PubMed Health⌕ Search

Biomedical subjects

G L Knatterud

Publications and source records attributed to G L Knatterud.

At least 37 records · Page 2Linked to original sources
PubMed1997

Management of unstable angina pectoris and non-Q-wave acute myocardial infarction in the United States and Canada (the TIMI III Registry).

Management of Q-wave acute myocardial infarction (AMI) has been shown to differ between the United States and Canada, with more catheterization and revascularization procedures performed in the United States, but with little or no apparent difference in clinical outcomes. No previous studies have evaluated management differences for the acute coronary syndromes of unstable angina pectoris and non-Q-wave AMI. We therefore compared treatments and outcomes between 14 United States and 4 Canadian tertiary care centers participating in an observational registry of all consecutive admissions for unstable angina or non-Q-wave AMI between 1990 and 1993. A random, stratified sample was selected for detailed assessment and follow-up. There were 1,733 patients enrolled in United States centers and 642 in Canadian ones. In United States centers patients were less likely to receive intravenous nitroglycerin, heparin, beta blockers, calcium antagonists, or > or = 2 anti-ischemic agents. Coronary arteriography during index hospitalization was equally frequent in both countries (63.4% vs 66.9%, p = 0.781), but at 6 weeks and 1 year coronary arteriography was slightly less frequent in the United States patients. Revascularization by coronary angioplasty or bypass surgery was equivalent at 6 weeks and 1 year; however, there were trends toward less angioplasty and more bypass surgery in the United States than in Canada. Patients at United States centers stayed in the hospital fewer days than patients at Canadian centers (mean 8.2 vs 12.1 days, p <0.001). Death or AMI by 6 weeks was not different (4.8% vs 4.4%, p = 0.633), nor was it different at 1 year (10.0% vs 10.2%, p = 0.836). The combined outcome of death, AMI, or recurrent ischemia was more common in United States than in Canadian patients at 6 weeks (18.4% vs 13.9%, p = 0.004). Our findings indicate that United States physicians and hospitals did not consistently utilize more resources and were not more aggressive than their Canadian counterparts when treating acute coronary syndromes during this period.

Aged↗
PubMed1997

Comparison of preoperative characteristics of men and women undergoing coronary artery bypass grafting (the Post Coronary Artery Bypass Graft [CABG] Biobehavioral Study).

A cohort of 759 coronary artery bypass grafting (CABG) patients (269 women and 490 men) was enrolled in the prospective POST CABG Biobehavioral Study at 5 clinical centers in the United States and Canada. Sociodemographic and medical data were obtained by interview and from medical charts. Health-related quality of life and psychosocial data were ascertained preoperatively by interview and questionnaire for those patients whose condition allowed preoperative assessment and was compared among patients from hospitals enrolling both male and female patients (143 women and 267 men). Women enrolled in the Biobehavioral Study were older than men (65.4 +/- 9.0 vs 61.8 +/- 9.7 years, p < 0.001) and more likely to have a preoperative medical condition which precluded biobehavioral evaluation (47% vs 34%, p < 0.001). Women were less likely to be high school graduates (59% vs 74%, p < 0.001), were less likely to be earning > or = $25,000 per year (39% vs 69%, p < 0.001), and were married less often at the time of surgery (59% vs 85%, p < 0.001). Fewer women than men were able to perform basic self-care activities (p < 0.001) and social activities (p < 0.001). Women were also less able to perform the more demanding activities required for independent living, recreation, and maintaining a household (p < 0.001). Women were also more anxious (p = 0.01) and reported more depressive symptoms (p < 0.001) than men. These data suggest that plans for perioperative and convalescent care for women undergoing CABG should take into account their less favorable medical and psychosocial status relative to men.

Activities of Daily Living↗
PubMed1997

Asymptomatic Cardiac Ischemia Pilot (ACIP) study two-year follow-up: outcomes of patients randomized to initial strategies of medical therapy versus revascularization.

