June 15, 2005

Routine vs Selective Invasive Strategies in Patients With Acute Coronary SyndromesA Collaborative Meta-analysis of Randomized Trials

Author Affiliations

Author Affiliations: Department of Medicine, McMaster University, and Population Health Research Institute, Hamilton Health Sciences, Hamilton, Ontario (Drs Mehta and Yusuf); TIMI Study Group and Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Mass (Drs Cannon and Braunwald); Department of Medicine, Royal Infirmary, Edinburgh, Scotland (Dr Fox); Uppsala Clinical Research Center, University Hospital, Uppsala, Sweden (Dr Wallentin); Henry Low Heart Center and Division of Cardiology, Hartford Hospital, Hartford, Conn (Dr Boden); Cardiocenter, University Hospital Kralovske Vinohrady, Third Medical School of Charles University, Prague, Czech Republic (Drs Spacek and Widimsky); William Beaumont Hospital, Royal Oak, Mich (Dr McCullough); and Royal Melbourne Hospital, Melbourne, Australia (Dr Hunt).

JAMA. 2005;293(23):2908-2917. doi:10.1001/jama.293.23.2908

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.