Page 95 - Biomarkers for risk stratification and guidance in heart failure

Chapter 4
therapy positively influenced mortality and combined endpoint rates in HFrEF only, where treatments that reduce mortality are available, in contrast to HFpEF.
The lack of benefit from (NT-pro)BNP-guided therapy in HFpEF was not detected in our previous meta-analysis, probably owing to the very limited power by the small number of HFpEF cases included.1 TIME-CHF contributes substantially to this lack of benefit in HFpEF and it might be argued that this is entirely caused by TIME-CHF. When excluding the TIME-CHF data the interaction between the treatment response on mortality and the two groups based on LVEF was no longer statistically significant (data not shown). However, the treatment effects were homogeneous between studies in both the HFpEF and the HFrEF group. In addition to the notion that HFrEF and HFpEF may be two distinct diseases,17 several other concepts may be relevant to these findings. Although a large cohort study found some positive results of renin-angiotensin system blockade in patients with LVEF of 40% or higher,29 such treatments failed to improve outcome in HFpEF in large prospective randomized therapeutic trials.5-7 Therefore, it is not surprising that delivering currently available HF therapies in an alternative manner does not affect outcome. Notably, HFpEF patients without hypertension and those with renal failure incurred worse outcomes when treated with guided therapy, whereas those with hypertension and/or without renal failure showed neutral results. In contrast, medical and device treatment has markedly improved prognosis in HFrEF over recent decades.4 Our findings support current treatment recommendations for HFpEF, which are restricted to treatment of comorbidities and symptoms4 and the role of natriuretic peptides in HFpEF appears limited, at least at present, to diagnosis and prognosis.30,31
Limitations
Our study has important limitations. We were able to include only those studies on NT-proBNP-guided therapy that provided individual patient data, which might introduce a bias. Although based on individual patient data, our analyses could not address potentially important aspects of management because such information was not collected equally in the trials. In particular, we do not know if effects of comorbidities on (NT-pro)BNP-guided therapy were mainly driven by less uptitration in such patients compared with those with little or no comorbidities. Uptitration was less in elderly patients irrespective of treatment if reported specifically (BATTLESCARRED, TIME-CHF),12,14 but it was still significantly more in the NT-proBNP-guided group than in the control group in TIME-CHF.14
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