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Emerging clinical role of ranolazine in the management of angina.

Vadnais DS, Wenger NK - Ther Clin Risk Manag (2010)

Bottom Line: These agents decrease myocardial oxygen demand and ischemia by reducing heart rate, lowering blood pressure, and/or optimizing ventricular loading characteristics.By inhibiting the late inward sodium current (I(Na)), ranolazine prevents pathologic intracellular calcium accumulation that leads to ischemia, myocardial dysfunction, and electrical instability.Ranolazine is a proven antianginal medication in patients with symptomatic coronary heart disease, and should be considered as an initial antianginal agent for those with hypotension or bradycardia.

View Article: PubMed Central - PubMed

Affiliation: Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia, USA.

ABSTRACT
Chronic stable angina is an exceedingly prevalent condition with tremendous clinical, social, and financial implications. Traditional medical therapy for angina consists of beta-blockers, calcium channel blockers, and nitrates. These agents decrease myocardial oxygen demand and ischemia by reducing heart rate, lowering blood pressure, and/or optimizing ventricular loading characteristics. Unique in its mechanism of action, ranolazine is the first new antianginal agent approved for use in the US for chronic angina in over 25 years. By inhibiting the late inward sodium current (I(Na)), ranolazine prevents pathologic intracellular calcium accumulation that leads to ischemia, myocardial dysfunction, and electrical instability. Ranolazine has been proven in multiple clinical trials to reduce the symptoms of angina safely and effectively and to improve exercise tolerance in patients with symptomatic coronary heart disease. These benefits occur without reduction in heart rate and blood pressure or increased mortality. Although ranolazine prolongs the QT(c), experimental data indicate that ranolazine may actually be antiarrhythmic. In a large acute coronary syndrome clinical trial, ranolazine reduced the incidence of supraventricular tachycardia, ventricular tachycardia, new-onset atrial fibrillation, and bradycardic events. Additional benefits of ranolazine under investigation include reductions in glycosylated hemoglobin levels and improved left ventricular function. Ranolazine is a proven antianginal medication in patients with symptomatic coronary heart disease, and should be considered as an initial antianginal agent for those with hypotension or bradycardia.

No MeSH data available.


Related in: MedlinePlus

Sites of action of anti-ischemia medication. Reprinted from Stone P. Ranolazine: new paradigm for management of myocardial ischemia, myocardial dysfunction, and arrhythmias. Cardiol Clin. 2008;26:603–614.58 Copyright © 2008, with permission from Elsevier.
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f3-tcrm-6-517: Sites of action of anti-ischemia medication. Reprinted from Stone P. Ranolazine: new paradigm for management of myocardial ischemia, myocardial dysfunction, and arrhythmias. Cardiol Clin. 2008;26:603–614.58 Copyright © 2008, with permission from Elsevier.

Mentions: Original investigations of ranolazine attributed its anti-ischemic effects primarily to selective inhibition of fatty acid oxidation, thus shifting metabolism to more energy-efficient glucose oxidation.12–15 Alternative explanations of ranolazine’s mechanism of action involving β1- and β2-adrenoceptor inhibition have also been proposed.16 Subsequent studies, however, have largely disproven these theories and concluded that ranolazine’s mechanism of action, at therapeutic serum levels, primarily involves inhibition of the late INa.17–19 By inhibiting the late INa, ranolazine prevents intracellular calcium overload and its subsequent deleterious electrical and mechanical effects. Therefore, under ischemic conditions, ranolazine’s effects are two-fold. First, it attenuates the abnormally prolonged and dysfunctional myocardial contraction that increases myocardial oxygen demand. At the same time, ranolazine is thought to improve coronary blood flow and myocardial oxygen supply by optimizing diastolic function. Ranolazine appears to have little effect on normal resting myocytes, where the contribution of late INa is minimal.20 Thus, ranolazine targets a unique downstream component of the ischemic cascade, only under pathologic conditions, to provide its antianginal benefit (Figure 3).


