Comparison of early invasive and conservative strategies in patients with unstable coronary syndromes treated with the glycoprotein IIb/IIIa inhibitor tirofiban.

BACKGROUND There is continued debate as to whether a routine, early invasive strategy is superior to a conservative strategy for the management of unstable angina and myocardial infarction without ST-segment elevation. METHODS We enrolled 2220 patients with unstable angina and myocardial infarction without ST-segment elevation who had electrocardiographic evidence of changes in the ST segment or T wave, elevated levels of cardiac markers, a history of coronary artery disease, or all three findings. All patients were treated with aspirin, heparin, and the glycoprotein IIb/IIIa inhibitor tirofiban. They were randomly assigned to an early invasive strategy, which included routine catheterization within 4 to 48 hours and revascularization as appropriate, or to a more conservative (selectively invasive) strategy, in which catheterization was performed only if the patient had objective evidence of recurrent ischemia or an abnormal stress test. The primary end point was a composite of death, nonfatal myocardial infarction, and rehospitalization for an acute coronary syndrome at six months. RESULTS At six months, the rate of the primary end point was 15.9 percent with use of the early invasive strategy and 19.4 percent with use of the conservative strategy (odds ratio, 0.78; 95 percent confidence interval, 0.62 to 0.97; P=0.025). The rate of death or nonfatal myocardial infarction at six months was similarly reduced (7.3 percent vs. 9.5 percent; odds ratio, 0.74; 95 percent confidence interval, 0.54 to 1.00; P<0.05). CONCLUSIONS In patients with unstable angina and myocardial infarction without ST-segment elevation who were treated with the glycoprotein IIb/IIIa inhibitor tirofiban, the use of an early invasive strategy significantly reduced the incidence of major cardiac events. These data support a policy involving broader use of the early inhibition of glycoprotein IIb/IIIa in combination with an early invasive strategy in such patients.

[1]  R. Califf,et al.  Platelet glycoprotein IIb/IIIa receptor inhibition in non-ST-elevation acute coronary syndromes: early benefit during medical treatment only, with additional protection during percutaneous coronary intervention. , 1999, Circulation.

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

[3]  A. Skene,et al.  Oral glycoprotein IIb/IIIa inhibition with orbofiban in patients with unstable coronary syndromes (OPUS-TIMI 16) trial. , 2000, Circulation.

[4]  F. Klocke,et al.  ACC/AHA guidelines for the early management of patients with acute myocardial infarction. A report of the American College of Cardiology/American Heart Association Task Force on Assessment of Diagnostic and Therapeutic Cardiovascular Procedures (subcommittee to develop guidelines for the early manag , 1990, Circulation.

[5]  J. W. Schaeffer,et al.  ACC/AHA guidelines for the management of patients with unstable angina and non–st-segment elevation myocardial infarction: A report of the american college of cardiology/ american heart association task force on practice guidelines (committee on the management of patients with unstable angina) , 2000 .

[6]  H. White,et al.  Troponin concentrations for stratification of patients with acute coronary syndromes in relation to therapeutic efficacy of tirofiban , 1999, The Lancet.

[7]  E. Antman,et al.  The TIMI risk score for unstable angina/non–ST-elevation MI: a method for prognostication and therapeutic decision making , 2001 .

[8]  E. Antman,et al.  Assessment of the treatment effect of enoxaparin for unstable angina/non-Q-wave myocardial infarction. TIMI 11B-ESSENCE meta-analysis. , 1999, Circulation.

[9]  M. Whooley,et al.  Adding heparin to aspirin reduces the incidence of myocardial infarction and death in patients with unstable angina. A meta-analysis. , 1997, JAMA.

[10]  R. Califf,et al.  Association between minor elevations of creatine kinase-MB level and mortality in patients with acute coronary syndromes without ST-segment elevation. PURSUIT Steering Committee. Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy. , 2000, JAMA.

[11]  R. Giugliano,et al.  Effects of tirofiban plus heparin versus heparin alone on troponin I levels in patients with acute coronary syndromes. , 2000, The American journal of cardiology.

[12]  H. Katus,et al.  The prognostic value of serum troponin T in unstable angina. , 1992, The New England journal of medicine.

