Combination reperfusion therapy with eptifibatide and reduced-dose tenecteplase for ST-elevation myocardial infarction: results of the integrilin and tenecteplase in acute myocardial infarction (INTEGRITI) Phase II Angiographic Trial

OBJECTIVES: The goal of this study was to evaluate combinations of eptifibatide with reduced-dose tenecteplase (TNK) in ST-elevation myocardial infarction (STEMI). BACKGROUND: Glycoprotein IIb/IIIa inhibitors enhance thrombolysis. The role of combination therapy in clinical practice remains to be established. METHODS: Patients (n = 438) with STEMI <6 h were enrolled. In dose-finding, 189 patients were randomized to different combinations of double-bolus eptifibatide and reduced-dose TNK. In dose-confirmation, 249 patients were randomized 1:1 to eptifibatide 180 microg/kg bolus, 2 microg/kg/min infusion, and 180 microg/kg bolus 10 min later (180/2/180) plus half-dose TNK (0.27 mg/kg) or standard-dose (0.53 mg/kg) TNK monotherapy. All patients received aspirin and unfractionated heparin (60 U/kg bolus; infusion 7 U/kg/h [combination], 12 U/kg/h [monotherapy]). The primary end point was Thrombolysis In Myocardial Infarction (TIMI) grade 3 epicardial flow at 60 min. RESULTS: In dose-finding, TIMI grade 3 flow rates were similar across groups (64% to 68%). Arterial patency was highest for eptifibatide 180/2/180 plus half-dose TNK (96%, p = 0.02 vs. eptifibatide 180/2/90 plus half-dose TNK). In dose-confirmation, this combination, compared with TNK monotherapy, tended to achieve more TIMI 3 flow (59% vs. 49%, p = 0.15), arterial patency (85% vs. 77%, p = 0.17), and ST-segment resolution (median 71% vs. 61%, p = 0.08) but was associated with more major hemorrhage (7.6% vs. 2.5%, p = 0.14) and transfusions (13.4% vs. 4.2%, p = 0.02). Intracranial hemorrhage occurred in 1.0%, 0.6%, and 1.7% of patients treated with any combination, eptifibatide 180/2/180 and half-dose TNK, and TNK monotherapy, respectively. CONCLUSIONS: Double-bolus eptifibatide (180/2/180) plus half-dose TNK tended to improve angiographic flow and ST-segment resolution compared with TNK monotherapy but was associated with more transfusions and non-cerebral bleeding. Further study is needed before this combination can be recommended for general use.     

Prophylactic lidocaine use in acute myocardial infarction: incidence and outcomes from two international trials. The GUSTO-I and GUSTO-IIb Investigators

BACKGROUND: Early meta-analyses suggested that prophylactic lidocaine use reduces ventricular fibrillation but increases mortality rates after acute myocardial infarction. We determined the frequency and effect on clinical outcomes with its use in the thrombolytic era. METHODS AND RESULTS: We studied 43,704 patients enrolled in GUSTO-I or GUSTO-IIb who had ST-segment elevation, underwent thrombolysis, and survived at least 1 hour after enrollment. Odds ratios (OR) and confidence intervals (CI) were calculated for the risk of asystole, atrioventricular block, ventricular fibrillation, and ventricular tachycardia during hospitalization; for 24-hour, in-hospital, and 30-day mortality rates; and for 24-hour and 30-day mortality rates after adjustment for baseline predictors of death. In GUSTO-I and GUSTO-IIb, 16% and 3.5% of patients, respectively, received prophylactic lidocaine. They had a lower risk of death at 24 hours (OR 0.81, 95% CI 0.67 to 0.97) and trends toward lower odds of in-hospital death (OR 0.90, 95% CI 0.81 to 1.01) and death at 30 days (OR 0.92, 95% CI 0.82 to 1. 02). After adjustment for baseline characteristics, however, the odds of death were similar with or without lidocaine (OR 0.90 and 0. 97, respectively). Outside the United States, lidocaine was associated with higher incidences of all serious arrhythmias, but in US patients it conferred a lower likelihood of ventricular fibrillation and no increase in asystole, atrioventricular block, or mortality rates. CONCLUSIONS: Prophylactic lidocaine use has decreased with the advent of thrombolysis, although its use may not be associated with increased mortality rates.     

Repeat percutaneous transluminal coronary angioplasty and predictors of recurrent restenosis

One hundred seventeen consecutive patients undergoing repeat percutaneous transluminal coronary angioplasty (PTCA) were studied to assess procedural success and recurrent restenosis rates. Clinical, anatomic and procedural variables were examined as predictors of recurrent restenosis using stepwise logistic regression analysis. Primary success was achieved in 114 patients (97.5%). One patient (0.8%) died after acute occlusion. No other in-hospital complications were encountered. After a mean follow-up interval of 218 +/- 160 days, 72 of 114 successfully dilated patients (63%) remained angina free. There were no late deaths. Three patients (2.6%) experienced a late myocardial infarction. Follow-up arteriography was performed in 100 patients (88%), of whom 32% had recurrent restenosis (greater than 50% luminal diameter narrowing). On univariate analysis, the presence of 3 clinical variables at repeat PTCA was associated with significantly higher recurrent restenosis rates compared with their absence, that is, unstable angina (48 vs 20%, p = 0.003), diabetes (61 vs 26%, p = 0.003) and hypertension (46 vs 18%, p = 0.003). Patients with recurrent restenosis had a shorter interval between first and second PTCA compared with those who remained patent (136 +/- 116 vs 214 +/- 163 days, p = 0.018). Multivariate analysis confirmed unstable angina, diabetes and hypertension as independent predictors of recurrent restenosis. Repeat PTCA may be performed for restenosis with a high likelihood of success and low incidence of complications. The rate of recurrent restenosis is similar to that reported for initial angioplasty. Patients with unstable angina, diabetes and hypertension appear to be at higher risk for recurrent restenosis.     

