低/中强度他汀类药物与依折麦布联合治疗与高强度他汀类药物单药治疗的临床疗效和安全性：系统评价和荟萃分析。

The clinical effectiveness and safety of low/moderate-intensity statins & ezetimibe combination therapy vs. high-intensity statin monotherapy: a systematic review and meta-analysis.

机构信息

Faculty of Medicine, Ain-Shams University, 56Th Abbaseyia Street, Cairo, Egypt.

出版信息

BMC Cardiovasc Disord. 2024 Nov 20;24(1):660. doi: 10.1186/s12872-024-04144-y.

DOI:10.1186/s12872-024-04144-y

PMID:39567875

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11577940/

Abstract

BACKGROUND

Despite widespread use of high-intensity statin monotherapy, achieving target LDL-C levels and reducing cardiovascular events in patients with or at high risk of developing ASCVD remains challenging. Our study measured the effects of low/moderate-intensity statins and ezetimibe combination therapy compared to high-dose statin monotherapy on major adverse cardiovascular events (MACEs) and coronary atherosclerotic plaque reduction.

METHODS

We searched PubMed, Scopus, Web of Science, and Cochrane CENTRAL register of trials for studies comparing the combination therapy to high-intensity statin monotherapy in terms of MACEs and coronary atherosclerotic plaque reduction. The primary outcome was a composite of cardiovascular death or major cardiovascular events (MI, HF, Revascularization, or non-fatal stroke). Other outcomes included other MACEs, lipid-lowering efficacy, and safety outcomes. A protocol was registered to PROSPERO under registration number [CRD42024545807].

RESULTS

15 studies encompassing 251,450 participants were included in our meta-analysis. In our pooled analysis of observational studies, combination therapy was associated with lower rates of the primary composite outcome (HR = 0.76, CI 95% [0.73, 0.80]), cardiovascular death (HR = 0.80, CI 95% [0.74, 0.88]), all-cause death (HR = 0.84, CI 95% [0.78, 0.91]), and non-fatal stroke (HR = 0.81, CI 95% [0.75, 0.87]). However, the pooled analysis of RCTs did not demonstrate a statistically significant difference between both arms concerning clinical endpoints. Combination therapy had a higher number of patients with LDL-C < 70 mg/dL (RR = 1.27, CI 95% [1.21, 1.34]), significantly lowered LDL-C (MD = -7.95, CI 95% [-10.02, -5.89]) and TC (MD = -26.77, CI 95% [-27.64, -25.89]) in the pooled analysis of RCTs. In terms of safety, the combination therapy lowered muscle-related adverse events (RR = 0.52, CI 95% [0.32, 0.85]) and number of patients with liver enzyme elevation (RR = 0.51, CI 95% [0.29, 0.89]) in the pooled analysis of RCTs and was associated with lower rates of new-onset diabetes (HR = 0.80, CI 95% [0.74, 0.87]) in the pooled analysis of observational studies.

CONCLUSION

Evidence from RCTs indicates that low/moderate statin therapy in combination with ezetimibe has a superior lipid-lowering effect and reduces side effects compared to high-dose statins. Observational studies suggest improved clinical outcomes but need to be corroborated by large, outcomes-powered RCTs over longer follow-up periods.

摘要

背景

尽管高强度他汀类药物单药治疗广泛应用，但对于 ASCVD 或有 ASCVD 风险的患者，达到 LDL-C 目标水平并降低心血管事件发生率仍具有挑战性。我们的研究评估了低/中强度他汀类药物联合依折麦布治疗与高强度他汀类药物单药治疗在主要不良心血管事件（MACE）和冠状动脉粥样硬化斑块减少方面的效果。

方法

我们检索了 PubMed、Scopus、Web of Science 和 Cochrane 临床试验注册中心，以比较联合治疗与高强度他汀类药物单药治疗在 MACE 和冠状动脉粥样硬化斑块减少方面的效果。主要结局是心血管死亡或主要心血管事件（MI、HF、血运重建或非致死性卒中）的复合结局。其他结局包括其他 MACE、降脂疗效和安全性结局。我们的方案已在 PROSPERO 注册，注册号为 [CRD42024545807]。

结果

共有 15 项研究纳入了 251450 名参与者，纳入我们的荟萃分析。在我们对观察性研究的汇总分析中，联合治疗与较低的主要复合结局发生率相关（HR=0.76，95%CI[0.73，0.80]）、心血管死亡（HR=0.80，95%CI[0.74，0.88]）、全因死亡（HR=0.84，95%CI[0.78，0.91]）和非致死性卒中（HR=0.81，95%CI[0.75，0.87]）。然而，RCT 的汇总分析并未显示两种治疗方案在临床终点方面存在统计学显著差异。联合治疗方案使 LDL-C<70mg/dL 的患者比例更高（RR=1.27，95%CI[1.21，1.34]），显著降低 LDL-C（MD=-7.95，95%CI[-10.02，-5.89]）和 TC（MD=-26.77，95%CI[-27.64，-25.89]）。在安全性方面，联合治疗方案使肌肉相关不良事件（RR=0.52，95%CI[0.32，0.85]）和肝酶升高的患者数量（RR=0.51，95%CI[0.29，0.89]）降低，在 RCT 的汇总分析中，与联合治疗方案相关的新发糖尿病发生率较低（HR=0.80，95%CI[0.74，0.87]），在观察性研究的汇总分析中。