[13]  L. Wallentin,et al.  Outcome at 1 year after an invasive compared with a non-invasive strategy in unstable coronary-artery disease: the FRISC II invasive randomised trial , 2000, The Lancet.

[14]  E. Antman,et al.  Cardiac troponin I for stratification of early outcomes and the efficacy of enoxaparin in unstable angina: a TIMI-11B substudy. , 2000, Journal of the American College of Cardiology.

[15]  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.

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

[17]  P. Théroux,et al.  Aspirin, heparin, or both to treat acute unstable angina. , 1988, The New England journal of medicine.

[18]  W Rutsch,et al.  A comparison of balloon-expandable-stent implantation with balloon angioplasty in patients with coronary artery disease. Benestent Study Group. , 1994, The New England journal of medicine.

[19]  L. Wallentin,et al.  Troponin T identifies patients with unstable coronary artery disease who benefit from long-term antithrombotic protection. Fragmin in Unstable Coronary Artery Disease (FRISC) Study Group. , 1997, Journal of the American College of Cardiology.

[20]  E. Braunwald,et al.  Unstable angina. A classification. , 1989, Circulation.

[21]  C. Cannon,et al.  One-year results of the Thrombolysis in Myocardial Infarction (TIMI) IIIB clinical trial. A randomized comparison of tissue-type plasminogen activator versus placebo and early invasive versus early conservative strategies in unstable angina and non-Q wave myocardial infarction. , 1995, Journal of the American College of Cardiology.

[22]  D Wybenga,et al.  Cardiac-specific troponin I levels to predict the risk of mortality in patients with acute coronary syndromes. , 1996, The New England journal of medicine.

[23]  Daniel B. Mark,et al.  Diagnosing and managing unstable angina. Agency for Health Care Policy and Research. , 1994, Circulation.

[24]  C. Heeschen,et al.  Benefit of abciximab in patients with refractory unstable angina in relation to serum troponin T levels. c7E3 Fab Antiplatelet Therapy in Unstable Refractory Angina (CAPTURE) Study Investigators. , 1999, The New England journal of medicine.

[25]  F. Harrell,et al.  Cardiac Troponin T Levels for Risk Stratification in Acute Myocardial Ischemia , 1996 .

[26]  E. Antman,et al.  Enoxaparin prevents death and cardiac ischemic events in unstable angina/non-Q-wave myocardial infarction. Results of the thrombolysis in myocardial infarction (TIMI) 11B trial. , 1999, Circulation.

[27]  S. Snapinn,et al.  Intracoronary thrombus and platelet glycoprotein IIb/IIIa receptor blockade with tirofiban in unstable angina or non-Q-wave myocardial infarction. Angiographic results from the PRISM-PLUS trial (Platelet receptor inhibition for ischemic syndrome management in patients limited by unstable signs and s , 1999, Circulation.

[28]  R. Califf,et al.  Management of Patients With Acute Coronary Syndromes in the United States by Platelet Glycoprotein IIb/IIIa Inhibition: Insights From the Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) Trial , 2000, Circulation.

[29]  E. Antman,et al.  The TIMI risk score for unstable angina/non-ST elevation MI: A method for prognostication and therapeutic decision making. , 2000, JAMA.

[30]  P. Teirstein,et al.  A randomized comparison of coronary-stent placement and balloon angioplasty in the treatment of coronary artery disease. Stent Restenosis Study Investigators. , 1994, The New England journal of medicine.

[31]  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.

[32]  E. Braunwald,et al.  Invasive versus conservative strategies in unstable angina and non\NQ-wave myocardial infarction following treatment with tirofiban: rationale and study design of the international TACTICS-TIMI 18 trial ☆ , 1998 .

[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]  David P Miller,et al.  Clinical outcomes of therapeutic agents that block the platelet glycoprotein IIb/IIIa integrin in ischemic heart disease. , 1998, Circulation.

[35]  M. Whooley,et al.  Adding Heparin to Aspirin Reduces the Incidence of Myocardial Infarction and Death in Patients With Unstable Angina: A Meta-analysis , 1996 .

[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]  C. Madden Risk of myocardial infarction and death during treatment with low dose aspirin and intravenous heparin in men with unstable coronary artery disease: The RISC Group Lancet 336: 827–830 Oct 1990 , 1991 .