Department of Surgery, Division of Vascular and Endovascular Surgery, Universidade Federal de São Paulo, São Paulo, Brazil.
Cochrane Brazil, Universidade Federal de São Paulo, São Paulo, Brazil.
Cochrane Database Syst Rev. 2022 Jul 25;7(7):CD012369. doi: 10.1002/14651858.CD012369.pub2.
BACKGROUND: Antiplatelet agents may be useful for the treatment of deep venous thrombosis (DVT) when used in addition to best medical practice (BMP), which includes anticoagulation, compression stockings, and clinical care such as physical exercise, skin hydration, etc. Antiplatelet agents could minimise complications such as post-thrombotic syndrome (PTS) and pulmonary embolism (PE). They may also reduce the recurrence of the disease (recurrent venous thromboembolism (recurrent VTE)). However, antiplatelet agents may increase the likelihood of bleeding events. OBJECTIVES: To assess the effects of antiplatelet agents in addition to current BMP compared to current BMP (with or without placebo) for the treatment of DVT. SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase and CINAHL databases and World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 7 December 2021. The review authors searched LILACS and IBECS databases (15 December 2021) and also checked the bibliographies of included trials for further references to relevant trials, and contacted specialists in the field, manufacturers and authors of the included trials. SELECTION CRITERIA: We considered randomised controlled trials (RCTs) examining antiplatelet agents compared to BMP following initial standard anticoagulation treatment for DVT. We included studies where antiplatelet agents were given in addition to current BMP compared to current BMP (with or without placebo) for the treatment of DVT (acute: treatment started within 21 days of symptom onset; chronic: treatment started after 21 days of symptom onset). We evaluated only RCTs where the antiplatelet agents were the unique difference between the groups (intervention and control). DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. Two review authors independently extracted data and assessed risk of bias of the trials. Any disagreements were resolved by discussion with a third review author. We calculated outcome effects using risk ratio (RR) or mean difference (MD) with a 95% confidence interval (CI) and the number needed to treat to benefit (NNTB). MAIN RESULTS: We included six studies with 1625 eligible participants, with data up to 37.2 months of follow-up. For one preplanned comparison (i.e. antiplatelet agents plus BMP versus BMP plus placebo) for acute DVT we identified no eligible studies for inclusion. In acute DVT, antiplatelet agents plus BMP versus BMP alone was assessed by one study (500 participants), which reported on four outcomes until 6 months of follow-up. There were no deaths and no cases of major bleeding reported. The participants who received antiplatelet agents showed a lower risk of PTS (RR 0.74, 95% CI 0.61 to 0.91; 1 study, 500 participants; very low-certainty evidence). The control group presented a lower risk of adverse events compared to the intervention group (RR 2.88, 95% CI 1.06 to 7.80; 1 study, 500 participants; very low-certainty evidence). This study did not provide information for recurrent VTE or PE. In chronic DVT, antiplatelet agents plus BMP versus BMP alone was assessed by one study (224 participants). The study authors reported four relevant outcomes, three of which (major bleeding, mortality and adverse events) showed no events during the 3 years of follow-up. Therefore, an effect estimate could only be reported for recurrent VTE, favouring antiplatelet agents plus BMP versus BMP alone (RR 0.12, 95% CI 0.05 to 0.34; 1 study, 224 participants; very low-certainty evidence). For the outcomes PE and PTS, this study did not present information which could be used for analysis. In chronic DVT, antiplatelet agents plus BMP versus BMP plus placebo was assessed by four studies (901 participants). The meta-analysis of this pooled data showed a lower risk of recurrent VTE for the antiplatelet agents group (RR 0.65, 95%, CI 0.43 to 0.96; NNTB = 14; low-certainty evidence). For major bleeding, we found no clear difference between placebo and intervention groups until 37.2 months of follow-up (RR 0.98, 95% CI 0.29 to 3.34; 1 study, 583 participants; moderate-certainty evidence). In PE fatal/non-fatal outcome, we found no clear difference with the use of antiplatelet agents (RR 0.52, 95% CI 0.23 to 1.14; 1 study, 583 participants; moderate-certainty evidence). For all-cause mortality, the overall effect of antiplatelet agents did not differ from the placebo group (RR 0.48, 95% CI 0.21 to 1.06; 3 studies, 649 participants; moderate-certainty evidence). The adverse events outcome did not show a clear difference (RR 1.57, 95% CI 0.34 to 7.19; 2 studies, 621 participants; moderate-certainty evidence). There is no assessment of PTS in these studies. We downgraded the certainty of evidence for risk of bias, indirectness, imprecision and publication bias. AUTHORS' CONCLUSIONS: In chronic DVT settings, following the initial standard treatment with anticoagulants, there is low-certainty evidence that antiplatelet agents in addition to BMP may reduce recurrent VTE, (NNTB = 14) when compared to BMP plus placebo. Moderate-certainty evidence shows no clear difference in adverse events, major bleeding and PE when antiplatelet agents are used in addition to BMP compared to BMP plus placebo. In acute and chronic DVT settings, following the initial standard treatment with anticoagulants, we can draw no conclusions for antiplatelet agents in addition to BMP compared to BMP alone due to very low-certainty evidence. Trials of high methodological quality, that are large and of sufficient duration to detect significant clinical outcomes are needed. Trials should ideally last more than 4 years in order to estimate the long-term effect of antiplatelet agents. Trials should include people with acute and chronic DVT and provide relevant individual data, such as the outcome for each index event (DVT or PE), the use of an inferior vena cava (IVC) filter, whether the DVT is provoked or unprovoked, and the age of participants.
