Page 83 - Biomarkers for risk stratification and guidance in heart failure

Chapter 4
METHODS
Criteria for inclusion of studies and patient data
For this analysis, we used the collaborative database formed for the recently published individual patient data meta-analysis on the effect of (NT-pro)BNP- guided treatment of chronic HF.1
As the current meta-analysis focuses on effects of (NT-pro)BNP-guided therapy on outcome in subgroups we have included only those studies that provided individual patient data8 - 15 and excluded aggregated data presented in the primary meta-analysis. In addition, data from STARBRITE16 were not included as we did not have access to perform additional analyses on this dataset. Conversely, we added the recently published results from the HFpEF subgroup in TIME-CHF to increase the number of HFpEF patients included,17 which increased the percentage of HFpEF from 8% to 15% of the total cohort. In 5% of cases LVEF was not known. These patients were excluded from endpoint analyses. The HF patients with no known LVEF did not differ significantly with respect to their baseline characteristics from those included except that chronic obstructive pulmonary disease (COPD) was more common in those without LVEF measured in BATTLESCARRED12 (43% vs. 18%, P = 0.004) and in PRIMA9 (34% vs. 15%, P = 0.01) and age was greater in BATTLESCARRED (77.3 ± 6.6 years vs. 73.6 ± 9.4 years, P = 0.04; other data not shown). The inclusion and exclusion criteria of each individual trial have been published previously. 8 - 15,17
Data extraction
Individual patient data from eligible studies were entered into the meta-analysis database. The data included patient age, sex, comorbidities, baseline BNP or NT- proBNP level (pg/mL), baseline creatinine (μmol/L), baseline LVEF (%), treatment assignment (NP-guided or clinically-guided) and randomization date. The presence or absence of comorbidities was based on the medical history listed in the medical records of individual patients in all trials. No specific additional testing was done for the diagnosis of comorbidities. Outcome data encompassed all-cause mortality, date of all-cause death or last follow-up, and first HF hospitalization along with the date of hospitalization. Only events occurring during the application of the treatment strategy were included in the analysis.
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