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Routine vs selective invasive strategies in patients with acute coronary syndromes: a collaborative meta-analysis of randomized trials.

Mehta SR, Cannon CP, Fox KA, Wallentin L, Boden WE, Spacek R, Widimsky P, McCullough PA, Hunt D, Braunwald E, Yusuf S

Department of Medicine, McMaster University, and Population Health Research Institute, Hamilton Health Sciences, Hamilton, Ontario, Canada L6K 1B8. smehta@mcmaster.ca

CONTEXT: Patients with unstable angina or non-ST-segment elevation myocardial infarction (NSTEMI) can be cared for with a routine invasive strategy involving coronary angiography and revascularization or more conservatively with a selective invasive strategy in which only those with recurrent or inducible ischemia are referred for acute intervention. OBJECTIVE: To conduct a meta-analysis that compares benefits and risks of routine invasive vs selective invasive strategies. DATA SOURCES: Randomized controlled trials identified through search of MEDLINE and the Cochrane databases (1970 through June 2004) and hand searching of cross-references from original articles and reviews. STUDY SELECTION: Trials were included that involved patients with unstable angina or NSTEMI who received a routine invasive or a selective invasive strategy. DATA EXTRACTION: Major outcomes of death and myocardial infarction (MI) occurring from initial hospitalization to the end of follow-up were extracted from published results of eligible trials. DATA SYNTHESIS: A total of 7 trials (N = 9212 patients) were eligible. Overall, death or MI was reduced from 663 (14.4%) of 4604 patients in the selective invasive group to 561 (12.2%) of 4608 patients in the routine invasive group (odds ratio [OR], 0.82; 95% confidence interval [CI], 0.72-0.93; P = .001). There was a nonsignificant trend toward fewer deaths (6.0% vs 5.5%; OR, 0.92; 95% CI, 0.77-1.09; P = .33) and a significant reduction in MI alone (9.4% vs 7.3%; OR, 0.75; 95% CI, 0.65-0.88; P<.001). Higher-risk patients with elevated cardiac biomarker levels at baseline benefited more from routine intervention, with no significant benefit observed in lower-risk patients with negative baseline marker levels. During the initial hospitalization, a routine invasive strategy was associated with a significantly higher early mortality (1.1% vs 1.8% for selective vs routine, respectively; OR, 1.60; 95% CI, 1.14-2.25; P = .007) and the composite of death or MI (3.8% vs 5.2%; OR, 1.36; 95% CI, 1.12-1.66; P = .002). But after discharge, the routine invasive strategy was associated with fewer subsequent deaths (4.9% vs 3.8%; OR, 0.76; 95% CI, 0.62-0.94; P = .01) and the composite of death or MI (11.0% vs 7.4%; OR, 0.64; 95% CI, 0.56-0.75; P<.001). At the end of follow-up, there was a 33% reduction in severe angina (14.0% vs 11.2%; OR, 0.77; 95% CI, 0.68-0.87; P<.001) and a 34% reduction in rehospitalization (41.3% vs 32.5%; OR, 0.66; 95% CI, 0.60-0.72; P<.001) with a routine invasive strategy. CONCLUSIONS: A routine invasive strategy exceeded a selective invasive strategy in reducing MI, severe angina, and rehospitalization over a mean follow-up of 17 months. But routine intervention was associated with a higher early mortality hazard and a trend toward a mortality reduction at follow-up. Future strategies should explore ways to minimize the early hazard and enhance later benefits by focusing on higher-risk patients and optimizing timing of intervention and use of proven therapies.

Published 15 June 2005 in JAMA, 293(23): 2908-17.
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