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May 3, 2022 Circulation. 2022;145:e895–e1032. DOI: 10.1161/CIR.0000000000001063 e962

CLINICAL STATEMENTS AND GUIDELINES 9.2 Maintenance or Optimization of GDMT

During Hospitalization Recommendations for Maintenance or Optimization of GDMT During Hospitalization Referenced studies that support the recommendations are summarized in the Online Data Supplements.

COR LOE Recommendations

1 B-NR 1.	 In patients with HFrEF requiring hospitalization, preexisting GDMT should be continued and optimized to improve outcomes, unless contraindicated.1–5

1 B-NR 2.	 In patients experiencing mild decrease of renal function or asymptomatic reduction of blood pressure during HF hospitalization, diuresis and other GDMT should not routinely be discontinued.6–11

1 B-NR 3.	 In patients with HFrEF, GDMT should be initiated during hospitalization after clinical stability is achieved.2,3,5,12–18

1 B-NR 4.	 In patients with HFrEF, if discontinuation of GDMT is necessary during hospitalization, it should be reinitiated and further optimized as soon as possible.19–22

Synopsis Hospitalization for HFrEF is a critical opportunity to continue, initiate, and further optimize GDMT.23–25 Continuation of oral GDMT during hospitalization for HF has been shown in registries to lower risk of postdischarge death and readmission compared with discontinuation.1–5 Initiation of oral GDMT during hospitalization for HF is associated with numerous clinical outcome benefits.2,5,12,16,17 Based on data from the CHAMP-HF (Change the Management of Patients with Heart Failure) registry, however, only 73%, 66%, and 33% of eligible patients with HFrEF were prescribed ACEi-ARB-ARNi, beta blockers, and MRA therapy, respectively.19 Furthermore, based on information obtained from claims data, roughly 42% of patients are not prescribed any GDMT within 30 days postindex hospitalization,20 and 45% are prescribed either no oral GDMT or monotherapy within 1-year post-hospitalization.21 In the management of patients with HFrEF in the community, very few receive target doses of oral GDMT.6 Moreover, most patients with HFrEF have no changes made to oral GDMT over 12 months,21 despite being discharged on suboptimal doses or no GDMT.22 It cannot be assumed that oral GDMT will be initiated or optimized after hospitalization for HFrEF.

Recommendation-Specific Supportive Text

1.	 In OPTIMIZE-HF (Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure), discontinuation of beta blockers was associated with a higher risk for mortality compared with those continued on beta blockers.1 In a meta-analysis of observational and trial data, discontinuation of beta blockers in hospitalized patients with HFrEF also was associated with a higher risk of in-hospital mortality, short-term mortality, and the combined endpoint of short-term rehospitalization or mortality.4 Withholding or reducing beta-blocker therapy should be considered in patients with marked volume overload or marginal low cardiac output. In the Get With The Guidelines-Heart Failure (GWTG-HF) registry, withdrawal of ACEi-ARB among patients hospitalized with HFrEF was associated with higher rates of postdischarge mortality and readmission.2 In the COACH (Coordinating study evaluating Outcomes of Advising and Counselling in Heart failure) study, continuation of spironolactone among hospitalized patients with HFrEF was associated with lower 30-day mortality and HF rehospitalization.3 From the ARIC (Atherosclerosis Risk in Communities) study, discontinuation of any oral GDMT among patients hospitalized with HFrEF was associated with higher mortality risk.5 Oral GDMT should not be withheld for mild or transient reductions in blood pressure6–9 or mild deteriorations in renal function.10,11 True contraindications are rare, such as advanced degree atrioventricular block for beta blockers in the absence of pacemakers; cardiogenic shock that may preclude use of certain medications until resolution of shock state; or angioedema for ACEi or ARNi. 2.	 In CHAMP-HF, very few patients with HF and SBP <110 mm Hg received target doses of beta blockers (17.5%) ACEi-ARB (6.2 %), or ARNi (1.8%).6 In PARADIGM-HF, patients with HF and lower SBP on sacubitril-valsartan had the same tolerance and relative benefit over enalapril compared with patients with higher SBP.7 From the SENIORS (Study of Effects of Nebivolol Intervention on Outcomes and Rehospitalization in Seniors With Heart Failure) trial, nebivolol had equivalent tolerance and benefits irrespective of SBP.8 In Val-HeFT (Valsartan Heart Failure Trial), decreases in SBP did not offset the beneficial effects of valsartan on HF morbidity.9 In patients with HF on oral GDMT, small to moderate worsening of renal function (defined as ≥20% decrease in eGFR in that study) was not associated with AKI.10 Moreover, it has been shown that spironolactone and beta blockers might be protective in patients with HF and worsening renal function.11

3.	 In OPTIMIZE-HF, discharge use of carvedilol was associated with a reduction in 60- to 90-day mortality and composite risk of mortality

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