Yang Hui-Qin, Liu Man-Cang, Yin Wen-Jun, Zhou Ling-Yun, Zuo Xiao-Cong
Department of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, China.
Center of Clinical Pharmacology, The Third Xiangya Hospital, Central South University, Changsha, China.
Front Pharmacol. 2021 Dec 10;12:783104. doi: 10.3389/fphar.2021.783104. eCollection 2021.
Given their changing pathophysiology, elderly patients carry a high risk of embolism and bleeding events; hence, use of appropriate anticoagulants is very important. Low molecular weight heparin (LMWH) is one of the most widely used anticoagulants although LMWHs differ in their anti-Xa, antithrombin, and anticoagulant activities. To date, no study has directly compared the safety and efficacy of different LMWHs in the elderly. We aimed to compare such differences by conducting a network meta-analysis. We searched the Pubmed, Embase, and Cochrane databases for randomized controlled trials (RCTs) of LMWHs that included patients ≥60 years old up to July 22, 2020. Safety outcomes included venous thromboembolism (VTE) or VTE-related death, deep thrombus embolism, and pulmonary embolism. Safety outcomes were clinically relevant bleeding, major bleeding, minor bleeding, and all-cause death. We calculated relative ratios (RR) and 95% confidence intervals (CI) for all outcomes. The cumulative ranking probabilities (SUCRA) were conducted to rank the comparative effects and safety of all LMWHs. We included 27 RCTs (30,441 elderly), comprising five LMWHs. LMWH was more effective than placebo in preventing VTE or VTE-related death (RR 0.36, 95% CI 0.25-0.53) but less effective than a novel oral anticoagulant (RR 1.59, 95% CI 1.33-1.91) and safer than acenocoumarol regarding risk of clinically relevant bleeding (RR 0.67, 95% CI 0.49-0.90). However, indirect comparison of efficacy and safety of the five LMWHs showed no significant difference in our network analysis, and the subgroup analyses (such as in patients with deep venous thrombosis, cardiac disease, or age >65 years old) supported the results. The SUCRA showed that tinzaparin performed best in preventing VTE or VTE-related death (SUCRA 68.8%, cumulative probability 42.3%) and all-cause death (SUCRA 84.2%, cumulative probability 40.7%), whereas nadroparin was predominant in decreasing the risk of clinically relevant bleeding (SUCRA 84.8%, cumulative probability 77.0%). On present evidence, there are no significant differences in the efficacy and safety of different LMWHs for the elderly. According to the rank probability analysis, nadroparin seems to be safer for the elderly with a high risk of bleeding, whereas tinzaparin is more effective for those with low bleeding risk.
鉴于老年患者不断变化的病理生理学特征，他们发生栓塞和出血事件的风险很高；因此，使用合适的抗凝剂非常重要。低分子量肝素（LMWH）是使用最广泛的抗凝剂之一，尽管不同的低分子量肝素在抗Xa、抗凝血酶和抗凝活性方面存在差异。迄今为止，尚无研究直接比较不同低分子量肝素在老年患者中的安全性和有效性。我们旨在通过进行网络荟萃分析来比较这些差异。我们在PubMed、Embase和Cochrane数据库中检索了截至2020年7月22日的、纳入≥60岁患者的低分子量肝素随机对照试验（RCT）。安全性结局包括静脉血栓栓塞（VTE）或VTE相关死亡、深静脉血栓形成和肺栓塞。安全性结局为临床相关出血、大出血、小出血和全因死亡。我们计算了所有结局的相对比值（RR）和95%置信区间（CI）。进行累积排序概率（SUCRA）以对所有低分子量肝素的比较效果和安全性进行排序。我们纳入了27项RCT（30441名老年患者），涉及五种低分子量肝素。低分子量肝素在预防VTE或VTE相关死亡方面比安慰剂更有效（RR 0.36，95%CI 0.25 - 0.53），但在预防方面比新型口服抗凝剂效果差（RR 1.59，95%CI 1.33 - 1.91），在临床相关出血风险方面比醋硝香豆素更安全（RR 0.67，95%CI 0.49 - 0.90）。然而，在我们的网络分析中，五种低分子量肝素的疗效和安全性的间接比较未显示出显著差异，亚组分析（如深静脉血栓形成患者、心脏病患者或年龄>65岁患者）支持了该结果。SUCRA显示，替扎肝素在预防VTE或VTE相关死亡（SUCRA 68.8%，累积概率42.3%）和全因死亡（SUCRA 84.2%，累积概率40.7%）方面表现最佳，而那屈肝素在降低临床相关出血风险方面占主导地位（SUCRA 84.8%，累积概率77.0%）。根据现有证据，不同低分子量肝素在老年患者中的疗效和安全性没有显著差异。根据排序概率分析，那屈肝素对于出血风险高的老年患者似乎更安全，而替扎肝素对于出血风险低的患者更有效。
