FRIC

FRagmin In unstable Coronary artery disease study (1997)

Condition

Treatment of unstable coronary artery disease

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Objective

To compare the efficacy and safety of dalteparin and UFH in the acute treatment of unstable angina or non-Q-wave myocardial infarction

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Trial design

Randomized, parallel-group study with 2 phases: days 1–6 open; days 6–45: double-blind, placebo-controlled

  • Phase 1 (days 1–6):

Active treatment: dalteparin 120 IU/kg s.c. twice daily (n=751)
Control treatment: UFH bolus of 5000 IU i.v. followed by 1000 IU/h i.v. adjusted to maintain the aPTT at >1.5 times the control value (n=731)

  • Phase 2 (days 6–45):

Active treatment: dalteparin 7500 IU s.c. once daily (n=567)
Control treatment: matched placebo (n=565)

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Endpoints

Primary efficacy endpoint: composite of death, myocardial infarction, and recurrence of angina during the double-blinded phase (days 6–45)
Secondary efficacy endpoints: composite of death, myocardial infarction, and recurrence of angina occurring in the acute phase of the study; revascularization by PTCA or CABG during either phase of the study
Safety endpoints: major and minor bleeding, thrombocytopenia, and allergic reactions

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Trial participants

1482 patients (mean age 65 years) with unstable angina or non-Q-wave myocardial infarction, admitted within 72 hours of last episode of chest pain and ECG evidence of ongoing ischemia; 1132 patients entered the double-blind phase

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Results

Efficacy outcome: 

  • Phase 1: During the acute treatment phase, no significant difference in the combined outcome was observed between dalteparin (55 of 731 patients, 9.3%) and UFH (69 of 751 patients, 7.6%). The corresponding rates of the composite endpoint of death or myocardial infarction were 3.6% and 3.9%. Revascularization procedures were undertaken in 4.8% of dalteparin-treated patients and in 5.3% of UFH-treated patients
  • Phase 2: The rate of the combined outcome over days 6–5 was 12.3% in both treatment groups. The composite endpoint of death or myocardial infarction occurred in 4.3% of patients assigned to dalteparin compared with 4.7% of patients given placebo. Revascularization procedures were undertaken in 14.3% of dalteparin-treated patients and in 14.2% of the placebo group

Safety outcome: The rates of major bleeding events were comparable throughout the study (phase 1: 1.1% with dalteparin and 1.0% with UFH; phase 2: 0.5% with dalteparin and 0.4% with placebo. In phase 2, minor bleedings occurred more frequently in the dalteparin-treated patients (5.1% vs. 2.8% in the placebo group)

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Summary

Efficacy: The frequency of the combined clinical outcome of death, myocardial infarction, and recurrence of angina was similar in both treatment groups. This suggested that body weight-adjusted low-molecular-weight heparins as dalteparin administered subcutaneously twice daily can be used as an alternative to intravenous UFH in the acute treatment of unstable coronary heart disease
Safety: In both groups, bleeding events were rare throughout the study

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Reference

Klein W, Buchwald A, Hillis SE, Monrad S, Sanz G, Turpie AG, van der Meer J, Olaisson E, Undeland S, Ludwig K. Comparison of low-molecular-weight heparin with unfractionated heparin acutely and with placebo for 6 weeks in the management of unstable coronary artery disease. Fragmin in unstable coronary artery disease study (FRIC). Circulation 1997;96:61-68

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Corresponding author

Prof. Werner Klein, MD, Division of Cardiology, Department of Internal Medicine, Auenbruggerplatz 15, A-8036 Graz, Austria

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