Adding intermittent pneumatic compression to UFH or LMWH did not reduce proximal DVT in critically ill patients

Abstract

Question In critically ill patients, does adding intermittent pneumatic compression (IPC) to pharmacologic thromboprophylaxis reduce risk for proximal lower limb deep venous thrombosis (DVT)? Methods Design Randomized controlled trial (Pneumatic Compression for Preventing Venous Thromboembolism [PREVENT] trial). ClinicalTrials.gov NCT02040103; ISRCTN 44653506. Allocation Concealed.* Blinding Blinded* {ultrasound adjudicators}. Follow-up period Until DVT, pulmonary embolism (PE), death, attainment of full mobility, ICU discharge, or 28 days. Setting 20 clinical centers in Australia, Canada, India, and Saudi Arabia. Patients 2027 critically ill adults (mean age 58 y, 57% men) who had been admitted to the intensive care unit (ICU) for <48 hours with an expected stay 72 hours and were eligible for pharmacologic thromboprophylaxis with unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH). Exclusion criteria included weight <45 kg, receipt of intermittent pneumatic compression for >24 hours in the same ICU admission, prophylaxis with medications other than UFH or LMWH, inability to use pneumatic compression on both legs, or inferior vena cava filter. Intervention IPC plus thromboprophylaxis with UFH or LMWH (n =1003) or thromboprophylaxis with UFH or LMWH (n =1024). IPC comprised use of devices applied to both lower limbs for 18 h/d, with sleeves removed for skin inspection and care every 8 hours. IPC continued until DVT or PE was suspected or confirmed, leg ulcer or ischemia occurred, care goals transitioned to palliation, full mobility was attained, the patient was discharged from the ICU, or day 28. Outcomes Incident proximal lower limb DVT >3 days after randomization. Secondary outcomes included incident proximal or distal DVT; PE; death in the ICU; and a composite of lower limb DVT, PE, or death at 28 days. 2000 patients were needed to detect a 3% absolute difference in the primary outcome with IPC vs control assuming a 7% event rate in the UFH or LMWH alone group, 5% rate of prevalent DVT, and 5% loss to follow-up (80% power, 2-sided =0.05). Patient follow-up 96% completed the study and did not have prevalent DVT (intention-to-treat analysis). Main results The main results are in the Table. Conclusion In critically ill patients, adding intermittent pneumatic compression to pharmacologic thromboprophylaxis did not reduce risk for proximal lower limb deep venous thrombosis. Intermittent pneumatic compression (IPC) + heparin thromboprophylaxis vs heparin thromboprophylaxis alone in critically ill patients in the intensive care unit Outcomes Event rates RRR (95% CI) IPC + heparin Heparin Incident proximal lower limb DVT 3.9% 4.2% 7% (41 to 39) Incident proximal or distal DVT 5.1% 5.6% 8% (33 to 37) PE 0.8% 1.0% 18% (106 to 68) Death in intensive care unit 15.27% 15.32% 0% (23 to 19) Lower limb DVT, PE, or death at 28 d 23.3% 24.0% 3% (14 to 17) DVT = deep venous thrombosis; PE = pulmonary embolism; other abbreviations defined in Glossary. RRR and CI calculated from heparin group event rates and relative risks in article. Adjusted for multiple factors. Commentary Venous thromboembolism (VTE) and PE are concerns among critically ill patients, and bleeding is the major adverse effect of VTE and PE prophylaxis. The PREVENT trial found that combined mechanical (IPC) and pharmacologic prophylaxis (UFH or LMWH) did not differ from pharmacologic prophylaxis alone for the primary outcome of new VTE nor the secondary outcomes in critically ill patients. The trial was underpowered due to a lower-than-expected incidence of proximal lower limb DVT in the pharmacologic prophylaxisalone group (4.2% vs 7% expected event rate). However, the observed event rate was similar to that in the large PROTECT trial of VTE prophylaxis in critically ill patients, which found a reduction in PE (1.3% vs 2.3%, P =0.01) but no difference in the rate of DVT (5.1% vs 5.8%, P =0.57) with dalteparin compared with heparin (1). A Cochrane Collaboration meta-analysis not limited to critically ill patients found that IPC plus pharmacologic prophylaxis reduces symptomatic PE (1.2% vs 2.9%) but not DVT (2.9% vs 6.2%) compared with pharmacologic prophylaxis alone (2). The findings of PREVENT support, but do not prove, equivalence in the effect of IPC plus pharmacologic prophylaxis vs pharmacologic prophylaxis alone. This may be due to power limitations as well as the size of the study population at highest risk (e.g., trauma, cancer, high-risk surgery), and the ability to extrapolate to general medical patients is limited. Because of these considerations, the findings of the large meta-analysis (2) that supports combined prophylaxis for prevention of PE in patients at appropriate risk remain robust.