TY - JOUR
T1 - Generalizability of randomized controlled trials in heart failure with reduced ejection fraction
AU - Lim, Yvonne Mei Fong
AU - Molnar, Megan
AU - Vaartjes, Ilonca
AU - Savarese, Gianluigi
AU - Eijkemans, Marinus J C
AU - Uijl, Alicia
AU - Vradi, Eleni
AU - Suzart-Woischnik, Kiliana
AU - Brugts, Jasper J
AU - Brunner-La Rocca, Hans-Peter
AU - Blanc-Guillemaud, Vanessa
AU - Couvelard, Fabrice
AU - Baudier, Claire
AU - Dyszynski, Tomasz
AU - Waechter, Sandra
AU - Lund, Lars H
AU - Hoes, Arno W
AU - Tyl, Benoit
AU - Asselbergs, Folkert W
AU - Gerlinger, Christoph
AU - Grobbee, Diederick E
AU - Cronin, Maureen
AU - Koudstaal, Stefan
N1 - © The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.
PY - 2022/10/26
Y1 - 2022/10/26
N2 - Background Heart failure (HF) trials have stringent inclusion and exclusion criteria, but limited data exist regarding generalizability of trials. We compared patient characteristics and outcomes between patients with HF and reduced ejection fraction (HFrEF) in trials and observational registries. Methods and Results Individual patient data for 16 922 patients from five randomized clinical trials and 46 914 patients from two HF registries were included. The registry patients were categorized into trial-eligible and non-eligible groups using the most commonly used inclusion and exclusion criteria. A total of 26 104 (56%) registry patients fulfilled the eligibility criteria. Unadjusted all-cause mortality rates at 1 year were lowest in the trial population (7%), followed by trial-eligible patients (12%) and trial-non-eligible registry patients (26%). After adjustment for age and sex, all-cause mortality rates were similar between trial participants and trial-eligible registry patients [standardized mortality ratio (SMR) 0.97; 95% confidence interval (CI) 0.92-1.03] but cardiovascular mortality was higher in trial participants (SMR 1.19; 1.12-1.27). After full case-mix adjustment, the SMR for cardiovascular mortality remained higher in the trials at 1.28 (1.20-1.37) compared to RCT-eligible registry patients. Conclusion In contemporary HF registries, over half of HFrEF patients would have been eligible for trial enrolment. Crude clinical event rates were lower in the trials, but, after adjustment for case-mix, trial participants had similar rates of survival as registries. Despite this, they had about 30% higher cardiovascular mortality rates. Age and sex were the main drivers of differences in clinical outcomes between HF trials and observational HF registries.
AB - Background Heart failure (HF) trials have stringent inclusion and exclusion criteria, but limited data exist regarding generalizability of trials. We compared patient characteristics and outcomes between patients with HF and reduced ejection fraction (HFrEF) in trials and observational registries. Methods and Results Individual patient data for 16 922 patients from five randomized clinical trials and 46 914 patients from two HF registries were included. The registry patients were categorized into trial-eligible and non-eligible groups using the most commonly used inclusion and exclusion criteria. A total of 26 104 (56%) registry patients fulfilled the eligibility criteria. Unadjusted all-cause mortality rates at 1 year were lowest in the trial population (7%), followed by trial-eligible patients (12%) and trial-non-eligible registry patients (26%). After adjustment for age and sex, all-cause mortality rates were similar between trial participants and trial-eligible registry patients [standardized mortality ratio (SMR) 0.97; 95% confidence interval (CI) 0.92-1.03] but cardiovascular mortality was higher in trial participants (SMR 1.19; 1.12-1.27). After full case-mix adjustment, the SMR for cardiovascular mortality remained higher in the trials at 1.28 (1.20-1.37) compared to RCT-eligible registry patients. Conclusion In contemporary HF registries, over half of HFrEF patients would have been eligible for trial enrolment. Crude clinical event rates were lower in the trials, but, after adjustment for case-mix, trial participants had similar rates of survival as registries. Despite this, they had about 30% higher cardiovascular mortality rates. Age and sex were the main drivers of differences in clinical outcomes between HF trials and observational HF registries.
KW - Generalizability
KW - External validity
KW - Heart failure with reduced ejection fraction
KW - Randomized clinical trials
KW - F INHIBITOR IVABRADINE
KW - DOUBLE-BLIND
KW - ELIGIBILITY CRITERIA
KW - EXTERNAL VALIDITY
KW - REAL-WORLD
KW - RELAX-AHF
KW - RATIONALE
KW - DESIGN
KW - WOMEN
KW - POPULATION
U2 - 10.1093/ehjqcco/qcab070
DO - 10.1093/ehjqcco/qcab070
M3 - Article
C2 - 34596659
SN - 2058-5225
VL - 8
SP - 761
EP - 769
JO - European heart journal - Quality of care & clinical outcomes
JF - European heart journal - Quality of care & clinical outcomes
IS - 7
ER -