Sisakian 2016.

Study characteristics
Methods	Study design: RCT Unit of randomisation: Computer‐based randomisation Total duration of study: No information Run‐in period: No information Intervention time: 3 months Follow‐up: 3 months Setting: Outpatient unit of the Department of General and Invasive Cardiology of University Hospital 1 of the Yerevan State Medical University
Participants	Types of heart failure: Systolic LV dysfunction, severely impaired diastolic dysfunction N = 54 (27 ivabradine, 27 control) Mean age: Ivabradine: 58.3 ± 12.2 years Control: 61.4 ± 9.67 years Gender: Ivabradine: 22 male, 5 female Control: 22 male, 5 female Severity of condition: LVEF < 40% Inclusion criteria: > 18 years NYHA class II‐IV Moderate to severe CHF of ischaemic or non‐ischaemic aetiology LV systolic dysfunction (LVEF < 40%) Pseudonormal/restrictive diastolic dysfunction Sinus rhythm Resting HR ≥ 70 bpm on 12‐lead‐ECG Clinically stable for > 3 months on current background therapy for HF (including BB) Exclusion criteria: Recent (< 3 months) acute decompensation Acute coronary syndrome Atrial fibrillation Complex ventricular arrhythmias Unlikely to co‐operate Legal incapacity Withdrawals: none
Interventions	Intervention: Ivabradine 5 mg twice a day added on baseline therapy Adjusted up to 7.5 mg if tolerated to achieve a resting HR < 70 bpm Adjusted down to 2.5 mg if HR < 55 bpm Comparison: Control Concomitant medication: BB ACE inhibitors ARB Diuretics Aldosterone antagonists Digitalis Excluded medication: No information
Outcomes	Outcomes and time points measured in the study: [Day 0, 3 months] E/A ratio E wave DT (deceleration time) LAVI (left atrial volume index) E/Em ratio Conclusion: "Treatment with ivabradine significantly improves LV diastolic function through reducing E/A ratio, E/Em ratio and increasing DT in patients with systolic HF and severe diastolic dysfunction. These changes may contribute to the improvement of intracardiac haemodynamics with decrease of LAVI and improvement of LV filling. The beneficial effect of ivabradine on diastolic function may potentially contribute to the better clinical state and prognosis in patients with CHF."
Notes	Funding for trial: No information Conflicts of interest: None to declare Contact to authors/unpublished data: We contacted H Sisakian via email on 6 June 2020 to ask for the randomisation tool used to allocate participants. H Sisakian answered on 10 June 2020, providing the information on the randomisation tool used.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Yes, it was computer generated" (H Sisakian on 10 June 2020 via email)
Allocation concealment (selection bias)	Low risk	"Patients were empirically allocated" "Yes, it was computer generated" (H Sisakian on 10 June 2020 via email)
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Insufficient information to base judgement
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Insufficient information to base judgement
Incomplete outcome data (attrition bias) All outcomes	Low risk	Less than 20% missing data. Outcomes reported for 54 of 54 participants (100%).
Selective reporting (reporting bias)	Unclear risk	Insufficient information to base judgement
Other bias	Unclear risk	Insufficient information to base judgement