Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We compared the ischemic diagnosis ability and adverse events of 201Tl myocardial perfusion imaging with SUNY4001 (adenosine) stress to that with exercise (ergometer) stress both on random crossover trial. Thirty one known or suspected chronic stable angina patients who are able to exercise and 10 healthy volunteers were enrolled for the trial. The early and delayed images were obtained by SPECT imaging. The concordance of diagnoses [ischemia vs. no ischemia] between the two types of stresses was 97.3% (36/37) [Kappa: 0.9068]. The sensitivity and specificity based on the exercise test were 100% (6/6) and 96.8% (30/31) respectively. The incidence of adverse events caused by SUNY4001 and the exercise were 44.7% (17/38) and 52.6% (20/38), respectively. Major adverse events caused by SUNY4001 were BP decrease, flushing and headache. And those by exercise were ST decrease, dyspnea and chest pain. None of the adverse events required the intervention or caused life-threatening complication in the trial. The trial showed that the ischemic diagnosis ability and safety of 201Tl scintigraphy with SUNY4001 stress are almost equal to those of the exercise stress that is considered as the standard stress method. We concluded that 201Tl imaging with SUNY4001 is safe and useful for detecting ischemic heart disease, especially for patients unable to exercise adequately.
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PMID:[Comparison of myocardial perfusion imaging by thallium-201 single-photon emission computed tomography with SUNY4001 (adenosine) and exercise--crossover clinical trial at multi-center]. 1535 27

Ranolazine is a novel new antianginal agent currently under investigation as monotherapy and adjunct therapy for the treatment of chronic stable angina. While the mechanism of action of ranolazine is not completely understood, it is believed to involve a reduction in fatty acid oxidation, ultimately leading to a shift in myocardial energy production 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. The clinical data with ranolazine focuses on its use in chronic stable angina, where it has been shown to increase exercise tolerance and decrease angina compared with placebo, as well as in combination with beta-blockers and calcium channel blockers. The use of ranolazine for other cardiac conditions and the effect of ranolazine on morbidity and mortality remains to be determined. Ongoing clinical trials will help further establish the role of ranolazine in the treatment of cardiovascular disorders.
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PMID:Ranolazine. A metabolic modulator for the treatment of chronic stable angina. 1594 56

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. In August 1999, the first of two pivotal phase III clinical trials in patients with stable angina was completed. In August 1999, CVT announced initial results from this trial, designated the MARISA trial, of ranolazine in patients with stable angina. At each of the three doses studied, ranolazine significantly increased patients' treadmill exercise duration compared to placebo, the primary endpoint for this trial. MARISA (monotherapy assessment of ranolazine in stable angina) was a randomized, double-blind, placebo-controlled trial of a sustained release formulation of ranolazine used in 175 patients who were not receiving other anti-anginal drugs. Compared to placebo, ranolazine taken bid at doses of 500, 1000 or 1500 mg significantly increased exercise duration at trough plasma concentrations, which occur at about 12 h after the previous dose. In addition, two key secondary endpoints, exercise time to onset of angina and exercise time to the electrocardiographic appearance of ischemia were also significantly increased by ranolazine compared to placebo at all three doses. The company plans on presenting additional data at a major medical conference, including safety and tolerability data, which are still under analysis. In July 1999 CVT initiated its second phase III trial. The CARISA trial (combination assessment of ranolazine in stable angina) is a randomized, double-blind, placebo-controlled trial of ranolazine used in combination with other anti-anginal drugs, in approximately 450 patients. The primary endpoint for this trial, duration of exercise on a treadmill, is identical to that used in phase II clinical trials. The CARISA trial, along with the pivotal phase III MARISA trial which completed treatment in June 1999, is expected to form the basis of the company's NDA submission to the FDA. In June 1999, results of a randomized, double-blind, placebo-controlled phase II study of ranolazine in chronic stable angina pectoris were published in the July 1, 1999 issue of the American Journal of Cardiology. The study of 312 patients demonstrated that ranolazine may increase exercise time in chronic stable angina patients. The results also indicate that there may be no change in heart rate or blood pressure among any of the ranolazine dosing regimens. In January 1999, CVT received regulatory clearance in Canada, the Czech Republic and Poland and initiated its first pivotal phase III trial for ranolazine in these countries. These new clinical trial centers complement the US centers enrolling American patients. The compound allows maintenance of energy output by muscle cells by improving oxygen metabolism to make the heart pump more efficiently. Ranolazine may be especially useful in angina patients in whom other therapies are ineffective. Clinical studies suggest that ranolazine lowers the heart's demand for oxygen, by increasing its ability to use carbohydrate rather than fat as a fuel. This is thought to be due to activation of pyruvate dehydrogenase, and also by modulating the activities of L-type calcium channels. This is achieved without reducing heart rate or blood pressure, or impairing pumping ability. In August 1998, CVT signed an agreement with Catalytica Pharmaceuticals, which will manufacture specified quantities of ranolazine for use in clinical trials.
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PMID:Ranolazine (Roche Bioscience). 1611 67

