NSTEMI INVASIVE TREATMENT-RATIONALE AND TIMING

DEV PAHLAJANI MD,FACC,FSCAIHOD INTERVENTIONAL CARDIOLOGY BREACH CANDY HOSPITAL MUMBAI

4.78.3

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/M

I/UR

by

14 D

ays

(%)

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 invasiveHazard ratio

0.1 1 10

Odds Ratio (95%CI)

Invasive strategy in non-ST elevation ACSRe-hospitalisation for unstable angina

Invasive better Conservative betterN=7966P=0.00001Heterogeneity 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 FUmonths

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 ACSIs 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=8375P=0.05Heterogeneity 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=622RR (95%CI) 0.79 (0.64-0.97)

Medium risk (score 2-3) N=1092RR (95%CI) 0.72 (0.55-1.13)

Low risk (score 0-1) N=369RR (95%CI) 1.26 (0.66-2.40)

Years since randomisation

Dea

th o

r myo

card

ial i

nfar

ctio

n (%

)

41 5320

10

20

30

40

0

32.7%

41.6%

14.6%

20.4%

10.3%8.2%

ConservativeInvasive

FRISC-2: cumulative risk of death or MIby 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 ImmediateIntervention (n = 162)

DelayedIntervention (n = 161)*

HR (95% CI) p Value

30 daysDeath or MI 4.3 13.0 0.32 (0.13–0.74) 0.008Death, 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) 0.97MI 2.5 9.9 0.24 (0.08–0.70) 0.01Recurrent ischemia 3.7 15.5 0.24 (0.10–0.57) 0.001Major bleeding 0.6 0.6 0.99 (0.06–15.89) 0.99 31 days to 1 yrDeath or MI 2.6 6.5 0.39 (0.12–1.27) 0.12Death, 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) 0.69MI 0.6 4.3 0.15 (0.02–1.22) 0.07Recurrent ischemia 6.5 2.2 2.99 (0.82–10.85) 0.06Major bleeding 0.0 2.5 0.01 (0.01–46.38) 0.301 yrDeath or MI 6.8 18.8 0.34 (0.17–0.67) 0.002Death, 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) 0.78MI 3.1 13.8 0.21 (0.08–0.55) 0.002Recurrent ischemia 9.9 16.9 0.28 (0.12–0.63) 0.002Major 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-ACS2015 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