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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Calcium antagonists are well accepted in the prevention of ischaemia in patients with chronic stable angina, unstable angina, variant angina, and silent ischaemia, and in the treatment of hypertension. Although all of these compounds increase myocardial oxygen supply by reducing coronary tone and decrease myocardial oxygen demand by reducing systolic pressure and myocardial contractility, the magnitude of these effects may differ from one agent to another. Some calcium antagonists, such as verapamil and diltiazem, reduce heart rate and attenuate heart rate increases in response to stress, while in contrast, dihydropyridine calcium antagonists such as nifedipine may cause reflex increases in heart rate. These differences may be of importance in light of epidemiologic evidence that lower heart rates are associated with a reduced long-term risk of cardiovascular mortality, and experimental data showing that a lower heart rate may protect against the development of atherosclerosis. Calcium antagonists also inhibit platelet aggregation and thrombus formation which may contribute to their anti-ischaemic effects. Clinical trial data suggest that calcium antagonists may stay the progression of atherosclerosis. Mechanisms underlying an anti-atherosclerotic effect may include attenuation of endothelial dysfunction, prevention of LDL, peroxidation, stimulation of LDL receptor activity, inhibition of superoxide radical generation, and inhibition of vascular smooth muscle cell growth. Heart-rate-controlling calcium antagonists, such as verapamil and diltiazem, may reduce reinfarction rates following acute myocardial infarction and thus may have a role in post-infarction patients who do not show evidence of heart failure. Their use in heart failure patients receiving an angiotension-converting enzyme inhibitor (ACE-I) is under investigation in several large trials. Because calcium antagonists have a mechanism of action different from ACE-I, the pairing of a heart-rate-controlling calcium antagonist with an ACE-I might be expected to offer additive cardioprotective and vascular protective effects.
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PMID:The role of calcium antagonists in ischaemic heart disease. 884 1

Nisoldipine coat-core is an extended-release once-daily formulation of a dihydropyridine calcium antagonist effective in the treatment of chronic stable angina pectoris. With immediate-release formulations of nisoldipine, plasma drug concentrations that produce therapeutic effects result rapidly, but are not sustained and do not maintain the effects throughout a 12-hour dosage interval. In contrast, with nisoldipine coat-core, a gradual increase in plasma nisoldipine concentrations occurs over 12 hours and therapeutic concentrations are then maintained for the duration of a 24-hour dosage interval. In dosages of 10 to 60 mg once daily, nisoldipine coat-core controls symptoms of angina and improves exercise-induced signs of ischaemia in patients with stable angina. Compared with placebo, daily nisoldipine coat-core doses of > or = 20 mg provide statistically significant increases in total exercise time and time to produce angina and a trend towards an increase in the time to produce 1 mm ST segment depression, in exercise tests conducted approximately 23 hours postdose. When administered in 20 and 40 mg daily doses, nisoldipine coat-core produces improvements in exercise test parameters that are similar to those seen with amlodipine 5 or 10 mg/day or regular-release or sustained-release (SR) diltiazem 240 mg/day. The frequency of daily angina attacks and consumption of short-acting nitrates are also reduced by nisoldipine to a similar extent to that observed with these other agents. After longer term (1 year) administration of 10 to 60 mg daily, improvements in exercise test parameters are maintained, with equivalent anti-ischaemic efficacy seen in patients receiving nisoldipine coat-core alone or with background nitrate or beta-blocker therapy. Adverse events associated with nisoldipine coat-core are typical of the dihydropyridine class of calcium antagonists, with peripheral oedema and headache being most common. Nisoldipine coat-core appears to be associated with fewer deaths than placebo, notably in the DEFIANT-II (Doppler Flow and Echocardiography in Functional Cardiac Insufficiency: Assessment of Nisoldipine Therapy II) study, where only 1 death occurred with nisoldipine compared with 7 in the placebo group. Nisoldipine should not be taken during phenytoin therapy. In addition, grapefruit juice should be avoided during nisoldipine therapy and nisoldipine should not be taken concurrently with high-fat meals. Thus, the coat-core formulation of nisoldipine appears to have overcome the limitations of the shorter duration of action of immediate-release nisoldipine. Nisoldipine coat-core is well tolerated and once-daily administration produces a long duration of effective anti-ischaemic relief in patients with chronic stable angina pectoris.
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PMID:Nisoldipine coat-core. A review of its pharmacodynamic and pharmacokinetic properties and clinical efficacy in the management of ischaemic heart disease. 912 71

