Preventing anthracycline-induced cardiotoxicity with ivabradine: A systematic review and meta-analysis

Table 1 Tabulated representation of baseline characteristics of included randomized controlled trials

Ref.	Type of study	Location	Total study population (n)	Ivabradine (n)	Placebo (n)	Duration of study
Čiburienė et al[13], 2023	Randomized open label trial	Lithuania	48	21	27	6 months
Rizk et al[14], 2025	Tripple blind randomized controlled trial	Spain	107	51	56	12 months
Vasyuk et al[15], 2017	Open labelled randomized controlled trial	Russia	55	23	32	12 months

Table 2 Tabulated representation of baseline characteristic of included population, n (%)

Characteristics		Čiburienė et al[13], 2023		Rizk et al[14], 2025		Vasyuk et al[15], 2017
		Ivabradine	Placebo	Ivabradine	Placebo	Ivabradine	Placebo
Age (years)		47.8 ± 9.9	48 ± 10.2	49 (32-59)	39 (26-60)	49.8 ± 9.4	48.7 ± 9.5
Female		21 (100)	27 (100)	24 (41)	18 (35.3)	28 (50.0)	4 (16.7)
Cancer type	Breast	21 (100)	25 (92.6)	0	0	23 (100)	32 (100)
	NHL	0	0	30 (58.8)	29 (51.8)	0	0
	HL	0	0	18 (35.3)	26 (46.4)	0	0
	Sarcoma	0	2 (7.4)	3 (5.9)	1 (1.8)	0	0
Anthracyclines commutative dose (mg/m2)	Doxorubicin	236 ± 70	246 ± 69	300 (250-300)	300 (250-300)	441.4 ± 84.5	391.7 +/- 103.8
	Epirubicin	360 ± 70	360 ± 70	-	-	-	-
Risk factors	HTN	3 (15)	2 (7.4)	13 (25.5)	9 (16.4)	5 (21.0)	9 (28.3)
	DM	0	0	4 (7.8)	5 (8.9)	1 (4.3)	1 (3.1)
	HLD	13 (65)	21 (77.8)	4 (8.0)	3 (5.4)	-	-
	Smoking	1 (5)	6 (22.2)	7 (13.7)	9 (16.4)	-	-
	CKD	0	0	-	-	1 (4.3)	3 (9.4)

NHL: Non-Hodgkins lymphoma; HL: Hodgkins lymphoma; HTN: Hypertension; DM: Diabetes mellitus; HLD: Hyperlipidemia; CKD: Chronic kidney disease.

Table 3 Certainty of evidence assessment using grading of recommendations, assessment, development, and evaluation

Certainty assessment							No. of patients		Effect		Certainty	Importance
No. of studies	Study design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	LVEF	Placebo	Relative (95%CI)	Absolute (95%CI)
LVEF
3	Randomised trials	Serious1	Not serious	Not serious	Serious2	None	95	115	-	SMD 0.01 lower (0.28 lower to 0.26 higher)	⊕⊕◯◯, low1,2	CRITICAL
GLS reduction
2	Randomised trials	Serious1	Not serious	Serious2	Serious2	None	31/72 (43.1%)	35/83 (42.2%)	RR = 0.80 (0.28-2.32)	84 fewer per 1000 (from 304 fewer to 557 more)	⊕◯◯◯, very low1,2,3	CRITICAL
NT-proBNP
2	Randomised trials	Serious1	Not serious	Not serious	Serious2	None	72	83	-	SMD 0.26 higher (1.39 Lower to 1.92 higher)	⊕⊕◯◯, low1,2	CRITICAL
Troponin
2	Randomised trials	Serious1	Not serious1	Not serious	Serious2	None	72	83	-	SMD 0.1 higher (2.14 lower to 2.33 higher)	⊕⊕◯◯, low1	CRITICAL
SBP
2	Randomised trials	Serious1	Not serious	Not serious	Serious2	None	74	79	-	SMD 0.13 lower (0.44 lower to 0.19 higher)	⊕⊕◯◯, low1,2	CRITICAL
DBP
2	Randomised trials	Serious1	Not serious	Not serious	Serious2	None	74	83	-	SMD 0.16 lower (0.47 lower to 0.16 higher)	⊕⊕◯◯, low1	CRITICAL

¹Ciburiene 2023 is an open-label study with no blinding.

²Study population differ in regards to underlying malignancy and outcome definitions vary (different global longitudinal strain thresholds; surrogate measures).

³Large confidence intervals around effect estimates, small sample sizes.

95%CI: 95% confidence interval; LVEF: Left ventricular ejection fraction; GLS: Global longitudinal strain; RR: Relative risk.