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E Braunwald

Publications and source records attributed to E Braunwald.

At least 163 records · Page 9Linked to original sources
PubMed1995

Predictors of non-Q-wave acute myocardial infarction in patients with acute ischemic syndromes: an analysis from the Thrombolysis in Myocardial Ischemia (TIMI) III trials.

Among patients with acute ischemic syndromes, patients with non-Q-wave acute myocardial infarction (AMI) are known to be at higher risk for death, reinfarction, and other morbidity than those with unstable angina. The aim of this study was to develop a clinically useful prediction rule to assist in distinguishing, at the time of presentation, patients with non-Q-wave AMI from those with unstable angina. The TIMI IIIB trial enrolled 1,473 patients presenting with ischemic pain at rest within 24 hours who had either electrocardiographic changes or documented coronary artery disease. Non-Q-wave AMI on presentation was documented by elevation of creatine kinase-MB in 33% of patients. Fifty clinical and electrocardiographic variables were compared between the patients with non-Q-wave AMI and unstable angina. After performing logistic regression, 4 baseline characteristics independently predicted non-Q-wave myocardial AMI: the absence of prior coronary angioplasty (odds ratio [OR] = 3.3, p < 0.001), duration of pain > or = 60 minutes (OR = 2.9, p < 0.001), ST-segment deviation on the qualifying electrocardiogram (OR = 2.0, p < 0.001), and recent-onset angina (OR = 1.7, p = 0.002). Using these 4 characteristics, a prediction rule for non-Q-wave AMI was developed. For the entire cohort of patients in TIMI III, the percentages of patients with non-Q-wave AMI when 0, 1, 2, 3, and 4 risk factors were present were 7.0%, 19.6%, 24.4%, 49.9%, and 70.6%, respectively (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1995

How do smokers differ from nonsmokers in their response to thrombolysis? (the TIMI-4 trial)

Smokers with acute myocardial infarction appear to have a better outcome after thrombolysis than do nonsmokers. To identify factors that could contribute to this curious finding, we analyzed data from the Thrombolysis in Myocardial Infarction (TIMI-4) trial, in which 382 patients with acute myocardial infarction were randomized to tissue plasminogen activator, anistreplase, or both. Coronary angiography was performed 90 minutes and 18 to 36 hours after randomization, a myocardial perfusion scan was performed at 18 to 36 hours and before discharge, and a radionuclide ventriculogram was obtained before discharge. Angiographic and clinical outcome variables were determined in current smokers, ex-smokers, and nonsmokers, and regression analysis was used to correct for differences in baseline characteristics. The in-hospital mortality of current smokers was lower than that of ex-smokers and nonsmokers: 2.3% versus 5.2% versus 7.0%, respectively (p = 0.04 by paired comparison, current vs nonsmokers). Ninety minutes after randomization, the incidence of TIMI grade 3 flow was significantly higher in smokers than in ex-smokers and nonsmokers (55% vs 43% and 45%, p = 0.02); this difference was no longer observed at the second angiogram, nor did smokers differ from nonsmokers with respect to residual stenosis, thrombus grade, infarct size, ejection fraction, or recurrent ischemia. Because a strong inverse relation exists between TIMI grade 3 flow at 90 minutes and mortality, our findings suggest that the lower mortality of current smokers after thrombolytic therapy may be related to a higher incidence of early, complete reperfusion.

Double-Blind Method↗
PubMed1995

Coronary artery bypass graft surgery after thrombolytic therapy in the Thrombolysis in Myocardial Infarction Trial, Phase II (TIMI II).

OBJECTIVES: We examined the results of coronary artery bypass graft surgery after thrombolytic therapy in the Thrombolysis in Myocardial Infarction trial, Phase II (TIMI II) with particular emphasis on patient characteristics, the impact of antecedent percutaneous transluminal coronary angioplasty and morbidity and mortality in certain subgroups. BACKGROUND: Coronary bypass surgery is frequently used after thrombolytic therapy, but there is relatively little information with regard to early and late outcomes. METHODS: We analyzed 3,339 patients enrolled in the TIMI II trial. Bypass surgery was performed in 390 patients (11.7%): 54 (14%) within 24 h after entry into the trial or within 24 h of coronary angioplasty and 336 (86%) between 24 h and 42 days after entry. RESULTS: Perioperative mortality rates were, respectively, 16.7% and 3.9% (p < 0.001); perioperative myocardial infarction rates were 5.6% and 6.2%, respectively; and major hemorrhagic events occurred in 74% and 50.9%, respectively (p = 0.002). On multivariate analysis, the only independent predictor of perioperative mortality was bypass surgery within 24 h after entry or after coronary angioplasty. Among patients undergoing bypass surgery within 24 h of entry or after coronary angioplasty, the prevalence of multivessel disease (59.1% vs. 77.8%) and use of the internal thoracic artery (18.5% vs. 62.5%) were lower than in the remaining surgical patients. Among the 322 perioperative survivors, the 1-year mortality rate after discharge was only 2.2% and 1.9%, respectively, in the two groups. Only one patient had a documented recurrent myocardial infarction during the first year. CONCLUSIONS: The increased mortality rate with bypass surgery after thrombolytic therapy, particularly in patients undergoing operation within 24 h of coronary angioplasty or during the involving phase of infarction, must be balanced against the excellent 1-year prognosis and perioperative survivors, who are in general a group at higher risk of death or recurrent infarction. These data provide a basis for comparison for future studies.

