TABLE 1.
Characteristics of included studies
| Study or Sub‐study | Method | Participants | Intervention | Outcome | Duration |
|---|---|---|---|---|---|
| Tsutsui H et al 201922 | Randomized Controlled Trial | 254 Japanese patients with age ≥ 20 years old, stable symptomatic chronic HF or NYHA class II‐IV, LVEF≤35%, resting HR ≥75 beats/min in sinus rhythm, received optimal, stable treatment according to Japanese Guideline for Treatment of Chronic Heart Failure and had a history of hospital for worsening HF within the preceding 52 weeks (127 assigned to Ivabradine group, 127 assigned to Placebo) | Ivabradine 5–7.5 mg bid | The primary endpoint was the composite of cardiovascular death or hospital admission for worsening HF. | 582 days |
| Sarullo et al 201024 | Randomized Controlled Trial | 60 patients with symptoms of heart failure, LVEF≤40%, NYHA classes II to III, sinus rhythm with heart rate at rest>70 beats per minute (bpm), on optimal medical treatment of HF. (30 assigned to Ivabradine group, 30 assigned to Placebo group) | Ivabradine 5 mg bid | Evaluate use of Ivabradine on exercise capacity, gas exchange, functional class, quality of life, and neurohormonal modulation in pts with ischemic CHF | 3 months |
| Mansour et al 201121 | Randomized Controlled Trial | 53 Idiopathic DCM patients with NYHA class III or IV, LVEF <40%, sinus rhythm, resting heart rate ≥ 70beats/min, on beta‐blocker and ACEI treatment. (30 assigned to Ivabradine group, 23 assigned to Placebo group) | Ivabradine 5–7.5 mg bid | The effect of Ivabradine on symptoms, quality of life, effort tolerance, and echocardiographic parameters in patients with idiopathic DCM with NYHA class III or IV. | 3 months |
| Tsutsui H et al 201623 | Randomized controlled trial | 126 Japanese patients with age ≥ 20 years old, resting HR ≥75 beats/min in sinus rhythm, stable symptomatic chronic HF of NYHA class II or higher, LVEF≤35%, and under optimal, stable treatment according to Japanese Guideline for Treatment of Chronic Heart Failure (JCS 2010) (84 assigned to Ivabradine group, 42 assigned to Placebo) | Ivabradine 2.5–5 mg bid | Reduction in resting heart rate after 6 weeks treatment. | 6 weeks |
| SHIFT 201020 | Randomized controlled trial | 6558 patients with symptomatic heart failure and LVEF≤35%, heart rate of 70 bpm or higher (3268 assigned to Ivabradine; 3290 assigned to Placebo group) | Ivabradine 2.5–7.5 mg bid | Cardiovascular death or Hospital readmission for worsening heart failure. | 27.8 months |
| Tardif JC et al 2011 (SHIFT sub‐study)26 | Randomized controlled Trial | 611 Eligible patients in sinus rhythm, resting heart rate ≥ 70 beats/min (bpm), clinically stable for ≥4 weeks, worsening HF within the previous 12 months, and on optimal background therapy for HF including a beta‐blocker. (304 assigned to Ivabradine, 307 assigned to Placebo group) | Ivabradine 2.5–7.5 mg bid | Evaluate the effect of Ivabradine on left ventricular (LV) remodeling in heart failure (HF) | 8 months |
| Volterrani M et al 201127 | Randomized controlled trial | 80 Eligible patients aged 18 to 90 years, had been diagnosed with HF at least 12 months prior, NYHA Class II‐III, clinically stable for 3 weeks prior to selection or discharged in stable conditions. Patients were receiving optimal background therapy for HF (beta‐blocker, ACEI, ARB, diuretics, aldosterone antagonist) for 3 months. (42 assigned to Ivabradine, 38 assigned to Placebo group) | Ivabradine 2.5–7.5 mg bid |
Effect of Ivabradine on the distance covered in 6 minutes walking test (6MWT) and maximal oxygen consumption (MVO2) on cardiopulmonary exercise test. |
3 months |