Who needs an angioplasty in 2008?
Unstable Angina
Rob Henderson
Trent Cardiac Centre
Nottingham University Hospitals
I have NO CONFLICTS OF
INTEREST TO DECLARE
but have received travel grants
and/or honoraria from
Cordis, Boston Scientific, Medtronic
Trials of revascularization strategies in
non-ST-elevation ACS (Unstable Angina & NQMI)
• Invasive strategy
Early coronary arteriography and PCI or
CABG as clinically indicated
versus
• Conservative strategy
Medical management and coronary
arteriography only for refractory ischaemia
No trials of PCI versus no PCI in Unstable Angina
Trials of invasive versus conservative strategies
in non-ST-elevation ACS
Revasc Δ in-hospital Follow-up
Year
rate Con revasc rate
(months)
N
Revasc
rate Inv
TIMI 3B
1473
60%
40%
20%
12
1995
MATE
201
58%
37%
21%
21
1998
VANQWISH
920
44%
33%
11%
23
1998
FRISC
2456
76%
13%
63%
60
1999
TRUCS
148
78%
38%
40%
12
2000
TACTICS
2220
60%
36%
24%
6
2001
RITA 3
1810
44%
10%
34%
60
2002
VINO
131
47%
3%
44%
6
2002
ISAR COOL
410
78%
72%
6%
1
2003
ICTUS
1200
76%
40%
36%
40
2005
Total*
10969
62%
28%
34%
33
Trial
*weighted means
RITA-3: invasive vs conservative
strategies in non-ST-elevation ACS
RITA-3
Event rates at one year
20%
P<0.0001
Invasive (n=895)
Conservative (n=915)
P<0.0002
15%
14.5%
11.6%
9.6%
10%
P=0.5
5%
4.6% 3.9%
P=0.29
3.8%
6.5%
4.8%
0%
Death
Myocardial
infarction
Refractory
Angina
Triple endpoint
Lancet 2002;360:743
Invasive strategy in non-ST elevation ACS
Re-hospitalisation for unstable angina
Trial
Odds Ratio (95%CI)
FU
months
Inv
Con
FRISC2
24
17.1%
28.2%
TRUCS
12
17.1%
23.6%
TACTICS
6
11.0%
13.7%
RITA 3
12
6.5%
11.6%
VINO
6
9.4%
17.9%
ICTUS
12
7.2%
10.7%
11.4%
17.5%
TOTAL
N=7966
P=0.00001
Heterogeneity p=0.01
OR 0.54
(95% CI 0.48-0.61)
NNT 16
0.1
Invasive better
1
Conservative better 10
Adapted from JACC 2006;48:1319
RITA-3: invasive vs conservative
strategies in non-ST-elevation ACS
Death or nonfatal MI
Death
OR 0.78
95% CI 0.61-0.99, p=0.044
Cumulative percentage
RITA-3
OR 0.76
95% CI 0.58-1.00, p=0.054
25
20.0%
25
20
20
15
15
16.6%
10
15.1%
10
12.1%
5
5
0
0
0
1
2
3
4
Follow-up time (years)
5
0
1
2
3
4
5
Follow-up time (years)
Conservative (n=915)
Invasive (n=895)
Lancet 2005;366:914
Invasive strategy in non-ST elevation ACS
Is there reduction in death or non-fatal MI?
Trial
Odds Ratio (95%CI)
FU
months
Inv
Con
FRISC2
60
19.9%
24.5%
TRUCS
12
7.9%
16.7%
TACTICS
6
7.3%
9.5%
RITA 3
60
15.9%
19.5%
VINO
6
6.3%
22.4%
ISAR COOL
1
5.8%
11.8%
ICTUS
32
23.0%
15.3%
TOTAL
37
14.8%
17.1%
OR 0.85
(95% CI 0.75-0.95)
NNT 43
0.1
N=8114
P=0.005
Heterogeneity p<0.0001
1
Invasive better
10
Conservative better
Invasive strategy in non-ST elevation ACS
Is there a mortality benefit?
