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Biomedical subjects

E M Antman

Publications and source records attributed to E M Antman.

At least 19 recordsLinked to original sources
PubMed1992

Cumulative meta-analysis of therapeutic trials for myocardial infarction.

BACKGROUND: The large volume of published randomized, controlled trials has led to a need for meta-analyses to track therapeutic advances. Performing a new meta-analysis whenever the results of a new trial of a particular therapy are published permits the study of trends in efficacy and makes it possible to determine when a new treatment appears to be significantly effective or deleterious. We describe the use of such a procedure, cumulative meta-analysis, to assess therapeutic trials among patients with myocardial infarction. METHODS: We performed cumulative meta-analyses of clinical trials that evaluated 15 treatments and preventive measures for acute myocardial infarction. RESULTS: An example of this method is its application to the use of intravenous streptokinase as thrombolytic therapy for acute infarction. Thirty-three trials evaluating this therapy were performed between 1959 and 1988. We found that a consistent, statistically significant reduction in total mortality (odds ratios, 0.74; 95 percent confidence interval, 0.59 to 0.92) was achieved in 1973, after only eight trials involving 2432 patients had been completed. The results of the 25 subsequent trials, which enrolled an additional 34,542 patients through 1988, had little or no effect on the odds ratio establishing efficacy, but simply narrowed the 95 percent confidence interval. In particular, two very large trials, the Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico trial in 1986 (11,712 patients) and the Second International Study of Infarct Survival trial in 1988 (17,187 patients) did not modify the already established evidence of efficacy. We used a similar approach to study the accumulating evidence of efficacy (or lack of efficacy) of 14 other therapies and preventive measures for myocardial infarction. CONCLUSIONS: Cumulative meta-analysis of therapeutic trials facilitates the determination of clinical efficacy and harm and may be helpful in tracking trials, planning future trials, and making clinical recommendations for therapy.

Confidence Intervals↗
PubMed1992

A comparison of results of meta-analyses of randomized control trials and recommendations of clinical experts. Treatments for myocardial infarction.

OBJECTIVE: To examine the temporal relationship between accumulating data from randomized control trials of treatments for myocardial infarction and the recommendations of clinical experts writing review articles and textbook chapters. DATA SOURCES: (1) MEDLINE search from 1966 to present; search terms used were myocardial infarction, clinical trials, multicenter studies, double-blind method, meta-analysis, and the text word "random:"; (2) references from pertinent articles and books; and (3) all editions of English-language general medical texts and manuals and review articles on treatment of myocardial infarction. STUDY SELECTION: Randomized control trials of therapies for reducing the risk of total mortality in myocardial infarction (acute and secondary prevention). Review articles and textbook chapters dealing with the general clinical management of patients with myocardial infarction. DATA EXTRACTION: Two authors read the material and recorded the results; disagreements were resolved by conference. DATA SYNTHESIS: We used the technique of cumulative meta-analysis (performing a new meta-analysis when the results of a new clinical trial are published) and compared the results with the recommendations of the experts for various treatments for myocardial infarction. Discrepancies were detected between the meta-analytic patterns of effectiveness in the randomized trials and the recommendations of reviewers. Review articles often failed to mention important advances or exhibited delays in recommending effective preventive measures. In some cases, treatments that have no effect on mortality or are potentially harmful continued to be recommended by several clinical experts. CONCLUSIONS: Finding and analyzing all therapeutic trials in a given field has become such a difficult and specialized task that the clinical experts called on to summarize the evidence in a timely fashion need access to better databases and new statistical techniques to assist them in this important task.

Humans↗
PubMed1992

Assessment of the efficacy and safety of antiarrhythmic therapy for chronic atrial fibrillation: observations on the role of trial design and implications of drug-related mortality.

