Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002962 (angina)
 21,142 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

More women than men with myocardial infarction have previous stable angina pectoris. Women also have an increased incidence of angina after percutaneous coronary intervention and coronary artery bypass grafting. Data from 1,737 patients with stable angina pectoris in 4 international trials (Monotherapy Assessment of Ranolazine In Stable Angina [MARISA], Combination Assessment of Ranolazine In Stable Angina [CARISA], Ranolazine Versus Atenolol Comparison in Chronic Angina [RAN080], and Efficacy of Ranolazine in Chronic Angina [ERICA]) were used to compare efficacy and safety of ranolazine therapy for angina in women and men. MARISA, CARISA, and RAN080 included exercise testing; CARISA, RAN080, and ERICA assessed angina frequency and nitroglycerin consumption; and ERICA included quality-of-life assessment using the Seattle Angina Questionnaire. MARISA, CARISA, and ERICA used the extended-release formulation of ranolazine; RAN080 used ranolazine immediate release. All 4 studies showed overall efficacy and safety of ranolazine. In subgroup analyses, women showed less improvement than men in exercise testing. However, similar improvements for women and men were noted in angina frequency and nitroglycerin consumption, and in ERICA, in the angina frequency dimension of the Seattle Angina Questionnaire. In conclusion, explanations for the gender treatment differences for exercise parameters but comparable effects on decrease in angina frequency and nitroglycerin use are uncertain, but may include differences in patient demographics, reasons for stopping exercise, and type of exercise protocol used.
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PMID:Gender comparison of efficacy and safety of ranolazine for chronic angina pectoris in four randomized clinical trials. 1719 54

Ranolazine is a selective inhibitor of the late sodium current relative to peak sodium channel current, and via this mechanism, it may decrease sodium-dependent intracellular calcium overload during ischemia and reperfusion. Ranolazine reduces the frequency of angina attacks, but there is little information on its effects on myocardial stunning after short-term ischemia. The objective of this study was to test the effects of ranolazine on left ventricular (LV) function and myocardial stunning after ischemia/reperfusion in rabbits. Myocardial stunning was induced in rabbits by 15 minutes of coronary artery occlusion (CAO) followed by 3 hours reperfusion. Ten minutes before CAO, rabbits were randomly assigned to vehicle (n = 15) or ranolazine (2 mg/kg bolus plus 60 microg/kg/min infusion, IV, n = 15). Myocardial stunning was assessed by LV 2-dimensional echocardiography using, as a marker of severity, ischemic free-wall fractional thickening (FWft; systolic wall thickness - diastolic wall thickness/diastolic wall thickness). Regional ejection fraction (EF) was also assessed. During CAO, FWft was depressed in both groups, indicating an ischemic insult (FWft was reduced from 0.62 +/- 0.05 at baseline to 0.10 +/- 0.04 in vehicle and from 0.73 +/- 0.05 to 0.26 +/- 0.07 in ranolazine, P < 0.05, ranolazine vs vehicle). After reperfusion, previously ischemic myocardium remained stunned; however, FWft recovered significantly better in ranolazine (0.51 +/- 0.05) than in vehicle (0.35 +/- 0.04, P = .027). Baseline EF was 0.65 +/- 0.02 in the ranolazine and 0.68 +/- 0.02 in vehicle (P = ns). During CAO, EF was reduced by 36% +/- 6% in vehicle versus only 20% +/- 6% in ranolazine (P < .05). At the end of reperfusion, EF remained depressed in both groups, but the reduction in the vehicle group (25% +/- 5%) was significantly worse than in ranolazine (9% +/- 4%, P = .017). Improvement in function was independent of necrosis (negligible) or differences in hemodynamics (no differences between groups). Ranolazine treatment reduced myocardial stunning following brief ischemia/reperfusion suggesting that inhibiting the late sodium channel current may be a novel approach to treating stunning independent of effects on hemodynamics.
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PMID:Ranolazine, an inhibitor of the late sodium channel current, reduces postischemic myocardial dysfunction in the rabbit. 1722 Apr 71

Treatment for coronary heart disease is usually directed at either increasing myocardial oxygen supply or decreasing myocardial oxygen demand. Although combination therapy with beta-blockers, calcium-channel blockers and nitrates are effective, many patients suffer from adverse effects of hypotension and bradycardia. Ranolazine is a novel medication that reduces ischaemia by preventing sodium induced calcium overload in myocardial cells without adversely affecting haemodynamic parameters. This agent is the first in the USA to be approved to treat angina in over 10 years. The purpose of this review is to evaluate the pharmacology, pharmacokinetics, clinical trials for safety and efficacy, precautions, adverse effects, drug interactions, and dosage and administration of ranolazine in the treatment of chronic stable angina and acute coronary syndrome.
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PMID:Ranolazine: a novel agent that improves dysfunctional sodium channels. 1749 93

