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1.
The 12 placebo controlled double-blind trials with beta-adrenergic blocking agents in post-MI patients were reviewed separately and the results were combined. The results of every single trial were compatible with the statement that beta blockade decreased total mortality by 20% to 30% in these post-MI patients. This was mainly related to a decrease in cardiac mortality, in particular sudden death. Reinfarctions were also reduced. Withdrawal for adverse reactions was higher in the beta blocker than in the control group. Beta blockade can therefore be considered as a potential treatment for secondary prevention in selected post-MI patients.  相似文献   

2.
Elihu Estey 《Haematologica》2009,94(10):1435-1439
This paper contends that commonly used clinical trial designs do not reflect clinical reality as viewed by patients or physicians. Specifically, randomized phase III designs focus on improvements that are more significant statistically than medically and put an emphasis on avoiding a false positive result that is more appropriate for diseases that are curable, in contrast to acute leukemias. The resultant large sample sizes needed for each treatment restrict the trial to one or two new treatments, although historical reality suggests the difficulty in knowing, without clinical data, whether these are the best of several new treatments. The p value-based statistics discourage use of data from previous patients in the trial to inform treatment of subsequent patients, contravening patients’ assumptions. Standard phase II trials focus on a single outcome, ignoring the complexity of medical practice, and ignore prognostic heterogeneity. Finally, although patients are more interested in whether a new treatment is better than another, rather than whether it is active, randomization between different treatments does not begin until phase II trials have been completed. This paper proposes alternatives based on the Bayesian statistical approach. The thesis that I will develop here is that commonly used clinical trial designs are unrealistic in the sense that they do not correspond well to patients’ views of medical practice and greatly over-simplify such practice. By emphasizing Bayesian rather than p value-based statistics and focusing on acute myeloid leukemia, I hope to familiarize physicians with some of the many new published designs that address these problems.  相似文献   

3.
Beta blockers in heart failure   总被引:2,自引:0,他引:2  
The rationale for beta blockade in heart failure is now well established. Heart failure mortality, which is predicted by neurohormonal activation, remains high despite modern treatment, including angiotensin-converting enzyme (ACE) inhibition, and additional neurohormonal blockade has further therapeutic potential. Previous clinical trial experience in heart failure, most of which has been in patients with idiopathic cardiomyopathy, indicates consistent improvement in ventricular function, although variable changes in symptoms and exercise performance. However, the major burden of heart failure occurs in patients with ischemic heart disease, and in this respect it is notable that beta blockade following myocardial infarction confers a significant mortality benefit in subgroups with heart failure. An overview of all currently available randomized clinical trials of beta blockade in heart failure, which includes more than 1600 patients, indicates a mortality risk reduction of approximately 20%, but with wide confidence intervals. A large scale trial with several thousand patients is required to confirm reliably a plausible 20% mortality reduction with beta blockade in heart failure. The dissociation of clinical and mortality effects demonstrated with other heart failure treatments indicates the necessity for an appropriately powered mortality study that could define a major improvement in heart failure therapy for the future. The response to beta blockade will vary according to heart failure severity. A cautious dosetitration approach is required in all cases. In severe heart failure, symptomatic improvement may result, but for the large group of patients with moderate and stable heart failure, the principal aim of treatment is improved longevity.  相似文献   

4.
Recent clinical trials have explored whether angiotensin receptor blockers (ARBs) or aldosterone blockade should be added to standard angiotensin-converting enzyme (ACE) inhibitor/beta blocker treatment in heart failure. Both strategies are of some value but it is unclear which strategy should be used first in patients with mild but symptomatic heart failure. The arguments for and against each strategy are discussed. The strongest argument for aldosterone blockade is the consistency in the results of the RALES (Randomized Aldactone Evaluation Study) and EPHESUS (Eplerenone Post-acute Myocardial Infarction Heart Failure Efficacy and Survival Study) studies, but what is lacking is a trial of aldosterone blockade in patients with mild, symptomatic heart failure as such. The strongest argument for ARBs is that the CHARM (Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity) Added trial result was positive in the precise patient population of interest (mild, symptomatic heart failure). The strength of this argument is diminished by the somewhat different results in Val-HeFT (Valsartan Heart Failure Trial). A third possibility is to use neither an ARB nor an aldosterone blocker and arguments can be marshalled for this position also. Clinicians should now assess these various arguments to select what they believe would be best for their patients.  相似文献   

