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)

Werner Klein, Arnd Buchwald, Stuart E. Hillis, E. Scott Monrad, Ginés Sanz, A. Graham G Turpie, Jan Van Der Meer, Eric Olaisson, Sven Undeland, Karin Ludwig

Research output: Contribution to journalArticle

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Abstract

Background: Low-molecular-weight heparin has a number of pharmacological and pharmacokinetic advantages over unfractionated heparin that make it potentially suitable, when used in combination with aspirin, for the treatment of unstable coronary artery disease. Method and Results: Patients with unstable angina or non-Q-wave myocardial infarction (1482) were included in the study, which had two phases. In an open, acute phase (days 1 to 6), patients were assigned either twice-daily weight-adjusted subcutaneous injections of dalteparin (120 IU/kg) or dose-adjusted intravenous infusion of unfractionated heparin. In the double-blind, prolonged treatment phase (days 6 to 45), patients received subcutaneously either dalteparin (7500 IU once daily) or placebo. During the first 6 days, the rate of death, myocardial infarction, or recurrence of angina was 7.6% in the unfractionated heparin- treated patients and 9.3% in the dalteparin-treated patients (relative risk, 1.18; 95% confidence interval [CI], 0.84 to 1.66). The corresponding rates in the two treatment groups for the composite end point of death or myocardial infarction were 3.6% and 3.9%, respectively (relative risk, 1.07; 95% CI, 0.63 to 1.80). Revascularization procedures were undertaken in 5.3% and 4.8% of patients in unfractionated heparin and dalteparin groups, respectively (relative risk, 0.88; 95% CI, 0.57 to 1.35). Between days 6 and 45, the rate of death, myocardial infarction, or recurrence of angina was 12.3% in both the placebo and dalteparin groups (relative risk, 1.01; 95% CI, 0.74 to 1.38). The corresponding rates for death or myocardial infarction were 4.7% and 4.3% (relative risk, 0.92; 95% CI, 0.54 to 1.57). Revascularization procedures were undertaken in 14.2% and 14.3% of patients in the placebo and dalteparin groups, respectively. Conclusions: Our results add to previous evidence suggesting that the low-molecular-weight heparin dalteparin administered by twice-daily subcutaneous injection may be an alternative to unfractionated heparin in the acute treatment of unstable angina or non-Q- wave myocardial infarction. Prolonged treatment with dalteparin at a lower once-daily dose in our study did not confer any additional benefit over aspirin (75 to 165 mg) alone.

Original languageEnglish (US)
Pages (from-to)61-68
Number of pages8
JournalCirculation
Volume96
Issue number1
StatePublished - Jul 1 1997
Externally publishedYes

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Dalteparin
Low Molecular Weight Heparin
Heparin
Coronary Artery Disease
Placebos
Myocardial Infarction
Confidence Intervals
Unstable Angina
Subcutaneous Injections
Aspirin
Mortality
Therapeutics
Recurrence
Intravenous Infusions
Pharmacokinetics
Pharmacology
Weights and Measures

Keywords

  • Angina
  • Heparin
  • Myocardial infarction

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

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). / Klein, Werner; Buchwald, Arnd; Hillis, Stuart E.; Monrad, E. Scott; Sanz, Ginés; Turpie, A. Graham G; Van Der Meer, Jan; Olaisson, Eric; Undeland, Sven; Ludwig, Karin.

In: Circulation, Vol. 96, No. 1, 01.07.1997, p. 61-68.

