Heart rate control with adrenergic blockade: clinical outcomes in cardiovascular medicine

Abstract

The sympathetic nervous system is involved in regulating various cardiovascular parameters including heart rate (HR) and HR variability. Aberrant sympathetic nervous system expression may result in elevated HR or decreased HR variability, and both are independent risk factors for development of cardiovascular disease, including heart failure, myocardial infarction, and hypertension. Epidemiologic studies have established that impaired HR control is linked to increased cardiovascular morbidity and mortality. One successful way of decreasing HR and cardiovascular mortality has been by utilizing beta-blockers, because their ability to alter cell signaling at the receptor level has been shown to mitigate the pathogenic effects of sympathetic nervous system hyperactivation. Numerous clinical studies have demonstrated that beta-blocker-mediated HR control improvements are associated with decreased mortality in postinfarct and heart failure patients. Although improved HR control benefits have yet to be established in hypertension, both traditional and vasodilating beta-blockers exert positive HR control effects in this patient population. However, differences exist between traditional and vasodilating beta-blockers; the latter reduce peripheral vascular resistance and exert neutral or positive effects on important metabolic parameters. Clinical evidence suggests that attainment of HR control is an important treatment objective for patients with cardiovascular conditions, and vasodilating beta-blocker efficacy may aid in accomplishing improved outcomes.

Keywords: adrenergic beta-antagonists; heart failure; hypertension; myocardial infarction.

Figure 1

Heart rate and mortality in healthy individuals: Relative risk of death from any cause, nonsudden death from myocardial infarction (MI), and sudden death from MI in 5713 people without known or suspected heart disease. Differences among quintiles with respect to risk of death from any cause, P < 0.001; nonsudden death from cardiac causes, P = 0.02; sudden death from cardiac causes, P < 0.001. Copyright @ 2005. Massachusetts Medical Society. All rights reserved. Reprinted with permission from Jouven X, Empana JP, Schwartz PJ, Desnos M, Courbon D, Ducimetiere P. Heart-rate profile during exercise as a predictor of sudden death. N Engl J Med. 2005;352(19):1951–1958.

Figure 2

Heart rate and mortality in coronary artery disease: Relationship between resting heart rate and all-cause and cardiovascular mortality in 24,913 patients with suspected or proven coronary artery disease. Based on data from Diaz et al. Copyright © 2007. Reprinted with permission from Fox K, Borer JS, Camm AJ, et al. Resting heart rate in cardiovascular disease. J Am Coll Cardiol. 2007;50(9):823–830. Abbreviation: bpm, beats per minute.

Figure 3

Heart rate reduction and mortality in heart failure: Relationship between change in heart rate and mean change in mortality among patients with chronic heart failure who received β-blocker therapy. Copytright © 1999. Reprinted with permission from Kjekshus Kjekshus J, Gullestad L. Heart rate as a therapeutic target in heart failure. Eur Heart J Suppl. 1999;1(Suppl H):H64–H69.

Figure 4

Heart rate reduction and mortality after myocardial infarction: Relationship between mean reduction in heart rate and mean change in mortality relative to placebo in randomized, placebo-controlled studies of β-blockers after myocardial infarction (r = 0.60; P < 0.05). Copyright © 1986. Reprinted with permission from Kjekshus JK. Importance of heart rate in determining beta-blocker efficacy in acute and long-term acute myocardial infarction intervention trials.Am J Cardiol. 1986;57(12):43F–49F.

Figure 5

Twenty-four-hour heart rate in patients with hypertension at baseline and after six weeks of treatment with carvedilol controlled-release (CR) or placebo. Copyright © 2006. Reprinted with permission from Weber MA, Bakris GL, Tarka EA, Iyengar M, Fleck R, Sica DA. Efficacy of a once-daily formulation of carvedilol for the treatment of hypertension. J Clin Hypertens (Greenwich). 2006;8(12):840–849.