Page 85 - Biomarkers for risk stratification and guidance in heart failure

Chapter 4
collected all the information used for this analysis (Table 1). In three trials, patients with HFrEF only were included,10,11,15 whereas five also included patients with relatively preserved LVEF (HFpEF, i.e. LVEF >45%).8,9,12,13,17 One study included only five such patients, none of which experienced an event.13 Therefore, HFpEF patients of this study (i.e. Signal-HF) were not included in the endpoint analysis, leaving four studies, which included a total of 296 HFpEF patients.8,9,12,17
Heart failure with preserved ejection fraction vs. heart failure with reduced ejection fraction
Patients with HFpEF were significantly older, more often female, with slightly higher body mass index (BMI) and lower NT-proBNP concentrations than patients with HFrEF (Table 2). Hypertension, renal disease and peripheral vascular disease (PVD) were more prevalent in HFpEF than in HFrEF. HFpEF was more often treated with loop diuretics, but less frequently with -blockers. There was no difference between HFpEF and HFrEF in terms of mortality (HR = 1.15, 95% CI 0.89 - 1.50, P = 0.28 for HFpEF vs. HFrEF) or HF admission (HR = 1.20, 95% CI 0.95 - 1.51, P = 0.12), but the combined endpoint of HF hospitalization or death was more common in HFpEF patients (HR = 1.24, 95% CI 1.02 - 1.51, P = 0.03; 1 and 2-year event rate in HFpEF vs. HFrEF 36% and 50% vs. 30% and 44%, respectively). This increased hazard in HFpEF was not independent of age (bivariate Cox regression: HR = 1.14, P = 0.18 after adjustment for age).
Figure 1 depicts the effects of (NT-pro)BNP-guided therapy on mortality based on the individual data of patients showing a significant beneficial effect in HFrEF (HR = 0.78, 95% CI 0.62 - 0.97), but not in HFpEF patients (HR = 1.22, 95% CI 0.76 - 1.96; interaction P = 0.016). Data from individual studies are depicted in Figure 2, showing no significant heterogeneity between studies according to LVEF subgroup.
Time to first HF admission was significantly prolonged by (NT-pro)BNP-guided therapy in the HFrEF group (HR = 0.80, 95% CI 0.67 - 0.97, P = 0.02), but not in the HFpEF group (HR = 1.01, 95% CI 0.67 - 1.53, P = 0.97; interaction P = 0.007) with no significant heterogeneity between studies. The combined endpoint of HF admission or death was also reduced in HFrEF patients by the use of (NT-pro) BNP-guided therapy (HR = 0.78, 95% CI 0.66 - 0.92, P = 0.004), but not in the HFpEF group (HR = 1.08, 95% CI 0.76 - 1.53, P = 0.66; interaction P = 0.001). There was no significant heterogeneity between studies.
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