Mibefradil is the first of a new class of calcium antagonists with a unique structure and pharmacology. Its novel mechanism of action is characterized by L-type and selective T-type calcium channel blockade. Mibefradil is selective for smooth muscle over cardiac muscle and selectively dilates the coronary vasculature over the peripheral vasculature. In animal studies, mibefradil increases coronary blood flow during induced ischemia. In addition, in vitro studies demonstrated that mibefradil decreases smooth muscle proliferation in response to vascular injury. The most intriguing effects of mibefradil include a lack of negative inotropy and reflex tachycardia, as well as inhibition of pathologic hypertrophy and remodeling in response to vascular injury. In clinical trials, mibefradil (100 mg) was more effective than diltiazem dual-release capsules (360 mg) and as effective as amlodipine (10 mg) in treating mild-to-moderate hypertension; mibefradil (100 mg) also resulted in a greater reduction in sitting diastolic blood pressure than did nifedipine GITS (60 mg) in patients with moderate-to-severe hypertension. In patients with chronic stable angina, mibefradil (100 mg) was as effective as diltiazem SR capsules (120 mg) twice daily and more effective than amlodipine (10 mg) in improving exercise tolerance and reducing ischemic episodes. Mibefradil improved survival in a rat model of heart failure as effectively as the angiotensin-converting enzyme (ACE) inhibitor, cilazapril. The apparent lack of negative inotropic activity and neurohormonal activity with mibefradil, as well as its favorable effects on cardiac remodeling in experimental models, suggest that this agent may be beneficial in congestive heart failure. This hypothesis is being tested in the ongoing Mortality Assessment in Congestive Heart Failure (MACH-1) trial.
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PMID:Mibefradil: a selective T-type calcium antagonist. 937 39

Recently, there has been some controversy concerning calcium antagonists, suggesting the need for further debate on this heterogeneous class of drugs. Three chemical families, dihydropyridines (DHP), phenylalkylamines (verapamil) and benzothiazepines (diltiazem) bind to the type L receptors of the calcium channels with different binding, modulation and tissue selectivity characteristics. DHP are selective for type L receptors and block the extracellular portion of the channel leading to vigorous vasodilatation and little or no cardiodepressive effect. Diltiazem and verapamil also interfere with type T channel receptors. These drugs have a cardiodepressive and a bradycardia effect. Verapamil blocks the intracellular portion of the calcium channel at the site where part of the catecholamine effect occurs, leading to less reflex sympathetic activation than with other calcium antagonists (namely DHP). Deleterious sympathetic stimulation is proportional to the intensity and degree of rapid onset of arterial vasodilatation and is attenuated with slow-release formulations. Calcium antagonists in general have an anti-angina effect but high-dose short-acting DHP can cause excessive vasodilatator leading to subsequent ischemia. In chronic stable angina, slow-release verapamil has been shown to have a preventive clinical effect comparable to that of beta blockers. Slow-release nifedipine is effective and safe but must be associated with betablockers. In unstable angina, only those calcium antagonists with a bradycardia effect appear to have an effect similar to beta blockers. Beta blockers are nevertheless to be preferred in these patients (excepting Prinzmetal angina) until results of convincing clinical studies are available. After the initial phase of myocardial infarction, again only calcium antagonists with a bradycardia effect have been shown to have a beneficial effect, in patients without cardiac failure: diltiazem in infarction without Q-wave and verapamil in all infarctions, in case of residual ischemia to reduce the risk of recurrence.
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PMID:[Calcium antagonists in ischemic heart disease]. 941 Oct 6

Previous observations have suggested that pulmonary artery pressure rises during sleep, whereas systemic artery pressure falls. A system has been developed for careful and accurate recording of pulmonary arterial pressure, and applied it to two groups of subjects: patients with heart failure, and patients with chronic stable angina. The results have largely confirmed the nocturnal pressure rise in pulmonary arterial pressure. Detailed analysis strongly suggests that the same physiological mechanisms producing a fall in systemic pressure are responsible for the rise in pulmonary pressure. The precise mechanism remains to be elucidated.
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PMID:Diurnal variation in pulmonary artery pressure. 1060 71

BACKGROUND: There is now a wealth of data supporting the use of beta-blockers in heart failure and the additional pharmacological properties of carvedilol are thought to play an important role in the therapeutic efficacy of carvedilol in this disease. METHODS AND RESULTS: Carvedilol is licensed for the treatment of essential hypertension, chronic stable angina, and mild to moderate chronic heart failure. This article provides an up-to-date review of the clinical pharmacology of carvedilol, with particular emphasis on its clinical effects in heart failure. CONCLUSION: Carvedilol is a multiple-action neurohormonal antagonist that offers nonselective beta-blockade, alpha-1 blockade, antioxidant, anti-ischemic mortality, and anti-proliferative properties. In addition to reductions in hospitalization and mortality rates, benefits of carvedilol in heart failure include dramatic improvements in left ventricular function and other parameters of cardiac remodeling.
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PMID:Clinical Pharmacology of Carvedilol. 1068 42

