risk of haematoma formation.
Direct comparisons of LMW heparins with unfractionated heparin in patients undergoing total hip replacement indicate that LMW heparins are more effective than low-dose unfractionated heparin, and at least as effective and safe as adjusted-dose unfractionated heparin or warfarin (E1).10 In knee-replacement surgery, LMW heparins are superior to both low-dose unfractionated heparin and warfarin (E1).11 There are insufficient trials directly comparing LMW heparins with unfractionated heparin in patients undergoing hip fracture surgery to be conclusive, but indirect comparisons suggest that LMW heparins and warfarin are most effective (E3).12
The optimal duration of thromboprophylaxis following hip or knee replacement surgery is unclear. LMW heparin given for 4–6 weeks is more effective than placebo for preventing venous thromboembolism after hospital discharge (E1), although symptomatic event rates remain low (about 3%) in patients treated with placebo.13
Ischaemic stroke and other medical conditions: Compared with placebo, LMW heparins reduce the risk of venous thromboembolism by about 50% in patients with immobility resulting from ischaemic stroke and in other general medical patients with risk factors for venous thromboembolism, including immobility, heart failure, severe lung disease, or malignancy (E2).14 In patients who have had ischaemic stroke, LMW heparins appear to be more effective than unfractionated heparin for the prevention of venous thromboembolism (E1).15 However, heparin therapy is associated with a dose-dependent increase in symptomatic haemorrhagic transformation of the cerebral infarct, which, at higher doses, may offset any antithrombotic benefit. Therefore, for patients at increased risk of haemorrhagic transformation (eg, large infarcts, uncontrolled hypertension, or other bleeding conditions), mechanical methods of thromboprophylaxis are recommended during the first two weeks after the stroke.16 Early anticoagulation therapy should nevertheless be considered in patients with cardioembolic stroke who are at high risk for early recurrent embolism (mechanical heart valves, established intracardiac thrombus, congestive heart failure, and atrial fibrillation with multiple risk factors for thromboembolism17) (E3).