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J Am Coll Cardiol, 2000; 35:895-902 © 2000 by the American College of Cardiology Foundation |


* Division of Cardiology, University of Washington, Seattle, Washington, USA
the Heart and Vascular Institute, Henry Ford Health System, Detroit, Michigan, USA
the Northwest Health Services Research and Development Center of Excellence, VA Puget Sound Healthcare System, Seattle, Washington, USA
Manuscript received November 2, 1998; revised manuscript received September 10, 1999, accepted December 2, 1999.
Reprint requests and correspondence: Dr. Nathan R. Every, COR Center, 1910 Fairview Avenue East, #205, Seattle, Washington 98102
nevery{at}u.washington.edu
| Abstract |
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To compare short- and long-term outcome after early invasive or conservative strategies in the treatment of non-ST segment elevation acute myocardial infarction (AMI).
BACKGROUND
It is uncertain whether or not there is benefit from emergent invasive diagnosis and treatment of AMI in patients without ST segment elevation on the admission electrocardiogram (ECG).
METHODS
In a cohort of 1,635 consecutive patients with AMI who presented to hospitals without ST segment elevation on their admission ECG, we compared treatments, hospital course and outcome in 308 patients who presented to hospitals whose initial strategy favored early angiography and appropriate intervention when indicated versus 1,327 similar patients who presented to hospitals that favor a more conservative initial approach.
RESULTS
At baseline, patients admitted to hospitals favoring an early invasive strategy were younger, more predominately Caucasian and had less comorbidity. Early coronary angiography occurred in 58.8% versus 8% (p < 0.001), and early angioplasty was performed in 44.8% versus 6.1% (p < 0.001) in the two different cohorts. Patients treated in hospitals favoring the early invasive strategy had a lower 30-day (5.5% vs. 9.5%, p = 0.026) and four-year mortality (20% vs. 37%, p < 0.001). Multivariate analysis showed a trend towards lower hospital mortality (OR = 0.56, 95% CI: 0.29 to 1.09) and a significant lower long-term mortality (hazard ratio = 0.61, 95% CI: 0.47 to 0.80) in patients admitted to hospitals favoring an early invasive strategy.
CONCLUSIONS
These data suggested that an early invasive strategy in patients with AMI and nondiagnostic ECG changes is associated with lower long-term mortality.
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Acute angiography and reperfusion by coronary angioplasty or bypass surgery has been shown to result in improved outcomes in patients with AMI who present with ST segment elevation (3). However, in the setting of AMI without ST elevation, the value of acute intervention is less certain (1,47). The Thrombolysis in Myocardial Infarction (TIMI) IIIB trial (1,6) showed no benefit from a strategy of early invasive coronary angiography with target vessel revascularization, and the recent Veterans Affairs Non-Q Wave Infarction Strategies in Hospital (VANQWISH) trial showed worse outcome in these patients (4). However, Lotan et al. (5) showed improved short-term outcome in anterior wall AMI patients without ST segment elevation who were treated with an initial early invasive approach. None of these studies evaluated very early (<6 h) revascularization at the time of admission, and there is little data on outcome beyond one year. Thus, there is no consensus as to the efficacy of an early invasive strategy in this high risk patient group.
The Myocardial Infarction Triage and Intervention (MITI) Registry contains detailed data on a cohort of 12,331 consecutive patients with AMI. Because there was substantial variation in the process of care among the 19 hospitals in the registry, the initial approach to treatment of patients was more often determined by where patients were admitted than by characteristics of the patients themselves. Some Seattle-area hospitals favored an early diagnostic and intervention strategy in patients with suspected non-ST segment elevation AMI, while other hospitals favored a much more conservative initial strategy. We were, thus, able to perform an observational study comparing the influence of early invasive strategies on short- and long-term patient outcome.
