206A ABSTRACTS - Cardiac Function and Heart Failure JACC March 3, 2004 Cardiac Function and Heart Failure p=0.0006). Differences were already observed after several months and were maintained over time. Changes in blood pressure from baseline, measured at 4 months treatment, were comparable (p>0.6) between C and M in patients dying from stroke. Stroke or myo- cardial infarction, combined, occurred in 130 C versus 168 M patients (HR 0.75, CI 0.60- 0.95, p=0.02) Conclusion: C reduced the major components of CV death in HF, sudden and HF death, more than metoprolol. In addition, carvedilol reduced stroke deaths and myocardial inf- arction compared to metoprolol. These results suggest a protective effect of C against major vascular events. 9:00 a.m. 835-3 Beta-Blocker Dose Does Not Influence the Beneficial Effects of Carvedilol Compared to Metoprolol in the Patients With Heart Failure: Results From the Carvedilol or Metoprolol European Trial (COMET) Marco Metra , Philip A. Poole-Wilson, John G. Cleland, Andrea Di Lenarda, Peter Hanrath, Michel Komajda, Jacobus Lubsen, Beatrix Lutiger, Willem J. Remme, Armin Scherhag, Andrew Charlesworth, Christian Torp-Pedersen, For the COMET investigators, University of Brescia, Brescia, Italy, National Heart and Lung Institute, London, United Kingdom Background: Beta-blockers (BB) are often used at doses lower than those shown to be of benefit in controlled trials. It is important to know whether outcome differences between carvedilol and metoprolol in COMET may be influenced by the dose adminis- tered. Methods: We compared the clinical characteristics and the outcome between the patients who reached target BB doses in COMET (carvedilol, 25 mg bid; metoprolol tar- trate, 50 mg bid) and those who did not. Results: At the end of uptitration, 4 months after randomization, the daily doses were 41.8+ 14.6 mg (980/1308 patients [75%] reached target dose) for carvedilol and 85+ 28.9 mg (1019/1313 [78%] on the target dose) for metoprolol. Compared to patients on low dose, those on the target doses were younger (61+ 11 versus 64+ 11 years), had higher body mass index (27+ 4 versus 26+ 4 kg/m 2 ), systolic and diastolic blood pressure (BP, 128+ 19 versus 122+ 19 mmHg and 78+ 11 versus 75+ 11 mmHg, respectively) and heart rate (HR, 82+ 13 versus 79+ 13 beats/minute), a higher prevalence of NYHA class II symptoms (55% versus 39%) and a lower prevalence of ischemic heart disease (IHD, 48% versus 61%) (all p<0.0001). Mortality rate was 29% in patients on target dose ver- sus 41% in the others (RR 0.60; 95% CI 0.52-0.699; p<0.00001). The beneficial effect of reaching target BB dose remained significant by multivariate analysis (RR 0.781; 95% CI 0.66-0.92; p=0.0036). The mortality reduction achieved with carvedilol was similar in patients on target doses (25.4% on carvedilol versus 32.4% on metoprolol; RR 0.75; 95% CI 0.64-0.89; p=0.0008) and in patients on low dose (36.9% on carvedilol versus 45.6% on metoprolol; RR 0.76; 95% CI 0.60-0.98; p=0.032). No interaction between the effect of carvedilol, compared to metoprolol, and the dose administered was found (RR 0.99; 95% CI 0.73-1.33). Conclusion: In COMET, patients titrated to higher BB doses were younger, with a higher baseline BP and HR, milder symptoms and a lower prevalence of IHD. Administration of the target BB doses was an independent predictor of a lower mortality risk. The survival benefits of carvedilol compared to metoprolol were maintained independently from the dose administered. 9:15 a.m. 835-4 Comparison of the Effects of Metoprolol and Carvedilol on Symptoms, Well-Being, and Quality-Adjusted Life- Years: A Description of the Patient-Journey in COMET John G. Cleland , Karl Swedberg, Andrea Di Lenarda, Peter Hanrath, Michel Komajda, Beatrix Lutiger, Jacobus Lubsen, Marco Metra, Willem J. Remme, Armin Scherhag, Andrew Charlesworth, Christian Torp-Pedersen, Philip A. Poole-Wilson, For the COMET investigators, The University of Hull, Kingston upon Hull, United Kingdom, Sahlgrenska University Hospital, Göteborg, Sweden 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) (25mg bd) and fol- lowed 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 (-0.30+ 0.59 in C, - 0.28+ 0.57 in M) and plateauing around 2 years (-0.42+ 0.66 in C, -0.39+ 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 (25.6+ 45 in C, 24.8+ 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 NYHA 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. 