Thirty studies were identified: 18 RCTs (n=2,639), of which six were double blind; and 12 cohort studies (n=5,098). The number of studies that investigated each intervention was: LMWH 11 studies; unfractionated heparin 12 studies; ICD 18 studies; and compression stockings 10 studies.
The reported mean Jadad score for the RCTs was 5.81 (range 2 to 8). The mean prognostic quality score was 7.0 (range 5 to 8) for the RCTs and 6.2 (range 3 to 8) for the cohort studies. Many studies were reported to show evidence of selection bias.
Efficacy: Meta-analysis of the RCTs for DVT or pulmonary embolism prophylaxis found only two statistically significant results: ICDs significantly reduced DVTs compared to placebo (RR 0.41, 95% CI 0.21 to 0.78; two studies, I2 squared=0%) and LMWH significantly reduced DVTs compared to compression stockings (RR 0.60, 95% CI 0.44 to 0.81; two studies, I2=0%).
Non-significant results were found for ICD versus compression stockings, LMWH versus ICD, LMWH versus unfractionated heparin and unfractionated heparin versus placebo. DVT rates and pulmonary embolism rates were reported and pooled for all studies; these gave similar results to those for the RCTs alone. Pulmonary embolism rates were lower than those for DVT.
Safety: Meta-analysis of the RCTs for intracranial haemorrhage, minor bleeding, major bleeding and death found only one statistically significant result: LMWH versus nonpharmacological prophylaxis significantly increased minor bleeding (RR 2.06, 95% CI 1.07 to 3.96; four studies, I2=0%).
Non-significant results were found for unfractionated heparin versus nonpharmacological prophylaxis and LMWH versus unfractionated heparin. When rates of intracranial haemorrhage were compared for all studies, patients who received LMWH had significantly higher bleeding rates than those who received mechanical prophylaxis (p<0.0005), although patients who received unfractionated heparin did not have higher intracranial haemorrhage rates (p=0.40). There were no significant differences found for minor bleeding rates and major bleeding rates. Major bleeding rates were relatively low.
Sensitivity analysis: Sensitivity analysis found that prospective cohort trials reported lower rates of DVT than RCTs (p=0.03). Older patients and those who were treated for neoplasms had higher DVT rates. Patients who received preoperative heparin had lower rates of DVT than those who received their first dose postoperatively (p<0.001). There was no difference in rates of intracranial haemorrhage between heparin administered preoperatively, intraoperatively or postoperatively. After adjustment for age, neoplasm and study design, LMWH (p=0.02), unfractionated heparin (p=0.001) and ICD (p=0.04) prophylaxes had lower DVT rates than either compression stockings or placebo. After adjustment, patients with LMWH had a higher intracranial haemorrhage incidence than those with mechanical prophylaxis.