Table 2.

Examples of studies that involved initiation or up-titration of GDMT in patients hospitalized with heart failure

GDMT Class	Study (year)	Study Design	Size	Key Outcome
RAASi	CONSENSUS (1987)	Randomized patients with severe HFrEF and NYHA class IV symptoms to Enalapril vs. standard of care	253	Enalapril improved survival in NYHA class IV HFrEF when added to standard therapy.
	PIONEER-HF (2018)	Randomized patients hospitalized with acute decompensated HFrEF, to initiation of sacubitril-valsartan vs. Enalapril	881	Sacubitril-valsartan reduced NT-proBNP compared to Enalapril at 4 and 8 weeks without significantly different rates of medication-related adverse effects
	LIFE (2021)	Randomized patients with advanced HFrEF (NYHA class IV) to sacubitril/valsartan vs. valsartan	335	There was no significant difference between sacubitril/valsartan vs. valsartan in reducing NT-proBNP. There was an increase in non–life-threatening hyperkalemia in the sacubitril/valsartan arm. Otherwise, there were no significant observed safety concerns.
BB	COPERNICUS (2002)	Randomized patients with HFrEF <25% and NYHA class III-IV symptoms to carvedilol vs. placebo	2,289	Carvedilol reduces the risk of death or HF hospitalization by 31% compared to placebo
	IMPACT HF (2004)	Randomized stabilized patients hospitalized for heart failure to carvedilol initiation predischarge vs. post-discharge initiation (> two weeks)	363	Initiation of BB with carvedilol predischarge was associated with increased beta-blocker use at 60-day follow-up, compared with initiation of BB therapy after discharge at the discretion of the physician
MRA	EPHESUS (2003)	Randomized patients with acute MI complicated by LV dysfunction and HF symptoms to eplerenone vs. placebo	6,642	Eplerenone reduced mortality among patients with acute MI complicated by LV dysfunction and HF symptoms
SGLT-2	SOLOIST-WHF (2021)	Randomized patients with DM-2 who were recently hospitalized for worsening heart failure to sotagliflozin vs. placebo	1222	Sotagliflozin, initiated before or shortly after discharge, was associated with significantly lower cardiovascular mortality and HF hospitalizations or urgent care visits for HF compared to placebo
	EMPULS (2022)	Randomized patients with acute decompensated HF (regardless of LVEF) to empagliflozin vs. placebo	530	Initiation of empagliflozin was associated with significant clinical benefit at 90 days in patients hospitalized for acute HF. Clinical benefits are defined as a hierarchical composite of death from any cause, number of HF events, and time to first HF event, or ≥ 5 points difference in change from baseline in the KCCQ
ACEi/ARB/ARNi, BB and MRA	STONG-HF (2022)	Randomized admitted patients with acute HF who are not on full doses of GDMT to high-intensity up-titration vs. usual care	1078	Rapid up-titration of GDMT with close follow-up was safe and associated with reduced risk of 180-day all-cause mortality or HF readmission compared to the usual care