Table 1.

Rationale for Generalizing Data from Outpatient HFrEF Trials to Hospitalized Patients Who Are Stabilized and/or Pre-Discharge

Location of care does not reliably distinguish biology or risk, and accumulating data suggest that “acute”/ hospitalized HFrEF and stable outpatient HFrEF are a single disease on a continuum.

Decisions to admit and discharge from the hospital are inherently subjective and influenced by several non-biologic factors independent from severity of HF presentation (e.g., country, local outpatient healthcare infrastructure, patient/clinician preferences, caregiving and living situation, medico-legal liability climate, financial incentives/penalties).(6)

“Acute” HF is often not acute, as many patients have filling pressures begin to rise several days before seeking medical care or presenting to the hospital.(6)

Location of care does not reliably distinguish clinical risk, with many outpatients with HF carrying short-term and longer-term mortality risk comparable to (or higher than) patients who are actively hospitalized.(6)

New-onset end-organ injury (e.g., new troponin elevation) has traditionally been considered specific to hospitalized HFrEF, but up to ~1 in 10 patients may develop new-onset troponin elevation after they leave the hospital despite apparent clinical stability.(26)

To our knowledge, there are no examples where a chronic therapy improved outcomes among outpatients with HFrEF and was ineffective as chronic therapy when initiated among stabilized patients in the hospital

Recent examples with ARNI (PARADIGM-HF and PIONEER-HF) and SGLT2i (DAPA-HF/ EMPEROR-Reduced and SOLOIST-WHF) show concordance in treatment effect when initiated among stable outpatients or stabilized inpatients.

Recently completed and ongoing large HF trials are increasingly including hospitalized patients and outpatients under a single trial protocol.

In-hospital initiation of GDMT for chronic HFrEF is consistent with regulatory labels and clinical practice guidelines.

US Food and Drug Administration drug labels do not reference location of care, and in-hospital vs outpatient status does not impact eligibility for any standard HFrEF therapy.

ACC Expert Consensus documents recommend in-hospital initiation of GDMT for chronic HFrEF among eligible patients, as tolerated.(10)

ACC/AHA HF guidelines have an explicit class I recommendation for in-hospital or before hospital discharge initiation of GDMT if not previously established, in absence of contraindications.(11)

Abbreviations: ACC, American College of Cardiology; AHA, American Heart Association; ARNI, angiotensin receptor-neprilysin inhibitor; GDMT, guideline-directed medical therapy; HFrEF, heart failure with reduced ejection fraction; SGLT2i, sodium glucose cotransporter-2 inhibitor