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Abstract: Aim: Patients with heart failure (HF) have reduced exercise capacity. The beneficial effect of beta-blocker on prognosis is not matched by an impact on exercise capacity and quality of life. We performed a randomised open blinded endpoint study to assess the effect of heart rate reduction with carvedilol, ivabradine, and their combination on exercise capacity in HF patients receiving maximal dose of ACE inhibitor. Methods and results: After a run-in phase patients were randomly allocated to 3 groups: carvedilol up to 25mg bid (n=38); ivabradine up to 7.5mg bid (n=41); and carvedilol/ivabradine up to 12.5/7.5mg bid (n=42). The maximal dose of study treatment was more frequently tolerated in patients receiving ivabradine (36/41) than in those receiving carvedilol (18/38) or combination therapy (32/42) (P <0.01 ivabradine versus carvedilol). Heart rate was reduced in all three groups, but to a greater extent by the combination. The distance walked on the 6-min walking test and the exercise time on MVO2 test significantly improved in the ivabradine and combination groups (both P <0.01 versus baseline), as did peak VO2 and VAT (P <0.01 for ivabradine and P <0.03 for combination versus carvedilol, respectively). No changes in these parameters were found with carvedilol. The patients receiving ivabradine or the combination had better quality of life (P <0.01 versus baseline for ivabradine and P< 0.02 for combination), versus no change with carvedilol. Conclusion: Ivabradine alone or in combination with carvedilol is more effective than carvedilol alone at improving exercise tolerance and quality of life in HF patients. [Copyright &y& Elsevier]