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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

Relation between peak and late sodium current and ventricular action potential (AP) and contraction (tracings are not actual recordings). Panels A and B illustrate a normal and an increased late INa (due to impaired inactivation of Na+ channel), respectively. The enhanced late INa is accompanied by delayed ventricular repolarization (longs APs, and occasional early after depolarization) and abnormal twitch (contraction composed of a phasic and tonic component.) Belardinelli L, Antzelevitch C, Fraser H. Inhibition of late (sustained/persistent) sodium current: a potential drug target to reduce intracellular sodium-dependent calcium overload and its detrimental effects on cardiomyocyte function. Eur Heart J. 2004;6(Suppl I):13–17.11 By permission Oxford University Press, copyright © 2004.
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f2-tcrm-6-517: Relation between peak and late sodium current and ventricular action potential (AP) and contraction (tracings are not actual recordings). Panels A and B illustrate a normal and an increased late INa (due to impaired inactivation of Na+ channel), respectively. The enhanced late INa is accompanied by delayed ventricular repolarization (longs APs, and occasional early after depolarization) and abnormal twitch (contraction composed of a phasic and tonic component.) Belardinelli L, Antzelevitch C, Fraser H. Inhibition of late (sustained/persistent) sodium current: a potential drug target to reduce intracellular sodium-dependent calcium overload and its detrimental effects on cardiomyocyte function. Eur Heart J. 2004;6(Suppl I):13–17.11 By permission Oxford University Press, copyright © 2004.

Mentions: In pathologic states, such as ischemia, left ventricular hypertrophy, and heart failure, there is a prolonged late sodium current (late INa) during Phase 2 of the action potential.9,10 Excess intracellular sodium results in intra-cellular Ca2+ overload via reverse transport across the Na+/Ca2+ exchanger. Sustained myocardial contraction ensues, eventually leading to myocardial dysfunction, electrical instability, increased diastolic wall tension, and mitochondrial dysfunction.11 Ultimately, the increased diastolic wall tension causes compression of the vascular beds, leading to further reduction of coronary blood flow, increased myocardial oxygen demand, and eventual cellular necrosis (Figures 1 and 2).


Emerging clinical role of ranolazine in the management of angina.

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

Relation between peak and late sodium current and ventricular action potential (AP) and contraction (tracings are not actual recordings). Panels A and B illustrate a normal and an increased late INa (due to impaired inactivation of Na+ channel), respectively. The enhanced late INa is accompanied by delayed ventricular repolarization (longs APs, and occasional early after depolarization) and abnormal twitch (contraction composed of a phasic and tonic component.) Belardinelli L, Antzelevitch C, Fraser H. Inhibition of late (sustained/persistent) sodium current: a potential drug target to reduce intracellular sodium-dependent calcium overload and its detrimental effects on cardiomyocyte function. Eur Heart J. 2004;6(Suppl I):13–17.11 By permission Oxford University Press, copyright © 2004.
© Copyright Policy
Related In: Results  -  Collection

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

f2-tcrm-6-517: Relation between peak and late sodium current and ventricular action potential (AP) and contraction (tracings are not actual recordings). Panels A and B illustrate a normal and an increased late INa (due to impaired inactivation of Na+ channel), respectively. The enhanced late INa is accompanied by delayed ventricular repolarization (longs APs, and occasional early after depolarization) and abnormal twitch (contraction composed of a phasic and tonic component.) Belardinelli L, Antzelevitch C, Fraser H. Inhibition of late (sustained/persistent) sodium current: a potential drug target to reduce intracellular sodium-dependent calcium overload and its detrimental effects on cardiomyocyte function. Eur Heart J. 2004;6(Suppl I):13–17.11 By permission Oxford University Press, copyright © 2004.
Mentions: In pathologic states, such as ischemia, left ventricular hypertrophy, and heart failure, there is a prolonged late sodium current (late INa) during Phase 2 of the action potential.9,10 Excess intracellular sodium results in intra-cellular Ca2+ overload via reverse transport across the Na+/Ca2+ exchanger. Sustained myocardial contraction ensues, eventually leading to myocardial dysfunction, electrical instability, increased diastolic wall tension, and mitochondrial dysfunction.11 Ultimately, the increased diastolic wall tension causes compression of the vascular beds, leading to further reduction of coronary blood flow, increased myocardial oxygen demand, and eventual cellular necrosis (Figures 1 and 2).

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