Reduction of myocardial damage by prolonged treatment with subcutaneous low molecular weight heparin in unstable coronary artery disease. FRISC study group. Fragmin during Instability in Coronary Artery Disease.

AIMS: Several studies have proved heparin useful in treating patients with unstable coronary artery disease. The present study investigates whether Selvester QRS scoring for estimation of myocardial infarct size increases the incidence of detection of acute myocardial infarction during follow-up in a trial of patients with unstable angina/non-Q wave myocardial infarction treated with low molecular weight heparin or placebo. Finally it will be discussed how the QRS score, used for end-point identification, impacts on the power calculation in clinical trials. METHODS AND RESULTS: Electrocardiographic data on 1276 patients (644 in the placebo group, 632 in the low molecular weight heparin treatment group) were available. All ECGs were scored according to the Selvester QRS scoring method. At 40 days, more patients in the placebo than in the heparin group had achieved a threshold level of QRS score (25.9% vs 21.1%, P=0.05). Myocardial infarction, diagnosed as per the classic Q wave criteria, occurred in 3.7% of patients in the placebo group and in 0.9% in the low molecular weight heparin group at 6 days (P=0.002). At 40 days, the rates were 8.2% (placebo) and 5.7% (low molecular weight heparin, P=0.2). By combining the classic criteria with the Selvester method the myocardial infarction end-point rate in both groups was almost doubled (8.2% to 14.4% in the placebo group and 5.7% to 11.1% in the low molecular weight heparin group, P=0.07). The 216 patients with non-evaluable electrocardiograms did not differ from the 1276 patients as regards baseline characteristics; however, they had a significantly poorer prognosis, with a death/myocardial infarction rate of 20% at 40 days, compared with 8% among the patients with evaluable electrocardiograms (P<0.00001). CONCLUSION: Long-term subcutaneous treatment with low molecular weight heparin decreases the number of subsequent myocardial infarctions - determined both conventionally and by an increase in QRS score - in patients with unstable coronary artery disease. Silent myocardial infarctions detected by QRS score, as well as clinical myocardial infarctions, could be used as end-points in clinical trials of ischaemic heart disease and thus lower the population needed for obtaining statistical power.