title: Greater benefit of early invasive strategy for unstable angina and non-ST elevation myocardial infarction in United States compared with non-United States patients: a TACTICS-TIMI 18 substudy.
abstract: BACKGROUND
  The TACTICS-TIMI 18 (Treat Angina with Aggrastat and Determine Cost of Therapy with an Invasive or Conservative Strategy - Thrombolysis in Myocardial Infarction 18) trial compared routine invasive to conservative care for the management of patients with unstable angina and non ST-elevation myocardial infarction, and included the routine use of the platelet glycoprotein IIb/IIIa inhibitor tirofiban in the initial medical stabilization of all patients.
  
  
  METHODS
  Because previous trials utilizing IIb/IIIa inhibition for acute coronary syndrome (ACS) patients have demonstrated different outcomes in non-US and US patients, the authors sought to determine whether differences in baseline characteristics and practice patterns between 1844 US and 376 non-US patients and physicians would affect outcomes in the TACTICS-TIMI 18 trial. Event rates were stratified by treatment strategy and adjusted for baseline and treatment differences between cohorts.
  
  
  RESULTS
  Although US subjects were more likely women, hypertensive, and diabetic, the US and non-US patients did not differ with respect to low, intermediate, or high TIMI risk scores. For US patients, the primary composite end point of death, myocardial infarction (MI), and rehospitalization for ACS was reduced with an invasive strategy by 40% (95% CI: 0.43-0.83) at 30 days and by 30% (95% CI: 0.55-0.88) at 180 days. Non-US patients managed conservatively had 35% fewer events at 180 days than their invasive counterparts resulting in no benefit for the invasive strategy (P = 0.016 for the interaction term between country and treatment group). Similar results were observed for the additional outcome of death and MI, and in troponin-positive patients. Adjustment for baseline characteristics, medications during the initial hospitalization, and the use of cardiac procedures suggested that a higher cross-over rate from conservative to invasive care in non-US patients (59% versus 49%, P = 0.02) was the most likely explanation for the lower event rate in the conservatively managed patients outside the US.
  
  
  CONCLUSIONS
  US patients treated with tirofiban and early routine cardiac catheterization had a 30% reduction in major cardiac events by 6 months compared with those treated with tirofiban and a conservative (selective invasive) approach. Non-US patients treated conservatively had fewer events than US patients, which appears to be related to a higher rate of cross-over to invasive care. These findings emphasize the importance of both risk stratification and invasive management for ACS patients.
authors.affiliation: University of Pennsylvania Medical Center, Philadelphia, Pennsylvania 19104, USA. howard.herrmann@uphs.upenn.edu
authors.forename: Howard C
authors.initials: HC
authors.lastname: Herrmann
authors.forename: Sabina A
authors.initials: SA
authors.lastname: Murphy
authors.forename: Peter M
authors.initials: PM
authors.lastname: Dibattiste
authors.forename: Paul T
authors.initials: PT
authors.lastname: Delucca
authors.forename: Laura A
authors.initials: LA
authors.lastname: Demopoulos
authors.forename: C Michael
authors.initials: CM
authors.lastname: Gibson
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Cannon