Generalizability of HFrEF trials 17 Eligibility criteria and outcomes The inclusion and exclusion criteria listed in the study protocol of the five RCTs were tabulated (Supplementary Table 1) to identify common study entry criteria. These criteria were cross-checked for data availability within the registries and a set of most commonly used eligibility criteria was then identified to select subsets of RCT-eligible and non-eligible patients from the registries. The following inclusion criteria were used: age ≥18 years, LVEF<40%, NYHA functional class II to IV, on optimallytolerated chronic HF medications of β-blocker and angiotensin-converting enzyme inhibitor (ACEI) or angiotensin-II receptor blocker (ARB). Then, the following exclusion criteria were applied: serum haemoglobin concentrations <11g/dL in men or <10g/dL in women, chronic liver disease, creatinine >220μmol/L and cancer. Comparisons were made based on (i) patient baseline characteristics (ii) cardiovascular medications and (iii) mortality outcomes. For summary statistics, aggregated data were extracted from each trial and there were instances of low patient numbers in the data contingency tables. To maintain patient anonymity, all table cells with counts of 3 and below were replaced with a central number of 2.19 For HF medications, the percentage of patients who received <50% or ≥ 50% target doses of the HF medications were assessed (Supplementary table 2). Lastly, the following clinical outcomes at one year were assessed: all-cause mortality, cardiovascular mortality (ICD-10 codes I00 – I99) and first HF hospitalization (main diagnosis with codes I50, I11.0, I42.0, I42.3-I42.9, I43, I25.5, K76.1, I13.0, I32.2 or J81). Follow-up duration differed between the five trials. Three trials (BEAUTIFUL, CONFIRM-HF and SHIFT) had follow-up data for at least one year, so outcome at one year was reported here. The remaining two trials (FAIR-HF and PANTHEON) had less than a year’s follow-up and patients were censored at the end of study. Statistical analysis Continuous data are presented as mean with standard deviation while categorical variables are reported in frequencies and percentages. Mean and proportion differences between the RCT and RCT-eligible registry patients were calculated and reported with their corresponding 99% confidence intervals (CI). Data are presented by three groups: (i) RCT participants, (ii) RCT-eligible, and (iii) RCT-non-eligible registry patients. Cumulative incidence curves were used to compare unadjusted outcomes between study groups. For cardiovascular mortality, deaths due to other 2.1
RkJQdWJsaXNoZXIy MjY0ODMw