Alzarroug Abdullah F, Al Gahtani Haif K, Algahtani Saad, Alghamdi Hatan K, Alhinti Mohammad F, Almutairi Khalid A, Algahtani Sara
College of Medicine, Imam Mohammad Ibn Saud Islamic University, Riyadh, SAU.
Adult Cardiology, King Khalid University Hospital, King Saud University, Riyadh, SAU.
Cureus. 2023 Feb 27;15(2):e35514. doi: 10.7759/cureus.35514. eCollection 2023 Feb.
Coronary artery disease (CAD), manifested mainly as acute coronary syndrome (ACS), continues to be a major cause of mortality globally and a significant contributing factor to the global disease burden. Elevation of low-density lipoprotein cholesterol levels attributed to proprotein convertase subtilisin/Kexin type-9 (PCSK9) during and following ACS puts patients at high risk of subsequent adverse events. Evolocumab is a PCSK9 inhibitor that is associated with a significant reduction in low-density lipoprotein cholesterol (LDL-C) levels through PCSK9 inhibition in comparison to traditional statin therapy.
We conducted a systematic review and meta-analysis of literature addressing the efficacy and safety of evolocumab compared to other lipid-lowering therapies or placebo. An extensive internet-based literature search using pre-determined key phrases supported by medical sub-headings and Boolean operators was performed in October 2022 to identify literature pertinent to the research topic. The search was primarily based on the National Library of Medicine (PubMed and Clinical Trials), MEDLINE, Cochrane, and the Science direct literature databases. Subsequently, the researchers devised PICOs-based screening criteria which had to be met by each identified study for inclusion in the review and meta-analysis. Two independent reviewers conducted data stratification and quality assessment of identified studies. Statistical analysis of the primary and secondary outcomes was conducted on the Cochrane REVMAN 5.4 statistical software for randomized trials.
Two thousand five hundred and seventy-six potential studies were identified for inclusion in the systematic review. Data stratification, screening, and quality assessment of these studies based on the eligibility criteria led to the exclusion of two thousand five hundred and sixty-seven studies as they did not meet the standards set. Nine randomized controlled trials progressed to numerical analysis for validity and reliability. Eight studies were included in the meta-analysis. Meta-analytical results showed a significant decrease in LDL-C changes from initiation of evolocumab therapy to 8 weeks following ACS compared to placebo. Similar results were derived in the sub-acute phase of ACS [SMD -1.95 (95% CI -2.29, -1.62)]. The meta-analysis revealed no statistically significant relationship between the risk of adverse effects, serious adverse effects, and major adverse cardiovascular events (MACE) from treatment using evolocumab in comparison to placebo [(relative risk, RR 1.04 (95% CI 0.99, 1.08) (Z = 1.53; p=0.12)].
Early evolocumab therapy initiation was associated with a significant decrease in LDL-C levels and was not associated with an increased risk of adverse effects in comparison to placebo.
冠状动脉疾病（CAD）主要表现为急性冠状动脉综合征（ACS），仍然是全球主要的死亡原因，也是全球疾病负担的一个重要促成因素。急性冠状动脉综合征期间及之后，由前蛋白转化酶枯草溶菌素/克新9型（PCSK9）导致的低密度脂蛋白胆固醇水平升高使患者面临后续不良事件的高风险。依洛尤单抗是一种PCSK9抑制剂，与传统他汀类药物治疗相比，通过抑制PCSK9可显著降低低密度脂蛋白胆固醇（LDL-C）水平。
我们对有关依洛尤单抗与其他降脂疗法或安慰剂相比的疗效和安全性的文献进行了系统评价和荟萃分析。2022年10月，我们使用医学副标题和布尔运算符支持的预先确定的关键词进行了广泛的基于互联网的文献检索，以确定与该研究主题相关的文献。检索主要基于美国国立医学图书馆（PubMed和临床试验）、MEDLINE、Cochrane和科学Direct文献数据库。随后，研究人员制定了基于PICOs的筛选标准，每项纳入的研究都必须符合这些标准才能纳入综述和荟萃分析。两名独立的评审员对纳入研究进行了数据分层和质量评估。使用Cochrane REVMAN 5.4统计软件对随机试验的主要和次要结果进行了统计分析。
共识别出2576项可能纳入系统评价的研究。根据纳入标准对这些研究进行数据分层、筛选和质量评估，导致排除2567项不符合设定标准的研究。9项随机对照试验进入数值分析以评估有效性和可靠性。8项研究纳入荟萃分析。荟萃分析结果显示，与安慰剂相比，从依洛尤单抗治疗开始到急性冠状动脉综合征后8周，LDL-C变化显著降低。在急性冠状动脉综合征的亚急性期也得出了类似的结果[标准化均数差-1.95（95%可信区间-2.29，-1.62）]。荟萃分析显示，与安慰剂相比，使用依洛尤单抗治疗的不良反应、严重不良反应和主要不良心血管事件（MACE）风险之间无统计学显著关系[相对风险，RR 1.04（95%可信区间0.99，1.08）（Z = 1.53；p = 0.12）]。
与安慰剂相比，早期开始依洛尤单抗治疗与LDL-C水平显著降低相关，且与不良反应风险增加无关。