The findings in clinical trials of antiarrhythmic drug efficacy and safety are frequently difficult to compare, since study design often has an important effect on trial outcome. To explore this problem further, we compared three designs--randomized control, nonrandomized control, and uncontrolled--collectively enrolling 2415 patients in 21 trials reporting on the role of quinidine in the prevention of chronic atrial fibrillation. The proportion of patients remaining in sinus rhythm at 3, 6, and 12 months after cardioversion was calculated by means of Kaplan-Meier techniques, and the data were pooled for each trial design. For the randomized control trials the difference in the absolute percentage of patients remaining in sinus rhythm in the quinidine and control groups was 24% at each of the three follow-up intervals. Contrary to findings in the randomized control trials, the magnitude of the treatment benefit in nonrandomized trials was smaller and declined markedly over time. The percentage of patients remaining in sinus rhythm in the uncontrolled trials was intermediate to the percentages in the other two trial designs. When the data from all three trial designs were pooled, the crude mortality rate was 2.0% in quinidine-treated patients and 0.6% in control patients. Sudden cardiac death or ventricular fibrillation was the cause of death in 13 of 19 patients for whom the cause of death was known, highlighting the potential risk of quinidine-induced proarrhythmia. Although quinidine is effective in maintaining sinus rhythm, estimates of the treatment effect vary among trial types.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Arrhythmia Agents↗
PubMed1992

Declining incidence of ventricular fibrillation in myocardial infarction. Implications for the prophylactic use of lidocaine.

BACKGROUND: The purposes of the present investigation were 1) to track the incidence of primary ventricular fibrillation (VF) in the control and lidocaine-treated groups in the randomized control trials (RCTs) of lidocaine prophylaxis against primary VF in acute myocardial infarction, with particular emphasis on the time frame of the randomized trial, and 2) to estimate the number of patients who must receive lidocaine currently to prevent one episode of VF. METHODS AND RESULTS: The following variables from RCTs published between 1969 and 1988 were entered into logistic regression models to predict the percent of patients developing VF: year of publication of the RCT, method of data analysis used in the RCT, route and technique of lidocaine administration, duration of monitoring for VF, and exclusion criteria before randomization (congestive heart failure/cardiogenic shock, ventricular tachycardia/VF, or bradycardia/atrioventricular block). Year of publication was a significant predictor of VF in both the control and lidocaine groups (p less than or equal to 0.002) even after adjusting for other covariates. Based on a univariate logistic regression model with year as the predictor variable, it was estimated that the incidence of primary VF in the control group fell from 4.51% in 1970 to 0.35% in 1990 and from 4.32% down to 0.11% for the lidocaine group over the same time period. Thus, about 400 patients would currently need prophylaxis with lidocaine to prevent one episode of VF. CONCLUSIONS: Present estimates of the risk:benefit ratio of lidocaine prophylaxis should consider the low risk of VF in control patients and the large number who need lidocaine prophylaxis to prevent one episode of VF. When added to the previously reported trend toward excess mortality in lidocaine-treated patients, these data argue against the routine prophylactic use of lidocaine in patients with acute myocardial infarction.

Humans↗
PubMed1991

Prevention of supraventricular arrhythmias after coronary artery bypass surgery. A meta-analysis of randomized control trials.

This meta-analysis was performed to determine the efficacy of digoxin, verapamil, and beta-adrenoceptor blockers as prophylaxis against supraventricular arrhythmias (SVAs) after coronary artery bypass graft surgery (CABG). Randomized control trials were included if the electrocardiographic monitoring technique was clearly defined and extended through at least the first 3 postoperative days. Twenty-four of 69 identified studies were included in the final analysis. A summary odds ratio (OR) of the likelihood of developing SVAs after CABG in the treatment versus control groups was calculated. The pooled mean ventricular rate during SVA in patients who developed such an arrhythmia was also calculated. Neither digoxin nor verapamil reduced the likelihood of SVAs after CABG (digoxin: OR = 0.97, 95% confidence interval [CI] = 0.62-1.49; verapamil: OR = 0.91, CI = 0.57-1.46). The likelihood of developing an SVA in patients treated with beta-blockers was markedly decreased compared with controls (OR = 0.28, CI = 0.21-0.36). The pooled ventricular rate when SVAs did occur was significantly lower in each of the treatment groups. Prophylactic beta-adrenoceptor blockers had a protective effect against the development of SVAs in a select population of patients undergoing CABG. No such beneficial effect was demonstrated for digoxin or verapamil. All three classes of agents reduced the ventricular rate in patients who developed the arrhythmia, although the ventricular rate reduction was not clinically optimal.

