Intravenous nicorandil for patients with acute decompensated heart failure: a meta-analysis of randomized controlled trials

Figures & data

Figure 1. Flowchart of literature search.

Table 1. Characteristics of the included studies.

Study	Country	Design	Patient number	Mean age	Male	LVEF	Ischemic HF	Background therapy	Nicorandil	Control	Treatment duration	Follow-up duration	Outcomes reported
				years	%	%	%				days
Shirakabe et al., 2010	Japan	R, OL	31	70.1	70.9	38.5	45.2	Diuretics, carperitide, ACEIs, BBs, and dobutamine	IV bolus 100 ug/kg, then 60-100 ug/kg/h	No nicorandil treatment	5	During hospitalization	UCG parameters, BNP/NT-proBNP, mortality
Kasama et al., 2015	Japan	R, OL	70	74.5	67.1	33.5	0	Diuretics, ACEIs/ARBs, BBs, MRAs, and dobutamine	IV 4-12 mg/h	No nicorandil treatment	6	28 days	UCG parameters, and NT-proBNP
Harada et al., 2017	Japan	R, OL	106	75	50	43.7	37.7	Diuretics, carperitide, ACEIs, BBs, and dobutamine	IV bolus 200 ug/kg, then 200 ug/kg/h	No nicorandil treatment	1	60 days	Likert scaling at 24h, UCG parameters, mortality, and rehospitalization
Xie et al., 2018	China	R, OL	60	56.7	60	42.1	NR	Diuretics, vasodilators, and inotropic agents	IV bolus 200 ug/kg, then 200 ug/kg/h	No nicorandil treatment	1	During hospitalization	UCG parameters, and BNP
Li et al., 2018	China	R, OL	128	75.1	50	NR	NR	Diuretics, ACEIs/ARBs, BBs, MRAs, and inotropic agents	IV bolus 200 ug/kg, then 200 ug/kg/h	No nicorandil treatment	1	90 days	Likert scaling at 24h, UCG parameters, mortality, and rehospitalization
Gan et al., 2021	China	R, OL	102	58.2	46.1	37.4	59.2	Diuretics, carperitide, ACEIs and BBs	IV bolus 4 mg, then 6 mg/h	No nicorandil treatment	1	During hospitalization	UCG parameters, and BNP
Zhang et al., 2022	China	R, OL	147	71.2	50.3	45.7	35.4	conventional Diuretics, positive inotropic agents etc.	IV bolus 200 ug/kg, then 200 ug/kg/h	No nicorandil treatment	1	90 days	UCG parameters, NT-proBNP, Likert scaling at 24h, and rehospitalization
Yang et al., 2022	China	R, OL	120	69.5	50.8	39.8	NR	Diuretics, carperitide, ACEIs, BBs, and dobutamine	IV bolus 200 ug/kg, then 200 ug/kg/h	No nicorandil treatment	1	During hospitalization	UCG parameters, and BNP

LVEF: left ventricular ejection fraction; HF: heart failure; R: randomized; OL: open-label; ACEIs: angiotensin-converting enzyme inhibitors; ARBs: angiotensin II receptor blockers; BBs: beta-blockers; MRAs: mineralocorticoid receptor antagonists; IV: intravenously; UCG: ultrasound cardiography; BNP: B type natriuretic peptide; NT-proBNP, N-terminal (NT)-pro hormone BNP.

Table 2. Quality evaluation of the included studies via Cochrane’s Risk of Bias Tool.

Study	Random sequence generation	Allocation concealment	Blinding of participants	Blinding of outcome assessment	Incomplete outcome data addressed	Selective reporting	Other sources of bias
Shirakabe et al., 2010	Unclear	Unclear	High risk	High risk	Low risk	Low risk	Low risk
Kasama et al., 2015	Unclear	Unclear	High risk	High risk	Low risk	Low risk	Low risk
Harada et al., 2017	Unclear	Unclear	High risk	High risk	Low risk	Low risk	Low risk
Xie et al., 2018	Low risk	Unclear	High risk	High risk	Low risk	Low risk	Low risk
Li et al., 2018	Unclear	Unclear	High risk	High risk	Low risk	Low risk	Low risk
Gan et al., 2021	Low risk	Unclear	High risk	High risk	Low risk	Low risk	Low risk
Zhang et al., 2022	Unclear	Unclear	High risk	High risk	Low risk	Low risk	Low risk
Yang et al., 2022	Low risk	Unclear	High risk	High risk	Low risk	Low risk	Low risk

Figure 2. Forest plots for the meta-analysis of the influences of nicorandil on Likert scale at 24 h after treatment and serum concentrations of BNP and NT-proBNP at discharge in patients with ADHF; (A) Forest plots for the meta-analysis of Likert scale; (B) Forest plots for the meta-analysis of serum concentration of BNP; and (C) Forest plots for the meta-analysis of serum concentration of NT-proBNP.

Figure 3. Forest plots for the meta-analysis of the influences of nicorandil on UCG parameters at discharge in patients with ADHF; (A) Forest plots for the meta-analysis of LVEF; (B) Forest plots for the meta-analysis of LVEDV; (C) Forest plots for the meta-analysis of LVESV; and (D) Forest plots for the meta-analysis of E/e’.

Figure 4. Forest plots for the meta-analyses of the effects of nicorandil on clinical outcomes and drug-related AEs during follow-up duration up to 90 days; (A) Forest plots for the meta-analysis of all-cause mortality; (B) Forest plots for the meta-analysis of HF-rehospitalization; (C) Forest plots for the meta-analysis of MACEs; and (D) Forest plots for the meta-analysis of drug-related AEs.