Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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

To assess the overall balance between efficacy and safety of the long-action calcium antagonist nifedipine gastrointestinal therapeutic system (GITS) in patients with stable symptomatic coronary artery disease (CAD), a large multicentre placebo-controlled double-blind trial called ACTION has been mounted (A Coronary Disease Trial Investigating Outcome with Nifedipine GITS). Patients are eligible if they have proven CAD on antianginal treatment in stable clinical condition for at least 3 months without heart failure. The left ventricular ejection fraction must be above 40%. Patients not already on lipid-lowering therapy will be evaluated and such treatment will be started based on current guidelines before randomisation. After washout of an already given calcium antagonist, more than 6000 patients in total will be randomised in equal proportions to either nifedipine GITS 60 mg once daily or placebo. The mean clinical follow-up will be 5 years, with no restrictions on concomitant medication (with the exception of digitalis, calcium antagonists and class III antiarrhythmics). The primary end-point will be survival free of major cardiovascular events (i.e. survival free of acute myocardial infarction, emergency coronary angiography, overt heart failure, stroke and peripheral revascularisation). The study has 95% power to detect a significant (p < 0.05) 18% improvement of this end-point and is of sufficient size to exclude an excess mortality of 3.1 per 1000 patient-years. In this first stable angina trial of this size and scope, 185 centres in Canada, Europe, Israel, Australia and New Zealand will participate. Recruitment will start in November 1996 and is planned to be completed in 2 years.
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PMID:Action: a 30,000 patient-years double-blind, placebo-controlled trial of nifedipine GITS in stable angina. ACTION Research Group. 951 4

Calcium-channel antagonist drugs are prescribed widely for angina and hypertension. A limiting side effect is edema, which can make heart failure worse. We show that nifedipine, a dihydropyridine-type calcium-channel antagonist, can increase vascular permeability in rat skeletal muscle and skin when injected locally. In nifedipine-injected cremaster muscle, the copper content, used to quantify Monastral blue dye accumulation, was 15.0 +/- 2.4 microgram/g compared with 5.3 +/- 0.7 microgram/g in control preparations (P < 0. 05). The injection of nifedipine in rat skin in vivo increased local plasma leakage in injected sites from 5.5 +/- 1.1 microliter in control sites to 9.9 +/- 2.5, 17.0 +/- 2.4, 24.3 +/- 5.9, and 23.3 +/- 5.4 microliter in sites injected with 10(-10), 10(-9), 10(-8), or 10(-7.2) mol/site, respectively (P < 0.05 in each case compared with control). Vascular labeling techniques using light microscopy, electron microscopy, and microanalysis show that the microvascular site of leakage is not from capillaries but from postcapillary venules of 12-36 micrometer in diameter, the same site that controls the edema response in inflammation. Nifedipine can act within the microcirculation to increase the permeability of the postcapillary venule.
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PMID:Nifedipine increases microvascular permeability via a direct local effect on postcapillary venules. 974 89

Nifedipine is a Ca-antagonist drug that reduces contractility of vascular smooth muscle, and is used in the treatment of arterial hypertension and of stable and vasospastic angina. Aim of this study is to evaluate long-term effect of nifedipine on distribution of body fluid compartment, assessed by BIA (Bio-Impedance Analysis), and on cardiac function, in hypertensive patients on dialysis. Two groups of hypertensive patients were compared: a) a first group of nine patients (5 Male, 4 Female; age 62.67 +/- 10.39) treated with nifedipine (30 mg/day) for one year; b) a control group of sixteen dialysis patients (9 Male, 7 Female; age 56.31 +/- 14.44), previously hypertensive, with normal blood pressure without anti-hypertensive drugs for three months or more. By BIA, extracellular water percentage (ECW%) is higher in nifedipine-treated patients (p < 0.001) in comparison with the control group before dialysis; no other difference is present. The intradialytical variations (before dialysis vs. the end of dialysis) of body fluid compartments are a significant decrease of total body water % (52.33 +/- 2.89 vs. 48.72 +/- 3.35, p < 0.001), ECW% (40.97 +/- 2.2 vs. 37.56 +/- 3.47, p < 0.005), Left Ventricular End-Diastolic Volume (81.1 +/- 14.6 vs. 63.4 +/- 21.66 ml/m2, p < 0.003), Cardiac Output (3.35 +/- 0.71 vs. 2.51 +/- 0.76 l/min/m2, p < 0.04) and Stroke Volume (45.76 +/- 10.21 vs. 34.34 +/- 9.98 ml/m2, p < 0.02) in nifedipine-treated patients. Our findings suggest that nifedipine induces intermittent and prolonged expansion of extra-cellular volume. This condition, in patients otherwise without clinical and echocardiographic signs of heart failure, can be potentially detrimental for cardiac function on long-term nifedipine treatment.
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PMID:Nifedipine and extracellular water in dialysis arterial hypertension. 979 73