Research output: Contribution to journalArticle

Klein, Werner ; Buchwald, Arnd ; Hillis, Stuart E. ; Monrad, E. Scott ; Sanz, Ginés ; Turpie, A. Graham G ; Van Der Meer, Jan ; Olaisson, Eric ; Undeland, Sven ; Ludwig, Karin. / 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). In: Circulation. 1997 ; Vol. 96, No. 1. pp. 61-68.
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title = "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)",
abstract = "Background: Low-molecular-weight heparin has a number of pharmacological and pharmacokinetic advantages over unfractionated heparin that make it potentially suitable, when used in combination with aspirin, for the treatment of unstable coronary artery disease. Method and Results: Patients with unstable angina or non-Q-wave myocardial infarction (1482) were included in the study, which had two phases. In an open, acute phase (days 1 to 6), patients were assigned either twice-daily weight-adjusted subcutaneous injections of dalteparin (120 IU/kg) or dose-adjusted intravenous infusion of unfractionated heparin. In the double-blind, prolonged treatment phase (days 6 to 45), patients received subcutaneously either dalteparin (7500 IU once daily) or placebo. During the first 6 days, the rate of death, myocardial infarction, or recurrence of angina was 7.6{\%} in the unfractionated heparin- treated patients and 9.3{\%} in the dalteparin-treated patients (relative risk, 1.18; 95{\%} confidence interval [CI], 0.84 to 1.66). The corresponding rates in the two treatment groups for the composite end point of death or myocardial infarction were 3.6{\%} and 3.9{\%}, respectively (relative risk, 1.07; 95{\%} CI, 0.63 to 1.80). Revascularization procedures were undertaken in 5.3{\%} and 4.8{\%} of patients in unfractionated heparin and dalteparin groups, respectively (relative risk, 0.88; 95{\%} CI, 0.57 to 1.35). Between days 6 and 45, the rate of death, myocardial infarction, or recurrence of angina was 12.3{\%} in both the placebo and dalteparin groups (relative risk, 1.01; 95{\%} CI, 0.74 to 1.38). The corresponding rates for death or myocardial infarction were 4.7{\%} and 4.3{\%} (relative risk, 0.92; 95{\%} CI, 0.54 to 1.57). Revascularization procedures were undertaken in 14.2{\%} and 14.3{\%} of patients in the placebo and dalteparin groups, respectively. Conclusions: Our results add to previous evidence suggesting that the low-molecular-weight heparin dalteparin administered by twice-daily subcutaneous injection may be an alternative to unfractionated heparin in the acute treatment of unstable angina or non-Q- wave myocardial infarction. Prolonged treatment with dalteparin at a lower once-daily dose in our study did not confer any additional benefit over aspirin (75 to 165 mg) alone.",
keywords = "Angina, Heparin, Myocardial infarction",
author = "Werner Klein and Arnd Buchwald and Hillis, {Stuart E.} and Monrad, {E. Scott} and Gin{\'e}s Sanz and Turpie, {A. Graham G} and {Van Der Meer}, Jan and Eric Olaisson and Sven Undeland and Karin Ludwig",
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T1 - Comparison of low-molecular-weight heparin with unfractionated heparin acutely and with placebo for 6 weeks in the management of unstable coronary artery disease

T2 - Fragmin in unstable coronary artery disease study (FRIC)

AU - Klein, Werner

AU - Buchwald, Arnd

AU - Hillis, Stuart E.

