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

In general, calcium channel blockers have not been used in patients during acute myocardial infarction as they may exacerbate heart failure, possibly by neuro-humoral stimulation. Amlodipine, a new dihydropyridine calcium channel blocker without neurohumoral stimulation, was tested in an experimental model of acute myocardial infarction with assessment of hemodynamics, left ventricular (LV) function, and infarct size. Anesthetized dogs were subjected to 3 h of coronary artery occlusion followed by 3 h of reperfusion. At 2 h of occlusion, they were randomized to receive either amlodipine (250 micrograms/kg, n = 11) or saline (n = 11). Before treatment, all variables were similar in both groups. The diastolic pressure was unchanged following saline, but was reduced following amlodipine by 1 h after therapy (from 94 +/- 5 to 71 +/- 3 mm Hg, p < 0.0001 vs. saline) and for the duration of the protocol. Indices of left ventricular (LV) function did not deteriorate with amlodipine treatment compared with saline. After 3 h of reperfusion, the LV dP/dt was 1,720 +/- 114 mm Hg/s in the saline group and 1,958 +/- 167 mm Hg/s with amlodipine (p = ns). The area ejection fraction, assessed by echocardiography, was similar in both groups (43 +/- 5%, saline; 45 +/- 3%, amlodipine; p = ns), as was the LV end-diastolic pressure (8 +/- 1 mm Hg, saline; 7 +/- 1 mm Hg, amlodipine; p = ns). Subendocardial regional myocardial blood flow, measured by radioactive microspheres, was 0.75 +/- 0.08 ml/min/g with saline and 1.34 +/- 0.33 ml/min/g with amlodipine in the previously ischemic reperfused subendocardium (p = 0.1).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Absence of hemodynamic deterioration in the presence of amlodipine following experimental myocardial infarction. 128 Jul 49

Calcium channel blockers are theoretically effective in the treatment of chronic systolic heart failure because of their actions as arteriolar dilators, antiischemic agents, and relaxants of diastolic left ventricular function, and because they may prevent progression of myocardial dysfunction. The first-generation calcium channel blockers nifedipine, verapamil, and diltiazem cause hemodynamic and clinical deterioration and may increase the frequency of cardiac events in postmyocardial infarction patients with heart failure. These drugs depress left ventricular contractility in the short term, and can activate neurohormonal systems due to their hypotensive effects. The second-generation calcium channel blocker felodipine does not activate the sympathetic nervous and renin-angiotensin systems, but has no effect on exercise capacity or mortality. Amlodipine increases exercise time and reduces symptoms and plasma norepinephrine concentration in heart failure. It also reduces morbidity and mortality in New York Heart Association class i.v. patients with nonischemic dilated cardiomyopathy, and appears to be effective as primary therapy for patients with dilated cardiomyopathy.
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PMID:Evolving role of calcium channel blockers in heart failure. 866 5