BACKGROUND: Patients with ischemia during stress testing and ambulatory ECG monitoring have an increased risk of cardiac events, but it is not known whether their prognosis is improved by more aggressive treatment with anti-ischemic drugs or revascularization. METHODS AND RESULTS: The Asymptomatic Cardiac Ischemia Pilot study randomized 558 such patients who had coronary anatomy suitable for revascularization to three treatment strategies: angina-guided drug therapy (n=183), angina plus ischemia-guided drug therapy (n=183), or revascularization by angioplasty or bypass surgery (n=192). Two years after randomization, the total mortality was 6.6% in the angina-guided strategy, 4.4% in the ischemia-guided strategy, and 1.1% in the revascularization strategy (P<.02). The rate of death or myocardial infarction was 12.1% in the angina-guided strategy, 8.8% in the ischemia-guided strategy, and 4.7% in the revascularization strategy (P<.04). The rate of death, myocardial infarction, or recurrent cardiac hospitalization was 41.8% in the angina-guided strategy, 38.5% in the ischemia-guided strategy, and 23.1% in the revascularization strategy (P<.001). Pairwise testing revealed significant differences between the revascularization and angina-guided strategies for each comparison. CONCLUSIONS: A strategy of initial revascularization appears to improve the prognosis of this population compared with angina-guided medical therapy. A larger long-term study is needed to confirm this benefit and to adequately test the potential of more aggressive drug therapy.

Adrenergic beta-Antagonists↗
PubMed1997

Anginal status and prediction of cardiac events in patients enrolled in the asymptomatic cardiac ischemia pilot (ACIP) study. ACIP investigators.

We hypothesized that among the patients enrolled in the Asymptomatic Cardiac Ischemia Pilot (ACIP) trial, those who reported angina either within the previous 6 weeks or experienced angina during ambulatory electrocardiographic (ECG) monitoring during activities of daily life or during stress testing would be more likely to experience an adverse cardiac event within a year than those who did not experience angina. Of the 558 patients enrolled in ACIP, 325 (58.2%) reported angina in the previous 6 weeks, 300 (53.8%) had stress-induced angina, and 63 (11.3%) reported angina during activities of daily life associated with ST-segment changes on the 48-hour ambulatory electrocardiogram. Some patients had > 1 of these angina symptoms and thus 8 angina status categories were identified. Adverse cardiac events were defined as death, nonfatal myocardial infarction (MI), or hospitalization for ischemic events, which included revascularization not specified by the ACIP protocol. One hundred and sixty-seven patients (29.9%) were asymptomatic (i.e., they never had angina) by our defined criteria. Three hundred ninety-one patients (70.1%) were symptomatic. Symptomatic patients had a higher incidence of death, MI, or hospitalization for ischemic events (15.3% symptomatic vs 7.8% asymptomatic, p = 0.016). History of angina within 6 weeks before randomization was predictive of death, MI, or hospitalization for ischemic event (p = 0.007). This finding was due to a large difference in the need for hospitalizations which would be expected to be driven by the presence of angina. By contrast, angina during ambulatory electrocardiogram or stress test was not predictive of an adverse cardiac event. The asymptomatic status of coronary disease patients who have objective documentation of ischemia is not uniformly defined and many different categories can be identified. In this population of patients with proven coronary artery disease and myocardial ischemia, a history of angina in the previous 6 weeks was a good predictor of an adverse event occurring in the next year.

Angina Pectoris↗
PubMed1997

Hemorrhagic events during therapy with recombinant tissue plasminogen activator, heparin, and aspirin for unstable angina (Thrombolysis in Myocardial Ischemia, phase IIIB trial).

