Early versus delayed invasive intervention in acute coronary syndromes.

BACKGROUND Earlier trials have shown that a routine invasive strategy improves outcomes in patients with acute coronary syndromes without ST-segment elevation. However, the optimal timing of such intervention remains uncertain. METHODS We randomly assigned 3031 patients with acute coronary syndromes to undergo either routine early intervention (coronary angiography < or = 24 hours after randomization) or delayed intervention (coronary angiography > or = 36 hours after randomization). The primary outcome was a composite of death, myocardial infarction, or stroke at 6 months. A prespecified secondary outcome was death, myocardial infarction, or refractory ischemia at 6 months. RESULTS Coronary angiography was performed in 97.6% of patients in the early-intervention group (median time, 14 hours) and in 95.7% of patients in the delayed-intervention group (median time, 50 hours). At 6 months, the primary outcome occurred in 9.6% of patients in the early-intervention group, as compared with 11.3% in the delayed-intervention group (hazard ratio in the early-intervention group, 0.85; 95% confidence interval [CI], 0.68 to 1.06; P=0.15). There was a relative reduction of 28% in the secondary outcome of death, myocardial infarction, or refractory ischemia in the early-intervention group (9.5%), as compared with the delayed-intervention group (12.9%) (hazard ratio, 0.72; 95% CI, 0.58 to 0.89; P=0.003). Prespecified analyses showed that early intervention improved the primary outcome in the third of patients who were at highest risk (hazard ratio, 0.65; 95% CI, 0.48 to 0.89) but not in the two thirds at low-to-intermediate risk (hazard ratio, 1.12; 95% CI, 0.81 to 1.56; P=0.01 for heterogeneity). CONCLUSIONS Early intervention did not differ greatly from delayed intervention in preventing the primary outcome, but it did reduce the rate of the composite secondary outcome of death, myocardial infarction, or refractory ischemia and was superior to delayed intervention in high-risk patients. (ClinicalTrials.gov number, NCT00552513.)

[1]  J. Bassand,et al.  Impact of anaemia, bleeding, and transfusions in acute coronary syndromes: a shift in the paradigm. , 2007, European heart journal.

[2]  F. Ragmin Invasive compared with non-invasive treatment in unstable coronary-artery disease: FRISC II prospective randomised multicentre study , 1999, The Lancet.

[3]  Rozália Klára Bakó,et al.  Romania , 2007 .

[4]  R. Califf,et al.  Time to Coronary Angiography and Outcomes Among Patients With High-Risk Non–ST-Segment–Elevation Acute Coronary Syndromes: Results From the SYNERGY Trial , 2007, Circulation.

[5]  Alexis Tsipras,et al.  Greece , 1940, Nature.

[6]  Deepak L. Bhatt,et al.  Benefit of early invasive therapy in acute coronary syndromes: a meta-analysis of contemporary randomized clinical trials. , 2006, Journal of the American College of Cardiology.

[7]  S. Yusuf,et al.  Design and rationale of the MICHELANGELO Organization to Assess Strategies in Acute Ischemic Syndromes (OASIS)-5 trial program evaluating fondaparinux, a synthetic factor Xa inhibitor, in patients with non-ST-segment elevation acute coronary syndromes. , 2005, American heart journal.

[8]  Salim Yusuf,et al.  Comparison of fondaparinux and enoxaparin in acute coronary syndromes. , 2006, The New England journal of medicine.

[9]  Lippincott Williams Wilkins,et al.  ACC/AHA/SCAI Practice Guidelines, February 21, 2006 , 2006 .

[10]  G. Lamas,et al.  ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction--executive summary. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to revise the 1999 guidelines for the management of patients wi , 2004, Journal of the American College of Cardiology.

[11]  A. Kastrati,et al.  Evaluation of prolonged antithrombotic pretreatment ("cooling-off" strategy) before intervention in patients with unstable coronary syndromes: a randomized controlled trial. , 2003, JAMA.

[12]  R. Kleiger,et al.  Correction: Outcomes in Patients with Acute Non-Q-Wave Myocardial Infarction Randomly Assigned to an Invasive as Compared with a Conservative Management Strategy. , 1998, The New England journal of medicine.

[13]  L. Wallentin,et al.  Invasive compared with non-invasive treatment in unstable coronary-artery disease: FRISC II prospective randomised multicentre study , 1999 .

[14]  Christopher E. Buller,et al.  2007 focused update of the ACC/AHA 2004 guidelines for the management of patients with ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. , 2008, Journal of the American College of Cardiology.

[15]  J. Ornato,et al.  ACC/AHA 2007 guidelines for the management of patients with unstable angina/non-ST-Elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patie , 2007, Journal of the American College of Cardiology.

