Table 3.

Summary of the clinical trials on new drugs for HF in pediatric and adult populations.

Drugs	Population	Title	Key Findings	Dose	Approval
Ivabradine	Adult	Ivabradine and outcomes in chronic heart failure (SHIFT): a randomized placebo-controlled study [18]	N = 6558 patients symptomatic for heart failure and an LVEF of 35% RCT with placebo, reduction of CV death, or hospital admission for worsening heart failure.	5 mg twice per day. Increase the dose after 2 weeks to 7.5 mg × 2/d	EMA approval in 2011
	Pediatric	Ivabradine in children with DCM and symptomatic chronic HF trial: a randomized, double-blind, placebo-controlled trial with 12-months follow-up [21]	N = 116; Ivabradine safely reduced the resting HR of children with chronic HF and CMD and an improvement in ejection fraction, functional class, and NT-pro BNP was noted.	Dose: 0.02–0.05 mg/kg × 2v/die < 40 kg, >40 Kg 2.5 mg × 2/die	FDA approval in 2019 EMA off label
Sacubitril/Valsartan		Angiotensin–Neprilysin Inhibition versus Enalapril in Heart Failure (PARADIGM-HF) [22]	N = 8442 patients with class NYHA II, III, or IV and FE ≤ 40% to receive either S/V (at a dose of 200 mg twice daily) or enalapril (at a dose of 10 mg twice daily), in addition to recommended therapy. S/V was superior to enalapril in reducing the risks of death and hospitalization for heart failure.	24/26 mg, 49/51 mg, and target dose 97/103 mg twice a day	FDA and EMA approval
	Pediatric	Design for the sacubitril/valsartan (LCZ696) compared with enalapril study of pediatric patients with heart failure due to systemic left ventricle systolic dysfunction (PANORAMA-HF study) [32]	N= 393 patients waiting for all subjects to complete the 52 weeks of therapy before performing data analysis.	<40 kg, the starting dose is 1.6 mg/kg of the combined amount of both valsartan and sacubitril. Aum every 2 weeks upward from 2.3 mg/kg up to a max dose of 3.1 mg/kg based on tolerance.	In October 2019, the FDA patients with symptomatic heart failure with LV systolic dysfunction, >1-year-old
Dapaglifozin	Adult	Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction [23] Effect of Empagliflozin on the Clinical Stability of Patients With Heart Failure and a Reduced Ejection Fraction [24]	N = 4744 patients with HFrEF, dapagliflozin reduces the risk of worsening heart failure or death from CV causes compared to placebo N = 3730 patients with HFrEF double-blind treatment with placebo or empagliflozin, reduced the risk and total number of inpatient and outpatient worsening HF events, with benefits seen early after 12 days	10 mg once daily	FDA and EMA approval
	Pediatric	Early Clinical Experience with Dapagliflozin in Children with Heart Failure [26]	N = 38 patients dapagliflozin was added to the HF regimen, and after 312 days of therapy, LVEF increased significantly from 32 to 37.2%	0.1–0.2 mg/kg once daily (max 10 mg)	No approval
Omecamtiv	Adult	Cardiac Myosin Activation with Omecamtiv Mecarbil in Systolic Heart Failure [27]	N = 8256 patients with HFrEF receive omecamtiv mecarbil or a placebo, in addition to standard heart-failure therapy, reduce the incidence of a composite of a heart-failure event or death from cardiovascular causes	25 mg, 37.5 mg, or 50 mg twice daily	No approval
	Pediatric	No data	No data	No data	No data
Vericiguat	Adult	Vericiguat in Patients with Heart Failure and Reduced Ejection Fraction (VICTORIA trial) [29]	N = 5050 patients with HFrEF, vericiguat reduced risk of cardiovascular death, all-cause death, and HF hospitalization (phase 3)	starting dose 2.5 mg orally once daily with food. Double the dose every 2 weeks to reach the target e dose of 10 mg once daily	FDA and EMA approval in 2021
	Pediatric	No data	No data	No data	No data