Page 88 - Biomarkers for risk stratification and guidance in heart failure

Which heart failure patients profit from natriuretic peptide-guided therapy?
Influence of comorbidities on (N-terminal pro-)brain natriuretic peptide-
guided therapy
Comorbidities influenced response to (NT-pro)BNP-guided therapy with respect
to mortality in both HFrEF and HFpEF (Figure 3). In HFrEF, the response to (NT- pro)BNP-guided therapy was primarily seen in patients without COPD, diabetes, cardiovascular insult (CVI)/transient ischaemic attack (TIA) or PVD. Although any
single co-morbidity interaction with treatment efficacy did not reach statistical
significance, when comorbidities were considered in combination, this interaction
was significant. Thus, compared with symptom-guided therapy, (NT-pro)BNP-
guided therapy reduced mortality (HR = 0.61, 95% CI 0.42 - 0.88, P = 0.008) in
patients with no history of CVA/TIA, diabetes or COPD. Such benefit was absent
in those with any one of these comorbidities (HR = 0.94, 95% CI 0.71 - 1.24, P =
0.65). When also considering PVD, patients with none or only one of these four 4 comorbidities (i.e. COPD, diabetes, CVI/TIA, PVD) had a mortality benefit of 33%
(HR = 0.67, 95% CI 0.51 - 0.89, P = 0.005), whereas those with two or more of them did not benefit (HR = 0.99, 95% CI 0.62 - 1.59, P = 0.97). Interestingly, a history of renal failure had no influence on treatment response (Figure 3). When using baseline estimated glomerular filtration rate (eGFR) to define renal failure (i.e. ≤60 mL/min.1.73m2 using simplified Modification of Diet in Renal Disease equation),18 treatment response was not influenced by either eGFR >60 (n = 776: HR = 0.78, 95% CI 0.51 - 1.20, P = 0.25) or eGFR ≤60 (n = 944: HR = 0.81, 95% CI 0.63 - 1.06, P = 0.12; interaction p > 0.2).
In HFpEF, comorbidities also influenced treatment response, but the pattern differed from that in HFrEF. Patients without hypertension allocated to (NT-pro) BNP-guided therapy had worse outcome than those allocated to clinically-guided therapy, whereas in those with hypertension no such harm was seen (interaction P = 0.02). Conversely, HFpEF patients with a history of renal failure fared worse on (NT-pro)BNP-guided therapy. This was also the case when using eGFR to define renal failure (eGFR >60 n = 98: HR = 0.71, 95% CI 0.27 - 1.86; eGFR ≤60 n = 203: HR = 1.47, 95% CI 0.85 - 2.55; interaction P = 0.05). In contrast to HFrEF, other comorbidities or combinations thereof did not influence treatment response (Figure 3).
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