The following are key points to remember from this review on initiation, continuation, switching, and withdrawal of heart failure medical therapies during hospitalization:

1. Hospitalization in patients with heart failure and reduced ejection fraction (HFrEF) provides a key opportunity to re-address guideline-directed medical therapies (GDMT). Pre-discharge initiation of GDMT is associated with improved rates of post-discharge use.
2. Landmark trials with beta-blockers in HFrEF patients showed that they were safely tolerated with a low risk for deterioration and demonstrated an early mortality benefit by week 8 of initiation. Small randomized trials suggest that pre-discharge initiation of low-dose beta-blockers in hemodynamically stable patients was well tolerated and reduced re-hospitalization and improved functional status at 6 months. Switching from nonevidence-based beta-blockers to evidence-based beta-blockers has not been studied, but based on clinical experience, is well tolerated.
3. Observational studies show that continuation of beta-blockers during HFrEF hospitalization is associated with lower risk for re-hospitalization and post-discharge mortality. Withdrawal or dose reduction of beta-blockers should be considered in patients with hemodynamic intolerance, borderline perfusion, cardiogenic shock, or inotrope requirement. Careful attention should be paid to patients with bradycardia due to risk for progression to heart block and tachycardia, which may be a compensatory mechanism for low stroke volume.
4. There are no randomized data assessing in-hospital initiation or continuation of angiotensin-converting enzyme inhibitor (ACEI)/angiotensin-receptor blocker (ARB). However, observational studies suggest that in-hospital initiation of ACEI/ARB correlate with lower 30-day re-hospitalization and mortality rates, which persist at 12 months as well.
5. Similarly, in-hospital continuation of ACEI/ARB was associated with lower post-discharge mortality and re-hospitalization. Common reasons for their discontinuation are hyperkalemia and renal dysfunction. In particular, caution should be used in initiating ACEI/ARB in hypovolemic patients, as this may be associated with hypotension.
6. Benefits of angiotensin receptor/neprilysin inhibitor (ARNI) therapy over ACEI are consistent across a wide spectrum of patients with HFrEF including patients with recent hospitalizations. This suggests clinical benefit with in-hospital switching from ACEI/ARB to ARNI. Inpatient initiation of ARNI therapy in euvolemic patients tolerating ACEI/ARB can be considered and will increase rates of post-discharge use. ACEI must be held for 36 hours prior to ARNI initiation and ARNI should not be used in patients with prior hypersensitivity or angioedema to ACEI/ARB.
7. Smaller trials with spironolactone show in-hospital initiation is associated with reduced rates for arrhythmia and greater congestion relief. These benefits have not been consistently demonstrated in observational studies, likely due to confounding with selection bias. In-hospital initiation of spironolactone correlates with higher post-discharge adherence.
8. Continuation of spironolactone during hospitalization has not been well studied. However, subgroup analysis of a randomized trial showed that patients initiated or continued on spironolactone had a lower 30-day mortality. It is safe and well tolerated in most hemodynamically stable patients.
9. Reasons for low use rates of spironolactone therapy at hospital discharge are not well understood. Nonetheless, based on randomized data, their safety profile has been favorable. Patients who are unable or unwilling to comply with post-discharge clinical and laboratory monitoring should not be considered for initiation or up-titration of spironolactone.
10. Patients in the hospital with HFrEF should be counseled and educated regarding need for GDMT and anticipated side effects. Close follow-up after discharge with lab monitoring is mandatory, especially in treatment-naïve patients.

Keywords: Adrenergic beta-Antagonists, Angioedema, Angiotensin Receptor Antagonists, Angiotensin-Converting Enzyme Inhibitors, Bradycardia, Guideline Adherence, Heart Block, Heart Failure, Hospitalization, Hyperkalemia, Hypotension, Hypovolemia, Medication Adherence, Neprilysin, Receptors, Angiotensin, Renal Insufficiency, Shock, Cardiogenic, Spironolactone, Stroke Volume, Tachycardia

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