This study assesses the effects of invasive procedures, hemostatic and clinical variables, and doses of recombinant tissue plasminogen activator (t-PA) on hemorrhagic events in the thrombolysis in myocardial ischemia (TIMI), phase 1B clinical trial (n = 1,425). Patients seen within 24 hours of the onset of ischemic chest pain at rest were randomized using a 2 x 2 factorial design for comparison of: (1) t-PA versus placebo as initial therapy, and (2) an early invasive (coronary arteriography with percutaneous angioplasty, if feasible) versus an early conservative strategy (coronary arteriography followed by revascularization if initial medical therapy failed). All patients received conventional medication for acute ischemic syndromes, including heparin, aspirin, beta blockers, nitrates, and calcium antagonists. The total dose of t-PA or placebo was 0.8 mg/kg, up to a maximum dose of 80 mg. In patients treated with t-PA, major and minor hemorrhagic events were more common than among those assigned to placebo (p < 0.001). Patients assigned to the invasive strategy arm had a higher hemorrhagic event rate than the noninvasive strategy, although the difference was not significant (p = 0.026). Patients > 75 years of age had higher intracranial hemorrhage rates than those < 75 years of age (6.7% vs 0.2%, respectively, p = 0.01). Major hemorrhagic events were more common in patients with higher heparin levels (p < 0.001), higher peak D-dimer levels (p = 0.007), and lower nadir fibrinogen levels (p = 0.005). Thus, increased morbidity due to hemorrhagic complications is associated with the use of t-PA, increased age, and selected hemostatic measures. Comparison to TIMI II demonstrates a significant association between the dose of t-PA and hemorrhagic complications.

Aged↗
PubMed1997

An application of the Zucker-Wittes modified ratio estimate statistic in the Post Coronary Artery Bypass Graft (CABG) clinical trial.

In the Post Coronary Artery Bypass Graft (POST CABG) clinical trial, the primary outcome is substantial worsening (i.e., narrowing of the lumen diameter) of the vein grafts upon comparison of the baseline and follow-up angiograms. The patients had one to five non-occluded vein grafts at entry, so there may be from one to five primary outcome responses per patient. A modified ratio estimate (MRE) statistic, as described previously by Zucker and Wittes, may be used to analyze data of this kind. In the present paper we propose a more powerful MRE statistic when the event rates and/ or intraclass correlations vary according to number of grafts per patient. We also adapt this statistic to the factorial treatment design of the POST CABG clinical trial.

Anticholesteremic Agents↗
PubMed1997

Ischemic cerebral infarction after rt-PA and heparin therapy for acute myocardial infarction. The TIMI-II pilot and randomized clinical trial combined experience.

BACKGROUND AND PURPOSE: Ischemic cerebral infarction (CI) is a serious complication of acute myocardial infarction (MI). Little information exists on CI after thrombolytic therapy for MI. METHODS: Of 3924 MI patients treated with recombinant tissue plasminogen activator (rt-PA) and heparin, 29 (0.7%) developed CI after treatment. All CI patients had detailed neurological evaluations, and 27 (93%) had CT scans centrally reviewed. RESULTS: Age range was 40 to 74 years (mean, 60 years); 25 patients (86%) were men, and 22 (76%) were white. The electrocardiographic location of MI was anterior in 22 (76%) and nonanterior in 7 (24%). Five CIs occurred within 6 hours, 4 between 6 to 24 hours, 8 during the remainder of the first week, 10 during the second week, and 2 others distributed over the 4 weeks after study entry. Six of 29 CIs did not involve the cerebral cortex; 9 patients (31%) had multiple CIs. Of 28 CIs thought to be embolic in origin, 17 showed strong evidence for at least one cardiac abnormality (mural clot, wall-motion abnormality, aneurysm, or atrial fibrillation) known to be associated more specifically with embolism than MI. Eight of 27 CIs (30%) with CT scans had hemorrhagic transformation of varying degrees; 5 were symptomatic. CONCLUSIONS: The time of occurrence and sites of CI after rt-PA and heparin therapy for acute MI are similar to those reported during the prethrombolytic era.

Adult↗
PubMed1996

Results of percutaneous transluminal coronary angioplasty in unstable angina and non-Q-wave myocardial infarction. Observations from the TIMI IIIB Trial.