Despite increasing pharmacological and mechanical treatment options, ischemic heart disease continues to be associated with considerable patient mortality and morbidity. The estimates of the direct and indirect costs associated with chronic stable angina amount to billions of dollars. Given the epidemiological and economic magnitude of the problem, the need for more effective therapies is self-evident. Based on current guidelines, the management of ischemic heart disease has progressively broadened to include risk factor modification, patient education, and pharmacological therapy. The latter includes i) classic antianginal agents such as beta-blockers, calcium antagonists, and nitrates, and ii) drugs for secondary prevention, such as aspirin, clopidogrel, statins, and angiotensin-converting enzyme inhibitors. Tailoring therapy to individual needs has become even more challenging because of the marked changes in the clinical profile of patients with chronic ischemic heart disease. Compared with the past, today's patients tend to be older, to have undergone revascularization procedures, and to frequently have associated illnesses, including heart failure and diabetes. Significant progress has been made in recent years in understanding the role of cardiac energy metabolism in the pathogenesis of myocardial ischemia. A better understanding of metabolic derangements associated with ischemia and reperfusion is translating into innovative therapeutic approaches. Optimization of cardiac energy metabolism is based on promoting cardiac glucose oxidation. This has been proved to enhance cardiac function and protect myocardial tissue against ischemia-reperfusion injury. A new class of metabolic agents, known as the 3-ketoacyl coenzyme A thiolase inhibitors (trimetazidine), is able to elicit an increase in glucose and lactate combustion secondary to partial inhibition of fatty acid oxidation, producing clinical benefits in patients with ischemic heart disease.
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PMID:["Persistent" angina: rationale for a metabolic approach]. 1507 76

This article provides information and a commentary on landmark trials presented at the European Society of Cardiology Congress in August 2004, relevant to the pathophysiology, prevention or treatment of heart failure. The SENIORS trial suggests that nebivolol is well tolerated and effective in older patients with heart failure, even if left ventricular systolic function is not markedly depressed. However, patients aged >75 years appeared to gain less benefit. Further data on the effects of nebivolol on symptoms and quality of life are awaited. Two new trials of long-term antibiotic prophylaxis after myocardial infarction (ACES and PROVE-IT) showed no benefit. The ACTION trial showed no reduction in serious cardiovascular events with nifedipine GITS in patients with chronic stable angina, despite a substantial reduction in blood pressure. The HF-ACTION trial announced that the first 700 patients of a projected 3000 had been randomised to either an exercise program or encouragement to exercise but without a formal program. The primary outcome measure is death or hospitalisation for any reason.
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PMID:Clinical trials update from the European Society of Cardiology: SENIORS, ACES, PROVE-IT, ACTION, and the HF-ACTION trial. 1554 17

Ranolazine (Ranexa), a piperazine derivative, is a new antianginal agent approved for the treatment of chronic stable angina pectoris for use as combination therapy when angina is not adequately controlled with other antianginal agents. While the exact mechanism of action of ranolazine is not known, its antianginal and anti-ischaemic effects do not appear to depend upon changes in blood pressure or heart rate. An extended-release (ER) oral formulation of ranolazine has been developed to facilitate twice-daily administration whilst maintaining therapeutically effective plasma concentrations. In patients with chronic stable angina, ranolazine ER monotherapy was shown to improve exercise duration at trough plasma drug concentration in a dose-dependent manner compared with placebo. The drug was effective as adjunctive therapy in patients with chronic stable angina whose condition was not controlled adequately with conventional antianginal therapy. In randomised clinical trials, ranolazine ER was well tolerated, with no overt effects on cardiovascular haemodynamics or conduction, apart from a modest increase in corrected QT (QTc) interval (but no torsades de pointes). Importantly, the efficacy and tolerability of ranolazine ER were not affected by comorbid conditions, including old age, heart failure (HF) or diabetes mellitus. Comparative trials of ranolazine ER with other antianginal agents and trials examining its effects on long-term morbidity and mortality in patients with ischaemic heart disease are required to determine with greater certainty the place of the drug in current antianginal therapy. Nevertheless, ranolazine ER may well prove to be a useful alternative and adjunct to conventional haemodynamic antianginal therapy in the treatment of chronic stable angina.
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PMID:Ranolazine: a review of its use in chronic stable angina pectoris. 1662 Jan 47

Pure heart rate reduction by ivabradine during exercise results in the decrease in oxygen demand and the increase in oxygen supply through the prolongation of diastole. These properties are crucial for its beneficial effect in patients with chronic stable angina. The ability of ivabradine to reduce the heart rate at rest can also have a potential use in clinical practice. In fact, the new directions for future clinical research are focused on this property. Chronic coronary artery disease, acute coronary syndromes and heart failure represent the areas in which resting heart rate reduction may improve cardiovascular prognosis. Application of ivabradine in these conditions deserves full attention, with dedicated and properly powered outcome trials.
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PMID:Future directions: what data do we need? 1693 76


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