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

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)

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)

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) http://www.trialresultscenter.org/study10790-SHIFT.htm

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).

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

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)

Eligible Patients

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

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)

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

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

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