AU - Monrad, E. Scott

AU - Sanz, Ginés

AU - Turpie, A. Graham G

AU - Van Der Meer, Jan

AU - Olaisson, Eric

AU - Undeland, Sven

AU - Ludwig, Karin

PY - 1997/7/1

Y1 - 1997/7/1

N2 - Background: Low-molecular-weight heparin has a number of pharmacological and pharmacokinetic advantages over unfractionated heparin that make it potentially suitable, when used in combination with aspirin, for the treatment of unstable coronary artery disease. Method and Results: Patients with unstable angina or non-Q-wave myocardial infarction (1482) were included in the study, which had two phases. In an open, acute phase (days 1 to 6), patients were assigned either twice-daily weight-adjusted subcutaneous injections of dalteparin (120 IU/kg) or dose-adjusted intravenous infusion of unfractionated heparin. In the double-blind, prolonged treatment phase (days 6 to 45), patients received subcutaneously either dalteparin (7500 IU once daily) or placebo. During the first 6 days, the rate of death, myocardial infarction, or recurrence of angina was 7.6% in the unfractionated heparin- treated patients and 9.3% in the dalteparin-treated patients (relative risk, 1.18; 95% confidence interval [CI], 0.84 to 1.66). The corresponding rates in the two treatment groups for the composite end point of death or myocardial infarction were 3.6% and 3.9%, respectively (relative risk, 1.07; 95% CI, 0.63 to 1.80). Revascularization procedures were undertaken in 5.3% and 4.8% of patients in unfractionated heparin and dalteparin groups, respectively (relative risk, 0.88; 95% CI, 0.57 to 1.35). Between days 6 and 45, the rate of death, myocardial infarction, or recurrence of angina was 12.3% in both the placebo and dalteparin groups (relative risk, 1.01; 95% CI, 0.74 to 1.38). The corresponding rates for death or myocardial infarction were 4.7% and 4.3% (relative risk, 0.92; 95% CI, 0.54 to 1.57). Revascularization procedures were undertaken in 14.2% and 14.3% of patients in the placebo and dalteparin groups, respectively. Conclusions: Our results add to previous evidence suggesting that the low-molecular-weight heparin dalteparin administered by twice-daily subcutaneous injection may be an alternative to unfractionated heparin in the acute treatment of unstable angina or non-Q- wave myocardial infarction. Prolonged treatment with dalteparin at a lower once-daily dose in our study did not confer any additional benefit over aspirin (75 to 165 mg) alone.

AB - Background: Low-molecular-weight heparin has a number of pharmacological and pharmacokinetic advantages over unfractionated heparin that make it potentially suitable, when used in combination with aspirin, for the treatment of unstable coronary artery disease. Method and Results: Patients with unstable angina or non-Q-wave myocardial infarction (1482) were included in the study, which had two phases. In an open, acute phase (days 1 to 6), patients were assigned either twice-daily weight-adjusted subcutaneous injections of dalteparin (120 IU/kg) or dose-adjusted intravenous infusion of unfractionated heparin. In the double-blind, prolonged treatment phase (days 6 to 45), patients received subcutaneously either dalteparin (7500 IU once daily) or placebo. During the first 6 days, the rate of death, myocardial infarction, or recurrence of angina was 7.6% in the unfractionated heparin- treated patients and 9.3% in the dalteparin-treated patients (relative risk, 1.18; 95% confidence interval [CI], 0.84 to 1.66). The corresponding rates in the two treatment groups for the composite end point of death or myocardial infarction were 3.6% and 3.9%, respectively (relative risk, 1.07; 95% CI, 0.63 to 1.80). Revascularization procedures were undertaken in 5.3% and 4.8% of patients in unfractionated heparin and dalteparin groups, respectively (relative risk, 0.88; 95% CI, 0.57 to 1.35). Between days 6 and 45, the rate of death, myocardial infarction, or recurrence of angina was 12.3% in both the placebo and dalteparin groups (relative risk, 1.01; 95% CI, 0.74 to 1.38). The corresponding rates for death or myocardial infarction were 4.7% and 4.3% (relative risk, 0.92; 95% CI, 0.54 to 1.57). Revascularization procedures were undertaken in 14.2% and 14.3% of patients in the placebo and dalteparin groups, respectively. Conclusions: Our results add to previous evidence suggesting that the low-molecular-weight heparin dalteparin administered by twice-daily subcutaneous injection may be an alternative to unfractionated heparin in the acute treatment of unstable angina or non-Q- wave myocardial infarction. Prolonged treatment with dalteparin at a lower once-daily dose in our study did not confer any additional benefit over aspirin (75 to 165 mg) alone.

KW - Angina

KW - Heparin

KW - Myocardial infarction

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M3 - Article

VL - 96

SP - 61

EP - 68

JO - Circulation

JF - Circulation

SN - 0009-7322

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