1. Ivabradine – A new option for Heart Failure Patients
Abela M, Caruana J, Cassar A
Malta Medical School Conference November 2012

2. Introduction Ivabradine (Procorolan ®)
Specific Inhibitor of the If current in the Sinoatrial Node
Decreases resting heart rate
Unlike β-Blockers, no other channels are affected (decreased risk of side effects)

3. Systolic Heart failure treatment with the If Inhibitor Ivabradine Trial (SHIFT Trial)
Study Design
Double-Blinded
Placebo Controlled
Parallel Group Clinical Trial
Event-Driven
Multinational (677 centres in 37 countries)
Patient Cohort
6558 patients
EF<=35%, NSR, Rx optimised, NYHAII-IV
Randomly assigned into
Ivabradine Sub-Group (3268 patients)
Placebo Sub-Group (3290 patients)

4. SHIFT Trial Observations
1. Patients on β-Blockers and Ivabradine had a significant reduction in hospital admission for heart failure by 19%
2. Ivabradine is overall well tolerated (study withdrawal in only 1% of overall population)
3. Β-Blocker doses were not decreased to enable Ivabradine administration (highlighting above point and difficulty in B-Blocker dose adjustment)

5. Eligible Patients:
Symptomatic heart failure patients (NYHA II-IV) despite maximal tolerated medical therapy (β-Blockers, ACEi/ARB, Mineralocorticoid Receptor Antagonist)
Contraindications to β-Blockers (Asthma, Chronic Obstructive Pulmonary Disease, Hypotension, etc.)
Ejection Fraction ≤ 35%
Sinus Rhythm
Heart Rate ≥ 70 b.p.m
Evidence based on the ‘Systolic Heart failure treatment with the If Inhibitor Ivabradine Trial’ (SHIFT Trial)
Adopted from ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012 (Figure 2: Treatment options for patients with chronic symptomatic systolic heart failure (NYHA functional class II–IV).

6. Ivabradine in Heart Failure Clinic Patients
Aim:
To identify the percentage of patients attending the Heart Failure Clinic (HFC) who would be eligible for Ivabradine as recommended by ESC
Methodology:
HFC patient notes reviewed for ESC inclusion Criteria
Patient Cohort:
Total cohort consisting of 190 patients where Ejection Fraction (EF) was quantified

7. Population Characteristics
No (%)
Age
Mean
Range
65.3
29-89
Sex
Male
Female
153 (80.6)
37 (19.4)
Ejection Fraction
≤ 35%
35-50%
≥ 50%
109 (57.4)
48 (25.3)
33 (17.4)
Cause of Heart Failure
Valvular
Ischaemic
Hypertension
Dilated Cardiomyopathy
Hypertrophic Cardiomyopathy
Rheumatic
Pregnancy
Toxicity
Others
Not Available
13 (6.8)
78 (41.1)
17 (8.9)
65 (34.2)
2 (1.1)
1 (0.5)
4 (2.1)
8 (4.2)

8. Eligible Patients

9. *Anti-CHF Conventional Drugs refers to ACEi (or ARBs), B-Blockers and MR Antagonists

10. 22 patients satisfy ESC recommendations
Results:
22 patients satisfy ESC recommendations
5 still symptomatic
Patients eligible for Ivabradine amounted to 3.18% (5 patients) out of all low HF-REF patients attending HFC (EF <50%)
Out of all low HF-REF patients, 2.5% (4 patients) were eligible for Ivabradine if according to European Medicines Agency (EMA) recommendations (HR of ≥75 b.p.m)

11. Applying results to the general Maltese CHF Population
ESC Epidemiology Data
Approximately 1–2% of the adult population has HF
At least half of patients with HF have a low EF (i.e. HF-REF).
Maltese HF Epidemiology
Total Maltese population: 40,9836 (July 2011)
345,491 older than 15 years (84.3%)
5182 (1.5% of adult population) suffer from HF
Approximately 2591 suffer from HF-REF
82 (3.18%) eligible for Ivabradine

12. Conclusion
Ivabradine is recommended for symptomatic fully medically optimized chronic heart failure patients with Ejection Fraction ≤35% Ivabradine is a useful anti-heart failure treatment in a subset of heart failure patients. The small percentage of patients needing Ivabradine should be taken into account when considering inclusion of Ivabradine on the national formulary for CHF

13. Thank You