Adrenergic beta-Antagonists↗
PubMed1990

Analysis of possible triggers of acute myocardial infarction (the MILIS study).

Recent documentation of a circadian variation in acute myocardial infarction (AMI) suggests that AMI is not a random event, but may frequently result from identifiable triggering activities. The possible triggers reported by 849 patients enrolled in the Multicenter Investigation of Limitation of Infarct Size were analyzed. Possible triggers were identified by 48.5% of the population; the most common were emotional upset (18.4%) and moderate physical activity (14.1%). Multiple possible triggers were reported by 13% of the population. Younger patients, men and those without diabetes mellitus were more likely to report a possible trigger than were older patients, women and those with diabetes. The likelihood of reporting a trigger was not affected by infarct size. This study suggests that potentially identifiable triggers may play an important role in AMI. Because potential triggering activities are common in persons with coronary artery disease, yet infrequently result in AMI, further studies are needed to identify (1) the circumstances in which a potential trigger may cause an event, (2) the specific nature of potential triggering activites, (3) the frequency of such activities in individuals who do not develop AMI and (4) the presence or absence of identifiable triggers in various subgroups of patients with infarction.

Aged↗
PubMed1990

Therapy of refractory symptomatic atrial fibrillation and atrial flutter: a staged care approach with new antiarrhythmic drugs.

One hundred nine patients with recurrent episodes of symptomatic atrial fibrillation or flutter, or both, who had failed one to five previous antiarrhythmic drug trials were treated with propafenone and, subsequently, sotalol if atrial fibrillation recurred. The clinical profile of the study group was as follows: age 63 +/- 13 years, left atrial anteroposterior dimension 4.4 +/- 0.9 cm and left ventricular ejection fraction 57 +/- 14%. Paroxysmal atrial fibrillation occurred in 56 patients (51%) and chronic atrial fibrillation occurred in 53 patients (49%). After loading and dose titration phases were completed, the maintenance doses of drugs were 450 to 900 mg/day for propafenone and 160 to 960 mg/day for sotalol. Life table estimates of the duration of freedom from atrial fibrillation were constructed for each drug trial. The percent of patients free of recurrent symptomatic arrhythmia at 6 months was 39% for propafenone and 50% for sotalol. The cumulative proportion of patients successfully treated with propafenone or sotalol, or both, by 6 months was 55% and remained relatively constant beyond that point. The incidence of intolerable side effects necessitating discontinuation of therapy ranged from 7% to 8%. Thus, despite previous unsuccessful drug trials, a substantial proportion of patients with recurrent symptomatic atrial fibrillation refractory to conventional therapy can be treated successfully and safely with newer antiarrhythmic drugs. Treatment failures tend to occur early in the course of follow-up, permitting easy identification of candidates for alternative therapeutic approaches.

Adult↗
PubMed1990

Efficacy and safety of perhexiline maleate in refractory angina. A double-blind placebo-controlled clinical trial of a novel antianginal agent.

Despite large gains in the medical and surgical treatment of angina pectoris in the past two decades, many patients are refractory to conventional medical therapy and are unsuitable for a first or, more commonly, repeat coronary revascularization procedure. We evaluated the efficacy of perhexiline maleate, a drug with an antianginal mechanism of action in humans that is as yet unknown, by using a randomized double-blind placebo-controlled crossover design in 17 patients with refractory angina who continued to receive maximal antianginal therapy, typically including nitrates, a beta-blocker, and a calcium channel antagonist. In view of perhexiline's potential for hepatic and neurological toxicity, plasma drug levels were monitored and maintained in the 150-600 ng/ml range. Sixty-three percent of patients were judged perhexiline responders by objective exercise testing criteria, as compared with 18% of patients on placebo (p less than 0.05). By blinded review of subjective measures of anginal frequency and severity, 65% of patients noted an improvement while on perhexiline, whereas no patient identified the placebo phase with improvement. Side effects observed in 29% of patients were minor and related to transient elevations of blood levels of more than 600 ng/ml; no patient suffered hemodynamic or cardiac conduction abnormalities attributable to perhexiline. With attention to the pharmacokinetics of perhexiline's elimination in individual patients, this novel antianginal agent seems to be safe and effective and deserves further evaluation in patients already receiving maximal antianginal therapy who are not candidates for revascularization procedures.

