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NSTEMI INVASIVE TREATMENT-
RATIONALE AND TIMING
DEV PAHLAJANI MD,FACC,FSCAI
HOD INTERVENTIONAL CARDIOLOGY
BREACH CANDY HOSPITAL MUMBAI
4.7
8.3
13.2
19.9
26.2
40.9
0
10
20
30
40
50
60
0/1 2 3 4 5
TIMI Risk Score for UA/NSTEMI
D/MI/URby14Days(%)
Antman RM et al JAMA 2000, 284, 835
% Population 4.3 17.3 32.0 29.3 13.0 3.4
6-7
SABATINE AND ANTMAN
TIMI RISK SCORE FOR UA/NSTEMI
Meta-analysis for CV death or MI
Overall
FRISC-II (N=2457)
ICTUS (N=1200)
RITA-3 (N=1810)
Study
0.81 (0.71, 0.93)
0.79 (0.66, 0.95)
0.99 (0.72, 1.35)
0.75 (0.58, 0.96)
0.81 (0.71, 0.93)
0.79 (0.66, 0.95)
0.99 (0.72, 1.35)
0.75 (0.58, 0.96)
Hazard ratio (95% CI)
0.5 0.75 1 1.33 2
Favors routine invasive Favors selective invasive
Hazard ratio
0.1 1 10
Odds Ratio (95%CI)
Invasive strategy in non-ST elevation ACS
Re-hospitalisation for unstable angina
Invasive better Conservative better
N=7966
P=0.00001
Heterogeneity p=0.01
OR 0.54
(95% CI 0.48-0.61)
NNT 16
Adapted from JACC 2006;48:1319
Inv Con
17.1% 28.2%
17.1% 23.6%
11.0% 13.7%
6.5% 11.6%
9.4% 17.9%
7.2% 10.7%
11.4% 17.5%
Trial
FU
months
FRISC2 24
TRUCS 12
TACTICS 6
RITA 3 12
VINO 6
ICTUS 12
TOTAL
0.1 1 10
Odds Ratio (95%CI)
Invasive strategy in non-ST elevation ACS
Is there a mortality benefit?
Invasive better Conservative better
Trial
FU
months
FRISC2 60
TRUCS 12
TACTICS 6
RITA 3 60
VINO 6
ISAR COOL 1
ICTUS 32
TOTAL 38
N=8375
P=0.05
Heterogeneity p=0.13
OR 0.85
(95% CI 0.73-1.00)
NNT 83
Inv Con
9.6% 10.0%
3.9% 12.5%
3.3% 3.5%
11.4% 14.4%
3.1% 13.4%
0.0% 1.4%
7.5% 6.7%
7.3% 8.5%
FRISC score (sum of): Age>65,
male gender, diabetes, previous
MI, ST-depression, elevated
troponin / Il-6 / CRP
Lancet 2006;368:998
High risk (score 4-7) N=622
RR (95%CI) 0.79 (0.64-0.97)
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)
Years since randomisation
Deathormyocardialinfarction(%)
41 5320
10
20
30
40
0
32.7%
41.6%
14.6%
20.4%
10.3%
8.2%
Conservative
Invasive
FRISC-2: cumulative risk of death or MI
by risk score
Δ8.9%
Δ5.8%
RITA 3 -10 YRS GRACE
SCORE
PROGNOSTIC VALUE OF
TN&ECG INACS
Invasive vs. Conservative
• Invasive strategy is favoured over conservative
management
• Unresolved Issues –
–Optimal timing
– need to balance the risks of intervention for
unstable plaque
– risk of new ischemic events while waiting to
perform an invasive procedure
Milosevic A, et al. J Am Coll Cardiol Intv 2016
ELISA 3 TRIAL
• 542 HIGH RISK NSTEMI
• RANDOMIZED TO IMMEDIATE-<12 HRS
INVASIVE AND DELAYED >48 HRS
• COMPOSITE OF DEATH,MI,AND RECURRENT
ISCH AT 30 DAYS
• IMMEDIATE 9.9%,DELAYED 14% P=0.35
• SAFE TO PERFORM IMMEDIATE
Cumulative incidence of primary endpoint of death or MI at 30 days for
immediate versus delayed. Dashed black line intersecting the X axis denotes
the median time to angiography (61h) in patients undergoing delayed
invasive intervention Milosevic A, et al. J Am Coll Cardiol Intv 2016
Variable Immediate
Intervention
(n = 162)
Delayed
Intervention
(n = 161)*
HR (95% CI) p Value
30 days
Death or MI 4.3 13.0 0.32 (0.13–0.74) 0.008
Death, MI, or recurrent
ischemia)
6.8 26.7 0.23 (0.12–0.45 <0.001
Death 3.1 3.1 0.98 (0.28–3.37) 0.97
MI 2.5 9.9 0.24 (0.08–0.70) 0.01
Recurrent ischemia 3.7 15.5 0.24 (0.10–0.57) 0.001
Major bleeding 0.6 0.6 0.99 (0.06–15.89) 0.99
31 days to 1 yr
Death or MI 2.6 6.5 0.39 (0.12–1.27) 0.12
Death, MI, or recurrent ischemia 9.3 9.3 0.99 (0.45–2.19) 0.71
Death§ 1.9 2.6 0.74 (0.17–3.31) 0.69
MI 0.6 4.3 0.15 (0.02–1.22) 0.07
Recurrent ischemia 6.5 2.2 2.99 (0.82–10.85) 0.06
Major bleeding 0.0 2.5 0.01 (0.01–46.38) 0.30
1 yr
Death or MI 6.8 18.8 0.34 (0.17–0.67) 0.002
Death, MI, or recurrent ischemia 15.4 33.1 0.28 (0.15–0.51) <0.001
Death 4.9 5.6 0.87 (0.34–2.26) 0.78
MI 3.1 13.8 0.21 (0.08–0.55) 0.002
Recurrent ischemia 9.9 16.9 0.28 (0.12–0.63) 0.002
Major bleeding 0.6 3.1 0.20 (0.02–1.68) 0.14
Clinical Outcomes Up to 1 Year
Cumulative incidence of the combined primary endpoint of death or new
myocardial infarction at 30 days and thereafter for patients undergoing
immediate versus delayed invasive intervention.
