P275 combined neuro–humoral modulation and outcome in patients with chronic heart failure and mildly reduced or preserved ejection fraction

Abstract Background Drug therapy of patients with chronic heart failure (HF) with mildly reduced (HFmrEF) and preserved ejection fraction (HFpEF) remains a challenge. We aimed to assess whether escalating neuro–humoral–modulation (NHM) (renin–angiotensin system inhibitors (RASI), betablockers (BB), mineralocorticoid receptor antagonists (MRA)) was differentially associated with outcome according to phenotype and age groups. Methods and Results Between 1999 and 2018 we recruited in a nationwide cardiology registry 4707 patients (HFmrEF n=2298, HFpEF n=2409) and classified them into 3 age groups: young (<65 years), old (65–79 years), oldest–old (80+ years). We analysed clinical characteristics and 1–year all–cause mortality/cardiovascular hospitalization according to none/single (RASI or BB or MRA), double (RASI+BB or RASI+MRA or BB+MRA), or triple (MRA+RASI+BB) NHM. Overall, approximately half of HFmrEF and HFpEF patients had double–NHM. Among HFmrEF, 25.1% received no/single and 26.7% triple NHM. In the HFpEF group, 36.5% had no/single and 17.9% triple NHM. Older age was associated with a higher prescription of no/single NHM among HFmrEF patients (ptrend=0.001); the reverse was observed among HFpEF patients (ptrend =0.005). Prescription of triple NHM increased over time in both phenotypes (all p for trend<0.0001). Compared to no/single NHM, triple, but not double, NHM was associated with better outcome in both HFmrEF (HR 0.700, 95% CI 0.505–0.969, p=0.032) and HFpEF (HR 0.700, 95% CI 0.499–0.983, p=0.039), with no interaction between NHM and age groups (p=0.58, p=0.80, respectively). Conclusions In a cardiology setting, among HF outpatient with EF>40%, prescription rates of triple NHM increased over time and were associated with better patient outcome.