BACKGROUND: This report describes the results of percutaneous transluminal coronary angioplasty (PTCA) in the Thrombolysis in Myocardial Ischemia (TIMI) IIIB Investigation. METHODS AND RESULTS: PTCA was performed before hospital discharge in 444 of 1473 patients with either unstable angina pectoris or non-Q-wave myocardial infarction (NQWMI) enrolled in TIMI IIIB. Angiographic success was observed in 96.1% of patients. For the entire cohort, the cumulative incidences of death and infarction at 1 year were 2.0% and 8.2%, respectively. The periprocedural incidence of myocardial infarction was 2.7%; emergency coronary bypass surgery, 1.4%; and death, 0.5%. By 1 year of follow-up, 122 patients (28.0%, Kaplan-Meier) had an additional revascularization procedure, 75 (61.5%) had PTCA only, 30 (24.6%) had coronary bypass surgery only, and 17 (13.9%) had both procedures. The results of PTCA were not improved by routine pretreatment with intravenous tissue plasminogen activator (TPA). Periprocedural myocardial infarction was more common among patients receiving TPA than placebo (odds ratio [OR], 2.19; P = .03) and among those with unstable angina than those with NQWMI (OR, 15.5; P = .007). No difference in outcome was observed when patients were analyzed according to age (OR, 1.06; P = .092) or sex (OR, 1.54; P = .51). Variables predictive of poor outcome were PTCA within the first 24 hours of enrollment, PTCA site being the left anterior descending coronary artery, and unsuccessful angiography. CONCLUSIONS: In TIMI IIIB, PTCA was performed for patients with unstable angina and NQWMI with a very high rate of angiographic success and a low incidence of complications. By 1 year, repeat revascularization was performed in 28.0% of patients. Routine pretreatment with thrombolysis did not enhance outcome.

Aged↗
PubMed1996

Prognostic value of plasma fibrinogen concentration in patients with unstable angina and non-Q-wave myocardial infarction (TIMI IIIB Trial)

Inflammation may play an important role in acute coronary syndromes. We studied the prognostic value of fibrinogen, an acute-phase protein directly involved in thrombotic process, measured serially in 1,473 patients with unstable angina and non-Q-wave myocardial infarction participating in the Thrombolysis in Myocardial Infarction IIIB trial. Overall, no association was found between baseline (pretreatment) fibrinogen and in-hospital (< or = 10 days) myocardial infarction (p=0.70) and death (p=0.64); however, patients with spontaneous ischemia (p=0.004) and the combined unsatisfactory outcome of death, myocardial infarction, and spontaneous ischemia (p=0.003) had higher fibrinogen concentrations than those without these events. This association was confined to patients with unstable angina. A baseline fibrinogen concentration > or = 300 mg/dl was associated with a modest trend toward an increased risk of death, myocardial infarction, or spontaneous ischemia (odds ratio 1.61, 95% confidence interval 1.02 to 2.52; p=0.04). Elevation of fibrinogen, a readily measurable acute-phase protein, at the time of hospital admission is associated with coronary ischemic events and a poor clinical outcome in patients with unstable angina.

Angina, Unstable↗
PubMed1996

Comparison of subgroups assigned to medical regimens used to suppress cardiac ischemia (the Asymptomatic Cardiac Ischemia Pilot [ACIP] Study).

This report focuses on the subset of 235 patients from the Asymptomatic Cardiac Ischemia Pilot (ACIP) study receiving randomly assigned medical therapy to treat angina and suppress ischemia detected on ambulatory electrocardiography: 121 patients received the sequence of atenolol and nifedipine, and 114 diltiazem and isosorbide dinitrate. After 12 weeks of therapy, the primary end point (absence of ambulatory electrocardiographic (ECG) ischemia and no clinical events) was reached in 47% of atenolol/nifedipine- versus 31% of diltiazem/isosorbide dinitrate-treated patients (adjusted p = 0.03). A trend to increased exercise time to ST depression was seen in the atenolol and nifedipine versus diltiazem and isosorbide dinitrate regimens (median treadmill duration 5.8 vs 4.8 minutes; p = 0.04). However, when adjusted for baseline imbalances in ambulatory ECG ischemia, the 2 medical combinations were similar in suppression of ambulatory ECG ischemia. In both medication regimens, an association between mean heart rate and ischemia on ambulatory electrocardiography after 12 weeks of treatment was observed so that patients on either regimen with a mean heart rate > 80 beats/min had ischemia detectable almost twice as often as those with a mean heart rate < 70 beats/min (p < 0.001).

