Study Question: Is heparin thromboprophylaxis safe and efficacious for use in medical-surgical ICU patients?
Study Description: This systematic review and meta-analysis included randomized controlled trials (RCTs) from 1980 to May 2012. Trials included adult patients in the medical or surgical ICU, comparison of any heparin thromboprophylaxis (unfractionated heparin [UFH] twice daily or low molecular weight heparin [LMWH]) to any other strategy or no prophylaxis, and evaluation of outcomes. These outcomes included the incidence of venous thromboembolism (VTE) outcomes (deep vein thrombosis [DVT] or pulmonary embolism [PE]), major bleeding, heparin-induced thrombocytopenia (HIT) or mortality.
Results: Seven RCTs met inclusion criteria (two UFH vs. placebo, one LMWH vs. placebo, one UFH vs. LMWH vs. placebo, and three UFH vs. LMWH trials; aggregate n = 7,226). The pooled analysis favored any heparin thromboprophylaxis in reducing the risk of DVT (4 trials; RR 0.51; 95% CI 0.41 – 0.63; p < 0.0001) and PE (3 trials; RR 0.52; 95% CI 0.28 – 0.97; p = 0.04), when compared to placebo. One trial comparing LMWH to placebo and the incidence of PE found no significant difference (RR 1.00; 95% CI 0.30 – 3.31; p = 1.0). There were no differences in the incidence of major bleeding, HIT, or ICU mortality when thromboprophylaxis was compared to placebo. In the pooled analysis evaluating UFH vs. LMWH, there was no difference in incidence of DVT (four trials) while LMWH thromboprophylaxis was associated with a decreased incidence of PE (two trials; RR 0.62; 95% CI 0.39 – 1.00; p = 0.05). LMWH was associated with a reduction in incidence of symptomatic PE (RR 0.58; 95% CI 0.34 – 0.97; p = 0.04). There were not differences in the incidence of major bleeding, HIT, or ICU mortality
Conclusion(s): The use of any heparin thromboprophylaxis decreases incidence of VTE but does not decrease mortality when compared to placebo. LMWH when compared to UFH is associated with a decreased incidence of PE but not DVT in medical-surgical ICU patients. The incidence of major bleeding, HIT, or mortality does not appear to be affected with any heparin thromboprophylaxis therapy.
Perspective: This meta-analysis has inherent limitations due to the heterogeneity of the individual trials. The authors did perform a sensitivity analysis and attribute the heterogeneity to the large difference in DVT rates in one abstract evaluating UFH vs. placebo. When this abstract was removed, the incidence of DVT was similar among the remaining three trials. Additionally, screening for DVT or PE was not systematic among the individual trials and the outcomes evaluated were not included in each of the qualifying trials. Finally, the twice daily dosing of UFH and the various LMWH regimens and dosing may not be reflective of all clinical practice.