Angioplasty, Balloon, Coronary↗
PubMed1995

Hirudin: initial results in acute myocardial infarction, unstable angina and angioplasty.

The central role of thrombosis in the pathogenesis of acute myocardial infarction, unstable angina and complications after angioplasty has led to intense interest in developing more effective antithrombotic agents for these disorders. Hirudin, a direct thrombin inhibitor, has undergone extensive testing in experimental models and has recently been evaluated in patients in several pilot trials. Across these three indications, hirudin has been found to achieve a more consistent level of anticoagulation than heparin, as gauged by the activated parital thromboplastin time. Similarly, as an adjunct to thrombolytic therapy in acute myocardial infarction, in the treatment of unstable angina and in support of angioplasty, hirudin appeared to improve indexes of coronary reperfusion and patency. Initial results with clinical end points, including death or myocardial infarction, appeared to favor hirudin over heparin. In several large phase III trials, hirudin is being compared with heparin for all three indications. In the first phases of these trials, the rate of hemorrhagic events, including intracranial hemorrhage, was higher than expected in both the hirudin and heparin arms, which demonstrated that a safety ceiling had been reached. The reformulated Thrombolysis in Myocardial Infarction (TIMI) 9 and Second Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO II) trials are using lower doses of hirudin and heparin, which should allow testing of whether the initial favorable results observed in pilot trials will translate into improved clinical outcome, with an acceptable safety profile, for patients with acute myocardial infarction or unstable angina or those undergoing angioplasty.

Angina, Unstable↗
PubMed1995

Value of radionuclide rest and exercise left ventricular ejection fraction in assessing survival of patients after thrombolytic therapy for acute myocardial infarction: results of Thrombolysis in Myocardial Infarction (TIMI) phase II study. The TIMI Study Group.

OBJECTIVES: This study sought to determine the prognostic value of rest and exercise left ventricular ejection fraction in patients receiving thrombolytic therapy as part of the Thrombolysis in Myocardial Infarction (TIMI) trial. BACKGROUND: In the prethrombolytic era, ejection fraction at rest as well as during exercise was an important prognostic index in patients recovering from acute myocardial infarction. The prognostic value of these measurements in the thrombolytic era is not clear. METHODS: As part of the TIMI II protocol, we obtained radionuclide left ventricular ejection fraction at rest and during symptom-limited submaximal supine exercise. Measurements were related to 1-year all-cause as well as cardiac mortality. In addition, the relation between ejection fraction obtained at rest and 1-year cardiac mortality in this study was compared with the relation established previously in the prethrombolytic era by the Multicenter Postinfarction Research Group. RESULTS: A distinct relation was noted between left ventricular ejection fraction at rest and all-cause mortality. The highest mortality rate (9.9%) was noted in patients with an ejection fraction < 30%. Those not undergoing a study had a 1-year mortality rate of 6.2%. Peak exercise ejection fraction provided prognostic information similar to that of rest ejection fraction. Likewise, change in ejection fraction from rest to exercise did not appreciably improve prognostic impact. CONCLUSIONS: Rest left ventricular ejection fraction is an important prognostic index in patients receiving thrombolytic therapy. Peak exercise ejection fraction and the change in ejection fraction from rest to exercise do not provide appreciable prognostic data beyond those obtained at rest. Patients unable to exercise or those not having a rest study have a poor prognosis. When compared with the Multicenter Postinfarction Research Group data, there was strong evidence of a difference in survival in the two studies. At any level of ejection fraction, mortality was lower in TIMI II patients than in patients in the prethrombolytic era.

Aged↗
PubMed1995

Prognostic significance of nonfatal reinfarction during 3-year follow-up: results of the Thrombolysis in Myocardial Infarction (TIMI) phase II clinical trial. The TIMI Investigators.

