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)

Health economy is often addressed in terms of acquisition cost, i.e. the cost of the pill. For various reasons, mainly the stricter demands from drug regulatory agencies (increased development costs), novel agents must be expected to be more expensive than older drugs. However, if the costs of changing therapy and the costs induced by side effects and extra clinic visits are considered, the economic aspects become less of a consideration. If compliance is enhanced and better blood pressure control is achieved with the newer agents, then the therapeutic gains must be weighed against the economic aspects. Losartan, the first agent of the new class of angiotensin II receptor antagonists of the AT1 type, has been available for clinical use for more than 2 years. Losartan has proven antihypertensive effects and its safety profile in the initial controlled trials (approximately 2900 patients) and in general practice (more than 14,000 patients in Sweden) has been very good. Its effect on long-term morbidity and mortality has not yet been established but a large mortality endpoint trial is underway in hypertensive patients with cardiac hypertrophy (the LIFE trial). In heart failure, losartan has been shown to reduce 3-month mortality (the ELITE trial). Although it is too early to assess the full therapeutic benefit of losartan in relation to the total patient costs, its efficacy and low incidence of side effects has made it a useful new therapy for the treatment of hypertension.
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PMID:Medical and cost-economy aspects of modern antihypertensive therapy--with special reference to 2 years of clinical experience with losartan. 928 10

Previous studies from our laboratory have shown that the cardiac sympathetic afferent reflex is enhanced in dogs with experimental heart failure. The aim of the present study was to determine if the central gain of the cardiac sympathetic afferent reflex was also enhanced in dogs with heart failure. Fifteen dogs with pacing-induced heart failure were used in this study. Seventeen sham-operated dogs served as control. At the time of the acute experiment the dogs were anesthetized with alpha-chloralose. Arterial blood pressure, heart rate, and renal sympathetic nerve activity were recorded. After sinoaortic denervation and cervical vagotomy, a thoracotomy was performed in the second intercostal space. The left stellate ganglion was identified, and the left cardiac sympathetic nerves were cut. The central end of the left cardiac sympathetic nerves was placed on bipolar stimulating electrodes. The renal sympathetic nerve activity responses to electrical stimulation (30 Hz, 1 ms with varying voltages from 1 to 10 V; or 10 V, 1 ms with varying frequencies from 1 to 30 Hz) of the afferent cardiac sympathetic nerves were compared between sham and heart failure groups. Reflex renal sympathetic nerve activity responses to stimulation of the cardiac sympathetic nerves were significantly greater in the heart failure group compared with that in the sham group (21.4 +/- 3.2 vs. 9.8 +/- 2.9% at 10 V, 30 Hz and 27.7 +/- 4.5 vs. 9.9 +/- 3.4% at 30 Hz, 10 V, heart failure vs. sham group, respectively; for both relationships, P < 0.05). This enhanced central gain of the cardiac sympathetic afferent reflex in the heart failure group was significantly attenuated after intravenous and cerebroventricular injection of the angiotensin II receptor antagonist losartan (5 mg/kg i.v. and 0.125 mg/kg in 0.1 ml i.c.v.). These data suggest that the central gain of the cardiac sympathetic afferent reflex is enhanced in dogs with heart failure and central angiotensin II plays an important role in this enhanced response.
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PMID:Central gain of the cardiac sympathetic afferent reflex in dogs with heart failure. 943 2

