Unexplained international differences in clinical outcomes after acute myocardial infarction and fibrinolytic therapy: lessons from the Hirulog and Early Reperfusion or Occlusion (HERO)-2 trial.
BACKGROUND
Despite advances in therapy, global mortality due to acute myocardial infarction remains high. The international Hirulog and Early Reperfusion or Occlusion (HERO-2) trial of 17,073 patients with ST-segment elevation myocardial infarction provided the opportunity to explore international differences in outcomes.


METHODS
Patient characteristics, treatment, and outcomes were compared across 5 diverse regions: Western countries, Latin America, Eastern Europe, Russia, and Asia. In addition, a representative sample of 1,743 screened patients was compared with enrolled patients.


RESULTS
Larger percentages of eligible patients were randomized in Eastern Europe, Russia, and Asia than Western countries. These regions enrolled more patients with anterior myocardial infarction, Killip class III or IV, and late presentation (>4 hours). More patients aged >75 years were enrolled from Western countries. Overall risk levels were similar. Eastern Europe and Russia had lower rates than Western countries of coronary revascularization (2% vs 18%) and longer hospital stays (median 18 vs 7 days). Thirty-day mortality was lower in Western countries; 6.7% versus 10.2% to 13.2% elsewhere, whereas reinfarction was more frequent (3.2% vs 1.5% to 3.0%; each, P < .001). Regional mortality differences persisted after adjustment for baseline risk factors, treatments, or national health and economic statistics (each P < .001).


CONCLUSIONS
The variation in mortality and other clinical outcomes across geographic regions was not adequately explained by risk factors, patterns of care, or national health statistics. Nevertheless, large international trials are a better way to assess potential new treatments across many countries than the alternative of separate smaller trials in each region.
Simes
R John
RJ
NHMRC Clinical Trials Center, University of Sydney, Sydney, Australia. john@ctc.usyd.edu.au
O'Connell
Rachel L
RL
Aylward
Philip E
PE
Varshavsky
Sergei
S
Diaz
Rafael
R
Wilcox
Robert G
RG
Armstrong
Paul W
PW
Granger
Christopher B
CB
French
John K
JK
Van de Werf
Frans
F
Marschner
Ian C
IC
Califf
Rob
R
White
Harvey D
HD
D000368:Aged; D001208:Asia / Q000453:epidemiology; D004562:Electrocardiography; D005061:Europe, Eastern / Q000453:epidemiology; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000401:mortality / Q000628:therapy*; D009204:Myocardial Revascularization / Q000379:methods*; D017063:Outcome Assessment, Health Care; D012426:Russia / Q000453:epidemiology; D015996:Survival Rate / Q000639:trends; D015912:Thrombolytic Therapy / Q000379:methods*; D013997:Time Factors; D014481:United States / Q000453:epidemiology
D005343:Fibrinolytic Agents