Nicorandil in ST-segment elevation myocardial infarction patients undergoing percutaneous coronary intervention: A systematic review and meta-analysis

Table 1 Baseline characteristics of studies included in systematic review and meta-analysis

Ref.	Country	N	C	Participants (n)		Age (years)		Male (%)		DM (%)		HTN (%)		Dyslipidemia (%)		Smokers (%)
				N	C	N	C	N	C	N	C	N	C	N	C	N	C
Ito et al[16], 1999	Japan	4 mg bolus IV; 6 mg/hour continuous infusion for 24 hours; 15 mg/day oral (for a mean of 28 days)	No agent	40	41	60	60	80	78	25	29	53	51	27	34	60	51
Fukuzawa et al[17], 2000	Japan	4 mg bolus IV; 6 mg/hour infusion for 24 hours	No agent	31	31	61.5	61.3	74.2	71	32.3	29	58.1	67.7	45.2	48.4	61.3	61.3
Ikeda et al[18], 2004	Japan	Infusion 6 mg/hour IV for 72 hours; 2 mg IC	Isosorbide dinitrate 6 mg/hour IV for 72 hours, 2 mg IC	30	30	60	63	76.7	83.3	16.7	20	NA	NA	NA	NA	NA	NA
Nameki et al[19], 2004	Japan	4 mg IV + 4 mg IC before reperfusion; 4 mg/hour IV for 24 hours	Control 1: Magnesium: 10 mmol IV before reperfusion, 0.4 mmol/hour for 24 hours; control 2: No agent	13	27	64	62	85	85	31	26	46	44	23	44	77	78
Ono et al[20], 2004	Japan	4 mg bolus IV, 8 mg/hour IV infusion for 24 hours after PCI	No agent	33	25	64	66	67	64	33	32	55	56	42	36	45	36
Ishii et al[21], 2005	Japan	12 mg dissolved in normal saline 100 mL IV	Normal saline	185	183	63	64	77.8	84.1	33	31.7	28.1	31.1	25.9	28.4	35.7	42
Kasama et al[22], 2005	Japan	2 mg bolus IV, continuous infusion 4 mg/hour, oral 15 mg/day	Isosorbide dinitrate 2 mg IV bolus, continuous infusion 4 mg/hour, oral 40 mg/day	25	25	62	63	72	76	24	32	48	44	32	40	52	60
Akagi et al[23], 2006	Japan	Intervention 1: Continuous infusion IV 4 mg/hour, 2 mg IC; intervention 2: Continuous infusion IV 4 mg/hour, 2 mg IC, oral 15 mg/day	No agent	20	10	65.5	61	50	90	NA	NA	NA	NA	NA	NA	NA	NA
Miyazawa et al[24], 2006	Japan	2 mg IC; 2 mg/hour infusion for 24 hours IV; 15 mg/day oral	No agent	35	35	64	60	88	74	28	40	48	57	31	37	54	57
Ota et al[25], 2006	Japan	Intervention 1: 1-2 mg IC (1-2 times); intervention 2: 96 mg dissolved in 100 mL saline, 4 mg IV, infusion 6 mg/hour, IC same dose as in intervention 1 group	No agent	63	27	62.2	64.2	82.5	74.1	29	33	44	41	60	44	54	52
Toyama et al[26], 2006	Japan	4 mg IV bolus, infusion 4 mg/hour over 24-hour period, 2 mg IC	No agent	33	35	65	63	68.5	57	24	34.5	35.5	37	35.5	22.5	69.5	77.5
Fujiwara et al[27], 2007	Japan	4 mg IV bolus, infusion 8 mg/hour for 24 hours	No agent	31	31	62	62	80.6	80.6	38.7	38.7	58.1	51.6	45.2	35.5	70.9	80.6
Kitakaze et al[28], 2007	Japan	0.067 mg/kg bolus IV, 1∙67 μg/kg per minute infusion IV for 24 hours	Normal saline	276	269	61.1	63.7	89.1	81.8	39.5	32.9	48.5	53.9	46.7	46.2	68.7	66.1
Lee et al[29], 2008	Korea	2 mg IC before CAG, 2 mg IC before stenting	No agent	37	36	56.4	60.2	83.8	83.3	27	36.1	51.4	66.7	NA	NA	86.5	69.3
Yamada et al[30], 2016	Japan	0.2 mg/kg IC before the initial and final angiograms, 2.0 mg/hour infusion IV for 4 days	Nitroglycerin 0.2 mg/kg IC before the initial and final angiograms; 2.0 mg/hour infusion IV for 4 days	28	24	67	65	82	91	21	41	32	33	14	37	32	37
Chen et al[31], 2015	China	Intervention 1: 2 mg IC, anisodamine 2 mg IC; intervention 2: 2 mg IC	Control 1: Anisodamine 2 mg IC; control 2: Only PCI	52	52	58.1	59.8	75	73.1	26.9	30.8	40.4	46.2	21.2	23.1	67.3	65.4
Qi et al[32], 2018	China	2 mg IC	Control 1: Nitroprusside: 200 μg IC; control 2: Saline only	40	80	56	60	72.5	71.3	42.5	33.8	55	53.8	40	35	44	46.3
Pi et al[33], 2019	China	Intervention 1: 4 mg IC, 4 mg/hour IV infusion for 24 hours; intervention 2: 4 mg IC, normal saline 4 mL/hour IV for 24 hours	Normal saline	95	45	68.5	68.7	72.6	72.1	63.2	62.2	62.1	66.7	61.1	57.8	71.6	71.1
Chen et al[34], 2020	China	0.06 mg/kg IC; 2 mg/hour IV infusion for 36 hours, tirofiban 10 μg/kg IC; 0.1 μg/kg/minute IV infusion for 36 hours	Tirofiban 10 μg/kg IC, 0.1 μg/kg/minute IV infusion for 36 hours	39	39	67	66.2	92.3	89.7	30.7	25.6	51.3	48.7	NA	NA	74.4	76.9
Feng et al[35], 2019	China	2-6 mg IC; thrombectomy; tirofiban 10 mg/kg IC	Saline 2-6 mL IC; thrombectomy; tirofiban 10 mg/kg IC	84	86	69.2	68.5	70	72	42	36	56	59	NA	NA	45	49
Wang et al[36], 2019	China	5 mg oral, 5 mg three times/day for 6 months	5 mg oral nicorandil	60	57	58.4	55.8	54	47	20	17.5	46.7	38.6	NA	NA	58.3	47.4
Akbari et al[37], 2020	Iran	40 mg oral	No agent	116	124	58.9	57.9	78.4	83.1	21.6	18.5	39.7	41.1	14.7	16.1	47.4	54
Wang et al[38], 2021	China	IV infusion	5 mg oral nicorandil before PCI, then no agent given	59	60	54	55	79.7	78.3	10.2	8.3	42.4	43.3	NA	NA	67.8	68.3
Qian et al[5], 2022	China	6 mg IV bolus, IV infusion 6 mg/hour	No agent	120	118	60	58	85	87.3	25.8	18.6	50	56.8	18.3	21.2	58.3	61
Choe et al[6], 2023	Korea	4 mg IV bolus, infusion IV 6 mg/hour for 24 hours (two 2 mg IC doses to reduce adverse events)	No agent	40	43	59.5	59.8	82.5	86	30	44.2	47.5	37.2	NA	NA	50	58.1
Ilyas et al[4], 2024	Pakistan	Nicorandil along with conventional treatment	Conventional treatment (tablet nitroglycerin 0.5 mg sublingually stat, tablet aspirin 300 mg orally stat, tablet clopidogrel 300 mg orally stat, injection heparin 5000 units IV)	70	70	35.1	25.7	82.1	92.9	NA	NA	NA	NA	NA	NA	NA	NA

