Sunday, 13 June 2004 37 ... Treatments that improve survival are likely to have their greatest effect in higher-risk ... well as survival in patients with heart failure.
Poster Display 11. Beta blockers BETA BLOCKERS 179 Comparison of the effects of metoprolol and Carvedilol on symptoms, well-being and quality-adjnsted life-years: a description of the "patient-journey" in COMET. J. Cleland I , A. DiLenarda 2, P. Hanrath 3, M. Komajda 4, J. Lubsen 5, B. Lutiger 6, M. Metra 7, W. Remme 8, K. Swedberg 9, R Poole-Wilson 1° on behalf of The COMET Investigators
1The Academic Cardiology Unit, Kingston upon Hull, United Kingdom; 20spedale di Cattinara, Department of Cardiology, Trieste, Italy; 3Med. Klinik I der Med. Fakultgitder RW, Aachen, Germany; 4Pitie Salpetriere Hospital, Department of Cardiology, Paris, France; 5SOCAR Research SA, Nyon 2, Switzerland; 6E Hoffmann - LaRoehe, PBA, Basel, Switzerland; 7University of Brescia, Cattedra di Cardiologia, Brescia, Italy; 8Sticares Foundation, GR Rhoon, Netherlands; 9Sahlgrenska University Hospital, Department of Medicine, GOteborg, Sweden; 1°National Heart & Lung Institute, London, United Kingdom Background: The objective of treating most patients (pts) with heart failure is to improve or maintain well-being and to delay death. However, the importance of well-being as a treatment outcome is often forgotten in large clinical trials. Both survival and quality of life (QoL) need to be considered at the same time to assess the true effect of treatment. Treatments that improve survival are likely to have their greatest effect in higher-risk pts. Accordingly, average symptom scores may improve with less effective treatment because sicker pts with more advanced disease die selectively. Adjusting symptoms and QoL for time alive, hospitalization and need for intensified therapy can compensate for such anomalies and better describe the pts experience of disease or 'Patient Journey'. Methods: 3029 pts with left ventricular systolic dysfunction and NYHA class II-IV heart failure were randomised to metoprolol (M) (50mg bd) or carvedilol (C) (25rag bd) and followed for a median of 58 months. Pts were reviewed every 4 months at which time heart failure symptoms and 'well-being' were recorded using a simple 5-point scale. The dates of hospitalizations and death were reported. Results: Baseline NYHA class was 2.6 and improved by 4 months (0.304-0.59 in C, -0.284-0.57 in M) and plateauing around 2 years (0.424-0.66 in C, -0.394-0.67 in M). Symptoms scores for breathlessness, fatigue and 'well-being' paralleled these changes. C reduced mortality (hazard ratio 0.83, 95% CI 0.74-0.93, p=0.0017) and prolonged median life expectancy by 1.4 years. Although the difference in survival led to different periods of risk for hospitalization, hospital days/patient were similar (25.64-45 in C, 24.8-4-42 days in M). Pts on C reported feeling 'good' or 'very good' for 48.7% of study days over the first 4 years versus 45.3% on M (p=0.0118), and 60.3% versus 56.9% were in N Y H class I/II, respectively (p=0.0192). This represents an average of 51 days of greater well-being per patient on C versus M over 4 years in addition to the benefit on survival. Data on health-utility related life-years will be presented. Conclusion: Compared to metoprolol, carvedilol improves symptoms as well as survival in patients with heart failure. 180 Effect of the administration of morning and evening doses of beta blocker (bisoprolol) on heart rate variability in patients with congestive heart failure. R. Targonski, J. Sadowski, L. Gromadzinski
City Hospital, Cardiology and Internal Diseases, Olsztyn, Poland Background and Aim: HRV indices are widely accepted markers of cardiac autonomic activity and are commonly used as indicators of the beneficial effects of the adrenergic beta-blockade in patients with congestive heart failure (CHF). There are well known instances of abnormally high resting plasma adrenergic activity in the case of CHF patients. In light of the high frequency of morning sudden cardiac death, there are raising questions of whether evening beta blocker administration is more
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efficient than a morning dose. The aim of this study was to assess the relationship between HRV indices and the morning or evening administration of long acting beta blocker (Bisoprolol) in the group of patients with CHF. Methods: 27 patients (14 male and 13 female, mean age 67.8 + 10.7 years) with congestive heart failure (NYHA IUIII) and sinus rhythm, all on ACE-inhibitors, loop diuretics and potassium sparing diuretics were included in the study. Time domain (TD) and frequency domain (FD) analyses were performed for daytime (10:00 am-7:00 pm), nighttime (11:00 pro-6:00 am) and for 24 hours period: first after 3-5 days with 2.5-5.0 mg of Bisoprolol administrated in the morning, and then again 3-5 days after evening administration. Results: Time domain and frequency domain analysis revealed a significant difference in subsequent parameters (Table 1) Table 1 HRV measures
Morning dose
Evening dose
p value
NN nighttime (ms) SDANN 24 hours LF daytime (ms2) LF/HF 24 hours (ms2) LF/HF daytime (ms2)
984,6h:152,5 107,8±29,9 490.7=t=491,3 1,96±1,01 2,34±1,46
1032+154,03 117,05±36,5 407,5±382,8 1,58±0,9 1,88±1,23
0,02 0,05 0,05 0,002 0,01
NN- mean RR interval, SDANN- standard deviation of the average NN intervals, LF- Low Frequency,HF- High Frequency
Conclusion: Patients with C/IF and sinus rhythm receiving an evening dose of Bisoprolol have significantly more affected adrenergic activity and produced a more beneficial modulation of LF/HF ratio observed in HRV spectral and time domain analyses. 181 Implementation of earvedilol treatment in elderly patients with heart failure: the bring up 2 strategy. G. Fabbri, C. Opasich, A. Boccanelli, S. De Feo, L. Gonzini, M. Porcu, C. Tomasi, A.P. Maggioni on behalf of BRING-UP 2 Investigators
ANMCO Research Center, Florence, Italy Background: Even if beta-blockers (BB) are a recommended treatment in all patients (pts) with symptomatic heart failure (HF), they are still underused in some subgroups of pts such as older patients. The BRINGUP 2 study was designed with the aim of improving BB use and of describing the applicability, safety profile and associated outcome of elderly pts with HF of routine clinical practice treated or not with BB. Methods: 94 Italian centers participated into the study enrolling, from March 2001 to January 2002, all consecutive HF pts aged >70 years. The choice of the treatment was left to the involved physician; if carvedilol was started it was after 2 weeks of clinical stability at dosage of 3,125 or 6,25 mg bid and then nptitrated every week to the maximal tolerated dosage (meanq-SD=23.74-21.2 rag/die). Pts were followed up for 1 year. Multivariable analyses were performed to identify the independent predictors of BB prescription and of 1-year all-cause mortality. Results: 1518 pts have been enrolled, 33.3% whom were already treated with BB. Carvedilol was newly prescribed in 464 pts (30.6%) more frequently in females, those with EF>=30% and higher heart rate. COPD limited but diabetes did not influence the prescription of carvedilol. The rate of pts treated increased, during the study period, from 33.3% to 63.9%. At one year follow up 58.7% of the pts were still in treatment. Discontinuation occurred in 59 (14.1%) pts mainly in the first month after starting the drug. The most t~equent reason for withdrawl was worsening HF. At one yem, there were no differences in hospitalization rate but pts not treated with BB had a higher mortality rate (18.0% for not treated vs 10.8% - OR 0.55, 95%CI [0.39-0.78] - and 11.2% - OR 0.57, 95%CI [0.39-0.83] for pts already treated and started respectively, p
