Summary of findings 2. Usual care with ivabradine compared to placebo, usual care, or no treatment in participants with HFrEF (short‐term treatment (< 6 months) with ivabradine).

Usual care with ivabradine compared to placebo, usual care, or no treatment in participants with HFrEF (short‐term treatment (< 6 months) with ivabradine)
Patient or population: adults (≥ 18 years of age) with a diagnosis of chronic heart failure with reduced ejection fraction (HFrEF) Setting: hospital or outpatient care Intervention: short‐term treatment (< 6 months) with ivabradine Comparison: placebo, usual care, or no treatment
Outcomes	Anticipated absolute effects* (95% CI)		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)
	Risk with placebo	Risk with usual care with ivabradine compared to placebo, usual care, or no treatment in participants with HFrEF (short‐term treatment (< 6 months) with ivabradine)
Mortality from cardiovascular causes (follow‐up range 19 to 23 months)	Not reported in studies that met the inclusion criteria for this comparison
Quality of life	Sarullo 2010: Minnesota Living with Heart Failure Questionnaire Significant improvement for ivabradine at 3 months vs baseline (37.5 + 1.9 vs 30.9 + 2.3) (P < 0.001); no significant difference for control at 3 months vs baseline (31.2 + 2.6 vs 30.6 + 2.1) (P = n.s.)			60 (1 RCT)	⊕⊕⊝⊝ LOW1, 2
Time to first hospitalisation for heart failure during follow‐up	Not reported in studies that met the inclusion criteria for this comparison
Number of days spent in hospital due to heart failure during follow‐up	Not reported in studies that met the inclusion criteria for this comparison
Rate of serious adverse events	Tsutsui 2016: Significant worsening of adverse events (heart failure, phosphenes, diarrhoea, nasopharyngitis): 54.8% (2.5 mg ivabradine); 64.3% (5 mg ivabradine) vs 29.3% (control) (P = 0.004) Adamyan 2008: Noticeable side effects requiring the withdrawal of drugs were not observed.			270 (2 RCTs)	⊕⊕⊕⊝ LOW1, 3
Exercise capacity	Abdel 2011: Significant improvement for ivabradine group in exercise duration at 3 months (497 s vs 328 s) (P = 0.024) Adamyan 2008: Significant improvement for ivabradine group in exercise duration at 90 days (495 ± 147 s vs 416 ± 128 s) (P < 0.05) Sarullo 2010: Significant improvement for ivabradine group in exercise duration at 3 months (28.2 ± 3.5 min vs 14.8 ± 2.5 min) (P < 0.001)			305 (3 RCTs)	⊕⊕⊝⊝ LOW1, 2
Economic costs	Not reported in studies that met the inclusion criteria for this comparison
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; HFrEF: heart failure with reduced ejection fraction;RCT: randomised controlled trial; RR: risk ratio
GRADE Working Group grades of evidence High certainty: We are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: We are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: Our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: We have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

¹Downgraded by one level due to imprecision (low number of participants).
²Downgraded by one level due to risk of bias (blinding).
³Downgraded by one level due to publication bias (low number of studies reporting on this outcome).