Recent publications purporting to show that calcium antagonists, when used for the treatment of hypertension or in the post myocardial infarction patient, would paradoxically increase the rate of heart attack and mortality have cast doubts on the safety and efficacy of this drug class. All three studies are retrospective, and have various drawbacks. Specifically, the metaanalysis of Furberg et al is fraught with mistakes, of borderline significance, and based on old data pertaining to short-acting nifedipine only (which should not be given in patients who have suffered an acute heart attack). The case control study of Psaty et al suggested that hypertensive patients who were treated with short-acting verapamil, diltiazem, and nifedipine had an excessive rate of myocardial infarction when compared with patients who were treated with diuretics. Two out of the three calcium antagonists that were used in this study were not approved for the treatment of hypertension by the US Food and Drug Administration. Some patients were taking these drugs only once a day whereas, because of their short duration of action, at least a three or four times daily regimen would be required to achieve an acceptable blood pressure control throughout a 24-h period. The cohort study of Pahor et al suggested distinct differences among various calcium antagonists with regard to survival. Blood pressure was controlled in < 40% of all patients, and in some patients blood pressure was never even measured. Recent studies, such as the Prospective Randomized Amlodipine Survival Evaluation (PRAISE), the third Vasodilator-Heart Failure Trial (VHeFT-III), the second Doppler Flow and Echocardiography in Functional Cardiac Insufficiency Assessment of Nisoldipine Therapy (DEFIANT II), the Angina Prognosis Study in Stockholm (APSIS), and the Shanghai Trial of Nifedipine in the Elderly (STONE), attest to the safety and efficacy of the newer long-acting calcium antagonists in patients with a wide spectrum of heart disease. Several ongoing trials including the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) with amlodipine, the International Nifedipine-GITS Study: Intervention as a Goal in Hypertension Treatment (INSIGHT) with nifedipine, the Hypertension Optimal Treatment study (HOT) with felodipine, the Systolic Hypertension in the Elderly in Europe Trial (SYST-EUR) with nicardipine, the Second Swedish Trial in Old Patients with Hypertension (STOP II) with felodipine, and Nordic Diltiazem Study (NORDIL) with diltiazem, will give us morbidity and mortality data in patients with high blood pressure within the next few years. Until these results are available, we can be confident that the lowering of blood pressure and providing relief of patients with symptomatic angina can be achieved safely and efficiently with the presently available long-acting calcium antagonists.
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PMID:What, if anything, is controversial about calcium antagonists? 896 30

Continuing high morbidity and mortality have spurred an ongoing search for new therapeutic agents for patients with congestive heart failure. Calcium antagonists (CAs) have been under active investigation in patients with heart failure since their introduction into clinical medicine, because their anti-ischemic and vasodilator properties were thought to be of potential benefit in this patient population. However, review of published clinical trials of CAs in patients with heart failure reveals that some of these drugs are associated with detrimental effects, including acute hemodynamic deterioration, increased symptoms of heart failure, and increased mortality. The adverse effects of short-acting CAs in patients with heart failure include negative inotropic effects and neurohormonal activation. Long-acting CAs, such as amlodipine and felodipine, had fewer negative inotropic effects, showed less evidence of neurohormonal activation, and were better tolerated in clinical trials. Amlodipine, in combination with an angiotensin-converting enzyme inhibitor, had a neutral effect in patients with ischemic heart failure and an unexplained benefit in a subgroup of patients with non-ischemic cardiomyopathy. Although the preliminary experience with long-acting dihydropyridine CAs in heart failure has been encouraging, safety concerns raised by past trials dictate that no CA can be recommended for the treatment of heart failure at this time.
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PMID:Safety of calcium antagonists in patients with congestive heart failure. 938 7

The therapeutic effects of calcium channel blockers on heart failure are controversial. However, a recent clinical trial demonstrated a favorable effect of amlodipine on survival rates in patients with heart failure resulting from nonischemic dilated cardiomyopathy. There are a number of studies showing that cytokines generated by activated immune cells cause an increase in nitric oxide (NO) via induction of NO synthase (NOS), which results in a direct negative inotropic effect and a modulation of inotropic responsiveness. Increases in inflammatory circulating cytokines have been detected in patients with heart failure and cardiomyopathy, elevated plasma levels of nitrite/nitrate in patients with heart failure have been reported, and inducible NOS (iNOS) has been found in ventricular tissue from patients with dilated cardiomyopathy. In our recent study, amlodipine improved histopathological lesions in the heart and survival rates in a murine model of nonischemic heart failure induced by encephalomyocarditis virus. Amlodipine inhibited NO production in vitro and decreased the number of iNOS positive cells in vivo. In this model, the therapeutic effect of amlodipine on myocardial injury is considered in part to result from inhibition of overproduction of NO. In this review, the possible roles of cytokines and NO in the pathophysiology of heart failure are discussed, along with the opportunities for therapeutic intervention.
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PMID:Calcium channel blocker-induced protection against cardiovascular damage. 948 94

