Controlled-release carvedilol in the management of systemic hypertension and myocardial dysfunction

Abstract

Cardiovascular disease is the leading cause of death worldwide. Within the treatment armamentarium, beta-blockers have demonstrated efficacy across the spectrum of cardiovascular disease--from modification of a risk factor (ie, hypertension) to treatment after an acute event (ie, myocardial infarction). Recently, the use of beta-blockers as a first-line therapy in hypertension has been called into question. Moreover, beta-blockers as a class are saddled with a misperception of having poor tolerability. However, vasodilatory beta-blockers such as carvedilol have a different hemodynamic action that provides the benefits of beta-blockade with the addition of vasodilation resulting from alpha 1-adrenergic receptor blockade. Vasodilation reduces total peripheral resistance, which may produce an overall positive effect on tolerability. Recently, a new, controlled-release carvedilol formulation has been developed that provides the clinical efficacy of carvedilol but is indicated for once-daily dosing. This review presents an overview of the clinical and pharmacologic carvedilol controlled-release data.

Keywords: beta-blockers; cardiovascular disease; heart failure; myocardial infarction; vasodilatory.

Figure 1

Mean steady state concentration-time profiles for S(−) and R(+) enantiomers for carvedilol immediate-release and controlled-release. Reprinted from Henderson LS, Tenero DM, Baidoo CA, et al 2006. Pharmacokinetic and pharmacodynamic comparison of controlled-release carvedilol and immediate-release carvedilol at steady state in patients with hypertension. Am J Cardiol, 98:17L–26L. Copyright © 2006, with permission from Elsevier. Abbreviations: IR, immediate release, CR, controlled release, QD, once daily.

Figure 2

Glycosylated hemoglobin (HbA_1c) at baseline and each maintenance month by treatment in GEMINI. Reproduced with permission from Bakris GL, Fonseca V, Katholi RE, et al 2004. Metabolic effects of carvedilol vs metoprolol in patients with type 2 diabetes mellitus and hypertension: a randomized controlled trial. JAMA, 292:2227–36. Copyright © 2004, American Medical Association. All Rights Reserved. Note: Data are means ± standard deviations.

Figure 3

Controlled-release carvedilol in hypertension. Adapted from Weber MA, Sica DA, Tarka EA, et al Controlled-release carvedilol in the treatment of essential hypertension. Am J Cardiol, 98:32L–38L. Copyright © 2006, with permission from Elsevier. Abbreviations: CR, controlled release, DBP, diastolic blood pressure, SBP, systolic blood pressure. Note: Data are change from baseline in model-adjusted peak (3 to 7 hours) diastolic blood pressure and systolic blood pressure measured by ambulatory blood pressure monitoring. *p < 0.05, ^†p < 0.001, ^‡p < 0.0001, based on pair-wise comparison of change from baseline with placebo.

Figure 4

Kaplan-Meier estimates of all-cause mortality in COMET. Reprinted from 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, 362:7–13. Copyright © 2003, with permission from Elsevier.

Figure 5

Kaplan-Meier estimates of event-free survival in CAPRICORN. Reprinted from Dargie HJ, for the CAPRICORN Investigators. Effect of carvedilol on outcome after myocardial infarction in patients with left-ventricular dysfunction: the CAPRICORN randomised trial. Lancet, 357:1385–90. Copyright © 2001, with permission from Elsevier.