OBJECTIVES: This study sought to assess the independent contribution of nonfatal reinfarction to the risk of subsequent death in patients with acute myocardial infarction undergoing thrombolytic therapy. BACKGROUND: A composite of "unsatisfactory outcomes" as an end point has increased statistical power and facilitated evaluation of evolving treatment regimens in acute myocardial infarction. The significance of nonfatal reinfarction as a component of a composite end point has not been evaluated in the thrombolytic era. METHODS: Event rate of nonfatal reinfarction over 3-year follow-up was evaluated in patients with acute myocardial infarction entered into the Thrombolysis in Myocardial Infarction Phase II trial. The independent risk of nonfatal reinfarction for subsequent death within various time intervals of follow-up was determined. The mortality rate after nonfatal reinfarction was compared with that of a matched control group. RESULTS: During 3-year follow-up, 349 of 3,339 patients had a nonfatal reinfarction. Univariate predictors were history (antedating the index event) of angina (p = 0.01), hypertension (p = 0.01), multivessel disease (p = 0.007) and not a current smoker (p = 0.003); the latter was an independent predictor (relative risk [RR] 1.3, 99% confidence interval [CI] 1.0 to 1.8). Forty-three of the 349 patients with a nonfatal reinfarction died: RR for death (vs. patients without a nonfatal reinfarction) was 1.9 (99% CI 1.1 to 3.2) if reinfarction occurred within 42 days of study entry, 6.2 (99% CI 3.0 to 12.9) if reinfarction occurred between 43 and 365 days and 2.9 (99% CI 0.6 to 13.4) if reinfarction occurred between 366 days and 3 years. The cumulative 3-year death rate was 14.1% in patients with a nonfatal reinfarction compared with 7.9% (p < 0.01) in a matched control group. Univariate predictors of death after nonfatal reinfarction were age > or = 65 years (p < 0.001), not low risk category (p = 0.015) and history of heart failure before the index event (p < 0.001). Age > or = 65 years was the only independent predictor (RR 5.4, 99% CI 2.3 to 12.4). CONCLUSIONS: Nonfatal reinfarction is a strong and independent predictor for subsequent death. It represents a powerful component for a composite end point in patients who received thrombolytic therapy after acute myocardial infarction.

Aged↗
PubMed1995

One-year results of the Thrombolysis in Myocardial Infarction (TIMI) IIIB clinical trial. A randomized comparison of tissue-type plasminogen activator versus placebo and early invasive versus early conservative strategies in unstable angina and non-Q wave myocardial infarction.

OBJECTIVES: We report mortality, infarction, revascularization and repeat hospital admission events for 1 year after enrollment and randomization in the Thrombolysis in Myocardial Ischemia (TIMI) IIIB clinical trial. BACKGROUND: The purpose of this trial was to investigate the role of a thrombolytic agent added to conventional medical therapies and to compare an early invasive management strategy to a more conservative early strategy in patients with unstable angina and non-Q wave myocardial infarction. METHODS: There were 1,473 patients enrolled, and they received conventional anti-ischemic medical therapies. They were randomized to therapy with either tissue-type plasminogen activator (t-PA) or placebo and also to an early invasive management strategy with coronary arteriography at 18 to 48 h, followed by revascularization as soon as possible if appropriate, or, alternatively, to an early conservative strategy with arteriography and revascularization reserved for failure of initial therapy to prevent recurrent ischemia. The primary end point was a composite outcome variable and was assessed at 42 days. Patients were then managed entirely at the discretion of their treating physician. Follow-up contacts were made at 1 year. RESULTS: The incidence of death or nonfatal infarction for the t-PA- and placebo-treated groups was similar after 1 year (12.4% vs. 10.6%, p = 0.24). The incidence of death or nonfatal infarction was also similar after 1 year for the early invasive and early conservative strategies (10.8% vs. 12.2%, p = 0.42). A trial of this size should be able to detect differences in relative risk for death or infarction > or = 1.81 with a power of 80% at a significance level (alpha) of 0.01. Revascularization by 1 year was common, but was slightly more common with the early invasive than the early conservative strategy (64% vs. 58%, p < 0.001). This result was related entirely to a small difference in angioplasty rates (39% vs. 32%, p < 0.001) inasmuch as rates of bypass grafting by 1 year were equivalent (30% in each group, p = 0.50). The high rate of revascularization in both strategies was accompanied by comparable clinical status at the 1-year follow-up contact. CONCLUSIONS: In this large study of unstable angina and non-Q wave myocardial infarction, the incidence of death and nonfatal infarction or reinfarction was low but not trivial after 1 year (4.3% mortality, 8.8% nonfatal infarction). An early invasive management strategy was associated with slightly more coronary angioplasty procedures but equivalent numbers of bypass surgery procedures than a more conservative early strategy of catheterization and revascularization only for signs of recurrent ischemia. The incidence of death or nonfatal infarction, or both, did not differ after 1 year by strategy assignment, but fewer patients in the early invasive strategy group underwent later repeat hospital admission (26% vs. 33%, p < 0.001). Either strategy is appropriate for patient management; differences in hospital admissions and revascularization procedures, with their attendant costs, are likely to be minimal.