Aged↗
PubMed1990

Treatment of 150 cases of life-threatening digitalis intoxication with digoxin-specific Fab antibody fragments. Final report of a multicenter study.

One hundred fifty patients with potentially life-threatening digitalis toxicity were treated with digoxin-specific antibody fragments (Fab) purified from immunoglobulin G produced in sheep. The dose of Fab fragments was equal to the amount of digoxin or digitoxin in the patient's body as estimated from medical histories or determinations of serum digoxin or digitoxin concentrations. The youngest patient received Fab fragments within several hours of birth, and the oldest patient was 94 years old. Seventy-five patients (50%) were receiving long-term digitalis therapy, 15 (10%) had taken a large overdose of digitalis accidentally, and 59 (39%) had ingested an overdose of digitalis with suicidal intent. The clinical response to Fab was unspecified in two cases, leaving 148 patients who could be evaluated. One hundred nineteen patients (80%) had resolution of all signs and symptoms of digitalis toxicity, 14 (10%) improved, and 15 (10%) showed no response. After termination of the Fab infusion, the median time to initial response was 19 minutes, and 75% of the patients had some evidence of a response by 60 minutes. There were only 14 patients with adverse events considered to possibly or probably have been caused by Fab; the most common events were rapid development of hypokalemia and exacerbation of congestive heart failure. No allergic reactions were identified in response to Fab treatment. Of patients who experienced cardiac arrest as a manifestation of digitalis toxicity, 54% survived hospitalization.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Efficacy and safety of quinidine therapy for maintenance of sinus rhythm after cardioversion. A meta-analysis of randomized control trials.

Because individual studies evaluating the role of quinidine in the maintenance of sinus rhythm after cardioversion from chronic atrial fibrillation have involved relatively few patients, a meta-analysis of randomized control trials was performed. Six trials published between 1970 and 1984 were selected by two blinded reviewers based on study design and statistical analysis. Data from these six trials involving 808 patients were pooled after testing for homogeneity of treatment effects across trials. Life table estimates of the percent of patients still in sinus rhythm at 3, 6, and 12 months after cardioversion were constructed for quinidine and control groups. The proportion of patients remaining in sinus rhythm in the quinidine group was 69%, 58%, and 50% at 3, 6, and 12 months postcardioversion respectively. The proportion of patients remaining in sinus rhythm in the control group was 45%, 33%, and 25% at the same time intervals. The pooled rate difference, or difference in proportion of patients in sinus rhythm between quinidine and control groups, was 24%, 23%, and 24% at 3, 6, and 12 months of follow-up (p less than 0.001 at all time intervals). The unadjusted total mortality rate in the quinidine-treated patients was 2.9% and in the control group was 0.8%. The odds of dying in the quinidine-treated group were approximately three times that of the control group ("typical" odds ratio = 2.98, p less than 0.05). Thus, quinidine treatment is more effective than no antiarrhythmic therapy in suppressing recurrences of atrial fibrillation but appears to be associated with increased total mortality.

Adolescent↗
PubMed1988

Documented symptomatic bradycardia and symptom relief in patients receiving permanent pacemakers: an evaluation of the joint ACC/AHA pacing guidelines.