5.
Several treatment guidelines have made strong recommendations to physicians that treatment of nephropathy and hypertension should be based on the use of a long-acting angiotensin converting enzyme (ACE) inhibitor if tolerated. The recently published clinical trials, based on angiotensin II receptor blockers' effects on diabetic nephropathy and essential hypertension, have also shown significant endpoint reduction. Perhaps the time has come to broaden the recommendations to include the use of a renin-angiotensin-aldosterone system altering drug. But what if the treatment goal cannot be reached, and incessant proteinuria and high blood pressure levels persist despite high dosage treatment of either drug? How should this be handled? The dual blockade principle can possibly provide the solution by obtaining the broadest and most efficient blockade of circulating angiotensin II by using the combination of an ACE inhibitor and an angiotensin II receptor blocker. But large clinical trials are yet to come, and at present large endpoint trials have not been published. This article provides an overview of how far we have come with dual blockade treatment in hypertension and nephropathy.  相似文献   

6.
Summary The goal of early intervention of acute coronary occlusion by beta blockers is to reduce ultimate infarct size and to consequently reduce morbidity and mortality. Until 1986 small early intervention trials suggested that infarct size may be reduced by 25% if treatment was started within 6 to 10 hours after the onset of symptoms. At this time, an average of 80% of the infarct is fully developed. On the basis of previous trials, the reduction of infarct size has been associated with improvement of symptoms, prevention of infarct development, reduced occurrence of arrhythmias and reinfarctions, and earlier discharge from the hospital. Although the trials suggested some benefit in mortality, this issue has not been solved. The MIAMI trial randomized 5778 patients to blind treatment with metoprolol or placebo. ISIS-I randomized 16,027 patients to atenolol with an open label. No titration of the effect on lowering myocardial oxygen requirement was attempted. Both studies included less than 25% of all eligible patients. Exclusions were chiefly due to current beta blocker or calcium blocker treatment. Thus, the results obtained concern only a selected group of patients. In MIAMI only 15% received treatment within 6 hours, while in ISIS 38% were treated within 4 hours. It is therefore likely that in most patients the infarcts were completed before intervention was started. Thus, the two trials did not differentiate between primary and secondary effects on the acute myocardial infarct. Mortality was reduced by 13% (NS) and 15% (p < 0.04), respectively, in MIAMI and ISIS. The trials suggest that early intravenous treatment with selective beta blockers is safe in a selected low-risk group of patients. Nevertheless, risk factors like age, previous myocardial infarctions, hypertension, previous angina pectoris, diabetes, and signs of congestive heart failure may identify patients who are particularly well suited for this therapy. The trials are inconculsive in defining the mechanism of effect; a combined effect of primary infarct size reduction and secondary prevention is likely. The magnitude of heart rate reduction may be instrumental for the effect but remains to be tested. Until more knowledge is obtained about effector mechanisms, the delay time, and risk group identification, a general recommendation for beta blocker use can not be given.  相似文献   

7.
Early initiation of beta blockade in heart failure: issues and evidence   总被引:1,自引:0,他引:1  
Despite clinical trials demonstrating that inhibitors of the renin-angiotensin and sympathetic nervous systems can reduce the mortality and morbidity risk associated with heart failure, these drugs have remained underutilized in general clinical practice. In particular, many patients with heart failure due to left ventricular systolic dysfunction fail to receive beta blockers, although this class of drugs, as well as other antihypertensive agents such as angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, are recommended as part of routine heart failure therapy by national expert consensus guidelines. In-hospital initiation of beta-blocker therapy may improve long-term utilization by physicians and compliance by patients through obviating many of the misperceived dangers associated with beta blockade. The following review of the clinical trial data from the Randomized Evaluation of Strategies for Left Ventricular Dysfunction (RESOLVD) trial, the Metoprolol Controlled-Release Randomized Intervention Trial in Heart Failure (MERIT-HF), the Cardiac Insufficiency Bisoprolol Study II (CIBIS-II), the Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) trial, and the Initiation Management Predischarge Process for Assessment of Carvedilol Therapy for Heart Failure (IMPACT-HF) trial on the efficacy, safety, and tolerability of beta blockers indicates that early initiation can be safely achieved and can improve patient outcomes.  相似文献   