N: Nicorandil; C: Control; DM: Diabetes mellitus; HTN: Hypertension; IV: Intravenous; IC: Intracoronary; CAG: Coronary angiogram; PCI: Percutaneous coronary intervention.

Table 2 Analysis of individual major adverse cardiovascular events demonstrating the safety of the nicorandil group

Outcome	Number of studies	Effect sizes		Heterogeneity
		RR (95%CI)	P value	Tau2	I2 (%)
VT/VF	15	0.51 (0.39-0.66)	< 0.01	0.01	0
Death	13	0.62 (0.33-1.15)	0.13	0	0
Myocardial infarction	6	0.79 (0.28-2.23)	0.66	0	0
TVR	5	0.60 (0.10-3.63)	0.58	0.87	25
Congestive heart failure	4	0.36 (0.20-0.66)	< 0.01	< 0.0001	0
Pericardial effusion	3	0.45 (0.17-1.21)	0.12	0.27	34
Chest pain	3	0.64 (0.31-1.33)	0.24	0.23	59
Acute stent thrombosis	2	0.65 (0.08-5.12)	0.69	0	0
Stroke	2	0.67 (0.08-5.35)	0.7	0	0
Heart failure	2	0.55 (0.25-1.22)	0.14	0	0
Angina	2	0.25 (0.11-0.59)	< 0.01	0	0
Postoperative hypotension	2	0.52 (0.15-1.81)	0.31	0	0
Cardiogenic shock	1	1.00 (0.06-15.43)	-	-	-
Intraoperative hypotension	1	0.13 (0.03-0.55)	-	-	-

RR: Risk ratio; CI: Confidence interval; VT: Ventricular tachycardia; VF: Ventricular fibrillation; TVR: Target vessel revascularization.