Recently, emphasis has been placed on documenting symptomatic bradycardia (DSB) before pacemaker placement can be justified in some patients. This study was designed to judge whether DSB improved the likelihood of symptom relief after pacing in 93 patients who had symptoms prior to pacing. Patients with complete heart block (Group A) had excellent symptomatic relief with or without pre-pacemaker DSB (100% vs 94%, P = NS). Patients with other diagnoses (Group B) also had a high incidence of symptomatic relief after pacing, regardless of whether or not DSB was present pre-implant (28/30 (93%) vs 23/28 (82%) P = NS). When evaluated as a test to predict the response to pacing for Group B patients, spontaneously occurring symptomatic bradycardia was neither highly sensitive (55%) nor highly specific (71%). Moreover, while the ability of a positive test to predict resolution of symptoms after pacing was high (93%), the ability of a negative test to predict a poor outcome after pacing was low (18%). The absence of DSB should not rule out permanent pacing for symptomatic patients in any diagnostic group. Future pacing guidelines should be revised to offer additional detail regarding the influence of symptoms, extent of asymptomatic bradycardia, and results of provocative tests in determining which implants should be classified as definitely indicated.

Bradycardia↗
PubMed1987

Drug interactions with cardiac glycosides: evaluation of a possible digoxin-ethmozine pharmacokinetic interaction.

Problems in studying pharmacokinetic interactions with digoxin were evaluated using as a test model the examination of a possible interaction between digoxin and ethmozine in a group of 11 patients with cardiac disease. A single-blind, placebo-controlled, nonrandomized protocol design was used. Considerable intrapatient variability in day-to-day serum digoxin levels was documented that could not be accounted for by laboratory variability in digoxin assay measurements (mean coefficient of variation 10.1%) or alterations in blood urea nitrogen (BUN), serum creatinine, or body weight during the course of the study. No consistent, statistically significant alteration of mean serum digoxin levels occurred when the baseline, placebo, and ethmozine phases were compared, although the study design would have permitted detection of a 0.29-ng/ml alteration in mean serum digoxin levels. A discussion of the sources of variability in digoxin levels is provided.

Aged↗
PubMed1985

Pacemaker-mediated tachycardia initiated by coincident P-wave undersensing and ventricular blanking period.

Pacemaker-mediated tachycardias (PMT) have received much recent attention. We describe the course and treatment of a 60-year-old man with an AV universal (DDD) pacemaker who developed a pacemaker-mediated tachycardia. The tachycardia was initiated by the coincidence of an unsensed P-wave, a QRS that was also not sensed due to the ventricular blanking period, and a short right ventricular myocardial effective refractory period. Treatment consisted of reprogramming the atrial sensitivity of the device. Physicians should be aware of the potential for the ventricular blanking period to participate in the initiation of pacemaker mediated tachycardias.

Arrhythmias, Cardiac↗
PubMed1979

Physiologic determinants of the electrocardiographic diagnosis of left ventricular hypertrophy.

The relative importance of left ventricular (LV) geometry, wall thickness, and mass on the inscription of left ventricular hypertrophy (LVH) on the ECG was examined in 93 patients; 36 had no LVH on the ECG, 10 had borderline voltage for LVH, and 47 had LVH on the ECG. LV cineangiograms in the right anterior oblique projection were analyzed for LV end-diastolic volume, free wall thickness (h), semiminor radius (R), LV mass index (LVMI), and the geometric relations described by h/R, mass/volume, and h . R. Although mean LVMI was greater in patients whose ECG voltage was either borderline or diagnostic of LVH, increased LVMI also occurred without LVH on the ECG. None of the variables (h, R, h/R or mass/volume) reliably indicated when LVH would be inscribed on the ECG. The product of h . R, however, defined three electrocardiographic groups; all patients with LVH on their ECG had h . R greater than 2.6 cm2. Wall thickening sufficient to result in an increased LV mass did not result in LVH on the ECG unless sufficient concurrent chamber dilatation was present. Thus, a critical geometric relationship resulting from the interplay of wall thickness and chamber dilatation is necessary for LVH to appear on the ECG. This finding is consistent with the solid-angle theory of electrocardiography as it relates to ventricular hypertrophy.

Action Potentials↗
PubMed1979

Low-pressure cardiac tamponade.

An elderly man developed cardiac tamponade from a tuberculous pericardial effusion but without such typical manifestations as pulsus paradoxus and jugular-vein distension. This case illustrates the difficulties in clinical recognition of low-pressure cardiac tamponade, which can develop in the presence of dehydration and hypovolemia. The hemodynamic factors that account for this phenomenon are discussed.

Aged↗