8.
A multicenter, double-blind, placebo-controlled, randomized trial of nifedipine, metoprolol and their combination was conducted in 338 patients with unstable angina (hospital admission diagnosis) who had not previously received treatment with a beta blocker. In addition, nifedipine was compared with placebo in 177 patients who were receiving beta blockers upon hospital admission. The main outcome event was the recurrence of ischemia or progression to myocardial infarction within 48 hours. Trial medication effects are expressed as ratios of event rates relative to placebo, e.g., for nifedipine as the event rate under nifedipine divided by that under placebo; 95% confidence intervals are also given. In patients not pretreated with a beta blocker the rate ratio for nifedipine was 1.15 (0.83, 1.64), for metoprolol 0.76 (0.49, 1.16) and for the combination 0.80 (0.53, 1.19). In patients already receiving a beta blocker, the addition of nifedipine was favorable and the rate ratio was 0.68 (0.47, 0.97). Equal numbers of patients developed myocardial infarction and reversible ischemia. Most infarctions occurred early, within 6 hours of randomization. In patients who were not already taking a beta blocker, the nifedipine rate ratio for infarction only was 1.51 (0.87, 2.74). These results suggest that, in patients not previously receiving beta blockers, metoprolol has a beneficial short-term effect on unstable angina, that a fixed combination with nifedipine provides no further gain and that nifedipine may be ineffective or counterproductive. On the other hand, the addition of nifedipine to existing beta blockade when the patient becomes unstable seems beneficial.  相似文献   

9.
Use of beta-blockers in obesity hypertension: potential role of weight gain   总被引:1,自引:0,他引:1  
Beta‐blockers are the most frequently used drugs for the treatment of hypertension. Apart from concerns regarding potential adverse metabolic effects on lipids or insulin sensitivity, beta‐blockers can also cause weight gain in some patients. This fact appears little known to clinical practitioners and trialists. Thus, only a minority of clinical trials with beta‐blockers report weight changes during treatment. In trials that do report weight changes, beta‐blockers are associated with a weight gain of 1.2 (range ?0.4–3.5) kg. This may be attributable to the fact that beta blockade can decrease metabolic rate by 10%. Beta‐blockers may also have other negative effects on energy metabolism. Obesity management in overweight hypertensive patients may therefore be more difficult in the presence of beta‐blocker treatment. We therefore question the use of beta‐blockers as first‐line therapy for overweight or obese patients with uncomplicated hypertension.  相似文献   

10.
International beta-blocker review in acute and postmyocardial infarction   总被引:1,自引:0,他引:1  
The benefits of beta blockade in acute and postmyocardial infarction are well documented. More than 50 placebo-controlled trials have been performed, involving more than 40,000 patients with short- or long-term follow-up. In long-term follow-up studies in approximately 20,000 patients, mortality was reduced by 21% and reinfarction by 24%. When high-risk patients were assessed separately, the reduction in mortality after early intervention was significantly greater than in low-risk patients. The trial medication was withdrawn in approximately 24% and 28% of patients in the placebo and beta-blocker groups, respectively, in the major trials. In addition to reduction of mortality and reinfarction rates, benefits have clearly been demonstrated in prevention of arrhythmias and thromboatherosclerotic complications. Significantly more patients had hypotension and bradycardia with beta-blocker treatment than with placebo; no clear-cut difference between the placebo and beta-blocker groups was found for atrioventricular block or congestive heart failure when patients with these conditions were excluded. In the Stockholm Metoprolol Trial, 3 years of metoprolol treatment in about 300 patients after myocardial infarction prolonged both survival and time spent completely asymptomatic, in an optimal functional state, or both. Patients receiving metoprolol spent less time disabled after serious atherosclerotic complications, including bypass surgery. Long-term beta blockade after myocardial infarction reduces mortality and morbidity in 80% of patients by 21% and 24%, respectively, but causes adverse reactions in approximately 10%. With proper selection of patients and the type and dose of beta blocker, survival without atherosclerotic complications or adverse effects can be prolonged.  相似文献   

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