| pathology | Demonstrated benefit and harm | k | | | |
|---|
| heart failure | versus placebo or control No demonstrated result for efficacy | 2 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| SHIFT, 2010 | ivabradine vs placebo | HF hospitalization 0.74 [0.66; 0.83] hospitalization for Cv reason 0.85 [0.78; 0.92] CV deaths, hospitalization for HF, MI 0.82 [0.75; 0.90] cardiovascular deaths or heart-failure hospitalisations 0.82 [0.75; 0.90] Death from heart failure
0.74 [0.58; 0.94] | | All cause death 0.90 [0.80; 1.02] cardiovascular death 0.92 [0.82; 1.04] | | ivabradine 15mg vs placebo | | | |
| Trial | Treatments | Patients | Method |
|---|
| SHIFT, 2010 | ivabradine (n=3241) vs. placebo (n=3264) | patients with NYHA class 2-4 heart failure, an LVEF <35%, a resting heart rate >70 bpm, and a heart-failure hospitalization within the previous year | double-blind Parallel groups Sample size: 3241/3264 Primary endpoint: cardiovascular death or hospitalization for heart failure FU duration: 23 months | | BEAUTIFUL, 2008 | ivabradine target dose of 7·5 mg twice a day
(n=5479) vs. placebo
(n=5438)
| patients with coronary artery disease and left-ventricular systolic
dysfunction (LVEF <=40%)
| double blind Sample size: 5479/5438 Primary endpoint: Cvdeath, MI, hospitalization for HF FU duration: 19 months (range 16-24)
|
|
| stable angina | versus placebo or control No demonstrated result for efficacy | 6 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| ivabradine 5mg vs placebo | | | | | ivabradine 15mg vs placebo | | | | | ivabradine 10mg vs placebo | | | | | ivabradine 20mg vs placebo | | | | | ivabradine 15mg vs placebo (on top standard treatment) | | | | | ivabradine 20mg vs placebo | | | |
| Trial | Treatments | Patients | Method |
|---|
| Borer (CL2-009) 5mg, 2003 | (n=90) vs. (n=91) | | double blind Parallel groups Sample size: 90/91 Primary endpoint: FU duration: 2 weeks | | BEAUTIFUL, 2008 | ivabradine target dose of 7·5 mg twice a day
(n=5479) vs. placebo
(n=5438)
| patients with coronary artery disease and left-ventricular systolic
dysfunction (LVEF <=40%)
| double blind Sample size: 5479/5438 Primary endpoint: Cvdeath, MI, hospitalization for HF FU duration: 19 months (range 16-24)
| | Borer (CL2-009) 10mg, 2003 | Ivabradine 5 mg twice daily (10mg/d)
(n=91) vs. placebo
(n=91)
|
| double blind Sample size: 91/91 Primary endpoint: FU duration: 2 weeks
| | Borer (CL2-009) 20mg, 2003 | ivabradine 10mg twice daily (20mg/d)
(n=88) vs. placebo
(n=91)
|
| double blind Sample size: 88/91 Primary endpoint: FU duration: 2 weeks
| | BEAUTIFUL (angina subgroup) | ivabradine target dose of 7·5 mg twice a day
(n=734) vs. placebo
(n=773)
| patients with stable
coronary artery disease and left ventricular
systolic dysfunction with limiting angina
| double blind Sample size: 734/773 Primary endpoint: Cvdeath, MI, hospitalization for HF FU duration: 19 months (range 16-24) post hoc analysis
| | SIGNIFY, 2014 | ivabradine, at a dose of up to 10 mg twice daily, with the dose adjusted to achieve a target heart rate of 55 to 60 beats per minute. (n=9550) vs. placebo (n=9552) | patients who had both stable coronary artery disease without clinical heart failure and a heart rate of 70 beats per minute or more | double-blind Parallel groups Sample size: 9550/9552 Primary endpoint: death from cardiovascular FU duration: 27.8 mo (median) |
