Abstract
Background: 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. Methods: 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. Results: 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%). Conclusions: 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.
Highlights
The number of elderly individuals continues to grow rapidly worldwide
The following search terms were included: “low-molecular-weight,” “Low molecular weight heparin (LMWH),” “nadroparin,” “enoxaparin,” “dalteparin,” and many other generic and trade names of LMWHs; “elderly,” “aged,” “elder people,” “old people,” “the old,” “old man,” and “aging.” The search details are provided in Supplementary Tables S1–S3
Studies were considered eligible if they fulfilled the following criteria: 1) studies that included patients aged ≥60 years; 2) interventions that were specific kinds of LMWHs, and the control group were unrestricted; 3) randomized controlled trials (RCTs); and 4) studies published in English
Summary
The number of elderly individuals continues to grow rapidly worldwide. In China, for instance, the proportion of older adults (≥65 years) is expected to rise from 12.6% of the total population (more than 176 million) in 2019 to 26.9% in 2050 (Yang et al, 2020). The incidence of VTE increases exponentially with age, rising from 1/10,000 in people aged 25–30 years to 8/1000 in those ≥85 years (Palareti and Poli, 2018). This increase can be explained by pathophysiological changes in the elderly, often associated with diverse diseases, multiple medications, and other risk factors for VTE as well as possible age-related liver and kidney dysfunction, endothelial dysfunction, inflammation, frailty, and immobility (Zhang et al, 2021); (Kozek-Langenecker et al, 2018). An appropriate anticoagulant treatment is important for elderly patients Given their changing pathophysiology, elderly patients carry a high risk of embolism and bleeding events; use of appropriate anticoagulants is very important. We aimed to compare such differences by conducting a network meta-analysis
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