Milosevic A, et al. J Am Coll Cardiol Intv 2016
2015 ESC Guidelines for the
management of acute coronary
syndromes in patients presenting
without persistent ST-segment
elevation
Risk criteria mandating invasive strategy in NSTE-ACS
2015 ESC Guidelines
NSTEMI NSTEMI 2015
NSTEMI ESC 2015
NSTEMI ESC 2015
Summary
• The routine invasive strategy reduces
cardiovascular death or MI at long-term follow-up
• 3.2% absolute risk reduction in CV death/MI
• 19% relative risk reduction
• Risk stratification identifies the patient group with
the greatest absolute benefits
• 11.1% absolute risk reduction in highest risk patients
• The absolute risk reductions in CV death/MI in
low (2.0%) and Intermediate groups (3.8%)
exceed those seen in many trials of
pharmacological agents
CONCLUSIONS
• INVASIVE TREATMENT SUPERIOR TO
CONSERVATIVE
• IN HIGH SCORE IMMEDIATE APPROACH
WITHIN 2 HOURS
• BIOMARKERS,RECURRENT ISCHEMIA,ECG AND
HEMODYNAMIC CHANGES DETERMINE THE
APPROACH
• LONG TERM OUTCOMES BETTER IN HIGH RISK

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Nstemi invasive treatment rationale and timing

  • 1. NSTEMI INVASIVE TREATMENT- RATIONALE AND TIMING DEV PAHLAJANI MD,FACC,FSCAI HOD INTERVENTIONAL CARDIOLOGY BREACH CANDY HOSPITAL MUMBAI
  • 2.
  • 3.
  • 4.
  • 5.
  • 6. 4.7 8.3 13.2 19.9 26.2 40.9 0 10 20 30 40 50 60 0/1 2 3 4 5 TIMI Risk Score for UA/NSTEMI D/MI/URby14Days(%) Antman RM et al JAMA 2000, 284, 835 % Population 4.3 17.3 32.0 29.3 13.0 3.4 6-7 SABATINE AND ANTMAN TIMI RISK SCORE FOR UA/NSTEMI
  • 7. Meta-analysis for CV death or MI Overall FRISC-II (N=2457) ICTUS (N=1200) RITA-3 (N=1810) Study 0.81 (0.71, 0.93) 0.79 (0.66, 0.95) 0.99 (0.72, 1.35) 0.75 (0.58, 0.96) 0.81 (0.71, 0.93) 0.79 (0.66, 0.95) 0.99 (0.72, 1.35) 0.75 (0.58, 0.96) Hazard ratio (95% CI) 0.5 0.75 1 1.33 2 Favors routine invasive Favors selective invasive Hazard ratio
  • 8. 0.1 1 10 Odds Ratio (95%CI) Invasive strategy in non-ST elevation ACS Re-hospitalisation for unstable angina Invasive better Conservative better N=7966 P=0.00001 Heterogeneity p=0.01 OR 0.54 (95% CI 0.48-0.61) NNT 16 Adapted from JACC 2006;48:1319 Inv Con 17.1% 28.2% 17.1% 23.6% 11.0% 13.7% 6.5% 11.6% 9.4% 17.9% 7.2% 10.7% 11.4% 17.5% Trial FU months FRISC2 24 TRUCS 12 TACTICS 6 RITA 3 12 VINO 6 ICTUS 12 TOTAL
  • 9. 0.1 1 10 Odds Ratio (95%CI) Invasive strategy in non-ST elevation ACS Is there a mortality benefit? Invasive better Conservative better Trial FU months FRISC2 60 TRUCS 12 TACTICS 6 RITA 3 60 VINO 6 ISAR COOL 1 ICTUS 32 TOTAL 38 N=8375 P=0.05 Heterogeneity p=0.13 OR 0.85 (95% CI 0.73-1.00) NNT 83 Inv Con 9.6% 10.0% 3.9% 12.5% 3.3% 3.5% 11.4% 14.4% 3.1% 13.4% 0.0% 1.4% 7.5% 6.7% 7.3% 8.5%
  • 10. FRISC score (sum of): Age>65, male gender, diabetes, previous MI, ST-depression, elevated troponin / Il-6 / CRP Lancet 2006;368:998 High risk (score 4-7) N=622 RR (95%CI) 0.79 (0.64-0.97) 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) Years since randomisation Deathormyocardialinfarction(%) 41 5320 10 20 30 40 0 32.7% 41.6% 14.6% 20.4% 10.3% 8.2% Conservative Invasive FRISC-2: cumulative risk of death or MI by risk score Δ8.9% Δ5.8%
  • 11. RITA 3 -10 YRS GRACE SCORE
  • 12.
