2. Study characteristics of studies with HFrEF.
| Reference | Number of centres | Intervention |
Ivabradine [n] |
Placebo/SC [n] |
Dosage | Duration IP | Timing outcomes | Ejection fraction [%] | Guideline adherence*** |
| Short‐term treatment (< 6 months) with ivabradine | |||||||||
| Abdel 2011* | 1 | Ivabradine Placebo | 50 | 50 | 5 mg/7.5 mg twice a day | ns | W 0, 12 | EF < 35 | ns |
| Adamyan 2008* | ns | Ivabradine SC | 70 | 75 | 7.5 mg twice a day | D 90 | D 0, 30, 90 | EF < 35 | Patients with intolerance to BB were included; ACE/ARB and MRA were given. |
| Bansal 2019 | 1 | Ivabradine SC | 157 | 152 | ns | ns | D 0 | ns | ns |
| Sarullo 2010 | 1 | Ivabradine Placebo | 30 | 30 | 5 mg/7.5 mg twice a day | M 3 | M 0, 3 | LVEF ≤ 40 | BB (60.1%); ACE inhibitor (85%) |
| Tsutsui 2016 | 73 | Ivabradine Placebo | 84 | 42 | 2.5 to 7.5 mg twice a day | W 6 | W 0, 6 | LVEF ≤ 35 | BB (92.9%); ACE inhibitor (45.8%); ARB (26.8%); ACE inhibitor or ARB (70.6%); MRA (55.1%) |
| Long‐term treatment (≥6 months) with ivabradine | |||||||||
| Chaudhari 2014* | 1 | Ivabradine SC | 78 | 80 | 5 mg twice a day | M 6 | M 0, 6 | LVEF < 40 | ns |
| Fox 2008 | 781 | Ivabradine Placebo | 5479 | 5438 | 5 mg/7.5 mg twice a day | ~M 19 | D 0, W 2, M 1, 3, 6, 12, 18, 24 | LVEF < 40 | BB (83.5%); ACE inhibitor or ARB or both (89.5%); MRA (29.5%) |
| Potapenko 2011 | 1 | Ivabradine SC | 23 | 26 | 5 mg/7.5 mg twice a day** | Y 3, 5 | Y 3, 5 | LVEF < 40 | BB (85.7%); ACE inhibitor (96%) |
| Sisakian 2016 | 1 | Ivabradine SC | 27 | 27 | 2.5 mg/5 mg/7.5 mg twice a day | M 3 | D 0, 14, 28 | LVEF < 40 | BB (79.7%); ACE inhibitor and/or ARB (85.2%); MRA (25.5%) |
| Swedberg 2010 | 677 | Ivabradine Placebo | 3268 | 3290 | 5 mg/7.5 mg twice a day | M 12 | D 0, M 12 | LVEF ≤ 35 | BB (89.5%); ACE inhibitor (78.5%); MRA (60.0%) |
| Tsutsui 2019 | 146 | Ivabradine Placebo | 127 | 127 | 2.5 to 7.5 mg twice a day | W 52 | every 2 M | LVEF ≤ 35 | ACE inhibitor (48.9%); ARB (20.1%); ACE inhibitor and/or ARB (68.5%); MRA (77.6%) |
| ∑ 9393 | ∑ 9337 | ||||||||
*Reported only as abstract. **Initial dose 5 mg twice a day; after 2 weeks with a heart rate of 60/min or higher: 7.5 mg twice a day; if heart rate dropped below 50/min or other clinical symptoms of bradycardia: again 5 mg twice a day; if symptoms did not improve: ivabradine treatment stopped. ***According to the European Society of Cardiology (ESC) Clinical Practice Guideline on Acute and Chronic Heart Failure (Ponikowski 2016).
Abbreviations: ns = not specified; Y = year; M = month; W = week; D = day; ACE inhibitor = angiotensin‐converting enzyme inhibitor; ARB = angiotensin II receptor blocker; BB = beta‐blockers; EF = ejection fraction; HFrEF = heart failure with reduced ejection fraction; IP = interventional product; LVEF = left ventricular ejection fraction; MRA = mineralocorticoid receptor antagonist; SC = standard care