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At least 199 records · Page 11Linked to original sources
PubMed1995

Link between the angiographic substudy and mortality outcomes in a large randomized trial of myocardial reperfusion. Importance of early and complete infarct artery reperfusion. GUSTO-I Investigators.

BACKGROUND: The Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries (GUSTO-I) trial was designed to test whether thrombolytic strategies achieving more complete, early, sustained coronary artery patency would lead to further reductions in mortality in patients with acute myocardial infarction. An angiographic substudy within GUSTO-I provided a unique opportunity to examine the relation between mortality and degrees of patency among the regimens. METHODS AND RESULTS: Four thrombolytic strategies were compared in 41,021 patients in GUSTO-I: streptokinase with subcutaneous or intravenous heparin, accelerated tissue plasminogen activator (TPA) with intravenous heparin, and combination streptokinase plus TPA with intravenous heparin. Accelerated TPA was associated with lower 30-day mortality (6.3%) than the other strategies (7.2%, 7.4%, and 7.0%, respectively). Among the 1210 patients in the angiographic substudy randomized to angiography 90 minutes after starting treatment, there was improved patency, particularly Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow, with accelerated TPA over the other regimens (P < .0001). Coronary artery perfusion (TIMI grade 3) at 90 minutes was also a significant predictor of 30-day survival (P < .01). To determine whether differences in mortality among the four strategies matched differences in 90-minute patency, a model was developed for predicting mortality differences in the main trial from the angiographic substudy. The model assumed that any differences in treatment effects on 30-day mortality were mediated through differences in 90-minute patency for the four treatments. The predicted rates were then compared with observed mortality rates of the remaining patients in the main trial for each treatment group. The predicted and observed 30-day mortality rates of the four treatments were streptokinase with subcutaneous heparin, 7.46% versus 7.28%; streptokinase with intravenous heparin, 7.26% versus 7.39%; accelerated TPA, 6.31% versus 6.37%; and streptokinase plus TPA, 6.98% versus 6.96%. The correlation between predicted and observed results was .97, and the proportion of squared error explained (R2) was .92. CONCLUSIONS: The close relation between the predicted and observed 30-day mortality rates supports the concept that an important mechanism for improved survival with thrombolytic therapy is achievement of early, complete perfusion. The close match provides a strong biological explanation for the mortality differences seen in GUSTO-I and a sound rationale for the additional survival advantage of the accelerated TPA regimen. Irrespective of which treatment is used, early and complete restoration of infarct artery perfusion represents an essential goal of myocardial reperfusion therapy.

Coronary Angiography↗
PubMed2006

Hospital delays in reperfusion for ST-elevation myocardial infarction: implications when selecting a reperfusion strategy.

BACKGROUND: It has been suggested that the survival benefit associated with primary percutaneous coronary intervention (PPCI) in ST-segment elevation myocardial infarction may be attenuated if door-to-balloon (DB) time is delayed by >1 hour beyond door-to-needle (DN) times for fibrinolytic therapy. Whereas DB times are rapid in randomized trials, they are often prolonged in routine practice. We hypothesized that in clinical practice, longer DB-DN times would be associated with higher mortality rates and reduced PPCI survival advantage. We also hypothesized that in addition to PPCI delays, patient risk factors would significantly modulate the relative survival advantage of PPCI over fibrinolysis. METHODS AND RESULTS: DB-DN times were calculated by subtracting median DN time from median DB time at a hospital using data from 192,509 patients at 645 National Registry of Myocardial Infarction hospitals. Hierarchical models that adjusted simultaneously for both patient-level risk factors and hospital-level covariates were used to evaluate the relationship between PCI-related delay, patient risk factors, and in-hospital mortality. Longer DB-DN times were associated with increased mortality (P<0.0001). The DB-DN time at which mortality rates with PPCI were no better than that of fibrinolysis varied considerably depending on patient age, symptom duration, and infarct location. CONCLUSIONS: As DB-DN times increase, the mortality advantage of PPCI over fibrinolysis declines, and this advantage varies considerably depending on patient characteristics. As indicated in the American College of Cardiology/American Heart Association guidelines, both the hospital-based PPCI-related delay (DB-DN time) and patient characteristics should be considered when a reperfusion strategy is selected.

Aged↗
PubMed1995

A study of biochemical markers of reperfusion early after thrombolysis for acute myocardial infarction. The PERM Study Group. Prospective Evaluation of Reperfusion Markers.

BACKGROUND: In acute myocardial infarction (AMI), early noninvasive identification of patients with occluded infarct-related arteries (IRAs) after thrombolysis has important prognostic and therapeutic implications. The aims of this study were to evaluate biochemical methods for the early diagnosis of patency after thrombolysis prospectively and to establish the optimal diagnostic criteria retrospectively. METHODS AND RESULTS: In 97 patients with AMI treated with thrombolytic agents < or = 6 hours after the onset of symptoms, myoglobin, troponin T, creatine kinase, the MB isoenzyme and MM isoforms of creatine kinase were measured just before thrombolysis began and 90 minutes later. IRA patency was assessed by means of 90-minute coronary angiography. For each marker, compared with the expected sensitivity and specificity based on published thresholds for the diagnosis of patency, the observed values were consistently lower but were markedly improved in a subset of patients treated > 3 hours after the onset of symptoms. With receiver-operator characteristic curve analysis of the slopes of increase and relative increases in each marker over 90 minutes, the best diagnostic performance was achieved by use of the relative increase in myoglobin, troponin T, and MM3/MM1 creatine kinase isoforms in patients treated > 3 hours after onset (areas under the curve of 0.84, 0.83, and 0.85, respectively). CONCLUSIONS: Effective early noninvasive diagnosis of patency after thrombolysis is possible in patients treated > 3 hours after symptom onset by use of criteria derived from the relative increase over 90 minutes in plasma markers, particularly myoglobin, troponin T, and MM3/MM1 creatine kinase isoforms. The diagnostic performance of the relative increase in myoglobin appears to be less susceptible to small changes in the diagnostic threshold value.

Biomarkers↗