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

Beta-blocker therapy is beneficial both after myocardial infarction and in mild, moderate and severe chronic heart failure. Recent sub-group analysis of the Goteborg Metoprolol Trial and the AIRE study confirm that patients receiving beta-blockers in the setting of post-MI heart failure fare better than patients not receiving this therapy. For all these reasons the CAPRICORN trial of carvedilol in post-MI LV dysfunction was an important and eagerly awaited trial. The results were presented for the first time at The American College of Cardiology on March 20 2001. CAPRICORN randomised 984 patients to placebo and 975 to carvedilol between 3 and 21 days (mean 10) after a confirmed MI. Patients had to have evidence of a left ventricular ejection fraction 40% or less. All patients had received ACEI therapy for at least 48 hours prior to randomisation. The mean ejection fraction of the patients recruited was 32.7% in the placebo group and 32.9% in the carvedilol group. Follow-up was for a mean of 15 months (maximum 2.7 years). All cause mortality was 15.3% (151 deaths) in the placebo group and 11.9% (116 deaths) in the carvedilol group, giving a hazard ratio of 0.77 (0.60-0.98) and a significance of p = 0.031. And yet this agent will probably not be given a licence for this indication in the European Union and the USA. The reason is one of trial design and statistical declarations. Some way into the trial the Steering Committee decided to change the primary end-point form all-cause mortality to two co-primary end-points and to allocate their alpha power of 0.05 unevenly between the combined end-points of all cause mortality and cardiovascular hospitalisation (alpha 0.045) and all cause mortality (alpha 0.005). In the end neither was achieved, one because of the large number of non-specific hospitalisations for chest pain and the mortality effect because it was allocated a punitive and unachievable target of p < 0.005. The trial is thus officially neutral despite showing convincing clinical benefit. Clearly arcane matters of statistical plans do matter and steering committees should think very carefully before changing the primary end-points of major trials.
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PMID:CAPRICORN: a story of alpha allocation and beta-blockers in left ventricular dysfunction post-MI. 1133 53

The importance of left ventricular hypertrophy (LVH) as a powerful predictor of cardiovascular morbidity and mortality, independent from blood pressure and other cardiovascular risk factors, is widely recognized. Women have a lower prevalence of LVH than men for any given level of blood pressure. The occurrence of LVH increases progressively with older age and LVH becomes more common in women after menopause. Available data indicate that both hypertension and LVH are stronger risk factors for stroke and for heart failure in women than in men. Women are more likely to maintain a better left ventricular systolic function than men with similar heart failure symptoms, and heart failure due to diastolic dysfunction is more common in women than in men. Few studies have demonstrated that patients who fail to achieve a reduction of LVH are much more likely to suffer cardiovascular events than those in whom the left ventricular mass is reduced by antihypertensive treatment. Reversal of LVH therefore represents a major goal in the treatment of hypertensive patients. The degree of cardiac hypertrophy reduction is influenced by baseline severity of LVH, by the duration of treatment and by the degree of 24-h blood pressure control. In addition, beyond the control of blood pressure, different classes of antihypertensive drugs may differently interfere with several non-hemodynamic stimuli, and therefore have a different effect on left ventricular mass. Data regarding the effect of antihypertensive therapy on LVH in women are not adequate. Few studies have suggested a possible additive effect of estrogen replacement therapy on left ventricular mass changes in hypertensive postmenopausal women. Many of the major heart failure intervention trials did not include women or had only a small proportion of female patients. In the SAVE, AIRE, TRACE and SOLVD trials, treatment with angiotensin-converting enzyme inhibitors resulted in similar benefit to women and in men. In studies evaluating the effect of beta-blocker treatment in patients with heart failure, the benefit was statistically significant in men but not in women. Results from further multicenter ongoing trials are awaited to definitely evaluate whether regression of LVH carries a similar benefit in women and men, and whether different therapeutic strategies may be applied to women to regress LVH and to prevent the progression to heart failure.
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PMID:Left ventricular hypertrophy and heart failure in women. 1218 49

The clinical value of inhibition of the renin-angiotensin-aldosterone-system (RAAS) in heart failure has clearly been documented for the ACE-inhibitors as well as for the angiotensin-I-receptor blocker (AT1) by extensive intervention studies (AIRE, CONSENSUS, SAVE, ELITE II, ValHeFT and others). The additional specific vascular and renal protection, acting beyond the lowering of blood pressure, has been investigated in the past years in numerous studies in patients with arterial hypertension, often accompanied by diabetes mellitus type II. Whereas for nephroprotection, especially also in additionally present diabetes mellitus type II, study results clearly support the assumption of additional protective effects, which exceed the purely blood-pressure lowering effect; the data available for vascular protection (coronary and cerebral vessels) are insufficient.
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PMID:Clinical studies on the blockade of the renin-angiotensin-aldosterone-system. 1294 May 34