Emerging clinical role of ranolazine in the management of angina.

Vadnais DS, Wenger NK - Ther Clin Risk Manag (2010)

Sites of action of anti-ischemia medication. Reprinted from Stone P. Ranolazine: new paradigm for management of myocardial ischemia, myocardial dysfunction, and arrhythmias. Cardiol Clin. 2008;26:603–614.58 Copyright © 2008, with permission from Elsevier.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2963161&req=5

f3-tcrm-6-517: Sites of action of anti-ischemia medication. Reprinted from Stone P. Ranolazine: new paradigm for management of myocardial ischemia, myocardial dysfunction, and arrhythmias. Cardiol Clin. 2008;26:603–614.58 Copyright © 2008, with permission from Elsevier.
Mentions: Original investigations of ranolazine attributed its anti-ischemic effects primarily to selective inhibition of fatty acid oxidation, thus shifting metabolism to more energy-efficient glucose oxidation.12–15 Alternative explanations of ranolazine’s mechanism of action involving β1- and β2-adrenoceptor inhibition have also been proposed.16 Subsequent studies, however, have largely disproven these theories and concluded that ranolazine’s mechanism of action, at therapeutic serum levels, primarily involves inhibition of the late INa.17–19 By inhibiting the late INa, ranolazine prevents intracellular calcium overload and its subsequent deleterious electrical and mechanical effects. Therefore, under ischemic conditions, ranolazine’s effects are two-fold. First, it attenuates the abnormally prolonged and dysfunctional myocardial contraction that increases myocardial oxygen demand. At the same time, ranolazine is thought to improve coronary blood flow and myocardial oxygen supply by optimizing diastolic function. Ranolazine appears to have little effect on normal resting myocytes, where the contribution of late INa is minimal.20 Thus, ranolazine targets a unique downstream component of the ischemic cascade, only under pathologic conditions, to provide its antianginal benefit (Figure 3).

Bottom Line: These agents decrease myocardial oxygen demand and ischemia by reducing heart rate, lowering blood pressure, and/or optimizing ventricular loading characteristics.By inhibiting the late inward sodium current (I(Na)), ranolazine prevents pathologic intracellular calcium accumulation that leads to ischemia, myocardial dysfunction, and electrical instability.Ranolazine is a proven antianginal medication in patients with symptomatic coronary heart disease, and should be considered as an initial antianginal agent for those with hypotension or bradycardia.

View Article: PubMed Central - PubMed

Affiliation: Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia, USA.

ABSTRACT
Chronic stable angina is an exceedingly prevalent condition with tremendous clinical, social, and financial implications. Traditional medical therapy for angina consists of beta-blockers, calcium channel blockers, and nitrates. These agents decrease myocardial oxygen demand and ischemia by reducing heart rate, lowering blood pressure, and/or optimizing ventricular loading characteristics. Unique in its mechanism of action, ranolazine is the first new antianginal agent approved for use in the US for chronic angina in over 25 years. By inhibiting the late inward sodium current (I(Na)), ranolazine prevents pathologic intracellular calcium accumulation that leads to ischemia, myocardial dysfunction, and electrical instability. Ranolazine has been proven in multiple clinical trials to reduce the symptoms of angina safely and effectively and to improve exercise tolerance in patients with symptomatic coronary heart disease. These benefits occur without reduction in heart rate and blood pressure or increased mortality. Although ranolazine prolongs the QT(c), experimental data indicate that ranolazine may actually be antiarrhythmic. In a large acute coronary syndrome clinical trial, ranolazine reduced the incidence of supraventricular tachycardia, ventricular tachycardia, new-onset atrial fibrillation, and bradycardic events. Additional benefits of ranolazine under investigation include reductions in glycosylated hemoglobin levels and improved left ventricular function. Ranolazine is a proven antianginal medication in patients with symptomatic coronary heart disease, and should be considered as an initial antianginal agent for those with hypotension or bradycardia.

No MeSH data available.


Related in: MedlinePlus