Schroeder Megan, Lim Yvonne Mei Fong, Savarese Gianluigi, Suzart-Woischnik Kiliana, Baudier Claire, Dyszynski Tomasz, Vaartjes Ilonca, Eijkemans Marinus J C, Uijl Alicia, Herrera Ronald, Vradi Eleni, Brugts Jasper J, Brunner-La Rocca Hans-Peter, Blanc-Guillemaud Vanessa, Waechter Sandra, Couvelard Fabrice, Tyl Benoit, Fatoba Samuel, Hoes Arno W, Lund Lars H, Gerlinger Christoph, Asselbergs Folkert W, Grobbee Diederick E, Cronin Maureen, Koudstaal Stefan
Institute for Medical Information Processing, Biometry, and Epidemiology Pettenkofer School of Public Health, LMU Munich, Munich, Germany.
Division of Cardiology, Department of Medicine, Karolinska Insitutet, Stockholm, Sweden.
Eur J Heart Fail. 2023 Jun;25(6):912-921. doi: 10.1002/ejhf.2868. Epub 2023 May 18.
In order to understand how sex differences impact the generalizability of randomized clinical trials (RCTs) in patients with heart failure (HF) and reduced ejection fraction (HFrEF), we sought to compare clinical characteristics and clinical outcomes between RCTs and HF observational registries stratified by sex.
Data from two HF registries and five HFrEF RCTs were used to create three subpopulations: one RCT population (n = 16 917; 21.7% females), registry patients eligible for RCT inclusion (n = 26 104; 31.8% females), and registry patients ineligible for RCT inclusion (n = 20 810; 30.2% females). Clinical endpoints included all-cause mortality, cardiovascular mortality, and first HF hospitalization at 1 year. Males and females were equally eligible for trial enrolment (56.9% of females and 55.1% of males in the registries). One-year mortality rates were 5.6%, 14.0%, and 28.6% for females and 6.9%, 10.7%, and 24.6% for males in the RCT, RCT-eligible, and RCT-ineligible groups, respectively. After adjusting for 11 HF prognostic variables, RCT females showed higher survival compared to RCT-eligible females (standardized mortality ratio [SMR] 0.72; 95% confidence interval [CI] 0.62-0.83), while RCT males showed higher adjusted mortality rates compared to RCT-eligible males (SMR 1.16; 95% CI 1.09-1.24). Similar results were also found for cardiovascular mortality (SMR 0.89; 95% CI 0.76-1.03 for females, SMR 1.43; 95% CI 1.33-1.53 for males).
Generalizability of HFrEF RCTs differed substantially between the sexes, with females having lower trial participation and female trial participants having lower mortality rates compared to similar females in the registries, while males had higher than expected cardiovascular mortality rates in RCTs compared to similar males in registries.
为了解性别差异如何影响射血分数降低的心力衰竭（HFrEF）患者随机临床试验（RCT）的普遍性，我们试图比较按性别分层的RCT与HF观察性登记研究中的临床特征和临床结局。
来自两个HF登记研究和五项HFrEF RCT的数据用于创建三个亚组：一个RCT亚组（n = 16917；21.7%为女性）、符合RCT纳入标准的登记患者（n = 26104；31.8%为女性）和不符合RCT纳入标准的登记患者（n = 20810；30.2%为女性）。临床终点包括1年时的全因死亡率、心血管死亡率和首次HF住院。男性和女性同样有资格入选试验（登记研究中56.9%的女性和55.1%的男性）。RCT组、符合RCT标准组和不符合RCT标准组中，女性的1年死亡率分别为5.6%、14.0%和28.6%，男性分别为6.9%、10.7%和24.6%。在调整了11个HF预后变量后，RCT中的女性与符合RCT标准的女性相比生存率更高（标准化死亡率[SMR]0.72；95%置信区间[CI]0.62 - 0.83），而RCT中的男性与符合RCT标准的男性相比调整后的死亡率更高（SMR 1.16；95% CI 1.09 - 1.24）。心血管死亡率也发现了类似结果（女性SMR 0.89；95% CI 0.76 - 1.03，男性SMR 1.43；95% CI 1.33 - 1.53）。
HFrEF RCT的普遍性在性别之间存在显著差异，女性参与试验的比例较低，与登记研究中类似女性相比，参与试验的女性死亡率较低，而与登记研究中类似男性相比，RCT中的男性心血管死亡率高于预期。