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

The indications for percutaneous coronary intervention (PCI) continue to evolve because of the steady improvement in technology, broadened patient and lesion selection criteria, and new evidence from clinical trials. Recently, the role of PCI in patients with chronic stable angina has received considerable scrutiny and has been the subject of great controversy. In these patients, the goals of therapy include the relief of symptom, treatment of ischemia, and reducing the need for subsequent interventions. Medical therapy is the cornerstone in the management of coronary artery disease and should be optimized in all patients. The COURAGE trial investigated the efficacy of combined PCI and optimal medical therapy (OMT) versus OMT alone in patients with stable disease. The trial confirmed several issues that have been already well delineated: (1) in low risk patients, the hard endpoints of death and MI are relatively infrequent and are not reduced by PCI - for prevention of these, OMT may be sufficient, (2) crossover from OMT to PCI is frequent, even in low risk patients, (3) PCI is very effective in reducing symptoms and myocardial ischemia, and (4) significant untreated ischemia is associated with greater likelihood of death and MI.
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PMID:The COURAGE trial in perspective. 1841 71

The management of chronic stable angina has undergone considerable evolution over the past two decades. This article highlights the need for a comprehensive approach to management that includes carefully identifying cardiac risk factors, using therapeutic lifestyle interventions, aggressive, multifaceted medical therapy, and judiciously using myocardial revascularization. For patients whose ischemia cannot be optimally controlled with traditional anti-ischemic agents, a novel antianginal and anti-ischemic agent (ie, ranolazine) has promise in reducing refractory ischemia as add-on therapy. This article discusses the role of coronary artery bypass graft surgery and percutaneous coronary intervention (PCI) in managing chronic stable angina patients and the clinical implications of the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive drug Evaluation) trial. The combined use of a "focal" approach (PCI to treat the culprit stenosis) and a "systemic" approach (lifestyle intervention and aggressive pharmacotherapy) may afford the best event-free survival and clinical outcomes in patients with stable angina.
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PMID:The evolving role of medical therapy for chronic stable angina. 1861 60

In patients with coronary artery disease, the need for more accurately defined treatment recommendations based on the distribution of atherosclerotic disease has given rise to multiple trials designed to evaluate the efficacy of medical therapy versus percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). To clarify these treatment recommendations, we reviewed relevant trials. Patients with chronic stable angina who have one-vessel or two-vessel coronary artery disease without involvement of the left main or left anterior descending coronary arteries fare similarly regardless of treatment modality. In contrast, patients with multivessel disease and inducible ischemia are better served by revascularization by either CABG or PCI. In patients who have left main involvement, diffuse disease with severe atherosclerosis, diabetes mellitus, advanced age, or left ventricular dysfunction, the outcome with regard to survival, anginal relief, and freedom from additional intervention is better with CABG than with PCI.
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PMID:Revascularization treatment recommendations based on atherosclerotic disease distribution: coronary artery bypass grafting versus stenting. 1870 85

Percutaneous coronary intervention (PCI) is not associated with reduction in risk of death or myocardial infarction in patients who have chronic stable angina with normal left ventricular function and moderate coronary artery disease. A substudy of the COURAGE trial has shown that both PCI plus optimal medical therapy (OMT) and OMT alone result in marked improvements in quality of life and angina, but that PCI can substantially benefit patients with more-severe and more-frequent angina. A number of caveats to this study exist, including the extent to which the findings can be applied to the general patient population and the large proportion of patients who had mild angina or were asymptomatic--it is difficult to make these patients feel better. In addition, the remarkable commitment of both healthcare providers and patients in this study would be hard to achieve in clinical practice. Nevertheless, for patients with mild or no angina and no significant ischemia on stress testing, the COURAGE trial reassures us that OMT alone can be efficacious in reducing angina and/or improving quality of life.
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PMID:Impact of optimal medical therapy and percutaneous coronary intervention on patients with stable angina. 1906 24

The ASSOCIATE study investigators have reported that the I(f) current inhibitor, ivabradine, is safe, improves exercise performance, and delays the development of ischemia in patients with chronic stable angina beingtreated with atenolol. ivabradine should be considered in the medical management of symptom-limited patients with angina, when heart rate is suboptimally controlled.
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PMID:Angina: Ivabradine for treatment of stable angina pectoris. 1937 92

As it approaches its fourth decade, percutaneous coronary intervention (PCI) is now the most widely used revascularization strategy around the world and has been tested in multiple clinical scenarios against both medical and surgical therapies. For each patient group and clinical scenario setting, the goals of therapy must be specifically defined and clearly understood as an integral component of the process of selecting the optimal strategy for the individual patient. In patients with chronic stable, often mild angina, the major achievable goals of PCI are to affect symptoms, either by decreasing them or preventing them, reduce the need for subsequent procedures, and relieve ischemia. Achievement of these goals has been documented in multiple randomized trials of PCI versus medical therapy. In these trials of patients with stable coronary artery disease (CAD), however, no reduction in death and myocardial infarction has been observed, and these limitations of PCI in this clinical setting need to be emphasized. Given the typically diffuse nature of CAD and the fact that PCI only treats a segment within a coronary artery, this is not surprising. Although optimal medical therapy forms the cornerstone of management for any patient with CAD, among stable patients who do fail medical therapy, percutaneous coronary revascularization plays a well-documented significant role in improving symptoms and preventing the subsequent need for revascularization. The appropriate utilization rates of PCI in patients with chronic stable angina and preserved left ventricular function should lead to more cost-effective care of patients with stable CAD.
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PMID:Percutaneous coronary intervention for chronic stable angina: a reassessment. 1939 42


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