In contrast to HFrEF, there has been limited therapeutic progress for patients with HF with preserved ejection fraction (HFpEF). Expert consensus statements endorse a strategy of in-hospital initiation of or switching to sacubitril/valsartan among patients with HFrEF ( 8, 9). The angiotensin receptor-neprilysin inhibitor, sacubitril/valsartan, when initiated during hospitalization for HF with reduced ejection fraction (HFrEF) was safe and led to short-term reductions in natriuretic peptides ( 4) and clinical events ( 7) compared with enalapril. Therapies initiated during or soon after hospitalization are associated with higher post-discharge use in follow-up ( 4– 6). Patients with recurrent readmissions for HF disproportionately contribute to healthcare costs and resource utilization ( 3). Hospitalization is a perturbational event in the clinical course of patients with heart failure (HF) the period shortly after hospitalization represents a high-risk window for recurrent clinical events, including rehospitalization or death ( 1, 2). Relative and absolute benefits of sacubitril/valsartan compared with valsartan in HFpEF appear to be amplified when initiated in the high-risk window after hospitalization and warrants prospective validation. In this post hoc analysis of 4,796 randomized patients with chronic HFpEF (≥45%) in the PARAGON-HF trial, over median 35 months follow-up, risk of total HF hospitalizations and cardiovascular death was inversely and non-linearly associated with timing from prior HF hospitalization (P180 days or who were never hospitalized (trend in absolute risk reduction P interaction=0.050). Compared with valsartan, absolute risk reductions with sacubitril/valsartan were more prominent in patients enrolled early after hospitalization: 6.4% (≤30 days), 4.6% (31-90 days), 3.4% (91-180 days), while no risk reduction was observed in patients screened >180 days or who were never hospitalized trend in absolute risk reduction P interaction=0.050.
Over median 35 months follow-up, risk of total HF hospitalizations and cardiovascular death was inversely and non-linearly associated with timing from prior HF hospitalization (P180 days), and 7.9 (not previously hospitalized) per 100 patient-years. Of 4,796 validly randomized patients in PARAGON-HF, 622 (13%) were screened during hospitalization or within 30 days of prior hospitalization, 555 (12%) within 31–90 days, 435 (9%) within 91–180 days, 694 (14%) after 180 days, and 2,490 (52%) were never previously hospitalized.