Adult↗
PubMed1994

Clinical and arteriographic characterization of patients with unstable angina without critical coronary arterial narrowing (from the TIMI-IIIA Trial).

Previous studies have reported that some patients presenting with unstable angina are found at coronary angiography to have no critical coronary stenosis. This study evaluated the clinical presentation and arteriographic findings in patients enrolled in the Thrombolysis in Myocardial Ischemia (TIMI-IIIA) trial, which assessed the effect of tissue-type plasminogen activator added to conventional therapy on the coronary arteriographic findings in patients presenting with ischemic pain at rest. Three hundred ninety-one patients were enrolled in the TIMI-IIIA trial and underwent coronary arteriography within 12 hours of enrollment. Fifty-three patients (14%) had no luminal diameter stenosis of a major coronary artery of > or = 60% on the baseline arteriogram. Compared with patients with unstable angina with an identifiable culprit lesion, patients without critical coronary obstruction were more likely to be women and non-white and less likely to have ST-segment deviation on the presenting electrocardiogram. Arteriography in such patients revealed no visually detectable coronary stenosis in half of the group; the remaining patients had noncritical coronary narrowing (i.e., < 60% luminal diameter stenosis) without morphologic features (ulceration or thrombus) suggestive of unstable or active coronary plaque. Nearly one third of the patients without critical coronary stenosis had impaired angiographic filling, suggesting a possible pathophysiologic role for coronary microvascular dysfunction. These patients with unstable angina and no critical coronary obstruction had an excellent short-term prognosis; 2% died or had myocardial infarction compared with 18% of patients with critical obstruction.

Angina, Unstable↗
PubMed1994

Comparison of patients with < 60% to > or = 60% diameter narrowing of the myocardial infarct-related artery after thrombolysis. The TIMI Investigators.

The purpose of this study was to analyze angiographic findings, clinical course, and follow-up data on 1,752 patients who underwent protocol cardiac catheterization 18 to 48 hours after enrollment in the Thrombolysis in Myocardial Infarction (TIMI) II pilot and randomized trial: 244 patients (14.0%) had < 60% diameter stenosis in the infarct-related artery and TIMI grade 2 or 3 flow, 1,249 (71.2%) had a narrowing > or = 60% in diameter with TIMI grade 2 or 3 flow, and 259 patients (15%) had TIMI grade 0 or 1 flow (total occlusion). Patients with < 60% narrowing in the infarct-related artery were younger (p < 0.001) and more likely to be current smokers than those with more severe narrowings (p < 0.003). Patients with < 60% diameter stenosis in the infarct-related artery were more likely to have a predischarge radionuclide ejection fraction > 55% (p < 0.001) than were other patient groups. The 1-year mortality rate of patients with < 60% diameter stenosis in the infarct-related artery was 1.6% compared with 4.4% for patients with stenosis > or = 60% and TIMI grade 2 or 3 flow (p = 0.05) and 7.0% for patients with total occlusion (p = 0.004). Patients with stenosis < 60% in the infarct-related artery 18 to 48 hours after thrombolytic therapy have a good prognosis. Infarct artery status predicts predischarge ejection fraction and 1-year mortality.

Aged↗
PubMed1994

Comparison of clinical outcomes for women and men after acute myocardial infarction. The Thrombolysis in Myocardial Infarction Investigators.

OBJECTIVES: To assess differences in morbidity and mortality between men and women with acute myocardial infarction treated with thrombolytic therapy and the relation of differences to baseline patient characteristics and clinical features. DESIGN: Secondary analysis of observational findings among women and men enrolled in a clinical trial. SETTING: Hospitals participating in the Thrombolysis in Myocardial Infarction Phase II trial. MEASUREMENTS: Recurrent infarctions and deaths were assessed. MAIN RESULTS: The 6-week mortality rate was greater for women than for men (9% compared with 4%; adjusted relative risk, 1.54; P = 0.01). Death or reinfarction occurred in 15.9% of women and 9.5% of men (adjusted relative risk, 1.33; P = 0.02). Among patients enrolled for treatment with 100 mg of recombinant tissue plasminogen activator and assigned to a conservative strategy of watchful waiting with appropriate backup, the 6-week incidence of death was 7.5% for women and 3.8% for men (P = 0.01). The 6-week incidences of death or reinfarction were 14.2% and 8.9% (P = 0.01) among women and men, respectively. CONCLUSIONS: Among patients in the Thrombolysis in Myocardial Infarction Phase II Trial, who all were diagnosed with myocardial infarction and were eligible to receive thrombolytic therapy, women had higher rates of mortality and morbidity than did men. Older age at the time of myocardial infarction and a history of diabetes accounted for much but probably not all of this difference.

