Department of Breast Surgery, The Second Xiangya Hospital, Central South University, Changsha, China.
Clinical Research Center for Breast Disease, Hunan Province, Changsha, China.
Cochrane Database Syst Rev. 2024 Nov 5;11(11):CD014769. doi: 10.1002/14651858.CD014769.pub2.
Venous thromboembolism (VTE) involves the formation of a blood clot in a vein, and includes deep venous thrombosis (DVT) or pulmonary embolism (PE). The annual incidence for VTE varies from 0.75 to 2.69 per 1000 individuals, with about 40 million people worldwide impacted by VTE. Statins, 3-hydroxy-3-methylglutaryl (HMG)-coenzyme A (CoA) reductase inhibitors, inhibit cholesterol biosynthesis and display several vascular-protective effects, including antithrombotic properties. However, the potential role of statins in the primary prevention of VTE is still not clear.
To evaluate the benefits and risks of statins in preventing venous thromboembolism (VTE) in individuals with no prior history of VTE.
We used standard Cochrane search methods. The search was last updated on 13 March 2023.
We included randomized controlled trials (RCTs) comparing statins with any control intervention (including placebo and usual care) in healthy individuals or participants with conditions other than VTE. There were no restrictions on the dose, duration, route, or timing of statins.
We used standard Cochrane methods. Our primary outcomes were VTE, DVT, and PE. Our secondary outcomes were serious adverse events, adverse events, and mortality. We used the trial sequential analysis (TSA) method to judge whether the evidence was sufficient, and we used the GRADE approach to assess the certainty of the evidence for each outcome.
We included 27 RCTs involving 122,601 adults (aged 18 years and above) who were healthy, had various medical conditions (e.g. hypercholesterolemia), or were at risk for cardiovascular disease. Both males and females were included in all studies. Two studies focused solely on participants over 60 years of age. We deemed four studies to have a low risk of bias overall, while 19 were at high risk of bias, and four were unclear. The 27 studies compared use of statins versus placebo or usual care in individuals who had never experienced VTE. The statins used in the studies were atorvastatin, rosuvastatin, pravastatin, lovastatin, fluvastatin, and simvastatin. Twenty-three studies followed up participants for over a year, with six of those extending follow-ups for over five years. Twenty-five studies were based in hospitals, and 24 studies were funded by industry. Only one study used VTE as a primary endpoint. The median incidence of VTE in the statins group was 0.72% (ranging from 0% to 10.53%), and in the control group it was 0.89% (ranging from 0% to 6.83%). Our pooled analysis of the 27 studies showed that, relative to control groups, statins may slightly reduce the overall incidence of VTE (odds ratio (OR) 0.86, 95% confidence intervals (CI) 0.76 to 0.98; 27 studies, 122,601 participants; low-certainty evidence). Of the statins we evaluated, only rosuvastatin seemed to be associated with a reduced incidence of VTE, albeit the reduction in incidence was very small. The evidence did not clearly indicate a difference between groups in the incidence of DVT (OR 0.70, 95% CI 0.41 to 1.18; six studies, 40,305 participants; low-certainty evidence), PE (OR 0.83, 95% CI 0.46 to 1.52; five studies, 28,427 participants; low-certainty evidence), or myopathy (OR 1.10, 95% CI 0.83 to 1.45; 10 studies, 75,551 participants; low-certainty evidence). Nonetheless, statin use might slightly decrease the incidence of any serious adverse event (OR 0.95, 95% CI 0.91 to 0.99; 13 studies, 67,020 participants; low-certainty evidence) and any death (OR 0.90, 95% CI 0.86 to 0.95; 24 studies, 116,761 participants; low-certainty evidence), compared to control.
AUTHORS' CONCLUSIONS: Using statins for the primary prevention of VTE may slightly reduce the incidence of VTE and all-cause mortality. However, this effect is likely too weak to be considered significant. Statin use may not decrease the occurrence of DVT and PE. The current evidence is insufficient to draw strong conclusions because of the risk of bias in the studies, imprecision in the effect estimates, and potential publication bias. More evidence from well conducted and fully reported RCTs is needed to assess the preventive effects of different types of statins, as well as the effects of different dosages and treatment durations in various populations.
