CAST:心律失常抑制试验

作　　者　 (a)CAST研究人员(b)EpsteinAE ,BiggerJT ,WyseDG等(c)WyseDG ,HallstromA ,McBrideR等(d)AndersonJL ,PlatiaEV ,HallstromA等(e)GoldsteinS ,BrooksMM ,LedinghamR等标　　题　 (a)初步报告 :心肌梗死后抑制心律失常随机试验中英卡胺和氟卡胺对死亡率的影响(b)抑制心律失常随机试验中的事件 (CAST) :参加试验人群的总体死亡率(c)抑制心律失常随机试验中的事件 (CAST) :非随机双盲治疗、开放、药量递增存活病人的死亡率(d)心肌梗死病人英卡胺、氟卡胺和莫雷西嗪风险治疗与基线特点的关系(e)容易控制的室性心…     

CASTⅡ:心律失常抑制试验Ⅱ

作　　者　 (a)CASTⅡ研究人员(b)BrooksMM ,GorkinL ,SchronEB ,WiklundI,等标　　题　 (a)心肌梗死后抗心律失常药物莫雷西嗪对生存率的影响(b)心律失常抑制试验中莫雷西嗪和生活质量的关系参考文献　 (a)NEnglJMed 1992 ,32 7:2 2 7～ 2 33(b)ControlClinTrials 1994 ,15 :4 37～ 4 4 9　　疾　　病　急性心肌梗死后室性心律失常。目　　的　了解心梗后控制无症状或轻症状的室性心律失常 ,莫雷西嗪是否减少心律失常的死亡率。研究设计　随机、开放、双盲、安慰剂对照。随　　访　 2w(开始试验 ) ,平均 18个月 (长期试验 )。病　…     

The Cardiac Arrhythmia Suppression Trial: How Has it Impacted on Contemporary Arrhythmia Management?

Implications of the Cardiac Arrhythmia Suppression Trial. A most important issue in cardiology practice has been when and how to treat asymptomatic patients with ventricular arrhythmia. This is a particularly thorny problem, since the presence of complex ventricular ectopy is an independent risk variable in patients with a variety of forms of heart disease. The Cardiac Arrhythmia Suppression Trial (CAST) was designed to answer the question of whether or not abolition of ventricular premature depolarizations, in those who had had a myocardial infarction, would confer any substantial benefit, especially in terms of a mortality reduction. Unfortunately, that question has not yet been answered, but the preliminary results of the CAST has had a major impact on physicians, patients, the scientific community, industry, and regulatory agencies. This article reviews the implications of the CAST and describe how it has affected the contemporary management of patients with cardiac arrhythmia. (J Cardiovasc Electrophysiol, Vol. 1, pp. 457–463, October 1990)     

The Cardiac Arrhythmia Suppression Trial: first CAST ... then CAST-II.

The Cardiac Arrhythmia Suppression Trial (CAST) was a study designed to test the hypothesis that suppression of ventricular premature complexes after a myocardial infarction would improve survival. Preliminary results showed that suppression of ventricular premature complexes with encainide and flecainide worsened survival, and the CAST continued as the CAST-II with moricizine compared with its placebo. The protocol for the CAST-II was changed to attempt to enroll patients more likely to experience serious arrhythmias. The enrollment time was narrowed to 4 to 90 days after myocardial infarction; the qualifying ejection fraction was lowered to less than or equal to 0.40; a higher dose of moricizine could be used; early titration itself was double-blind with a placebo, and the definition of disqualifying ventricular tachycardia was changed to allow patients with more serious arrhythmias to be entered into the trial. The Cardiac Arrhythmia Suppression Trial-II was subsequently terminated prematurely because 1) patients treated with moricizine had an excessive cardiac mortality rate during the 1st 2 weeks of exposure to the drug, and 2) there appeared to be little chance of showing a long-term survival benefit from treatment with moricizine. This report outlines the rationale behind the Cardiac Arrhythmia Suppression Trial and the reasons for selection of the drugs used in the CAST and CAST-II.     

