Page 93 - Biomarkers for risk stratification and guidance in heart failure

Chapter 4
DISCUSSION
There is considerable uncertainty as to which patients will benefit from (NT-pro) BNP-guided therapy for HF. The present analysis based on individual patient data from eight randomized trials provides important insights, showing that positive effects were seen almost exclusively in patients with reduced LVEF. Importantly, comorbidities strongly influenced the response to guided therapy and explained the lower efficacy of this approach in elderly patients. These findings better define the group of patients possibly benefiting from guided therapy and suggests lack of uniformity of response to evidence-based treatments among HF patients.
Influence of comorbidities on biomarker-guided therapy
In addition to the interactions with age and LVEF outlined above, the efficacy of (NT-pro)BNP-guided therapy was significantly influenced by comorbidities. In fact, the suggested effect of age on (NT-pro)BNP-guided therapy efficacy can be explained entirely by the presence of comorbidities. This was true with respect to mortality but less to the combined endpoint and not to HF hospitalizations (data not shown), in line with the finding that the effect of age was only seen with respect to mortality, but not HF hospitalizations.1 Thus, HF hospitalization might be reduced by more intense HF-specific treatment irrespective of the presence or absence of comorbidities.
Our results call into question the belief that (NT-pro)BNP-guided HFrEF care is limited simply by age. We hypothesize that comorbidities rather than age per se globally affect HF care. Thus, it might be that comorbidities influence the treatment response to HF medication. It is well known that comorbidities negatively influence prognosis in HF patients. Moreover, there are numerous studies showing the potential risk of drug-drug interactions leading to adverse effects with the increasing number of comorbidities and, as a consequence, increasing number of prescribed drugs.19 However, it is less clear if this may result in fewer beneficial effects of HF-specific medication. Unfortunately, full understanding of how multiple comorbidities in‘real world’ patients affect effectiveness of proven therapies for HF is lacking. Based on the large randomized treatment trials in HF, trends were seen towards less positive effects of active treatment in patients with comorbidities (e.g. SENIORS, EMPHASIS-HF),20,21 but a systematic evaluation of such potential interaction is, to the best of our knowledge, still lacking. Therefore, the potential reason(s) for lower effectiveness of more intensified therapy in HF patients with comorbidities must remain speculative.
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