FRISC II: Fragmin and fast Revascularization during InStability in Coronary artery disease - INVASIVE TREATMENT -
Purpose
To compare early invasive with non-invasive treatment in unstable coronary artery disease
Reference
FRISC II Investigators. Invasive compared with non-invasive treatment in unstable coronary-artery disease: FRISC II prospective randomised multicentre study. Lancet 1999;354:708-15.
FRISC II: Fragmin and fast Revascularization during InStability in Coronary artery disease - INVASIVE TREATMENT: TRIAL DESIGN -
Design
Randomized, multicenter, open: invasive arm of trial also investigating long-term low molecular mass heparin (dalteparin)
Patient selection
Hospitalized with ischemia symptoms for <48h 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 12h or infusion of standard heparin
FRISC II: Fragmin and fast Revascularization during InStability in Coronary artery disease - INVASIVE TREATMENT: 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 - INVASIVE TREATMENT: TRIAL DESIGN cont. -
Patients
2457 (median age 66 years) entered invasive vs. non-invasive arm
Follow up and primary endpoint
Composite endpoint death or MI at 6 months
Treatment
All patients: placebo-controlled dalteparin for 3 months
Patients randomized to early invasive treatment:
- coronary angiography
- revascularization within 7 days if 70% obstruction of any artery supplying substantial part of myocardium
Patients randomized to non-invasive treatment considered for invasive treatment on basis of exercise test and, during follow up, in setting of incapacitating symptoms, recurrence of instability or MI
FRISC II: Fragmin and fast Revascularization during InStability in Coronary artery disease - INVASIVE TREATMENT: RESULTS -
At 6 months, combined endpoint of death or MI significantly decreased in invasive treatment group: 9.4% versus 12.1% in non-invasive group (relative risk reduction 22%)
Symptoms of angina and readmission approximately halved in all subgroups by invasive treatment
Despite dalteparin treatment, risk of bleeding associated with revascularization was low
Results were independent of placebo-controlled dalteparin treatment
Analysis was based on intention to treat
FRISC II: Fragmin and fast Revascularization during InStability in Coronary artery disease - INVASIVE TREATMENT: RESULTS cont. -
0
0
30
60
90
120
160
180
0.02
0.04
0.06
0.08
0.10
0.12
0.14
Non-invasive strategy
Invasive strategy
Probability of death or MI in invasive and non-invasive treatment
Days after start of
open-label dalteparin
Death or MI
FRISC II Investigators.
Lancet
1999;
354
:708
–
15.
0
0
30
60
90
120
160
180
0.02
0.04
0.06
0.08
0.10
0.12
0.14
Days after start of
open-label dalteparin
MI
P=0.031
P=0.045
Probability
FRISC II: Fragmin and fast Revascularization during InStability in Coronary artery disease - INVASIVE TREATMENT: RESULTS cont. -
Death, MI or both*
MI
Death
113 (9.4%)
94 (7.8%)
23 (1.9%)
148 (12.1%)
124 (10.1%)
36 (2.9%)
0.78 (0.62
–
0.98)
0.77 (0.60
–
0.99)
0.65 (0.39
–
1.09)
0.031
0.045
0.10
Invasive
P
Non-invasive
Risk ratio
(95% CI)
Death or MI at 6 months
FRISC II Investigators.
Lancet
1999;
354
:708
–
15.
* In invasive group, 6 (0.5%) events occurred before randomized revascularization
FRISC II: Fragmin and fast Revascularization during InStability in Coronary artery disease - INVASIVE TREATMENT: SUMMARY -
Benefit of early invasive treatment in reduction of death or MI significant at 6 months
Results independent of randomized dalteparin treatment following revascularization