Predictors of cardiogenic shock after thrombolytic therapy for acute myocardial infarction

OBJECTIVES: This study characterized clinical factors predictive of cardiogenic shock developing after thrombolytic therapy for acute myocardial infarction (AMI). BACKGROUND: Cardiogenic shock remains a common and ominous complication of AMI. By identifying patients at risk of developing shock, preventive measures may be implemented to avert its development. METHODS: We analyzed baseline variables associated with the development of shock after thrombolytic therapy in the Global Utilization of Streptikonase and Tissue-Plasminogen Activator for Occluded Coronary Arteries (GUSTO-I) trial. Using a Cox proportional hazards model, we devised a scoring system predicting the risk of shock. This model was then validated in the Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO-III) cohort. RESULTS: Shock developed in 1,889 patients a median of 11.6 h after enrollment. The major factors associated with increased adjusted risk of shock were age (chi2 = 285, hazard ratio [95% confidence interval] 1.47 [1.40, 1.53]), systolic blood pressure (chi2 = 280), heart rate (chi2 = 225) and Killip class (chi2 = 161, hazard ratio 1.70 [1.52, 1.90] and 2.95 [2.39, 3.63] for Killip II versus I and Killip III versus I, respectively) upon presentation. Together, these four variables accounted for >85% of the predictive information. These findings were transformed into an algorithm with a validated concordance index of 0.758. Applied to the GUSTO-III cohort, the four variables accounted for > 95% of the predictive information, and the validated concordance index was 0.796. CONCLUSIONS: A scoring system accurately predicts the risk of shock after thrombolytic therapy for AMI based primarily on the patient's age and physical examination on presentation.     

Exercise treadmill score for predicting prognosis in coronary artery disease

To determine the prognostic value of the treadmill exercise test, we evaluated 2842 consecutive patients with chest pain who had both treadmill testing cardiac catheterization. The population was randomly divided into two equal-sized groups and the Cox regression model was used in one to form a treadmill score that was then validated in the other group. The final treadmill score was calculated as follows: exercise time--(5 X ST deviation)--(4 X treadmill angina index). Using this treadmill score, 13% of the patients were found to be at high risk; 53%, at moderate risk; and 34%, at low risk. The treadmill score added independent prognostic information to that provided by clinical data, coronary anatomy, and left ventricular ejection fraction: patients with three-vessel disease with a score of -11 or less had a 5-year survival rate of 67%, and those with a score of +7 or more had a 5-year survival rate of 93%. The treadmill score was useful for stratifying prognosis in patients with suspected coronary artery disease who were referred to us for catheterization, and may provide a useful adjunct to clinical decision making in the larger population of patients being evaluated for chest pain.     

Favorable early and long-term prognosis following coronary bypass surgery therapy for myocardial infarction: results of a multicenter trial. TAMI Study Group

Coronary bypass surgery was performed before hospital discharge on 82 (21%) of 386 consecutive patients enrolled in the Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) multicenter trial of intravenous tissue plasminogen activator and coronary angioplasty for acute myocardial infarction. Time from infarct symptom onset to coronary bypass surgery was 7.3 +/- 1.9 hours for 24 patients operated upon on an emergency basis and 9.3 +/- 5.2 days for 58 patients having late in-hospital surgery. There were no operative deaths and five in-hospital deaths in the surgical group, all of which occurred in patients with preoperative cardiogenic shock. Although patients in the surgical group were older (59.7 +/- 10.4 years versus 54.9 +/- 10.2 years; p = 0.03), had more extensive coronary artery disease (42% three-vessel disease versus 11%; p = 0.001), and had a higher incidence of anterior wall myocardial infarction (48% versus 39%; p = 0.02), in-hospital mortality for the surgical group (6%) was similar to that in 301 patients not undergoing surgery (7%) in this trial. For patients discharged from the hospital, mortality at 1 year was 2.5% in the surgical group and 1.8% in patients not having coronary bypass surgery before hospital discharge. At a 1 year follow-up, there were no significant differences in the frequency of cardiac or noncardiac-related hospitalizations or in event-free survival between surgical and nonsurgical groups. The majority of patients in both groups considered themselves to be in excellent or good condition. Coronary bypass surgery can be performed with low morbidity and mortality rates in close temporal association to acute myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS)     

Trends in physician management of uncomplicated acute myocardial infarction, 1970 to 1987

To document current management of uncomplicated acute myocardial infarction (AMI), a national survey of 1,065 physicians was performed. Items from previous surveys in 1970 and 1979 were included to permit analysis of time trends in management. Median hospital stay dropped from 21 days in 1970 to 9 days in 1987. Use of beta blockers and aspirin doubled between 1979 and 1987, while use of anticoagulation and sulfinpyrazone dropped 4- to 10-fold. In 1987, coronary angiography was used commonly, especially in younger patients or those with either a non-Q-wave AMI, intravenous thrombolytic therapy or a positive exercise test. These findings document the increasingly aggressive approach to the management of patients with uncomplicated AMI.