Investigations of calcium antagonists in patients with advanced heart failure have raised concern over an increased risk of worsening heart failure and heart failure deaths. We assessed the effect of amlodipine on cause-specific mortality in such patients enrolled in a randomized, double-blind, placebo-controlled trial. In total, 1,153 patients in New York Heart Association class IIIb or IV heart failure were randomized to receive amlodipine or placebo, along with angiotensin-converting enzyme inhibitors, diuretics, and digitalis. Over a median 14.5 months of follow-up, 413 patients died. Cardiovascular deaths accounted for 89% of fatalities, 50% of which were sudden deaths and 45% of which were due to pump failure, with fewer attributed to myocardial infarction (3.3%) or other cardiovascular causes (1.6%). Amlodipine treatment resulted in a greater relative reduction in sudden deaths (21%) than in pump failure deaths (6.6%) overall. When patients were classified by etiology of heart failure (ischemic or nonischemic), cause-specific mortality did not differ significantly between treatment groups in the ischemic stratum. In the nonischemic stratum, however, sudden deaths and pump failure deaths were reduced by 38% and 45%, respectively, with amlodipine. Thus, when added to digitalis, diuretics, and angiotensin-converting enzyme inhibitors in patients with advanced heart failure, amlodipine appears to have no effect on cause-specific mortality in ischemic cardiomyopathy, but both pump failure and sudden deaths appear to be decreased in nonischemic heart failure patients treated with amlodipine.
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PMID:Effect of amlodipine on mode of death among patients with advanced heart failure in the PRAISE trial. Prospective Randomized Amlodipine Survival Evaluation. 978 71

Increasing evidence suggests that angiotensin-converting enzyme (ACE) inhibitors can increase vascular nitric oxide (NO) production. Recent studies have found that combined inhibition of ACE and neutral endopeptidase (NEP) may have a greater beneficial effect in the treatment of heart failure than inhibition of ACE alone. Amlodipine, a calcium channel antagonist, has also been reported to have a favorable effect in the treatment of patients with cardiac dysfunction. The purpose of this study was to determine whether and the extent to which all of these agents used in the treatment of heart failure stimulate vascular NO production. Heart failure was induced by rapid ventricular pacing in conscious dogs. Coronary microvessels were isolated from normal and failing dog hearts. Nitrite, the stable metabolite of NO, was measured by the Griess reaction. ACE and NEP inhibitors and amlodipine significantly increased nitrite production from coronary microvessels in both normal and failing dog hearts. However, nitrite release was reduced after heart failure. For instance, the highest concentration of enalaprilat, thiorphan, and amlodipine increased nitrite release from 85 +/- 4 to 156 +/- 9, 82 +/- 7 to 139 +/- 8, and 74 +/- 4 to 134 +/-10 pmol/mg (all *p <.01 versus control), respectively, in normal dog hearts. Nitrite release in response to the highest concentration of these two inhibitors and amlodipine was reduced by 41% and 31% and 32% (all #p <.01 versus normal), respectively, in microvessels after heart failure. The increase in nitrite induced by either ACE or NEP inhibitors or amlodipine was entirely abolished by Nw-nitro-L-arginine methyl ester, HOE 140 (a B2-kinin receptor antagonist), and dichloroisocoumarin (a serine protease inhibitor) in both groups. Our results indicate that: 1) there is an impaired endothelial NO production after pacing-induced heart failure; 2) both ACE and NEP are largely responsible for the metabolism of kinins and modulate canine coronary NO production in normal and failing heart; and 3) amlodipine releases NO even after heart failure and this may be partly responsible for the favorable effect of amlodipine in the treatment of heart failure. Thus, the restoration of reduced coronary vascular NO production may contribute to the beneficial effects of these agents in the treatment of heart failure.
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PMID:Kinin-mediated coronary nitric oxide production contributes to the therapeutic action of angiotensin-converting enzyme and neutral endopeptidase inhibitors and amlodipine in the treatment in heart failure. 991 84

