Influence of heart rate, blood pressure, and beta-blocker dose on outcome and the differences in outcome between carvedilol and metoprolol tartrate in patients with chronic heart failure: results from the COMET trial

Aims We studied the influence of heart rate (HR), systolic blood pressure (SBP), and beta-blocker dose on outcome in the 2599 out of 3029 patients in Carvedilol Or Metoprolol European Trial (COMET) who were alive and on study drug at 4 months after randomization (time of first visit on maintenance therapy). Methods and results By multivariable analysis, baseline HR, baseline SBP, and their change after 4 months were not independently related to subsequent outcome. In a multivariable analysis including clinical variables, HR above and SBP below the median value achieved at 4 months predicted subsequent increased mortality [relative risk (RR) for HR > 68 b.p.m. 1.333; 95% confidence intervals (CI) 1.152-1.542; P < 0.0001 and RR for SBP > 120 mmHg 0.78; 95% CI 0.671-0.907; P < 0.0013]. Achieving target beta-blocker dose was associated with a better outcome (RR 0.779; 95% CI 0.662-0.916; P < 0.0025). The superiority of carvedilol as compared to metoprolol tartrate was maintained in a multivariable model (RR 0.767; 95% CI 0.663-0.887; P=0.0004) and there was no interaction with HR, SBP, or beta-blocker dose. Conclusion Beta-blocker dose, HR, and SBP achieved during beta-blocker therapy have independent prognostic value in heart failure. None of these factors influenced the beneficial effects of carvedilol when compared with metoprolol tartrate at the pre-defined target doses used in COMET.