Permanent residents at high altitude may develop excessive polycythaemia (H-Hb) and pulmonary hypertension, which often leads to cardiac failure. Inhibitors of calcium channels have been shown to reverse pulmonary hypertension in respiratory diseases and in primary pulmonary hypertension, but their efficiency has not been evaluated in high-altitude-induced pulmonary hypertension. Systolic pulmonary arterial pressure (Ppa) was studied by Doppler echocardiography, at rest and after sublingual nifedipine, in 31 asymptomatic residents at 3,600 m. Individuals were separated into two groups according to resting Ppa: a group with low Ppa (< or =4.7 kPa, n=17) and a group with high Ppa (>4.7 kPa, n=14). Individuals were also split into two groups according to haemoglobin (Hb) concentration: a normocythaemic (L-Hb) group ([Hb] < or =180 g.L(-1), n=17) and a H-Hb group ([Hb] >180 g.L.(-1), n=14). No significant difference in Ppa was observed between the L-Hb and H-Hb groups. There was no correlation between [Hb] and Ppa. Nifedipine induced a decrease of >20% in Ppa in two-thirds of the subjects. This response was correlated with higher levels of basal Ppa (p<0.001) and was inversely correlated with age in the L-Hb group (p<0.05). Pulmonary vasoreactivity to nifedipine was independent of the degree of H-Hb. Pulmonary hypertension secondary to chronic altitude hypoxia may be reversible, despite a possible remodelling of the pulmonary arterioles.
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PMID:Pulmonary hypertension in high-altitude chronic hypoxia: response to nifedipine. 986 18

The potential of Ca(2+) channel antagonists, particularly nifedipine, to cause apoptotic cell death has been controversial and is of considerable importance for cardiomyocytes as loss of these cells is an important component of the pathophysiology leading to heart failure. To examine the hypothesis that nifedipine induces cell death and modulates calcium-induced apoptosis, cardiomyocytes in culture from embryonic chick hearts, that readily manifest apoptosis, were studied. Apoptosis was evaluated by fluorescent activated cell sorting (FACS) analysis and by quantitative analysis of DNA fragmentation by an enzyme-linked immunosorbent assay (ELISA) specific for histone-associated DNA fragments of mono- and oligonucleosome size. Cell death was evaluated by using the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) assay. Cardiomyocytes were treated with various concentrations of nifedipine over a concentration range relevant to serum concentrations in man. Nifedipine, 1 to 100 microM, did not produce cell death in cardiomyocytes. There was no evidence of apoptosis on FACS analysis of cardiomyocytes stained with fluoresceine diacetate or propidum iodide (PI). Neither was there any evidence of apoptotic nuclei on PI staining of permeabilized cardiomyocytes treated with nifedipine. In contrast, DNA fragmentation consistent with apoptosis was induced in a significant (P<0.05) concentration-dependent manner, by increases in extracellular Ca(2+) concentration ([Ca(2+)](o)). Importantly, nifedipine reduced DNA fragmentation produced by increased [Ca(2+)](o). Furthermore, nifedipine blocked calcium-induced cell death as high [Ca(2+)](o) significantly (P<0. 05) reduced cell viability. These data indicate that nifedipine does not induce apoptosis in cardiomyocytes rather apoptosis in cardiomyocytes is under regulatory control by Ca(2+) and nifedipine can antagonize Ca(2+)-mediated apoptotic cell death.
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PMID:Nifedipine does not induce but rather prevents apoptosis in cardiomyocytes. 1067 28