Treatment of ventricular arrhythmias by United States cardiologists: a survey before the Cardiac Arrhythmia Suppression Trial results were available.

To define the practice habits of United States cardiologists and the treatment of ventricular arrhythmias, a random sample of 1,000 of 12,000 cardiologists was sent a pretested questionnaire. After follow-up procedures, 252 responded, of which 18% were academically-based, 29% were hospital-based and 53% were office-based. Attitudes about antiarrhythmic drug therapy for the treatment of ventricular arrhythmias were influenced by the presence and severity of cardiac disease, the presence and severity of cardiac disease, the presence of symptoms and the type of ventricular arrhythmias. In this survey, only 1% of cardiologists treated patients with asymptomatic ventricular premature complexes and no heart disease, but 17% treated such patients if unsustained ventricular tachycardia was present. The treatment rate among cardiologists increased to 38% when coronary artery disease with left ventricular dysfunction was present in patients with asymptomatic ventricular premature complexes. The presence of any cardiac disease and symptomatic ventricular arrhythmias increased the treatment rate to 80 to 100%. Approximately 50% of responding physicians treated patients comparable to the Cardiac Arrhythmia Suppression Trial study population with antiarrhythmic drugs. Beta blockers were the most common antiarrhythmic drug class chosen as the most appropriate initial therapy in new patients with ventricular arrhythmias. Whereas no cardiologists thought that amiodarone was appropriate to initiate in new patients with benign or potentially malignant ventricular arrhythmias, as many as 33 to 43% of cardiologists would use amiodarone for refractory patients with such arrhythmias, a response contradictory to the approved labeling for this drug. Less than one half of cardiologists recognize the high potential organ toxicity for quinidine, procainamide and tocainide.(ABSTRACT TRUNCATED AT 250 WORDS)     

Events in the Cardiac Arrhythmia Suppression Trial (CAST): mortality in the entire population enrolled

To test the hypothesis that suppression of ventricular arrhythmias by antiarrhythmic drugs after myocardial infarction improves survival, the Cardiac Arrhythmia Suppression Trial (CAST) was initiated. Suppression was evaluated before randomization during an open label titration period. Patients whose arrhythmias were suppressed were randomized in the main study and those whose arrhythmias were partially suppressed were randomized in a substudy. Overall survival and survival free of arrhythmic death or cardiac arrest were lower [corrected] in patients treated with encainide or flecainide than in patients treated with placebo. However, the death rate in patients randomized to placebo therapy was lower than expected. This report describes the survival experience of all patients enrolled in CAST and compares it with mortality in other studies of patients with ventricular arrhythmias after myocardial infarction. As of April 18, 1989, 2,371 patients had enrolled in CAST and entered prerandomization, open label titration: 1,913 (81%) were randomized to double-blind, placebo-controlled therapy (1,775 patients whose arrhythmias were suppressed and 138 patients whose arrhythmias were partially suppressed during open label titration); and 458 patients (19%) were not randomized because they were still in titration, had died during titration or had withdrawn. Including all patients who enrolled in CAST, the actuarial (Kaplan-Meier) estimate of 1-year mortality was 10.3%. To estimate the "natural" mortality rate of patients enrolled in CAST, an analysis was done that adjusted for deaths that might be attributable to encainide or flecainide treatment either during prerandomization, open label drug titration or after randomization. Because the censoring procedure excluded patients treated with encainide or flecainide after randomization, the mortality estimate will be less than the unadjusted mortality estimate of 10.3%.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pet ownership, social support, and one-year survival after acute myocardial infarction in the Cardiac Arrhythmia Suppression Trial (CAST)