| Methods |
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We performed a retrospective cohort analysis. The study cohort included 1,635 patients from the MITI Registry who had a confirmed AMI during their index hospitalization (based on a peak serum CPK/CPK-MB >/= 2x normal) but showed no ST segment elevation on their admission 12-lead ECG. Patients with evidence of cardiogenic shock at the time of admission were excluded. This cohort was divided into two groups: those patients initially admitted to hospitals that favored an early invasive strategy versus those that favored an initial conservative medical strategy. Hospitals favoring an early invasive strategy were defined as those hospitals that performed cardiac catheterization within 6 h of admission on 25% or more of patients with chest pain and nondiagnostic ECG changes. There were 308 patients included in the early invasive group admitted to two hospitals and 1,327 patients included in the conservative group admitted to the 17 remaining hospitals that favored a more conservative initial strategy. Eight of the 17 hospitals favoring a conservative initial strategy had on-site cardiac catheterization facilities.
Data collected. Trained abstractors collected detailed data on the patients demographic characteristics, clinical presentation, hospital course and procedures within 3 months after discharge. Socioeconomic status (SES) was obtained by linking the registry to U.S. census data that assigns averages of education and income based on the address of the Registry patient. Readmissions and the rates of subsequent use of procedures were obtained by linking the MITI Registry to the Washington State Comprehensive Hospital Abstract Reporting System (CHARS). The CHARS database includes vital status for every hospital admission in the state of Washington. The rates of readmission and use of cardiac procedures were calculated at one and three years and are cumulative. The cardiac procedure use rate after discharge did not include procedures performed during the index admission.
Statistical analysis. Chi-square test, ANOVA and Student t tests were used to test for significant differences in baseline characteristics between patients in the early invasive and conservative cohorts. The rates of cardiac procedure use after discharge were compared at one and three years, and long-term mortality was compared with Kaplan-Meier plots and the log-rank test. To test whether there was an association between early invasive use of coronary angiography in suspected non-ST elevation AMI and hospital mortality independent of baseline differences, we constructed a series of logistic regression models. Factors associated with mortality in univariate comparisons were entered into the model in a step-wise fashion with type of admitting hospital (early invasive vs. conservative) forced into the model in the final step. The multivariate association between type of admitting hospital and long-term mortality was performed in a similar fashion using Cox regression models.
| Results |
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Long-term outcome. Patients were followed for a mean of 3.2 years. After hospital discharge, patients admitted to hospitals favoring an early invasive strategy were more likely to undergo subsequent cardiac catheterization (23% vs. 16%, p = 0.012 at three years) (Fig. 4). There were no differences between the groups in the rate of cardiac-related rehospitalizations, coronary angioplasty or bypass surgery at one and three year follow-up.
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| Discussion |
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The early use of coronary angiography and revascularization, if needed, holds theoretical promise for identification and treatment of high-risk infarct patients. We evaluated data from the MITI Registry in 1,635 AMI patients to see if admission to hospitals that favor early angiography and revascularization in these patients was associated with improved short-term or long-term outcomes.
Findings. In this observational study, we found that patients admitted to hospitals favoring an early invasive strategy were far more likely to undergo cardiac procedures both emergently (<6 h) and electively. This treatment strategy was associated with lower rates of heart failure during the index hospitalization and lower 30-day mortality. Indeed, after a mean of 3.2 years of follow-up, patients admitted to hospitals favoring an early invasive strategy had lower mortality in comparison with those admitted to hospitals favoring a conservative initial strategy. Multivariate analysis showed that admission to hospitals favoring an early invasive strategy was an independent predictor of decreased long-term mortality. This observed lower mortality in the early invasive cohort may have been a function of either earlier revascularization and associated improved myocardial salvage or simply more revascularization than those patients admitted to hospitals favoring a conservative initial strategy. However, the remarkably low mortality observed in our subgroup analysis of patients admitted to hospitals favoring an early invasive strategy who actually underwent angiography within 6 h of admission (1.1% vs. 7.1%, p = 0.005 in hospital, 10% vs. 32.5%, p < 0.001 at four years post-index event) argues that myocardial salvage may play an important role.