(1) Ranolazine-- an adjunctive treatment to beta-blockers, calcium channel blockers, or long-acting nitrates-- is indicated for patients with chronic stable angina who have not responded to standard anti-anginal therapy. (2) In three randomized controlled trials (RCTs), ranolazine, in combination with standard anti-anginal medications, led to modest but statistically significant improvements in exercise duration, and reductions in the frequency of angina episodes and nitroglycerin consumption, when compared to standard anti-anginal medications only. The clinical significance of these improvements is unknown. Most of the participants in studies were male and Caucasian. Thus, there are questions about the drug's efficacy in other populations. (3) One RCT suggests that the addition of ranolazine to standard treatment is ineffective in reducing major cardiovascular events that are associated with acute coronary syndromes. (4) The adverse effects reported with ranolazine include dizziness, nausea, asthenia (weakness), constipation, and headache. Long-term data from one trial indicate that there is no significant increase in the incidence of death or arrhythmia among those taking ranolazine. More clinical trials of ranolazine are needed to confirm its long-term safety, its optimal dosing, its efficacy in combination with full dose beta-blockers with or without calcium channel blockers, and its potential role in the treatment of other cardiovascular conditions.
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PMID:Ranolazine (Ranexa) for chronic stable angina. 1759 50

The optimal management of coronary artery disease is based on achieving two parallel objectives: 1) prevention of major cardiovascular events, and 2) resolution of symptoms. Traditional antianginal agents improve ischemic symptoms by reducing myocardial oxygen demand through modulation of heart rate, preload, and/or afterload. Ranolazine is a novel antianginal agent believed to relieve ischemia by reducing myocardial cellular sodium and calcium overload via inhibition of the late sodium current of the cardiac action potential. In three randomized double-blind trials in selected patients with chronic angina, ranolazine prolonged exercise duration and reduced symptoms when compared with placebo when given as either monotherapy or in combination with traditional antianginal pharmacotherapy. When evaluated in patients with non-ST-elevation acute coronary syndromes, ranolazine reduced recurrent ischemia but did not significantly reduce the risk of death or myocardial infarction at 1 year. Ranolazine complements traditional antianginal agents and offers clinicians a new option in the long-term treatment of patients with angina.
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PMID:Ranolazine in patients with angina and coronary artery disease. 1760 93

Traditional anti-anginal agents such as beta-blockers and nitrates improve symptoms of cardiac ischemia by affecting either blood pressure or heart rates. Despite aggressive therapy, many patients suffer persistent angina, and optimal therapy is limited by intolerance to traditional agents. Ranolazine, a novel anti-anginal agent that is approved for use in the US, is felt to improve ischemic symptoms by reducing myocardial cellular sodium and calcium overload via inhibition of the late sodium current (I(Na)) of the cardiac action potential. Several Phase-III trials in patients with chronic angina have demonstrated that ranolazine improves exercise tolerance and reduces ischemic symptoms as compared with placebo. In the largest evaluation of ranolazine, the MERLIN-TIMI 36 trial (Metabolic Efficiency with Ranolazine for Less Ischemia in non ST elevation acute coronary syndrome), ranolazine did not reduce the risk of death or recurrent myocardial infarction in patients with non-ST-elevation acute coronary syndromes, but it did improve ischemic symptoms over the subsequent year of therapy. Thus, ranolazine offers clinicians a new therapy in the long-term treatment of patients with chronic angina.
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PMID:Ranolazine in patients with coronary artery disease. 1771 67

Pharmacotherapy for the management of chronic stable angina has not changed much in the past 10-20 years. Although the use of revascularization has increased, beta-blockers, calcium channel blockers, and long-acting nitrates are still widely used in the management of patients with chronic stable angina. Despite the demonstrated effectiveness of these agents, a number of patients do not achieve the American College of Cardiology-American Heart Association goal of freedom from exertional angina attacks. For the first time in more than a decade, a new agent, ranolazine, is available to assist in controlling exertional angina. Ranolazine has a novel mechanism of action of inhibiting the late sodium current during ventricular depolarization. This mechanism contributes to a reduction in intracellular sodium and, therefore, a reduction in intracellular calcium, reducing ischemic injury. Unlike currently available pharmacotherapy for chronic stable angina, ranolazine does not produce clinically meaningful changes in heart rate or blood pressure. A number of clinical trials have demonstrated the ability of ranolazine to increase exercise tolerance, decrease weekly anginal episodes, and decrease sublingual nitroglycerin consumption for breakthrough angina. Based on the results of these trials, ranolazine recently was approved by the United States Food and Drug Administration for treatment of patients with chronic stable angina. Because of ranolazine's pharmacokinetic and pharmacodynamic profile, pharmacists will have to play a significant role in patient selection and monitoring.
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PMID:Ranolazine: a new option in the management of chronic stable angina. 1804 87

