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Am Fam Physician. 2007;76(10):1542-1545

Background: The optimal treatment strategy for non-ST-elevation acute coronary syndrome has been controversial for many years. Initial data indicated that routine invasive therapy was more effective than selective invasive treatment in reducing subsequent major cardiovascular events. Although the routine invasive strategy was associated with greater early risk, this was balanced by fewer adverse cardiovascular events during follow-up. More recently, large trials with up to five years' follow-up have had contrasting results. A large study in the Netherlands showed no significant benefit from an early invasive strategy after one year. Three- and four-year follow-up data from this study have now been published.

The Study: The researchers enrolled 1,200 patients 18 to 80 years of age between 2001 and 2003. The three criteria for enrollment were symptoms of increasing cardiac ischemia, elevated serum cardiac troponin T, and ischemic changes on electrocardiography or documented coronary artery disease. Exclusion criteria included ST elevation, clinical indications for reperfusion therapy, cardiac failure, and risk of bleeding.

Patients were randomly assigned to receive early invasive therapy or initial medical management with intervention only if clinically indicated. All patients received aspirin, statins, and other medications as indicated. Patients were reassessed at one, six, and 12 months. Data were gathered by telephone interview after two and four years. Data were also accessed from primary care physicians and national hospital and national mortality records. The primary outcome was the composite of death, recurrent myocardial infarction, or hospitalization for anginal symptoms. Secondary outcomes included death from any cause, cardiovascular death, myocardial infarction, and hospitalization for anginal symptoms.

Results: The 604 patients assigned to early intervention were comparable with the 596 assigned to selective intervention in all significant respects. The median age was 62 years; 73 percent were men, 38 percent had used aspirin before the study, 23 percent had a history of myocardial infarction, and 14 percent had diabetes. Angiography was performed in 98 percent of the intervention group and 53 percent of the selective group during initial hospitalization. Percutaneous coronary intervention or coronary artery bypass surgery was performed during hospitalization in 76 percent of the early intervention group and 40 percent of those assigned to selective intervention.

The cumulative three-year results for the primary composite end point (death, recurrent myocardial infarction, or hospitalization) were 30 percent in the early invasive group and 26 percent in the selective intervention group (P = .09). The selective group had more hospitalizations for anginal symptoms, but the intervention group had significantly more myocardial infarctions. This difference resulted from procedure-related myocardial infarctions. Overall, 85 patients died. After four years, total mortality and cardiovascular mortality did not differ significantly between the two groups (7.9 compared with 7.7 percent, respectively, for total mortality; and 4.5 compared with 5.0 percent, respectively, for cardiovascular mortality).

Conclusion: The authors conclude that early invasive treatment did not provide better outcomes over four years than the selective strategy in patients with non-ST-elevation acute coronary syndrome and elevated cardiac troponin. The authors emphasize that all patients received intensive medical therapy and that 58 percent of the selective group underwent revascularization during the follow-up period.

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Copyright © 2007 by the American Academy of Family Physicians.

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