Previous studies. These findings differ from previous studies evaluating early invasive therapy in non-ST elevation AMI patients. In the TIMI IIIB randomized trial (1), there was no mortality benefit in patients with non-Q wave AMI or unstable angina randomized to an early invasive strategy (arteriography with revascularization if indicated). In this trial, early invasive angiography was designed to be performed 18 to 48 h after randomization, and patients randomized to early invasive therapy were treated relatively late after hospital admission (mean 36 h). After such a delay, there may be less myocardial salvage and, therefore, less benefit from revascularization. In addition, the TIMI IIIB study consisted predominately of patients with unstable angina in whom the risk of death is less than for AMI.
More recently, the results of the VANQWISH trial were reported (4). In this trial, patients with nonQ Wave AMI were randomized to either catheterization and revascularization (invasive strategy) or a more conservative approach, with catheterization and revascularization reserved only for patients with either rest or inducible ischemia before discharge. In this trial, patients randomized to the invasive strategy had higher mortality and more cardiac events than the conservative strategy in-hospital and up to 12 months after randomization but showed no significant difference in outcome at 23 months. The VANQWISH trial differed from the MITI study in that catheterizations in the VANQWISH trial were performed electively after admission, with a mean time from randomization to revascularization of eight days in the invasive strategy group. This delay in revascularization could account for the difference in results between VANQWISH and our study. Early angiography was performed earlier in the Medicine Versus Angiography in Thrombolytic Exclusion trial (mean time 27 h); however, there still was no observed difference in outcome in patients randomized to a strategy of early catheterization and intervention (7).
In contrast to those trials, the recently reported Fast Revascularization during Instability in Coronary Disease study (FRISC II) showed a 21% reduction in death or MI in patients randomized to early angiography (2 to 7 days) versus a more conservative ischemia-driven strategy (13). Lotan et al. (5) also observed improved outcomes with an early invasive strategy in a study of 110 patients with non-Q wave AMI. In this study, patients with nonQ wave anterior wall AMIs were retrospectively evaluated by whether or not they received early invasive therapy. Lotan found that patients treated with an early invasive strategy had fewer recurrent AMIs, decreased angina pectoris, less congestive heart failure and improved long-term survival at three years. The patients in Lotans study were assigned to cohorts based on treatment, unlike our study in which patients were assigned to cohorts based on their admission hospitals.
Implications. Taken together, these studies imply that there may be a benefit of early catheterization without prior noninvasive testing in select patients after non-ST segment elevation MI. The conflicting results are more likely a result of patient selection and choice of revascularization protocols in the trials. What is less clear is the value of early catheterization (within 6 h of admission) as was evaluated in the present MITI Registry study. Although we found an association between early catheterization and improved outcome, our findings should be confirmed in a randomized trial.
Study limitations. Although our findings are provocative, there are limitations inherent in a retrospective cohort analysis. Because neither the admitting hospital nor treatments received were randomly assigned, there could be selection bias in our analyses. We attempted to control bias by performing analyses based on the admitting hospital rather than by the treatments a patient had received. This resulted in some balance between cohorts. However, patients admitted to hospitals favoring an early invasive strategy were, in fact, younger, had higher SES and had less comorbidity. Although we could adjust for these measured factors by performing multivariate analyses, we could not adjust for unmeasured differences between cohorts. Unlike many other registry studies, however, in the MITI Registry, we were able to account for patient transfer, measure and adjust for differences in SES and obtain accurate long-term follow-up. These advantages minimize, but do not eliminate, the selection bias inherent in observational studies.
Conclusions. We conclude that admission to a hospital that favors a strategy of early coronary angiography and revascularization is associated with lower long-term mortality in select patients presenting with nonspecific findings on admission ECG. Our data support performing a randomized trial to evaluate an early invasive strategy in the treatment of patients who present with symptoms of AMI but without ST segment elevation on their admission ECG.
| Footnotes |
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