To investigate the impact of treatment on cardiovascular mortality and morbidity, we assessed outcomes in patients with hypertension and diabetes who received co-amilozide or nifedipine in the International Nifedipine GITS Study: Intervention as a Goal in Hypertension. Participants had to be 55 to 80 years of age, with hypertension (> or =150/95 or > or =160 mm Hg) and at least one additional cardiovascular risk factor. Patients received 30 mg nifedipine once daily or co-amilozide (25 mg hydrochlorothiazide and 2.5 mg amiloride) daily. Doses were doubled if target blood pressures (<140/90 mm Hg) were not achieved. Primary (composite of cardiovascular death, myocardial infarction, heart failure, and stroke) and secondary outcomes (composite of primary outcomes, including all-cause mortality and death from vascular and nonvascular causes) were assessed by means of intent-to-treat analyses. There was no significant difference in the incidence of primary outcomes between nifedipine-treated and co-amilozide-treated patients with diabetes at baseline (n=1302) (8.3% versus 8.4%; relative risk, 0.99, 95% CI, 0.69 to 1.42; P=1.00). A significant benefit for nifedipine-treated patients was seen for the composite secondary outcome (14.2% versus 18.7%; relative risk, 0.76, 95% CI, 0.59 to 0.97; P=0.03). Among patients without diabetes at baseline (n=5019), there was a significant difference in the incidence of new diabetes (nifedipine 4.3% versus co-amilozide 5.6%, P=0.023). Nifedipine GITS once daily is as effective as diuretic therapy in reducing cardiovascular complications in hypertensive diabetics. Nifedipine-treated patients were also less likely to have diabetes or have secondary events (a composite of all-cause mortality, death from a vascular cause, and death from a nonvascular cause) than co-amilozide recipients. Our results suggest that nifedipine could be considered as first-line therapy for hypertensive diabetics.
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PMID:Outcomes with nifedipine GITS or Co-amilozide in hypertensive diabetics and nondiabetics in Intervention as a Goal in Hypertension (INSIGHT). 1292 58

When planning treatment for patients with hypertension, current guidelines emphasise the importance of risk stratification, based on blood pressure, the presence of end-organ damage and other cardiovascular risk factors. Because the beneficial effect of antihypertensive therapy seems to be linked to the degree of blood pressure reduction, guidelines recommend reducing blood pressure below 140/90mm Hg, with a lower target in patients who are young or who have diabetes mellitus (with or without nephropathy) or non-diabetic nephropathy. Blood pressure reduction can be achieved with several classes of drugs, including diuretics, beta-blockers, ACE inhibitors, angiotensin II antagonists and calcium channel antagonists. Calcium channel antagonists have been shown to reduce the risk of stroke and major cardiovascular events. However, it is still controversial whether different treatment regimens based on different drug classes can offer advantages beyond similar degrees of blood pressure control in preventing cardiovascular morbidity and mortality. The International Nifedipine GITS Study: Intervention as a Goal in Hypertension Treatment (INSIGHT) was a controlled clinical trial aimed at comparing the efficacy of a long-acting calcium channel antagonist, nifedipine gastrointestinal-transport-system (GITS), versus co-amilozide, a combination of the diuretics hydrochlorothiazide (HCTZ) and amiloride, on morbidity and mortality in high-risk hypertensive patients. Nifedipine GITS and HCTZ/amiloride were equally effective at reducing blood pressure and the risk of primary outcomes (a composite of death from any cardiovascular or cerebrovascular cause, non-fatal stroke, myocardial infarction and heart failure). Results from other studies indicate that there may be greater benefits for stroke and smaller benefits for coronary artery disease with calcium channel antagonist-based regimens than with diuretic or beta-blocker-based regimens. However, there is at present insufficient evidence to recommend a specific drug choice based on patient risk profile. Thus, the choice of antihypertensive drug(s) should be according to efficacy and tolerability. In addition to the reductions in cardiovascular risk, two substudies of INSIGHT showed that nifedipine GITS was able to prevent the progression of intima media thickness in the common carotid artery and slow the progression of coronary calcification. The clinical significance of this effect in the prevention of cardiovascular events still remains to be established.
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PMID:Current treatment of patients with hypertension: therapeutic implications of INSIGHT. 1283 62