Ranolazine is a piperazine derivative believed to reduce anginal symptoms by preventing ischemia-mediated sodium and calcium overload in myocardial cells through inhibition of the late sodium current (late INa). Three small studies demonstrated the antianginal efficacy of ranolazine alone and in combination with betablockers or calcium channel blockers on conventional end points such as total exercise duration and time to ischemia/angina on a treadmill; however, questions of safety related to QT prolongation, efficacy in women and potential utility in higher risk populations remained. Metabolic Efficiency with Ranolazine for Less Ischemia in Non-ST Elevation Acute Coronary Syndromes-Thrombolysis in Myocardial Infarction (MERLIN-TIMI) 36 was a large randomized, double-blind, placebo-controlled trial, which evaluated the efficacy and safety of ranolazine initiated acutely and continued as chronic therapy following a non-ST-segment elevation acute coronary syndrome event. A total of 6560 patients were randomized 1:1 to ranolazine or placebo; the primary efficacy end point of the trial was a composite of cardiovascular death, myocardial infarction or recurrent ischemia. The key safety end points were death from any cause and symptomatic documented arrhythmia. Although statistically significant differences between the ranolazine and placebo groups were not reached in the primary efficacy analysis or in the major secondary outcome end point analyses (cardiovascular death, myocardial infarction or severe recurrent ischemia), the individual component of recurrent ischemia was significantly reduced by ranolazine, and ranolazine was demonstrated to be safe.
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PMID:Metabolic efficiency with ranolazine for less ischemia in non-ST elevation acute coronary syndromes (MERLIN TIMI-36) study. 1809 3

Chronic Angina resistant to medical treatment with hemodynamically acting agents is a major problem in clinical setup. For such patients, large number of clinical trials have documented the beneficial effect of Ranolazine. It acts as an anti-anginal agent that controls myocardial ischemia through intracellular metabolic changes. Ranolazine is a partial fatty acid oxidation inhibitor which shifts cardiac energy metabolism from fatty acid oxidation to glucose oxidation. Since the oxidation of glucose requires less oxygen than the oxidation of fatty acids, ranolazine can help maintain myocardial function in times of ischemia. In addition, ranolazine has minimal effect on blood pressure and heart rate. Ranolazine, by inhibiting cellular ionic channels, prolongs the corrected QT interval. However, ranolazine has not yet been associated with any incidences of ventricular arrhythmia. Other possible mechanism by which Ranolazine could act is by reducing the formation of reactive oxygen species (ROS) and improves reperfusion mechanical function. Ranolazine has been approved by US FDA for the treatment of chronic angina pectoris in combination with amlodipine, beta-blockers or nitrates in patients who do not show adequate response to other anti-anginals. Ranolazine is a metabolic modulator that is being developed by CV Therapeutics (CVT), under license from Roche (formerly Syntex), as a potential treatment for angina. Ranolazine is available as brand name 'Ranexa' as extended release oral tablets. This review focuses on the clinical effects, the mechanism of actions, drug interactions and beneficial effects of Ranolazine in chronic angina and other cardiometabolic disorders.
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PMID:Ranolazine, a partial fatty acid oxidation inhibitor, its potential benefit in angina and other cardiovascular disorders. 1822 Nov 1

William Heberden in 1772 published "some account of the disorder of the breast" which contains the essential elements of angina pectoris as we understand it today. The number of existing cases in the U.S. population today is 6.4 million. Myocardial ischemia manifested by angina pectoris can be either acute or chronic. Patients with chronic stable angina will be the focus of this supplement. The majority of patients are symptomatic but approximately 25% can be asymptomatic. The clinical manifestations of myocardial ischemia generally are chest discomfort, arrhythmias, and LV dysfunction. Myocardial ischemia is a result of imbalance between myocardial oxygen supply and myocardial oxygen demand. High grade coronary stenosis are the usual cause of decreased oxygen supply. The classic hemodynamic factors increasing myocardial oxygen demand include hypertension and increased heart rate due to tachyarrhythmias of any etiology. Exertion is the usual precipitating cause of chronic myocardial ischemia. New information has come forward indicating that myocardial ischemia is associated with disruption of cellular sodium and calcium homeostasis. Ischemia results in a rise of intracellular sodium concentration and thus sodium overload which then activates the sodium calcium exchanger and leads to increased intracellular calcium. When this occurs there is electrical instability and mechanical dysfunction which increases oxygen demand and decreases oxygen supply. The compound Ranolazine is thought to selectively inhibit the late sodium current and attenuates the abnormalities of ventricular repolarization and contractility associated with myocardial ischemia. This compound is the first new class of anti-anginal medication approved in 25 years which may provide physicians with additional therapy for chronic stable angina along with the other anti-angina agents, beta blockers, calcium antagonists and nitrates.
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PMID:Re-thinking angina. 1837 24


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