Ivabradine HR-slowing agents

Description Results

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]

all cause death 1.04 [0.93; 1.16]

cardiovascular death 1.07 [0.94; 1.21]

MI 0.87 [0.73; 1.05]

Admission to hospital for heart failure 0.99 [0.87; 1.13]

cardiac death 0.89 [0.71; 1.12]

CV events 1.01 [0.92; 1.10]

CV death, MI hospitalization for HF 1.01 [0.92; 1.10]

CV death or HF hospitalization 1.04 [0.95; 1.14]

ivabradine (n=3241)

vs.

placebo (n=3264)

double-blind

Parallel groups

Sample size: 3241/3264

Primary endpoint: cardiovascular death or hospitalization for heart failure

FU duration: 23 months

ivabradine target dose of 7·5 mg twice a day (n=5479)

vs.

placebo (n=5438)

double blind

Sample size: 5479/5438

Primary endpoint: Cvdeath, MI, hospitalization for HF

FU duration: 19 months (range 16-24)

all cause death 1.04 [0.93; 1.16]

cardiovascular death 1.07 [0.94; 1.21]

MI 0.87 [0.73; 1.05]

Admission to hospital for heart failure 0.99 [0.87; 1.13]

cardiac death 0.89 [0.71; 1.12]

CV events 1.01 [0.92; 1.10]

CV death, MI hospitalization for HF 1.01 [0.92; 1.10]

CV death or HF hospitalization 1.04 [0.95; 1.14]

non fatal MI 0.61 [0.38; 0.98]

MI 0.59 [0.38; 0.93]

CV events 0.77 [0.60; 1.00]

CV death, MI hospitalization for HF 0.77 [0.60; 1.00]

Hospitalization for angina 0.61 [0.38; 0.98]

all cause death 0.88 [0.64; 1.20]

coronary events 0.90 [0.66; 1.22]

cardiovascular death 0.89 [0.63; 1.26]

Admission to hospital for heart failure 0.85 [0.54; 1.33]

cardiac death 0.72 [0.34; 1.55]

CABG 0.75 [0.34; 1.68]

unstable angina 1.44 [0.84; 2.47]

revascularization 0.71 [0.42; 1.20]

CV death or HF hospitalization 0.81 [0.61; 1.08]

PCI 0.62 [0.32; 1.23]

all cause death 1.06 [0.94; 1.20]

coronary events 1.07 [0.96; 1.19]

cardiovascular death 1.09 [0.94; 1.27]

non fatal MI 1.04 [0.89; 1.20]

MI 1.05 [0.92; 1.21]

Admission to hospital for heart failure 1.19 [0.98; 1.45]

cardiac death 1.06 [0.89; 1.25]

CV events 1.06 [0.96; 1.17]

revascularization 1.00 [0.89; 1.12]

(n=90)

vs.

(n=91)

double blind

Parallel groups

Sample size: 90/91

Primary endpoint:

FU duration: 2 weeks

ivabradine 7.5mg twice daily (n=400)

vs.

amlodipine 10mg once daily (n=404)

double-blind

Parallel groups

Sample size: 400/404

Primary endpoint: total exercise duration

FU duration: 3 months

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

double-blind

Parallel groups

Sample size: 317/307

Primary endpoint:

FU duration: 16 weeks

ivabradine target dose of 7·5 mg twice a day (n=5479)

vs.

placebo (n=5438)

double blind

Sample size: 5479/5438

Primary endpoint: Cvdeath, MI, hospitalization for HF

FU duration: 19 months (range 16-24)

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)

double blind

Parallel groups

Sample size: 449/440

Primary endpoint: total exercise duration

FU duration: 4 months

ivabradine 7.5mg twice daily (15mg/d) (n=244)

vs.

placebo (n=252)

Sample size: 244/252

Primary endpoint:

FU duration:

ivabradine 5mg twice daily (10mg/d) (n=232)

vs.

placebo (n=252)

Parallel groups

Sample size: 232/252

Primary endpoint:

FU duration: 12 weeks

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

ivabradine 10mg twice daily (20mg/d) (n=88)

vs.

placebo (n=91)

double blind

Sample size: 88/91

Primary endpoint:

FU duration: 2 weeks

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

double-blind

Sample size: 315/307

Primary endpoint:

FU duration: 16 weeks

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

ivabradine 10mg twice daily (n=376)

vs.

amlodipine (n=398)

double-blind

Sample size: 376/398

Primary endpoint:

FU duration: 3 months

ivabradine 10mg twice daily (n=391)

vs.

amlodipine 10mg once daily (n=404)

double-blind

Parallel groups

Sample size: 391/404

Primary endpoint: total exercise duration

FU duration: 3 months

ivabradine target dose of 7·5 mg twice a day (n=734)

vs.

placebo (n=773)

double blind

Sample size: 734/773

Primary endpoint: Cvdeath, MI, hospitalization for HF

FU duration: 19 months (range 16-24)

post hoc analysis

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)

double-blind

Parallel groups

Sample size: 9550/9552

Primary endpoint: death from cardiovascular

FU duration: 27.8 mo (median)