Trial
Odds Ratio (95%CI)
FU
months
Inv
Con
FRISC2
60
9.6%
10.0%
TRUCS
12
3.9%
12.5%
TACTICS
6
3.3%
3.5%
RITA 3
60
11.4%
14.4%
VINO
6
3.1%
13.4%
ISAR COOL
1
0.0%
1.4%
ICTUS
32
7.5%
6.7%
TOTAL
38
7.3%
8.5%
OR 0.85
(95% CI 0.73-1.00)
NNT 83
0.1
N=8375
P=0.05
Heterogeneity p=0.13
10
1
Invasive better
Conservative better
Trials of invasive strategy in non-ST-elevation ACS
Rates of revascularization in-hospital
100%
80%
Invasive
Conservative
78%
76%
78%
76%
72%
60%
60%
47%
44%
36%
40%
20%
10%
38%
40%
13%
3%
0%
VINO
RITA3
FRISC2
TACTICS
TRUCS
ICTUS
VINO - EHJ 2002;23:230
RITA 3 - Lancet 2002;360:743
FRISC - Lancet 1999;354:708
TACTICS - NEJM 2001;344:1879
TRUCS - EHJ 2000;21:1954
ICTUS - NEJM 2005;353:1095
ISAR COOL - JAMA 2003;290:1593
ISAR COOL
Interventional trials in non-ST elevation ACS
Stratified by revascularization rate in conservative arm
Mortality
OR
95% CI
P
Heterogeneity P
FRISC-2, RITA-3, VINO
0.83
0.69-1.00
0.05
0.12
TACTICS, ICTUS,
TRUCS, ISAR COOL
0.92
0.68-1.24
0.58
0.16
All Trials
0.85
0.73-1.00
0.05
0.13
FRISC-2, RITA-3, VINO
0.75
0.64-0.88
0.003
0.13
TACTICS, ICTUS,
TRUCS, ISAR COOL
1.01
0.84-1.23
0.88
<0.0001
All Trials
0.85
0.75-0.95
0.005
<0.0001
Death or MI
N=8114
Heterogeneity
0.5
1
Invasive better
1.5
Conservative better
2
RITA-3: cumulative risk of death or MI
by risk score
Cumulative percentage
Invasive group
RITA-3
Conservative group
50
50
40
40
31.3%
30
48.5%
35.4%
30
29.2%
20
10
20
10
6.6%
0
0
1
2
3
4
Follow-up time (years)
5
1 Low risk quartile
2 Medium risk quartile
3 Medium risk quartile
6.1%
0
0
1
2
3
4
Follow-up time (years)
5
4a High risk quartile – lower
4b High risk quartile – upper
Risk score: age, diabetes, prev MI, smoking, pulse rate, ST
depression, angina grade, gender, LBBB, randomised treatment
Lancet 2005;366:914
FRISC-2: cumulative risk of death or MI
by risk score
Death or myocardial infarction (%)
41.6%
Conservative
Invasive
40
Δ8.9%
High risk (score 4-7) N=622
RR (95%CI) 0.79 (0.64-0.97)
32.7%
30
20.4%
20
Δ5.8% 14.6%
10.3%
8.2%
10
Medium risk (score 2-3) N=1092
RR (95%CI) 0.72 (0.55-1.13)
Low risk (score 0-1) N=369
RR (95%CI) 1.26 (0.66-2.40)
0
0
1
2
3
4
Years since randomisation
Lancet 2006;368:998
5
FRISC score (sum of): Age>65,
male gender, diabetes, previous
MI, ST-depression, elevated
troponin / Il-6 / CRP
Trials of invasive versus conservative strategies
in non-ST-elevation ACS
• Interpretation confounded by high
revascularization rates in ‘conservative’ arm &
different definitions of myocardial infarction
(benefit may be underestimated)
• Nevertheless, good evidence to support early
invasive strategy in non-ST-elevation ACS
• Benefit greatest in high risk patients
• (determined by risk scores: FRISC, RITA, TIMI, GRACE)
• Optimal timing of invasive strategy uncertain
2007 ACC/AHA & ESC Guidelines
Indications for early invasive strategy
Class*
1
Evidence
Refractory angina or haemodynamic or
electrical instability
Stabilized patients with elevated risk for
clinical events
B
2b
Patients with chronic renal insufficiency
C
3
Not recommended in patients with
extensive co-morbidities or patients with
low likelihood of ACS (in whom risks
outweigh benefits)
C
*1 Should be done
*2b May be done
*3 Should not be done
A
Circulation 2007;116:e148
Eur Heart J 2007;28:1598