FRISC II: Fragmin and fast Revascularization during InStability in Coronary artery disease - LONG-TERM HEPARIN -
Purpose
To assess efficacy of long-term treatment with the low molecular mass heparin dalteparin, in non-invasive treatment strategy for unstable coronary artery disease
Reference
FRISC II Investigators. Long-term low-molecular-mass heparin in unstable coronary-artery disease: FRISC II prospective randomised multicentre study. Lancet 1999;354:701–7.
FRISC II: Fragmin and fast Revascularization during InStability in Coronary artery disease - LONG-TERM HEPARIN: TRIAL DESIGN -
Design
Randomized, multicenter, double-blind, placebo-controlled: non-invasive arm of trial also investigating invasive treatment
Patient selection
Hospitalized with ischemia symptoms for <48 h before start of heparin/dalteparin increasing or at rest (chest pain with ST depression, T inversion or raised biochemical markers)
Pre-randomization therapy
Aspirin 300–600 mg; b-blockade unless contraindicated; organic nitrates, Ca++ antagonists as required; statins, ACE inhibitors, aggressive antidiabetic treatment according to guidelines
Dalteparin 120 U/kg every 12 h or infusion of standard heparin
FRISC II: Fragmin and fast Revascularization during InStability in Coronary artery disease - LONG-TERM HEPARIN: TRIAL DESIGN cont. -
Randomization
Up to 72h after start of open-label dalteparin, patients randomized to:
early invasive or non-invasive treatment (in absence of contraindications for invasive treatment) or
dalteparin or placebo for 90 days (all patients)
All patients received open-label dalteparin 120 U/kg every 12h for at least 5 days until:
non-invasive double-blind dalteparin/placebo treatment started or
revascularization and double-blind dalteparin/placebo started
FRISC II: Fragmin and fast Revascularization during InStability in Coronary artery disease - LONG-TERM HEPARIN: TRIAL DESIGN cont. -
Patients
2267 (median age 67 years) entered long-term heparin vs. placebo arm
Follow up and primary endpoint
Primary endpoint death or MI at 30 days
Treatment
Dalteparin 5000 (women <80 kg, men <70 kg) or 7000 U SC twice daily or placebo for 90 days
FRISC II: Fragmin and fast Revascularization during InStability in Coronary artery disease - LONG-TERM HEPARIN: RESULTS -
For double-blind period:
Decrease in death or MI significant at 30 days but not at 3 months
For total treatment period:
Significant decrease at 3 months in triple endpoint of MI, death or revascularization for total cohort but this benefit not carried over to end of 6 months
Subgroups:
Patients with raised troponin-T at entry showed 30% relative (2.7% absolute) decrease in MI or death at 3 months (P=0.07); this effect not seen in patients with normal troponin T
FRISC II: Fragmin and fast Revascularization during InStability in Coronary artery disease - LONG-TERM HEPARIN: RESULTS cont. -
0
0
10
20
40
50
60
70
30
90
80
0.08
0.06
0.04
0.02
0.10
0.12
0.14
Days after start of treatment
Death or MI during double-blind and total treatment period
FRISC II Investigators.
Lancet
1999;
354
:701
–
7.
Placebo
Dalteparin
Double-blind
period
Total
treatment
period
Probability of
death, MI or revascularization
FRISC II: Fragmin and fast Revascularization during InStability in Coronary artery disease - LONG-TERM HEPARIN: RESULTS cont. -
Days after start of open-label dalteparin
0
0
10
20
30
50
60
70
90
40
80
0.10
0.20
0.30
0.40
Placebo
Dalteparin
Triple outcome: death, MI or revascularization
FRISC II Investigators.
Lancet
1999;
354
:701
–
7.
Probability of
death, MI or revascularization
FRISC II: Fragmin and fast Revascularization during InStability in Coronary artery disease - LONG-TERM HEPARIN: RESULTS cont. -
FRISC II: Fragmin and fast Revascularization during InStability in Coronary artery disease - LONG-TERM HEPARIN: SUMMARY -
Dalteparin lowers risk of death, MI and the need for revascularization during the first month
Initial benefits not sustained during longer term follow up within non-invasive treatment strategy