背景:抗血小板药物与最佳医疗实践(BMP,包括抗凝、弹力袜和物理运动、皮肤保湿等临床护理)联合使用,可能有助于治疗深静脉血栓形成(DVT)。抗血小板药物可以减少血栓后综合征(PTS)和肺栓塞(PE)等并发症的发生。它们还可以降低疾病复发的风险(复发性静脉血栓栓塞症(recurrent VTE))。然而,抗血小板药物可能会增加出血事件的风险。
目的:评估在 DVT 治疗中,抗血小板药物与当前 BMP 加或不加安慰剂相比,除当前 BMP 外的作用。
检索方法:Cochrane 血管专业信息员检索了 Cochrane 血管特刊注册库、CENTRAL、MEDLINE、Embase 和 CINAHL 数据库以及世界卫生组织国际临床试验注册平台和 ClinicalTrials.gov 试验注册库,检索时间截至 2021 年 12 月 7 日。审查员检索了 LILACS 和 IBECS 数据库(2021 年 12 月 15 日),并查阅了纳入试验的参考文献以寻找其他相关试验,还联系了该领域的专家、制造商和纳入试验的作者。
纳入标准:我们纳入了比较抗血小板药物与初始标准抗凝治疗后 DVT 治疗中 BMP 的随机对照试验(RCT)。我们纳入了在急性 DVT(症状发作后 21 天内开始治疗)和慢性 DVT(症状发作后 21 天开始治疗)中,抗血小板药物加 BMP 与 BMP(加或不加安慰剂)治疗 DVT 的研究。我们仅评估了抗血小板药物是组间唯一差异(干预组和对照组)的 RCT。
数据收集和分析:我们使用了标准的 Cochrane 方法学程序。两名审查员独立提取数据并评估了试验的偏倚风险。任何分歧都通过与第三名审查员讨论解决。我们使用风险比(RR)或均数差(MD)及 95%置信区间(CI)和需要治疗人数(NNTB)计算结局效应。
主要结果:我们纳入了六项研究,共纳入 1625 名合格参与者,随访时间最长为 37.2 个月。对于一项预先计划的比较(即抗血小板药物加 BMP 与 BMP 加安慰剂),我们没有找到符合纳入条件的急性 DVT 研究。在急性 DVT 中,一项研究(500 名参与者)评估了抗血小板药物加 BMP 与 BMP 单独治疗的效果,该研究报告了 6 个月随访时的四项结局。没有死亡和主要出血的报告。接受抗血小板药物治疗的患者 PTS 风险较低(RR 0.74,95%CI 0.61 至 0.91;1 项研究,500 名参与者;极低确定性证据)。与干预组相比,对照组的不良事件风险较低(RR 2.88,95%CI 1.06 至 7.80;1 项研究,500 名参与者;极低确定性证据)。这项研究没有提供关于复发性 VTE 或 PE 的信息。在慢性 DVT 中,一项研究(224 名参与者)评估了抗血小板药物加 BMP 与 BMP 单独治疗的效果。研究作者报告了四项相关结局,其中三项(主要出血、死亡率和不良事件)在 3 年随访期间均未发生。因此,只能报告复发性 VTE 的效果估计,抗血小板药物加 BMP 优于 BMP 单独治疗(RR 0.12,95%CI 0.05 至 0.34;1 项研究,224 名参与者;极低确定性证据)。对于 PE 和 PTS 结局,该研究没有提供可用于分析的数据。在慢性 DVT 中,四项研究(901 名参与者)评估了抗血小板药物加 BMP 与 BMP 加安慰剂的效果。对这组数据的荟萃分析显示,抗血小板药物组的复发性 VTE 风险较低(RR 0.65,95%CI 0.43 至 0.96;NNTB = 14;低确定性证据)。对于主要出血,我们发现在 37.2 个月的随访中,安慰剂和干预组之间没有明显差异(RR 0.98,95%CI 0.29 至 3.34;1 项研究,583 名参与者;中等确定性证据)。在致命/非致命性 PE 结局中,我们发现使用抗血小板药物没有明显差异(RR 0.52,95%CI 0.23 至 1.14;1 项研究,583 名参与者;中等确定性证据)。对于全因死亡率,抗血小板药物的总体效果与安慰剂组无差异(RR 0.48,95%CI 0.21 至 1.06;3 项研究,649 名参与者;中等确定性证据)。不良事件结局没有明显差异(RR 1.57,95%CI 0.34 至 7.19;2 项研究,621 名参与者;中等确定性证据)。这些研究均未评估 PTS。我们降低了对偏倚、间接性、不精确性和发表偏倚的证据确定性。
作者结论:在慢性 DVT 环境中,在初始标准抗凝治疗后,低确定性证据表明,与 BMP 加安慰剂相比,抗血小板药物加 BMP 可能会降低复发性 VTE(NNTB = 14)。中等确定性证据表明,与 BMP 加安慰剂相比,抗血小板药物加 BMP 与不良事件、主要出血和 PE 无明显差异。在急性和慢性 DVT 环境中,在初始标准抗凝治疗后,由于极低确定性证据,我们不能得出抗血小板药物加 BMP 与 BMP 单独治疗相比的结论。需要进行高质量的临床试验,这些试验应规模大且持续时间足够长,以检测出有临床意义的结局。试验应至少持续 4 年,以估计抗血小板药物的长期效果。试验应纳入急性和慢性 DVT 患者,并提供相关的个体数据,例如每个指数事件(DVT 或 PE)的结局、下腔静脉(IVC)滤器的使用、DVT 是否为诱因或非诱因、以及参与者的年龄。
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