1. The crucial role played by the renin-angiotensin-aldosterone system in the cardiovascular system and the immense therapeutic potential of angiotensin-converting enzyme inhibitors and, more recently, angiotensin II receptor blocking agents, in both heart failure and post-myocardial infarction is becoming increasingly evident. Polymorphisms within the genes controlling this enzyme system are candidates for the elucidation of the pathogenesis of cardiovascular disease and this link is both intriguing and provocative. Recently, an association between a polymorphism of the angiotensin-converting enzyme gene and phenotypic expression of cardiovascular disease, namely myocardial infarction, was reported. Since then, several small case-controlled studies have confirmed an association with manifestations of ischaemic heart disease or various other cardiac end-points. However, in a large prospective study the angiotensin-converting enzyme gene conferred no appreciable risk. 2. Our aim was to review the evidence that links polymorphisms of the angiotensin-converting enzyme gene with cardiovascular disease. We searched the Medline database (1990-1997) using the key words myocardial infarction, ischaemic heart disease, angiotensin-converting enzyme and polymorphisms and performed a search of the reference citation of relevant articles. We selected clinical studies on cardiovascular disease related to the angiotensin-converting enzyme genotype. 3. Taken together, the available evidence supports the notion that the DD-angiotensin-converting enzyme genotype adversely influences specific cardiovascular diseases but appears to do so in specific geographical areas and in particular patient subgroups. It is not yet known whether it does this through an interaction with other genes or by as yet unexplained biochemical mechanisms. 4. We should regard the current data with the angiotensin-converting enzyme genotype as an intriguing clue in the pathogenesis of cardiovascular disease. However, the main factor against this potential benefit is that the impact of the DD genotype appears to be small and its clinical manifestations rather heterogeneous.
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PMID:Angiotensin-converting enzyme gene polymorphism and cardiovascular disease. 948 84

Calcium antagonists are useful for treating hypertension, stable exertional and vasospastic angina, and supraventricular arrhythmias. Recent studies have proven their ability to decrease the rate of nonfatal strokes. Short-acting calcium antagonists should be avoided with hypertensive emergencies and urgencies, unstable angina, and acute myocardial infarction. The use of calcium antagonists in systolic heart failure should not be as the primary therapy. Care must be taken in using non-dihydropyridines because of multiple drug-drug interactions. Prospective trials are in progress through the next decade that will compare traditional drugs such as diuretics and beta-blockers to calcium antagonists, converting enzyme inhibitors, and angiotensin II receptor blockers.
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PMID:Calcium antagonists--clinical considerations. 959 57

The pharmacokinetics of a selective AT1-subtype, nonpeptide, orally active, angiotensin II receptor antagonist, losartan, were characterized in 11 patients with heart failure (New York Heart Association class II, n = 6; class III, n = 4; class IV, n = 1) after oral and intravenous administration. In these patients, average plasma clearance of losartan was 566 mL/min, volume of distribution at steady-state was 34 L, and terminal plasma half-life was 1.5 hours. Average bioavailability was 36%. No clinically significant accumulation of losartan or its active metabolite, EXP3174, occurred after multiple-dose oral administration for 7 to 8 days. Terminal plasma half-life of EXP3174 after oral administration of losartan was 7.6 hours. The pharmacokinetics of losartan in patients in this study appear to be similar to those in healthy subjects studied previously.
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PMID:Pharmacokinetics of intravenous and oral losartan in patients with heart failure. 965 May 42

Eprosartan is an angiotensin II receptor antagonist being developed for the treatment of hypertension and heart failure. The effect of eprosartan on the steady-state anticoagulant activity of warfarin was evaluated in 18 healthy male volunteers. Each subject's daily warfarin dose was titrated over 9 days to achieve a stable international normalized ratio (INR) of 1.3 to 1.6 by day 14. After the 14-day warfarin titration phase, subjects were randomized to receive either eprosartan 300 mg or matching placebo twice a day for 7 days. All subjects continued to take the warfarin dose established during the 14-day titration phase. The anticoagulant activity of warfarin was statistically equivalent when coadministered with eprosartan or with placebo. No serious or unexpected adverse events suggestive of abnormal bleeding occurred during coadministration of eprosartan and warfarin. As measured by the INR, there is no apparent effect of eprosartan on the anticoagulant effect of warfarin.
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PMID:Eprosartan does not affect the pharmacodynamics of warfarin. 970 51