Social support and pet ownership, a nonhuman form of social support, have both been associated with increased coronary artery disease survival. The independent effects of pet ownership, social support, disease severity, and other psychosocial factors on 1 year survival after acute myocardial infarction are examined prospectively. The Cardiac Arrhythmia Suppression Trial provided physiologic data on a group of post-myocardial infarction patients with asymptomatic ventricular arrhythmias. An ancillary study provided psychosocial data, including pet ownership, social support, recent life events, future life events, anxiety, depression, coronary prone behavior, and expression of anger. Subjects (n = 424) were randomly selected from patients attending participating Cardiac Arrhythmia Suppression Trial sites and completed baseline psycho-social questionnaires. One year survival data were obtained from 369 patients (87%), of whom 112 (30.4%) owned pets and 20 (5.4%) died. Logistic regression indicates that high social support (p <0.068) and owning a pet (p = 0.085) tend to predict survival independent of physiologic severity and demographic and other psychosocial factors. Dog owners (n = 87, 1 died) are significantly less likely to die within 1 year than those who did not own dogs (n = 282, 19 died; p <0.05); amount of social support is also an independent predictor of survival (p = 0.065). Both pet ownership and social support are significant predictors of survival, independent of the effects of the other psychosocial factors and physiologic status. These data confirm and extend previous findings relating pet ownership and social support to survival among patients with coronary artery disease.     

Cardiac resynchronization for heart failure: background, methods, indications and results

Heart failure is one of the most prevalent diseases in industrialized countries. Although the prognosis of patients with heart failure is still poor, in recent decades new therapies have been investigated in order to improve quality of life and survival. However, up to 30% of the patients with advanced heart failure present disturbances in intraventricular conduction, and this produces asynchrony of ventricular contractility, leading to further deterioration in heart function. Cardiac resynchronization therapy can improve the synchrony of ventricular contractility. Numerous studies have demonstrated the benefits of biventricular stimulation therapy for improving hemodynamic parameters, quality of life, 6-minute walking test performance and functional class in patients with heart failure, ventricular systolic dysfunction and disturbances in intraventricular conduction. Some studies have demonstrated longer survival times in patients treated with cardiac resynchronization plus a defibrillator. Nonetheless, many questions about the benefits of heart resynchronization therapy, site of stimulation and best type of device (pacemaker or defibrillator) remain unresolved.     

Events in the Cardiac Arrhythmia Suppression Trial (CAST): mortality in patients surviving open label titration but not randomized to double-blind therapy

The patient characteristics and outcomes were studied in the 318 patients who survived open label drug titration in the Cardiac Arrhythmia Suppression Trial (CAST) and who were not randomized to double-blind therapy and in 942 patients, who were randomized to double-blind placebo therapy. The patients randomized to placebo therapy had a lower total mortality or resuscitated cardiac arrest rate (4% vs. 8.5%). However, at baseline, nonrandomized patients were dissimilar from patients randomized to placebo in the following ways: older; lower left ventricular ejection fraction; greater use of digitalis, diuretic drugs and antihypertensive agents; lesser use of beta-adrenoceptor blocking agents and more frequent prior cardiac problems, including runs of ventricular tachycardia and left bundle branch block. A matched comparison that took these inequities into account showed no significant differences in mortality or rate of resuscitation from cardiac arrest between nonrandomized patients and clinically equivalent patients randomized to placebo. Cox regression analysis indicated that two factors significantly increased the hazard ratio for arrhythmic death or resuscitated cardiac arrest in the nonrandomized patients: female gender (4.7, p less than 0.05) and electrocardiographic events (ventricular tachycardia, proarrhythmia, widened QRS complex, heart block, bradycardia) during open label titration (7.0, p less than 0.005). However, some potentially important differences between men and women were not included in the Cox regression model. Of the nonrandomized patients, approximately 70% were not randomized because of lack of suppression of ventricular premature depolarizations or adverse events, or both, and the remaining 30% because of patient or private physician request with no indication of another reason.(ABSTRACT TRUNCATED AT 250 WORDS)