1. Procoralan plus beta-blockers as first-step therapy in heart failure?
Effects of ivabradine plus beta blockers as first step therapy on heart rate, compliance, quality of life and
exercise tolerance in patients with chronic heart failure
A. Macchi1, I. Franzoni1, I. Rosa1, M.C. Pedrigi1, F. Buzzetti1,
R. Gorla1, G.V. Gaudio2, P.G. Camici1, A. Margonato1
1.San Raffaele Hospital, Milan, Italy; 2. Antonio Abate Hospital, Somma Lombardo (VA), Italy

2. Rationale & objective Rationale
Beta-blockers are a cornerstone of chronic heart failure treatment and when added to renin-angiotensin-aldosterone system antagonists further reduce mortality and morbidity.
Because of side effects (hypotension, asthenia, dyspnea, claudication), few patients reach optimal doses of beta-blockers and optimal heart rate.
Procoralan, which is devoid of effects on hemodynamics and contractility, has proven effective in reducing mortality and hospitalization for heart failure.
Objective
To evaluate the effects of a combination of beta-blockers and Procoralan versus beta-blockers alone on heart rate, compliance to therapy, quality of life, and exercise tolerance.

3. Study design Patients Methods
111 patients (87 males, 62±7 years) with stable heart failure (NYHA IIb-III)
Ejection fraction <35%
Renin-angiotensin-aldosterone system antagonists and diuretics
No beta-blockers
Heart rate at rest >70 bpm, in sinus rhythm
Methods
Prospective, randomized, open, blinded end point design study
Beta-blockers
Baseline
Resting heart rate
Quality of life, symptoms
ETT parameters (modified Bruce protocol)
Increase dose of beta-blocker or Procoralan if possible
Resting heart rate
Quality of life, symptoms
ETT parameters (modified Bruce protocol)
Procoralan + beta-blockers
3 weeks
6 weeks

4. (Total exercise duration), min
Procoralan plus beta-blocker as first-step combination therapy in heart failure increases exercise capacity
TED
(Total exercise duration), min
P=0.05
The combination of Procoralan with beta-blockers resulted in better exercise tolerance compared with beta-blocker alone
Baseline
6 weeks
Baseline
6 weeks
Procoralan + beta-blockers (n= 56)
Uptitration of beta-blockers (n=55)
Mean daily dose, mg: 1st group – Procoralan, 12.5; Bisoprolol, 3.6; Carvedilol, 13.4; Nebivolol, 12;5; nd group – Bisoprolol, 5.4; Carvedilol, 25.3; Nebivolol, 5.1
Macchi A, et al. Eur Heart J. 2011;32( Abstract Supplement ): ; Abs 3720

5. Procoralan + beta-blockers Uptitration of beta-blockers
Procoralan plus beta-blocker as first-step combination therapy in heart failure improves quality of life
Quality of life scale
P<0.001
Baseline
6 weeks
Health-related quality of life assessed using the LVD36 questionnaire and quality of life scale was improved by combination of Procoralan with β-blockers compared with β-blocker alone.
Baseline
6 weeks
Procoralan + beta-blockers
(n= 56)
Uptitration of beta-blockers
(n=55)
Macchi A, et al. Eur Heart J 2011;32( Abstract Supplement): ; Abs 3720

6. Conclusions
The combination of Procoralan with a beta-blocker can be introduced safely as first-step therapy in chronic heart failure.
This combination ensures optimal heart rate control, and ameliorates exercise capacity and quality of life compared with beta-blocker alone.
The combination of Procoralan with a beta-blocker is well tolerated compared with beta-blocker alone.