Blockade of the renin-angiotensin system with angiotensin-converting enzyme (ACE) inhibitors is now recognized as an effective approach for the treatment of hypertension and congestive heart failure. In addition, ACE inhibitors are very effective for the prevention of chronic renal failure. Today, it is possible to antagonize the effects of angiotensin II more specifically using AT1 receptor antagonists. Several non-peptide, orally active angiotensin II receptor antagonists have recently been developed clinically. These new molecules are as effective as ACE inhibitors, calcium antagonists and beta-blockers at reducing blood pressure in hypertensive patients. Furthermore, they appear to have similar systemic and renal hemodynamic properties in patients with congestive heart failure and renal diseases. Now, several large clinical trials such as the LIFE, the RENAAL and the ELITE II studies are under way to investigate the long-term benefits of one of these compounds in hypertension, heart failure and type II diabetic nephropathy.
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PMID:[Angiotensin II AT1 receptor antagonists: clinical development and future perspectives]. 977 27

Activation of the renin-angiotensin system may contribute to the derangement in renal and cardiac function in congestive heart failure. The present study evaluated the effects of eprosartan, a selective angiotensin II receptor antagonist, on renal hemodynamic and excretory parameters and on the development of cardiac hypertrophy in rats with aortocaval fistula, an experimental model of congestive heart failure. Infusion of eprosartan (1.0 mg/kg) in rats with aortocaval fistula produced a significant increase (+34%) in total renal blood flow and a sustained decrease (-33%) in the calculated renal vascular resistance. These effects on renal hemodynamics were more pronounced than those observed in sham-operated control rats and occurred despite a significant fall (-12%) in mean arterial blood pressure. Moreover, eprosartan caused a preferential increase in renal cortical blood perfusion and significantly increased glomerular filtration in rats with congestive heart failure. Chronic administration of eprosartan (5.0 mg/kg per day for 7 days through osmotic minipumps inserted intraperitoneally on the day of operation) resulted in a significant enhancement of urinary sodium excretion compared with nontreated rats with heart failure. Moreover, administration of eprosartan to salt-retaining rats with congestive heart failure resulted in a progressive increase and ultimate recovery in urinary sodium excretion. Finally, early treatment with eprosartan blocked the development of cardiac hypertrophy in rats with aortocaval fistula to a larger extent than the angiotensin-converting enzyme inhibitor enalapril. These findings emphasize the importance of angiotensin II in mediating the impairment in renal function and induction of cardiac hypertrophy in heart failure and further suggest that angiotensin II receptor blockade may be a useful treatment of these consequences in severe cardiac failure.
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PMID:Effects of eprosartan on renal function and cardiac hypertrophy in rats with experimental heart failure. 977 74

Blockade of the renin-angiotensin system is now recognized as an effective approach to the treatment of hypertension and congestive heart failure. Today, it is possible to antagonize the effects of angiotensin II more specifically by blocking its receptors by using nonpeptide receptor antagonists. These compounds that first have been used to recognize the various subtypes of angiotensin II receptors are now available clinically. Four of them have recently been launched on the market and several others are preregistered for the treatment of hypertension. These new molecules are as effective as ACE inhibitors, calcium antagonists and beta-blockers in lowering blood pressure in hypertensive patients. When compared to ACE inhibitors, they appear to have comparable favorable effects on systemic and renal hemodynamic properties. One of the major characteristics of angiotensin II receptor antagonists as a class is the excellent tolerability with an incidence of side effects that is generally similar to that of placebo. Large clinical trials are now underway to demonstrate the long-term benefits of these agents in hypertension, heart failure and type II diabetic nephropathy.
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PMID:Angiotensin II receptor antagonists in hypertension. 983 93

Development of guidelines can be a difficult process; each organization or institution must establish the rules and criteria for including specific therapies and the level of complexity needed. Specific outcomes must be incorporated, including maintenance of comfort and functionality, freedom from hospitalization, and survival. In existing guidelines for the management of heart failure, angiotensin-converting enzyme (ACE) inhibitor therapy is clearly the gold standard. However, there is still a high mortality with ACE inhibitor therapy; the key may be choosing the right patients. Current guidelines reflect the uncertainty regarding digoxin before the Digitalis Investigation Group (DIG) trial; obviously, these guidelines should be revisited. Clinical practice guidelines for the management of heart failure need to be revised to include a better consensus on beta-blockade, the new data on digoxin, emerging data on angiotensin II receptor antagonists, and current thinking on anticoagulant therapy.
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PMID:Clinical practice guidelines for heart failure. 1018 25


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