The Japan Multicenter Investigation for Cardiovascular Diseases-B was performed to investigate whether nifedipine retard treatment was associated with a significantly higher incidence of cardiac events than angiotensin converting enzyme inhibitor treatment in Japanese patients. The study used a prospective, randomized, open, blinded endpoint (PROBE) design. Patients were enrolled at 354 Japanese hospitals specializing in cardiovascular disease. The subjects were 1,650 outpatients aged under 75 years who had diagnoses of both hypertension and coronary artery disease. There were 828 patients subjected to intention-to-treat analysis in the nifedipine retard group and 822 patients in the angiotensin converting enzyme inhibitor group. The patients were randomized to 3 years of treatment with either nifedipine retard or angiotensin converting enzyme inhibitor. The primary endpoint was the overall incidence of cardiac events (cardiac death or sudden death, myocardial infarction, hospitalization for angina pectoris or heart failure, serious arrhythmia, and coronary interventions). The primary endpoint occurred in 116 patients (14.0%) from the nifedipine retard group and 106 patients (12.9%) from the angiotensin converting enzyme inhibitor group (relative risk, 1.05; 95% confidence interval, 0.81-1.37; p = 0.75). In the Kaplan-Meier estimates, there were no significant differences between the two groups (log-rank test: p = 0.86). The incidence of cardiac events and mortality did not differ between the nifedipine retard and angiotensin converting enzyme inhibitor therapies. Nifedipine retard seems to be as effective as angiotensin converting enzyme inhibitors in reducing the incidence of cardiac events and mortality.
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PMID:Comparison of nifedipine retard with angiotensin converting enzyme inhibitors in Japanese hypertensive patients with coronary artery disease: the Japan Multicenter Investigation for Cardiovascular Diseases-B (JMIC-B) randomized trial. 1508 Mar 77

Nifedipine (Adalat) is marketed as an anti-hypertensive agent. Nifedipine inhibits voltage-dependent L-type calcium channels, which leads to vascular (and other) smooth muscle relaxation and negative inotropic and chronotropic effects on the heart. Vasodilation, followed by a baroreceptor-mediated increase in sympathetic tone then results in indirect cardiostimulation. Nifedipine was introduced as a tocolytic agent at a time when beta-agonists and magnesium sulphate dominated the arena for the prevention of preterm birth. The oral administration route, the availability of immediate and slow-release preparations, the low incidence of (mild) side effects, and its limited costs explain the attraction to this medication from the obstetric field and its rapid and widespread distribution. Currently, over 40 studies have been published on nifedipine's tocolytic effectiveness, including seven meta-analyses. The quality of the studies suffers particularly from performance bias because the majority of them failed to ensure adequate blinding to treatment both for providers and patients. Concerns about other methodological flaws include measurements, outcome assessment and attrition bias. In particular, the safety aspects of nifedipine for tocolysis have been under-assessed. Conclusions from the meta-analyses, favouring the use of nifedipine as a tocolytic agent, are not supported by close examination of the data. The tocolytic effectiveness and "safety" of nifedipine has been studied primarily in normal pregnancies. Based on its pharmacological properties, one should be cautious to administer nifedipine when the maternal cardiovascular condition is compromised, such as with intrauterine infection, twin pregnancy, maternal hypertension, cardiac disease, etc. Life-threatening pulmonary oedema and/or cardiac failure are definite risks and have been reported. Under such circumstances, the baroreceptor-mediated increase in sympathetic tone may not balance the cardiac-depressant activity of nifedipine.
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PMID:Nifedipine trials: effectiveness and safety aspects. 1571 1

Major advances in the diagnostic, evaluation, and particularly surgical treatment of aortic regurgitation (AR) have redefined the role of medical treatment. In acute AR, aortic valve replacement (AVR) is the only life-saving treatment. Medical treatment may improve the hemodynamic state temporarily before surgery. Rationale of medical treatment in chronic AR is based on the natural history and pathophysiology of the disease. The primary goal is to optimize the time of the AVR. If there is any symptom and/or left ventricular (LV) dysfunction, early AVR is required. Vasodilators should only be considered as a short-term treatment before surgery if there is evidence of severe heart failure or as a long-term treatment if AVR is contraindicated because of cardiac or noncardiac factors. In asymptomatic patients with severe chronic AR and normal LV function (even if the left ventricle is moderately dilated), vasodilators may prolong the compensated phase of chronic AR, although proof of their efficacy in delaying AVR is limited. Nifedipine is the best evidence-based treatment in this indication. ACE inhibitors are particularly useful for hypertensive patients with AR. beta-Adrenoceptor antagonists (beta-blockers) may be indicated to slow the rate of aortic dilatation and delay the need for surgery in patients with AR associated with aortic root disease. Furthermore, they may improve cardiac performance by reducing cardiac volume and LV mass in patients with impaired LV function after AVR for AR.
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PMID:Aortic insufficiency: defining the role of pharmacotherapy. 1572 42


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