Angiotensin II (AT II) is a final product of the renin-anglotensin-aldosterone system (RAS) and presents one of the most influential factors in the pathogenesis of atherosclerosis, acute coronary syndrome, myocardial dysfunction and heart failure. ACE-inhibitors (ACEI), beside beta adrenergic blockers, are a cornerstone of the current chronic heart failure (CHF) treatment. Evidence based medicine has not yet proved any significant beneficial effects of ACEI in patients with unstable angina pectoris (UAP), although according to the SoLVD study testing the possible effects of ACEI in patients with significant left ventricular dysfunction and/or CHF, there was a significant hospitalization rate reduction as well as less transformation of UAP to myocardial infarction in patients treated with ACEI. In the GISSI 3, ISIS 4 and CCS studies, ACEI was given within the first 24 hours and continued for 4-6 weeks. According to pooled results, ACE inhibitor could save 11/1000 patients with ST-elevation myocardial infarction (STEMI) and only 1/1000 patients with non ST-elevation myocardial infarction (NSTEMI). In the SAVE, AIRE and TRACE studies, ACEI was started later, i.e. 3-16 days after acute myocardial infarction and continued for several years. ACEI therapy resulted in a significantly lower mortality during the first year, and an even 20% relative reduction in the total mortality during the 4-year follow up. The effects of ACEI were even more prominent in more severe myocardial dysfunction, as it was well known that they could slow or stop unfavorable myocardial remodeling. Conclusively, ACEI should be given as early as possible to all patients with acute myocardial infarction, if no contraindications. The HOPE study showed efficacy of ACEI in the primary prevention of ischemic heart disease in high risk individuals, and the EUROPA study showed a favorable effect of ACEI in the secondary prevention of ischemic heart disease in low risk patients. According to these findings, ACEI should be given permenantly following myocardial infarction. These findings suggest the need of a permanent treatment with ACEI in patients having sustaned myocardial infarction. Angiotensin-1 receptor antagonists (AT-1 antagonists) are a newer generation of neurohormonal antagonists, which block the effects of AT II produced not only through a classic, ACE-dependent pathway but also via alternative pathways (non ACE-dependent) and selectively bind to AT-1 receptors for AT II. Therefore, they have some theoretical advances in comparison with ACEI. There are 2 relevant studies elucidating their possible role in treating patients with or post-myocardial infarction. The OPTIMAAL study did not prove losartan to be better than an ACEI (captopril), while the VALIANT study showed that the effects of valsartan vs. captopril were statistically nonsignificantly different. Furthermore, there is no sense to combine AT-1 antagonist and ACEI, while a combination of AT-1 antagonist and a beta blocker is justified. In other words, AT-1 antagonist (the class effect is disputable) should be given to patients with acute myocardial infarction or to post-myocardial infarction patients who cannot take ACEI.
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PMID:[ACE inhibitors and angiotensin II receptor antagonists in acute coronary syndrome]. 1520 98

Beneficial effects of angiotensin converting enzyme inhibitors (ACEI) and angiotensin type 1 receptor (AT1) blockers in patients with cardiovascular and renal diseases have been clearly demonstrated in numerous large outcomes studies. In patients with heart failure (HF), ACEI have been shown to reduce overall mortality, mortality from cardiovascular causes, to increase life expectancy, as well as to preserve the renal function (CONSENSUS, SAVE, TRACE, AIRE, AIREX, CATS trials). In addition, in the PROGRESS study ACEI substantially decreased the risk of stroke and transient ischemic attacks in patients with cerebrovascular disorders. The HOPE and EUROPA studies confirmed that long term therapy with ACEI provides significant survival benefit in patients with broad range of atherosclerotic cardiovascular diseases. After these large and well designed clinical studies, ACEI have become standard therapy for routine secondary prevention in all patients with cardiovascular diseases, unless contraindicated. AT1 receptor blockers have been recently added to the cardiovascular therapeutic armamentarium. They are believed to provide additional protection by inhibition of locally synthesized angiotensin II on the level of AT1 receptor. The ELITE II, ValHeFT and CHARM studies have shown that AT1 receptor blockers are equally effective as ACEI in reduction of mortality and morbidity in patients with HF. Importantly, they may be used together with ACEI, or as alternative treatment in ACEI intolerant patients. Renal protection is another important effect of both ACEI and AT1 blockers that has been confirmed in several large clinical trials. The North American Microalbuminemia Study group and EUCLID group demonstrated significant reduction in progression of diabetic nephropathy in patients with insulin dependent diabetes mellitus (IDDM) treated with ACEI. AT1 receptor blockers are mainly studied in the non-insulin dependent diabetes mellitus (NIDDM) nephropathy. Four recent clinical trials (IRMA-2, DETAIL, RENAAL and IDNT) examined the effect of AT1 receptor blockers in patients with NIDDM nephropathy. These studies confirmed the beneficial effect of AT1 receptor blockers in patients with NIDDM nephropathy that was extended beyond the blood pressure reduction. Ongoing studies (ONTARGET, TRANSCEND and PROTECTION) should provide us with additional insights about cardiovascular, renal and other end-organ protective effects of these therapeutics.
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PMID:Role of renin angiotensin system inhibitors in cardiovascular and renal protection: a lesson from clinical trials. 1750 19


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