|
| stable angina | versus beta-blockers No demonstrated result for efficacy | 3 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| ivabradine 20mg vs atenolol | | | | | ivabradine 15mg vs placebo on top of atenolol | | | | | ivabradine 15mg vs atenolol | | | |
| Trial | Treatments | Patients | Method |
|---|
| INITIATIVE (CL3-017, Tardif) 20mg, 2005 | ivabradine 5 mg bid for 4 weeks and then 10 mg bid for 12 weeks
(n=317) vs. atenolol 50 mg od for 4 weeks and then 100 mg od for 12 weeks
(n=307) 3 arms: ivabradine 15, 20 mg/d and atenolol 100mg/d
| patients with stable angina
| double-blind Parallel groups Sample size: 317/307 Primary endpoint: FU duration: 16 weeks
| | ASSOCIATE (Tardif), 2009 | ivabradine 5 mg b.i.d. for 2 months, increased to 7.5 mg b.i.d. for a further 2 months (on top atenolol 50 mg/day )
(n=449) vs. placebo on top atenolol 50 mg/day
(n=440)
| patients with stable angina receiving atenolol 50 mg/day or another beta-blocker at equivalent doses for at least
3 months
| double blind Parallel groups Sample size: 449/440 Primary endpoint: total exercise duration FU duration: 4 months
| | INITIATIVE (CL3-017, Tardif) 15mg, 2005 | ivabradine 5 mg bid for 4 weeks and then either 7.5 or 10 mg bid for 12 weeks
(n=315) vs. atenolol 50 mg od for 4 weeks and then 100 mg od for 12 weeks
(n=307) 3 arms: ivabradine 15, 20 mg/d and atenolol 100mg/d
| patients with stable angina
| double-blind Sample size: 315/307 Primary endpoint: FU duration: 16 weeks
|
|
| stable angina | versus calcium blockers No demonstrated result for efficacy | 6 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| ivabradine 15mg vs amlodipine | | | | | ivabradine 15mg vs placebo on top of amlodipine | | | | | ivabradine 10mg vs placebo on top of amlodipine | | | | | ivabradine vs amlodipine | | | | | ivabradine vs amlodipine | | | | | Ruzyllo (CL3-023) 20mg, 2007 | ivabradine 20mg vs amlodipine | | | |
| Trial | Treatments | Patients | Method |
|---|
| Ruzyllo (CL3-023) 15mg, 2007 | ivabradine 7.5mg twice daily (n=400) vs. amlodipine 10mg once daily (n=404) | Patients with a >/=3-month history of chronic, stable effort-induced angina | double-blind Parallel groups Sample size: 400/404 Primary endpoint: total exercise duration FU duration: 3 months | | CL3-018 15mg | ivabradine 7.5mg twice daily (15mg/d) (n=244) vs. placebo (n=252) | | Sample size: 244/252 Primary endpoint: FU duration: | | CL3-018 10mg | ivabradine 5mg twice daily (10mg/d) (n=232) vs. placebo (n=252) | | Parallel groups Sample size: 232/252 Primary endpoint: FU duration: 12 weeks | | CL3-023 (15mg) | ivabradine 7.5mg twice daily
(n=381) vs. amlodipine
(n=398) 3 arms: ivabradine 15 and 20 mg, amlodipine
|
| double-blind Parallel groups Sample size: 381/398 Primary endpoint: FU duration: 3 months
| | CL3-023 (20mg) | ivabradine 10mg twice daily
(n=376) vs. amlodipine
(n=398)
|
| double-blind Sample size: 376/398 Primary endpoint: FU duration: 3 months
| | Ruzyllo (CL3-023) 20mg, 2007 | ivabradine 10mg twice daily (n=391) vs. amlodipine 10mg once daily (n=404)
| Patients with a >/=3-month history of chronic, stable effort-induced angina
| double-blind Parallel groups Sample size: 391/404 Primary endpoint: total exercise duration FU duration: 3 months
|
|