Angina Pectoris↗
PubMed1996

Influence of race, sex, and age on management of unstable angina and non-Q-wave myocardial infarction: The TIMI III registry.

OBJECTIVE: To investigate the natural history and response to treatment of patients with unstable angina or non-Q-wave myocardial infarction (MI). DESIGN: Inception cohort. SETTING: Patients in general community, primary care, or referral hospitals. PATIENTS: All patients with an episode of unstable exertional chest pain or chest pain at rest presumed to be ischemic in origin lasting 5 minutes or more but without persisting ST-segment elevation greater than 30 minutes or the development of Q-waves were identified and enumerated in 18 participating hospitals. A subset of enumerated patients was selected to be followed prospectively using specific sampling strategies that would provide adequate numbers of black, women, and elderly (aged > or = 75 years) patients for comparison with their respective counterparts. MAIN OUTCOME MEASURES: The primary analysis compared the incidence of death or MI at 42 days after entry into the prospective study according to race, sex, and age. Other outcomes considered were recurrent ischemia and the combined outcomes of death, MI, or recurrent ischemia by 42 days after entry. RESULTS: A total of 8676 admissions with unstable angina or non-Q-wave MI were enumerated and, of these, 3318 patients were selected for the prospective study. The direct adjusted mean age of 3318 patients was 63.8 years. There were 943 blacks and 2375 nonblacks. Compared with nonblacks, blacks were less likely to be treated with intensive anti-ischemic therapy for their qualifying anginal episode and less likely to undergo invasive procedures (risk ratio [RR], 0.65%; 95% confidence interval [CI], 0.58 to 0.72; P<.001). However, of those who underwent angiography (45% of blacks and 61% of nonblacks), blacks had less extensive and severe coronary stenoses than nonblacks. The incidence of death and MI was similar for blacks and nonblacks, but blacks had a lower incidence of recurrent ischemia. There were 1678 men and 1640 women. Women were less likely than men to receive intensive anti-ischemic therapy and less likely to undergo coronary angiography (RR, 0.71; 95% CI, 0.65 to 0.78; P<.001). Women had less severe and extensive coronary disease and were less likely to undergo revascularization, yet had a similar risk of experiencing an adverse cardiac event by 6 weeks. There were 2490 patients aged 75 years or less and 828 patients aged more than 75 years. Elderly patients received less aggressive anti-ischemic therapy and were less likely to undergo coronary angiography than their younger counterparts. Elderly patients had more severe and extensive coronary disease but fewer revascularization procedures than younger patients and experienced a much higher incidence of adverse cardiac events both in hospital and by 6 weeks. CONCLUSIONS: Among patients presenting with acute ischemic chest pain without persistent ST-segment elevation, blacks appeared to have less severe coronary disease, received revascularization less frequently, and had less recurrent ischemia compared with nonblacks. Women were also found to have less severe coronary disease and were treated less intensely than men, but experienced similar outcomes. Elderly patients had more severe coronary disease than younger patients on coronary angiography, but were more likely to be treated medically, and they experienced far more adverse outcomes. These data suggest that more aggressive strategies should be directed to those patients with the greatest likelihood of adverse outcomes.

Age Factors↗
PubMed1995

Asymptomatic Cardiac Ischemia Pilot (ACIP) Study. Improvement of cardiac ischemia at 1 year after PTCA and CABG.