Age Factors↗
PubMed1994

Time as an Adjunctive Agent to Thrombolytic Therapy.

Thrombolytic therapy has dramatically reduced mortality following acute myocardial infarction (MI) with the major effect coming from early achievement of infarct-related artery patency. A major factor in achieving rapid reperfusion is early treatment with thrombolytic therapy. Recent trials have shown that mortality can be reduced if time to treatment is shortened: In the Thrombolysis in Myocardial Infarction (TIMI) 2 trial, for each hour earlier that thrombolytic therapy was started, approximately 10 lives were saved per 1000 patients treated. Thus, one must consider time as an adjunctive agent to thrombolytic therapy. There are four components of the time delay between the onset of MI and achievement of reperfusion: (1) patient delays in seeking medical attention; (2) transport delays; (3) the so-called door to needle time, the interval between the patient's arrival at the medical facility and the initiation of thrombolytic therapy; and (4) thrombolytic reperfusion time, the time between the administration of thrombolytic therapy and the achievement of roperfusion, Efforts to reduce each of these components will lead to additive benefits in improving time to reperfusion and survival of patients with acute MI.

Journal Article↗
PubMed1994

Diagnosing and managing unstable angina. Agency for Health Care Policy and Research.

This Quick Reference Guide for Clinicians contains recommendations on the care of patients with unstable angina based on a combination of evidence obtained through extensive literature reviews and consensus among members of an expert panel. Principal conclusions include the following. (1) Many patients suspected of having unstable angina can be discharged home after adequate initial evaluation. (2) Further outpatient evaluation may be scheduled for up to 72 hours after initial presentation for patients with clinical symptoms of unstable angina judged at initial evaluation to be at low risk for complications. (3) Patients with acute ischemic heart disease judged to be at intermediate or high risk of complications should be hospitalized for careful monitoring of their clinical course. (4) Intravenous thrombolytic therapy should not be administered to patients without evidence of ST segment elevation and acute myocardial infarction. (5) Assessment of prognosis by noninvasive testing often aids selection of appropriate therapy. (6) Coronary angiography is appropriate for patients judged to be at high risk for cardiac complications or death based on their clinical course or results of noninvasive testing. (7) Coronary artery bypass surgery should be recommended for almost all patients with left main disease and many patients with three-vessel disease, especially those with left ventricular dysfunction. (8) The discharge care plan should include continued monitoring of symptoms; appropriate drug therapy, including aspirin; risk-factor modification; and counseling.

Ambulatory Care↗
PubMed1993

Use of composite endpoints in thrombolysis trials of acute myocardial infarction.

Although preventing early mortality following acute myocardial infarction (MI) is the most important goal of thrombolytic therapy, insistence on its use as the only or principal endpoint in trials of acute MI will limit the number of new thrombolytic-antithrombotic regimens that can be tested, and thus may inhibit future progress of this important area of cardiovascular therapeutics. Trials of thrombolytic therapy over the past decade, as discussed in this article, have demonstrated that: (1) thrombolytic therapy improves both mortality and intermediate endpoints, and (2) intermediate nonfatal endpoints are strongly linked to long-term mortality. Taken together, these facts provide strong evidence that intermediate nonfatal events can be used as valid endpoints in future trials of thrombolytic therapy. The unsatisfactory outcome composite endpoint, which incorporates mortality and important intermediate endpoints, will make it possible to compare innovative new regimens in much smaller trials. Ultimately, both of these approaches (i.e., megatrials using a mortality endpoint and smaller trials utilizing a composite unsatisfactory outcome endpoint) can be used in a complementary fashion. A new regimen could first be tested using the unsatisfactory outcome endpoint; if it showed particular promise, it could then become a candidate for testing in a megatrial. Conversely, if it did not prove better than standard regimens, futile research in tens of thousands of patients might be prevented. Thus, the use of composite endpoints will expand the number of new thrombolytic-antithrombotic regimens that can be tested and, it is hoped, accelerate progress in the treatment of acute MI.

Clinical Trials as Topic↗