9:30 a.m. 835-5 Candesartan Improves Functional Class Across a Broad Spectrum of Patients With Chronic Heart Failure: Results of the Candesartan in Heart Failure- Assessment of Reduction in Mortality and Morbidity Programme (CHARM) John J. McMurray , Jan Östergren, Bertil Olofsson, Christopher B. Granger, Eric Michelson, James B. Young, Mark Dunlap, Salim Yusuf, Karl Swedberg, Marc A. Pfeffer, for the CHARM Investigators, Western Infirmary, Glasgow, United Kingdom Background: Improving symptoms and functional capacity is a major goal of treatment of chronic heart failure (CHF). The New York Heart Association (NYHA) functional classi- fication is a widely used and validated measure of symptomatic limitation in CHF. We have examined the effect of candesartan on NYHA class in CHARM. Methods: CHARM had three component trials: i) CHARM-Alternative (n= 2028): LVEF < 0.40 not receiving an ACE inhibitor due to prior intolerance ii) CHARM–Added (n=2548): LVEF < 0.40 currently receiving an ACE inhibitor and iii) CHARM-Preserved (n=3025): LVEF > 0.40. Patients were randomized to placebo or candesartan (target dose 32mg once daily). The primary outcome in each trial was the composite of cardiovascular (CV) death or CHF hospitalization. NYHA class was also recorded at baseline and at each visit (4 monthly after titration), over a mean follow-up of 37.7 months. The difference between treatments in change in NYHA class from baseline was analyzed using the Wil- coxon rank-sum test with last visit carried forward. Results: These findings were supported by a favorable change in the Overall Treatment Evalua- tion (OTE) in the candesartan group compared to the placebo group (P=0.01). Conclusion: In addition to reducing CV death and CHF hospitalization, candesartan resulted in a favorable overall change in NYHA class in a broad spectrum of patients with CHF. 9:45 a.m. 835-6 The Effect of a Calcium Sensitizer or an Inotrope or None in Chronic Low Output Decompensated Heart Failure: Results From the Calcium Sensitizer or Inotrope or None in Low Output Heart Failure Study (CASINO) Michael N. Zairis , Charalambos Apostolatos, Philippos Anastasiadis, Dimitris Mytas, Christos Katsaris, Nikolaos Kouris, Hristos Grassos, Kostas Karidis, Evdokia Adamopoulou, Spyros Argyrakis, Athanasios Prekates, Stefanos Foussas, Tzanio Hospital, Piraeus, Greece, Sotiria Hospital, Athens, Greece BACKGROUND Previous studies have shown that levosimendan, a novel calcium sensi- tiser, is associated with better long-term prognosis as compared to dobutamin in patients with low output heart failure. However, a parallel group assigned to placebo was not included in these studies. METHODS A total of 227 patients with decompansated low output chronic heart failure (LVEF<35%) were recruited into a multicentre, randomised, double-blind, double-dummy, placebo-control parallel-group trial. Levosimedan, dob- utamin, or placebo was infused intavenously for 24 h. The composite of death or rehospi- talization due to heart failure deterioration during the follow-up, was the primary endpoint.. RESULTS 74, 76 and 77 patients were assigned to levosimendan, dobutamine and placebo respectively. By 6-month the primary endpoint was achieved in 30.6%, 52.7% and 48.1% of the patients in levosimendan, dobutamine and placebo group respectively (P=0.01) (Fig 1).CONCLUSIONS Levosimedan significantly improves long- term prognosis in patients with decompansated low-output heart failure, as compared to either dobutamine or placebo. Change in NYHA class from baseline in overall CHARM Programme Placebo (n=3796) Candesartan (n=3803) NYHA class (%) improved 32.5 35.4 unchanged 57.2 55.6 worse 10.3 9.0 P=0.004 brought to you by CORE View metadata, citation and similar papers at core.ac.uk provided by Elsevier - Publisher Connector