静脉血栓栓塞症（VTE）涉及静脉中血栓的形成，包括深静脉血栓形成（DVT）或肺栓塞（PE）。VTE 的年发病率为每 1000 人 0.75 至 2.69 例，全世界约有 4 亿人受到 VTE 的影响。他汀类药物，即 3-羟基-3-甲基戊二酰辅酶 A（HMG-CoA）还原酶抑制剂，可抑制胆固醇的生物合成，并具有多种血管保护作用，包括抗血栓特性。然而，他汀类药物在 VTE 的一级预防中的潜在作用尚不清楚。
评估他汀类药物在无 VTE 既往史的个体中预防静脉血栓栓塞症（VTE）的益处和风险。
我们使用了标准的 Cochrane 检索方法。检索最后一次更新于 2023 年 3 月 13 日。
我们纳入了比较他汀类药物与任何对照干预（包括安慰剂和常规护理）在健康个体或患有除 VTE 以外的疾病的个体中预防 VTE 的随机对照试验（RCT）。他汀类药物的剂量、持续时间、途径或时间没有限制。
我们使用了标准的 Cochrane 方法。我们的主要结局是 VTE、DVT 和 PE。我们的次要结局是严重不良事件、不良事件和死亡率。我们使用试验序贯分析（TSA）方法来判断证据是否充分，并使用 GRADE 方法来评估每个结局的证据确定性。
我们纳入了 27 项 RCT，涉及 122601 名成年人（年龄在 18 岁及以上），他们健康、患有各种疾病（如高胆固醇血症）或有心血管疾病风险。所有研究均纳入了男性和女性。两项研究仅关注 60 岁以上的参与者。我们认为四项研究总体偏倚风险低，而 19 项研究偏倚风险高，四项研究偏倚情况不清楚。这 27 项研究比较了他汀类药物与安慰剂或常规护理在从未经历过 VTE 的个体中的使用。研究中使用的他汀类药物有阿托伐他汀、瑞舒伐他汀、普伐他汀、洛伐他汀、氟伐他汀和辛伐他汀。23 项研究的随访时间超过一年，其中 6 项研究的随访时间超过五年。25 项研究基于医院，24 项研究由行业资助。只有一项研究将 VTE 作为主要终点。他汀类药物组的 VTE 发生率中位数为 0.72%（范围为 0%至 10.53%），对照组为 0.89%（范围为 0%至 6.83%）。我们对 27 项研究的汇总分析显示，与对照组相比，他汀类药物可能略微降低 VTE 的总体发生率（比值比（OR）0.86，95%置信区间（CI）0.76 至 0.98；27 项研究，122601 名参与者；低确定性证据）。在我们评估的他汀类药物中，只有瑞舒伐他汀似乎与 VTE 发生率降低相关，尽管发生率的降低非常小。证据并未清楚表明两组之间 DVT（OR 0.70，95%CI 0.41 至 1.18；六项研究，40305 名参与者；低确定性证据）、PE（OR 0.83，95%CI 0.46 至 1.52；五项研究，28427 名参与者；低确定性证据）或肌病（OR 1.10，95%CI 0.83 至 1.45；十项研究，75551 名参与者；低确定性证据）的发生率存在差异。尽管如此，与对照组相比，他汀类药物的使用可能会略微降低任何严重不良事件（OR 0.95，95%CI 0.91 至 0.99；13 项研究，67020 名参与者；低确定性证据）和任何死亡（OR 0.90，95%CI 0.86 至 0.95；24 项研究，116761 名参与者；低确定性证据）的发生率。
使用他汀类药物预防 VTE 可能会略微降低 VTE 和全因死亡率的发生率。然而，这种效果可能太弱，不足以被认为具有显著意义。他汀类药物的使用可能不会降低 DVT 和 PE 的发生。由于研究中的偏倚风险、效果估计的不准确性以及潜在的发表偏倚，目前的证据不足以得出强有力的结论。需要更多来自精心设计和充分报告的 RCT 的证据，以评估不同类型的他汀类药物的预防效果，以及在不同人群中不同剂量和治疗持续时间的效果。
