Heart rate achieved or beta-blocker dose in patients with chronic heart failure: which is the better target?
Cullington D, Goode KM, Clark AL, Cleland JG.
Eur J Heart Fail. 2012 May 22.
Beta-blockers are important in the treatment of heart failure [1-5] by blocking the effects of adrenergic receptor stimulation. In clinical trials in patients with heart failure, beta-blockers were titrated to target doses derived from studies in hypertension and angina. Analyses of most landmark trials suggest that achieved heart rate rather than beta-blocker dose is the main determinant of beta-blocker effect [3,4].
Heart rate reduction is important to decrease the risk of cardiovascular events and improve prognosis and might also be achieved by alternative methods other than beta-blockers, if beta-blockers are contraindicated or if side effects are troublesome.
This study evaluated whether beta-blocker dose or heart rate was more strongly associated with mortality in patients with stable chronic heart failure.
Patients with EF ≤40% with a sinus rhythm both at initiation and at 4 months were followed for max. 36 months (n=654). Prior to the initial visit, 58% of them were on beta-blockers, increasing to 82% after 4 months.
- A resting heart rate > 65 bpm at 4 months was associated with a substantially worse survival (fig. 1).
- Patients with a heart rate between 58-64 bpm at 4 months had the highest survival.
Kaplan–Meier curves showing the effects of heart rate measured at visit 2 on survival and adjusted for beta blocker use, left ventricular impairment, loop diuretic use, creatinine, and age.
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- Beta-blocker use at 4 months was associated with better survival, but there was no clear relationship between beta-blocker dose and mortality reduction.
Achieving a target heart rate may be an important goal for patients with chronic heart failure. This can be achieved by beta-blockers, but in some patients, other heart rate slowing agents, possibly in addition to a low dose of beta-blocker, might be preferred rather than using higher doses of beta-blockers alone .
1. Poole-Wilson PA, Swedberg K, Cleland JG, et al. Comparison of carvedilol and metoprolol on clinical outcomes in patients with chronic heart failure in the Carvedilol Or Metoprolol European Trial (COMET): randomised controlled trial. Lancet 2003;362:7–13.
2. Packer M, Bristow MR, Cohn JN. The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. N Engl J Med 1996;334:1349–1355.
3. The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial. Lancet 1999;353:9–13.
4. Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF). Lancet 1999;353:2001–2007.
5. Flather MD, Shibata MC, Coats AJ, et al; SENIORS Investigators. Randomised trial to determine the effect of nebivolol on mortality and cardiovascular hospital admission in elderly patients with heart failure (SENIORS). Eur Heart J 2005;26:215–225.
6. Volterrani M, Cice G, Caminiti G, et al. Effect of carvedilol, ivabradine or their combination on exercise capacity in patients with heart failure (the CARVIVA HF trial). Int J Cardiol 2011;151:218–224.
To investigate whether the mortality of patients with chronic heart failure (CHF) due to left ventricular systolic dysfunction (LVSD) is more strongly related to beta-blocker dose or to heart rate. It is known that beta-blockers reduce mortality in patients with CHF and LVSD, but the primary mechanism of action is uncertain.
Methods and results:
Patients with an ejection fraction ≤40%, who were in sinus rhythm both at an initial (visit 1) and at a 4-month clinic review (visit 2), were followed for a maximum of 36 months. The relationships between heart rate, beta-blocker dose, and survival in a multivariable model were examined. Of 654 eligible patients, 381 (58%) were started on beta-blockers prior to the initial visit, increasing to 537 (82%) by visit 2. During follow-up, 142 (22%) patients died. Neither resting heart rate nor beta-blocker dose at visit 1 predicted mortality (P = 0.09 and P = 0.99), but resting heart rate at visit 2 did (P = 0.02). Beta-blocker use at visit 2 was associated with better outcome (P = 0.03) but with little variation in outcome according to dose. Patients with a heart rate of 58-64 b.p.m. at visit 2 had the best prognosis.
Conclusions: The use of beta-blockers and resting heart rate at visit 2 both independently indicated prognosis, but beta-blocker dose did not. Beta-blockers may reduce mortality by several mechanisms; one that may be specific to blockade of adrenergic receptors and another related to heart rate reduction. Achieving a target heart rate range may be an appropriate therapeutic goal for patients with CHF.