Department of Critical Care Medicine, University of Pittsburgh, 606B Scaife Hall, 3550 Terrace Street, Pittsburgh, PA 15261, USA.
Crit Care. 2011;15(6):315. doi: 10.1186/cc10581. Epub 2011 Dec 8.
The PROTECT Investigators for the Canadian Critical Care Trials Group and the Australian and New Zealand Intensive Care Society Clinical Trials Group: Dalteparin versus Unfractionated Heparin in Critically Ill Patients. 2011, 364:1305-1314.
It is unclear whether there is a clinically significant advantage to prophylactic low-molecular-weight heparin (LMWH) versus unfractionated heparin (UFH) in mixed medical/surgical critically ill adult patients.
To compare once daily dalteparin with twice daily unfractionated heparin for primary prophylaxis of proximal deep venous thrombosis in critically ill adults. A superiority randomized double-blinded controlled trial from 2006 to 2010 in both medical and surgical ICUs. (ClinicalTrials.gov registration number: NCT00182143) Multi-center, international medical and surgical intensive care units (ICUs) Critically ill adults expected to remain in the ICU for at least 3 days. Patients were randomized to either twice daily UFH or daily dalteparin for the duration of ICU admission. The primary endpoint was proximal leg deep venous thrombosis (DVT), at least three days after randomization, detected on twice weekly screening ultrasound. Secondary endpoints were: any DVT, pulmonary embolism (PE), venous thromboembolism (VTE), death, heparin-induced thrombocytopenia (HIT), major bleeding, and composite death/VTE.
Three thousand seven hundred and forty-six subjects were included in the intention-to-treat analysis. Proximal leg DVT occurred in 96 of 1873 (5.1%) patients randomized to dalteparin versus 109 of 1873 (5.8%) patients randomized to UFH (hazard ratio in the dalteparin group, 0.92; 95% confidence interval [CI], 0.68 to 1.23; = 0.57). The incidence of PE was 1.3% in the dalteparin group compared to 2.3% in the UFH group (hazard ratio, 0.51; 95% CI, 0.30 to 0.88; = 0.01). There was no mortality difference and no difference in major bleeding between the two study arms. There was a statistically significant decrease in incidence of HIT in the dalteparin group in the per-protocol analysis, but not in the intention-to-treat analysis.
Comparing the incidence of PE was a secondary endpoint and the study was not appropriately powered for this conclusion.
Among critically ill adult patients, dalteparin was not superior to UFH at preventing proximal lower extremity DVTs. There is a suggestion that dalteparin might be superior to UFH at preventing pulmonary embolism but a larger trial is necessary to confirm this result.
The PROTECT Investigators for the Canadian Critical Care Trials Group and the Australian and New Zealand Intensive Care Society Clinical Trials Group: Dalteparin versus Unfractionated Heparin in Critically Ill Patients. 2011, 364:1305-1314.
在混合内科/外科危重病成年患者中，预防性使用低分子肝素（LMWH）与普通肝素（UFH）相比，是否具有临床意义上的优势尚不清楚。
比较每日一次达肝素与每日两次普通肝素用于预防重症成年患者近端深静脉血栓形成。这是一项 2006 年至 2010 年在内科和外科 ICU 进行的、比较每日一次达肝素与每日两次普通肝素用于预防重症成年患者近端深静脉血栓形成的优效性随机双盲对照试验（ClinicalTrials.gov 注册号：NCT00182143）。多中心、国际性内科和外科重症监护病房（ICU）预计至少在 ICU 内停留 3 天的危重病成年患者。患者被随机分配至每日两次普通肝素或每日一次达肝素治疗，直至 ICU 出院。主要终点为随机分组后至少 3 天通过每周两次的超声筛查检测到的近端腿部深静脉血栓形成（DVT）。次要终点为：任何 DVT、肺栓塞（PE）、静脉血栓栓塞症（VTE）、死亡、肝素诱导的血小板减少症（HIT）、大出血和死亡/VTE 复合终点。
3746 例患者被纳入意向治疗分析。1873 例患者中，96 例（5.1%）随机分配至达肝素组，1873 例患者中 109 例（5.8%）随机分配至普通肝素组，达肝素组近端腿部 DVT 发生率低于普通肝素组（风险比为 0.92；95%置信区间[CI]为 0.68 至 1.23；=0.57）。达肝素组的 PE 发生率为 1.3%，普通肝素组为 2.3%（风险比为 0.51；95%CI 为 0.30 至 0.88；=0.01）。两组间死亡率和大出血发生率无差异。在方案预设分析中，达肝素组的 HIT 发生率显著降低，但在意向治疗分析中无差异。
比较 PE 发生率是次要终点，且该研究对此结论的支持力度不足。
在危重病成年患者中，达肝素在预防近端下肢 DVT 方面并不优于普通肝素。达肝素可能在预防 PE 方面优于普通肝素，但需要更大规模的试验来证实这一结果。