  • 13.
  • 15.
  • 16.
  • 17. Invasive vs. Conservative • Invasive strategy is favoured over conservative management • Unresolved Issues – –Optimal timing – need to balance the risks of intervention for unstable plaque – risk of new ischemic events while waiting to perform an invasive procedure Milosevic A, et al. J Am Coll Cardiol Intv 2016
  • 18. ELISA 3 TRIAL • 542 HIGH RISK NSTEMI • RANDOMIZED TO IMMEDIATE-<12 HRS INVASIVE AND DELAYED >48 HRS • COMPOSITE OF DEATH,MI,AND RECURRENT ISCH AT 30 DAYS • IMMEDIATE 9.9%,DELAYED 14% P=0.35 • SAFE TO PERFORM IMMEDIATE
  • 19.
  • 20.
  • 21. Cumulative incidence of primary endpoint of death or MI at 30 days for immediate versus delayed. Dashed black line intersecting the X axis denotes the median time to angiography (61h) in patients undergoing delayed invasive intervention Milosevic A, et al. J Am Coll Cardiol Intv 2016
  • 22. Variable Immediate Intervention (n = 162) Delayed Intervention (n = 161)* HR (95% CI) p Value 30 days Death or MI 4.3 13.0 0.32 (0.13–0.74) 0.008 Death, MI, or recurrent ischemia) 6.8 26.7 0.23 (0.12–0.45 <0.001 Death 3.1 3.1 0.98 (0.28–3.37) 0.97 MI 2.5 9.9 0.24 (0.08–0.70) 0.01 Recurrent ischemia 3.7 15.5 0.24 (0.10–0.57) 0.001 Major bleeding 0.6 0.6 0.99 (0.06–15.89) 0.99 31 days to 1 yr Death or MI 2.6 6.5 0.39 (0.12–1.27) 0.12 Death, MI, or recurrent ischemia 9.3 9.3 0.99 (0.45–2.19) 0.71 Death§ 1.9 2.6 0.74 (0.17–3.31) 0.69 MI 0.6 4.3 0.15 (0.02–1.22) 0.07 Recurrent ischemia 6.5 2.2 2.99 (0.82–10.85) 0.06 Major bleeding 0.0 2.5 0.01 (0.01–46.38) 0.30 1 yr Death or MI 6.8 18.8 0.34 (0.17–0.67) 0.002 Death, MI, or recurrent ischemia 15.4 33.1 0.28 (0.15–0.51) <0.001 Death 4.9 5.6 0.87 (0.34–2.26) 0.78 MI 3.1 13.8 0.21 (0.08–0.55) 0.002 Recurrent ischemia 9.9 16.9 0.28 (0.12–0.63) 0.002 Major bleeding 0.6 3.1 0.20 (0.02–1.68) 0.14 Clinical Outcomes Up to 1 Year
  • 23. Cumulative incidence of the combined primary endpoint of death or new myocardial infarction at 30 days and thereafter for patients undergoing immediate versus delayed invasive intervention. Milosevic A, et al. J Am Coll Cardiol Intv 2016
  • 24. 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation
  • 25. Risk criteria mandating invasive strategy in NSTE-ACS 2015 ESC Guidelines
  • 29. Summary • The routine invasive strategy reduces cardiovascular death or MI at long-term follow-up • 3.2% absolute risk reduction in CV death/MI • 19% relative risk reduction • Risk stratification identifies the patient group with the greatest absolute benefits • 11.1% absolute risk reduction in highest risk patients • The absolute risk reductions in CV death/MI in low (2.0%) and Intermediate groups (3.8%) exceed those seen in many trials of pharmacological agents
  • 30. CONCLUSIONS • INVASIVE TREATMENT SUPERIOR TO CONSERVATIVE • IN HIGH SCORE IMMEDIATE APPROACH WITHIN 2 HOURS • BIOMARKERS,RECURRENT ISCHEMIA,ECG AND HEMODYNAMIC CHANGES DETERMINE THE APPROACH • LONG TERM OUTCOMES BETTER IN HIGH RISK