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

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.