Short-acting calcium antagonists exert a sympathoexcitation that in heart failure further enhances an already elevated sympathetic activity. Whether this is also the case for long-acting formulations is not yet established, despite the prognostic importance of sympathetic activation in heart failure. It is also undetermined whether in this condition long-acting calcium antagonists favorably affect a mechanism potentially responsible for the sympathetic activation, ie, the baroreflex impairment. In 28 heart failure patients (NYHA functional class II) under conventional treatment we measured plasma norepinephrine and efferent postganglionic muscle sympathetic nerve activity (microneurography) at rest and during arterial baroreceptor stimulation and deactivation induced by stepwise intravenous infusions of phenylephrine and nitroprusside, respectively. Measurements were performed at baseline and after 8 weeks of daily oral amlodipine administration (10 mg/d, 14 patients) or before and after an 8-week period without calcium antagonist administration (14 patients). Amlodipine caused a small and insignificant blood pressure reduction. Heart rate, left ventricular ejection fraction, and plasma renin and aldosterone concentrations were not affected. This was the case also for plasma norepinephrine (from 2.43+/-0.41 to 2.50+/-0.34 nmol/L, mean+/-SEM), muscle sympathetic nerve activity (from 54.4+/-5.9 to 51.0+/-4.3 bursts/min), and arterial baroreflex responses. No change in the above-mentioned variables was seen in the control group. Thus, in mild heart failure amlodipine treatment does not adversely affect sympathetic activity and baroreflex control of the heart and sympathetic tone. This implies that in this condition long-acting calcium antagonists can be administered without untoward neurohumoral effects anytime conventional treatment needs to be complemented by drugs causing additional vasodilatation.
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PMID:Effects of amlodipine on sympathetic nerve traffic and baroreflex control of circulation in heart failure. 1002 25

No one would now believe that all infections will respond to a single antibiotic, nor that all known antibiotics should be given to all patients with infection. It is obvious that some patients with specific causes of heart failure need specific treatment, but whether heart failure of ischaemic or nonischaemic origin need different treatments is not certain. Only when parallel clinical trials have been conducted with individual drugs in separate groups of patients with ischaemic or nonischaemic heart failure will the need for different treatment strategies be known. Until then, there will be a dependency on second-rank evidence (that which can be derived from trials with 'surrogate' end-points, from meta-analysis of small trials and from subset analysis of different patient groups within single trials). The best evidence at present comes from subset analysis of two studies, with bisoprolol (Cardiac Insufficiency Bisoprolol Study; CIBIS) and amlodipine (Prospective Randomised Amlodipine Survival Evaluation; PRAISE). These suggest that patients with different causes of heart failure respond to treatment in different ways.
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PMID:Different causes of heart failure need different treatment strategies. 1044 83

The incidence of hospitalizations, lengths of stay, and per-diem costs were determined for 421 patients (amlodipine, 209; placebo, 212) with nonischemic cardiomyopathy in the first Prospective Randomized Amlodipine Survival Evaluation (PRAISE) study to assess the impact of amlodipine on hospital use and to compare the costs of hospitalization with the cost of amlodipine treatment. Treatment with amlodipine versus placebo significantly delayed the mean (+/- SD) time to first hospitalization (447 +/- 26 d vs 315 +/- 18 d, respectively; P = 0.0139). Both treatment groups showed a similar number of hospital admissions per patient per year. The overall hospital length of stay was 1.17 days less per year with amlodipine than with placebo, at a cost of $1098 less per person per year although these differences were not statistically significant. Significantly fewer amlodipine patients were admitted for unexplained cardiac arrest (odds ratio, 0.235; P = 0.002) and ventricular arrhythmias (odds ratio, 0.497; P = 0.004). These findings are consistent with clinical reports from PRAISE of prolonged survival and a reduction in sudden cardiac death among patients with severe heart failure due to nonischemic heart disease. This analysis suggests that in patients with nonischemic cardiomyopathy, treatment with amlodipine can delay the time to hospitalization and may reduce the number of hospital admissions related to ventricular arrhythmias. The estimated reduction in hospital costs of $1098 per year would more than offset the amlodipine treatment cost of approximately $700 per year.
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PMID:Hospital use and costs among patients with nonischemic cardiomyopathy in the first prospective randomized amlodipine survival evaluation study. 1046 22


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