.

Aim
Effect of intravenous Ivabradine
on heart rate

The study was performed in accordance

with the ethical principles stated in the
Declaration of Helsinki (1964) and its
revisions

The protocol was approved

by the independent Ethics Committees
in the countries concerned
All patients gave written
informed consent

The study is registered on

www.controlled-trials.com

(ISRCTN number 66067800)

Methods

Multicenter
Placebo
Controlled

Randomized
Blinded

Methods
Pilot trial included two
unbalanced parallel
groups of patients
undergoing PCI following
STEMI

Main
study
Effect of
Ivabradine on
heart rate

MRI
substudy
Effect of
Ivabradine on
infarc size

Statistical methods
Descriptive statistics

baseline characteristics
and cardiac markers.

Parametric method

Estimate (E)
Standard errors (SEs)
95% confidence intervals (CIs)
and p-value

p value of less than 0.05

was considered as being
statistically
significant.
95% confidence intervals (CIs)
SAS version 9.1 software

Full analysis set (FAS)

Efficacy analyses & MRI

Exclusion criteria
Second- or third-degree atrioventricular block
Trifascicular block
PR interval >240 ms
Atrial fibrillation or flutter
Ventricular tachycardia (duration >30 s and heart rate >100 bpm)
QT interval >450 ms
Killip class IV heart failure

Need for IV inotropic agents

Urgent need for cardiac surgery

Moderate or severe liver disease

Inclusion criteria
Men or women of non-childbearing potential
4080 years old
Weighing between 50100kg
Diagnosed with a STEMI in the previous 9 h and were undergoing PCI
Sinus rhythm with HR > 80 bpm Systolic blood pressure (SBP) >90 mm Hg

Exclusion criteria
(MRI substudy)
Glomerular filtration rate
(GFR) <60 ml/min/1.73 m2

Claustrophobia
Devices not compatible
with magnetic fields

Placebo group

Control group

2:1
Ivabradine 5 mg bolus
+ 5 mg infusion over 8 hr

Placebo bolus
+ Plcebo infusion over 8 hr

An unbalanced
randomization (2:1)

Study protocol

PCI

D/C
0

DAY 3
4 months

1 Hr
Treat

Result

Result

Result : Characteristic

Result : Characteristic

Result : Effect on heart rate

Result : Cardiac marker

Result : Cardiac marker

Result : Echocardiographic

Result : MRI

Safety and tolerability

There were five cases of hypotension
Control group

Ivabradine 5 mg bolus
+ 5 mg infusion over 8 hr

5 Cases

Placebo group

Placebo bolus
+ Plcebo infusion over 8 hr
NONE

Safety and tolerability

Adverse event report

tachyarrhythmias

ventricular
tachycardia

headache

Not related in treatment

hypotension

Safety and tolerability

Adverse event report
Bradycardia
4%
Control group
NONE
Placebo group

Related in treatment

Safety and tolerability

Ivabradine
Severe bradycardia
40 bpm

Recovered
uneventfully

Safety and tolerability

Two patients died
(both in the ivabradine group)

Control group

Ivabradine 5 mg bolus
+ 5 mg infusion over 8 hr

2 cases

worsening chronic obstructive

pulmonary disease
(five days after the bolus)
mesenteric infarction
(seven days after the bolus)

Neither case was considered by the

investigator as being related to study
treatment.

Discussion

HR
Ivabradine
Ivabradine was not associated with any
impact on SBP or DBP but was associated
with lower LVESV and LVEDV at ECG

Discussion

There were five patients with hypotension

Ivabradine

Discussion

Ivabradine

Bradycardia
4%

Discussion

did not affect

Ivabradine

Beta-blocker

Limitation of study

Small number of patients

The study lacks the power to demonstrate
a reduction in biomarker release,
infarct size or clinical outcomes.

Conclusion

IV ivabradine may be of potential value in STEMI,

by allowing rapid heart rate control without affecting
blood pressure or hemodynamics. However, to
characterize its effect, further controlled trials are
required to assess its impact on infarct size, left
ventricular function and, ultimately,clinical outcomes.