BACKGROUND: Cardiac ischemia on the ambulatory ECG (AECG) and/or on the exercise treadmill test (ETT) is associated with an increased risk of adverse outcome. Myocardial revascularization more often suppresses cardiac ischemia than does medical management alone. However, few studies have compared the effects of percutaneous transluminal coronary angioplasty (PTCA) with those of coronary artery bypass grafting (CABG) on cardiac ischemia and clinical outcome. METHODS AND RESULTS: A total of 558 patients were randomly assigned to one of three treatment strategies in the Asymptomatic Cardiac Ischemia Pilot (ACIP) study: angina-guided medical strategy (n = 184), ischemia-guided medical strategy (n = 182), or revascularization (n = 192). In patients assigned to revascularization, the choice of the procedure, PTCA or CABG, was made by the clinical unit staff and patient based on a coronary angiogram usually performed within 2 months of enrollment. CABG was selected in 78 patients and PTCA in 92 patients. At 12 weeks, ischemia on the AECG was suppressed in 70% of CABG patients versus 46% of PTCA patients (P = .002). Ischemia on the ETT was no longer present in 46% versus 23% of the patients, respectively (P = .005). Angina, within 4 weeks of the follow-up visit, was absent in 90% versus 68%, respectively (P = .001). These clinical variables remained improved in both groups at 1 year. Clinical events (myocardial infarction or repeat revascularization) occurred in 1 CABG patient versus 7 PTCA patients at 12 weeks, and in 1 versus 16 patients, respectively, at 12 months (P < .001). CONCLUSIONS: Ischemia on the AECG and ETT and angina were relieved in many patients after both procedures; however, CABG was superior to PTCA, and it was associated with a lower incidence of clinical events at 1 year. These results suggest that more complete revascularization relates to better clinical outcome. However, a large trial is needed to confirm these results.

Angina Pectoris↗
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

Asymptomatic Cardiac Ischemia Pilot (ACIP) study: impact of anti-ischemia therapy on 12-week rest electrocardiogram and exercise test outcomes. The ACIP Investigators.

OBJECTIVES: This report from the Asymptomatic Cardiac Ischemia Pilot (ACIP) study examines differences in the magnitude of reduction of myocardial ischemia as determined by exercise treadmill testing in patients randomized to three different treatment strategies: angina-guided medical therapy, ischemia-guided medical therapy and coronary revascularization. BACKGROUND: No prospective randomized clinical trials in patients with exercise electrocardiographic (ECG) abnormalities and asymptomatic cardiac ischemia on ambulatory ECG monitoring have compared the impact of different treatment strategies, including coronary revascularization, in terms of reducing myocardial ischemia. METHODS: The ACIP exercise protocol was used. Exercise variables measured included final exercise stage; presence of exercise-induced angina or ischemia; time to angina; time to 1-mm ST segment depression; number of exercise ECG leads with abnormalities; maximal depth of ST segment depression in any lead; sum of ST segment depression; ST/HR index; and rate-pressure product at time to angina, at time to 1-mm ST segment depression and at peak exertion. RESULTS: Peak exercise time was increased by 0.5, 0.7 and 1.6 min in patients assigned to the angina-guided, ischemia-guided and coronary revascularization strategies, respectively, from the qualifying visit to the 12-week visit (p < 0.001). At the qualifying visit, the sum of exercise-induced ST segment depression was 9.4 +/- 5.0 (mean +/- SD), 9.6 +/- 4.7 and 9.9 +/- 5.5 mm (p = NS) in the three treatment strategies, respectively. At the 12-week visit, the sum of exercise-induced ST segment depression was 7.4 +/- 5.7, 6.8 +/- 5.3 and 5.6 +/- 5.6 mm (p = 0.02) in the three treatment strategies, respectively. Each treatment strategy resulted in a significant reduction in all exercise-induced variables of myocardial ischemia measured at 12 weeks. CONCLUSIONS: Coronary revascularization significantly reduced the extent and frequency of exercise-induced myocardial ischemia compared with either medical strategy. The prognostic impact of these observations should be evaluated in a large-scale multicenter clinical trial.

Analysis of Variance↗
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↗