[16]  V. Fuster,et al.  Coronary artery disease: pathogenesis and acute coronary syndromes. , 2001, The Mount Sinai journal of medicine, New York.

[17]  J. Tijssen,et al.  Early invasive versus selectively invasive management for acute coronary syndromes. , 2005, The New England journal of medicine.

[18]  V. Fuster,et al.  The pathogenesis of coronary artery disease and the acute coronary syndromes (2). , 1992, The New England journal of medicine.

[19]  J. Ornato,et al.  ACC/AHA/SCAI 2005 guideline update for percutaneous coronary intervention: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/SCAI Writing Committee to Update 2001 Guidelines for Percutaneous Coronary Intervention). , 2006, Circulation.

[20]  P. Poole‐Wilson,et al.  5-year outcome of an interventional strategy in non-ST-elevation acute coronary syndrome: the British Heart Foundation RITA 3 randomised trial , 2005, The Lancet.

[21]  D. Roberts,et al.  Immediate versus deferred coronary angioplasty in non-ST-elevation acute coronary syndromes , 2009, Heart.

[22]  P. Widimsky,et al.  Value of first day angiography/angioplasty in evolving non-ST segment elevation myocardial infarction: an open multicenter randomized trial. The VINO study☆ , 2002 .

[23]  E. Braunwald,et al.  Comparison of early invasive and conservative strategies in patients with unstable coronary syndromes treated with the glycoprotein IIb/IIIa inhibitor tirofiban. , 2001, The New England journal of medicine.

[24]  J. Boura,et al.  Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction : a quantitative review of 23 randomised trials , 2022 .

[25]  A. Hanks Canada , 2002 .

[26]  E. DeLong,et al.  Optimal Timing of Intervention in Non–ST-Segment Elevation Acute Coronary Syndromes: Insights From the CRUSADE (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA guidelines) Registry , 2005, Circulation.

[27]  C M Gibson,et al.  Relationship of symptom-onset-to-balloon time and door-to-balloon time with mortality in patients undergoing angioplasty for acute myocardial infarction. , 2000, JAMA.

[28]  R. Kleiger,et al.  Outcomes in patients with acute non-Q-wave myocardial infarction randomly assigned to an invasive as compared with a conservative management strategy. Veterans Affairs Non-Q-Wave Infarction Strategies in Hospital (VANQWISH) Trial Investigators. , 1999, The New England journal of medicine.

[29]  K. Eagle,et al.  Delay to angiography and outcomes following presentation with high-risk, non-ST-elevation acute coronary syndromes: results from the Global Registry of Acute Coronary Events , 2008, Heart.

[30]  Carl J Pepine,et al.  ACC/AHA guideline update for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction--2002: summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients , 2002, Circulation.

[31]  K. Eagle,et al.  Prediction of risk of death and myocardial infarction in the six months after presentation with acute coronary syndrome: prospective multinational observational study (GRACE) , 2006, BMJ : British Medical Journal.

[32]  William Wijns,et al.  [Guidelines for the diagnosis and treatment of non-ST-segment elevation acute coronary syndromes]. , 2007, Revista portuguesa de cardiologia : orgao oficial da Sociedade Portuguesa de Cardiologia = Portuguese journal of cardiology : an official journal of the Portuguese Society of Cardiology.

[33]  W. O’Neill,et al.  A prospective randomized trial of triage angiography in acute coronary syndromes ineligible for thrombolytic therapy. Results of the medicine versus angiography in thrombolytic exclusion (MATE) trial. , 1998, Journal of the American College of Cardiology.

[34]  S. Yusuf,et al.  Routine vs selective invasive strategies in patients with acute coronary syndromes: a collaborative meta-analysis of randomized trials. , 2005, JAMA.

[35]  S. Pocock,et al.  Do men benefit more than women from an interventional strategy in patients with unstable angina or non-ST-elevation myocardial infarction? The impact of gender in the RITA 3 trial , 2005 .

[36]  L. Wilkins Effects of tissue plasminogen activator and a comparison of early invasive and conservative strategies in unstable angina and non-Q-wave myocardial infarction. Results of the TIMI IIIB Trial. Thrombolysis in Myocardial Ischemia. , 1994, Circulation.

[37]  Joseph P Ornato,et al.  ACC/AHA/SCAI 2005 guideline update for percutaneous coronary intervention: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/SCAI Writing Committee to Update the 2001 Guidelines for Percutaneous Coronary Intervention). , 2006, Journal of the American College of Cardiology.

[38]  D. Roberts,et al.  Immediate versus deferred coronary angioplasty in non-ST-segment elevation acute coronary syndromes , 2009 .