Cardiovascular Disease Unit, IRCCS Ospedale Policlinico San Martino, IRCCS Italian Cardiology Network, Genoa, Italy.
Department of Health Sciences, Section of Biostatistics, University of Genova, Genoa, Italy.
ESC Heart Fail. 2021 Oct;8(5):3547-3556. doi: 10.1002/ehf2.13547. Epub 2021 Aug 2.
We systematically reviewed the European real-world evidence (RWE) about sacubitril-valsartan for heart failure with reduced ejection fraction.
Twenty-one articles, including 16 952 subjects, were identified until 31 October 2020. Taking as reference the PARADIGM-HF cohort, few baseline characteristics were presented in >80% of these studies, most often with high heterogeneity. In random-effects model meta-analysis, age was higher (mean difference +3.84, 95% CI 1.92-5.76), ischaemic aetiology (OR 0.76, 95% CI 0.64-0.91), hypertension (OR 0.55, 95% CI 0.37-0.82), and diabetes (OR 0.77, 95% CI 0.64-0.92) were less common, and the use of mineralocorticoid receptor antagonists was more frequent (OR 3.54, 95% CI 2.27-5.53) in real-life than in PARADIGM-HF. Other clinical and medical features were presented in 19-76% of the selected publications and suggested more severe heart failure with reduced ejection fraction. Sacubitril-valsartan was titrated to 97/103 mg b.i.d. in 35% (95% CI 23-47) and discontinued in 12.8% (95% CI 7.4-18.3) patients. When reported, the incidence of hyperkalaemia (six studies, no. 1076), all-cause mortality (five studies, no. 684), and any hospitalization (three studies, no. 390) was 12 (95% CI 5-19)/100 person-year, 8 (95% CI 4-12)/100 person-year, and 24 (95% CI 5-42)/100 person-year, respectively. Knowledge contribution, a metric measuring the proportion of RWE provided by each article based on the number of reported variables and the sample size, was 58.8% and 13.6% for the two biggest investigations (12 082 and 2037 patients), and <5% for all others (most with <100 subjects).
Limited-quality RWE indicates that there are important differences between European patients prescribed sacubitril-valsartan and the PARADIGM-HF population, including the frequency of target dose achievement.
我们系统地回顾了欧洲真实世界证据（RWE）中关于沙库巴曲缬沙坦治疗射血分数降低的心力衰竭的相关内容。
截至 2020 年 10 月 31 日，共确定了 21 篇文章，包括 16952 例患者。以 PARADIGM-HF 队列为参考，这些研究中只有不到 80%的研究报告了基线特征，且大多数研究的异质性较高。在随机效应模型荟萃分析中，欧洲患者的年龄较高（平均差异+3.84，95%置信区间 1.92-5.76），缺血性病因（OR 0.76，95%置信区间 0.64-0.91）、高血压（OR 0.55，95%置信区间 0.37-0.82）和糖尿病（OR 0.77，95%置信区间 0.64-0.92）的发生率较低，而盐皮质激素受体拮抗剂的使用率（OR 3.54，95%置信区间 2.27-5.53）较高。其他临床和医学特征在 19%-76%的选定出版物中有所报道，表明射血分数降低的心力衰竭更为严重。沙库巴曲缬沙坦在欧洲患者中的滴定剂量为 97/103mg 每日两次（95%置信区间 23-47），停药率为 12.8%（95%置信区间 7.4-18.3）。当报告时，高钾血症（6 项研究，共 1076 例患者）、全因死亡率（5 项研究，共 684 例患者）和任何原因住院（3 项研究，共 390 例患者）的发生率分别为 12（95%置信区间 5-19）/100 人年、8（95%置信区间 4-12）/100 人年和 24（95%置信区间 5-42）/100 人年。知识贡献度（Knowledge Contribution），这一指标基于报告变量的数量和样本量来衡量每项研究提供的 RWE 比例，在两项最大的研究（12082 例和 2037 例患者）中分别为 58.8%和 13.6%，而其他所有研究的贡献度均低于 5%（大多数研究的样本量均低于 100 例）。
有限质量的 RWE 表明，在接受沙库巴曲缬沙坦治疗的欧洲患者和 PARADIGM-HF 人群之间存在重要差异，包括目标剂量的实现频率。
