NSTEMI INVASIVE TREATMENT-RATIONALE AND TIMING

- Dr. DEV PAHLAJANI MD,FACC,FSCAIHOD, INTERVENTIONAL CARDIOLOGY

BREACH CANDY HOSPITAL, MUMBAI

ACS: Common pathophysiology

Ruptured fibrous cap with luminal and intraplaque occlusive thrombus

The TIMI unstable angina risk score

0/1 2 3 4 50

10

20

30

40

50

60

4.78.3

13.2

19.9

26.2

40.9

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

RITA-3: invasive vs conservative strategies in non-ST-elevation ACS

Lancet 2002;360:743

Death Myocardial in-farction

Refractory Angina

Triple endpoint0%

5%

10%

15%

20%

4.6% 3.8%

6.5%

9.6%

3.9% 4.8%

11.6%

14.5%

Invasive (n=895)Conservative (n=915)

P=0.5 P=0.29

P<0.0002

P<0.0001

Event rates at one year

RITA-3: invasive vs conservative strategies in non-ST-elevation ACS

0

5

10

15

20

25

Cum

ulat

ive

perc

enta

ge

0 1 2 3 4 5Follow-up time (years)

OR 0.7895% CI 0.61-0.99, p=0.044

20.0%

16.6%

Lancet 2005;366:914

15.1%

12.1%

OR 0.7695% CI 0.58-1.00, p=0.054

0

5

10

15

20

25

0 1 2 3 4 5Follow-up time (years)

Death or nonfatal MI Death

Conservative (n=915)Invasive (n=895)

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 better

N=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

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

Deat

h or

myo

card

ial i

nfar

ction

(%)

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: cumulative risk of death or MIby risk score

Lancet 2005;366:914

0

10

20

30

40

50

0 1 2 3 4 5

Cum

ulat

ive

perc

enta

ge

Follow-up time (years)

0

10

20

30

40

50

0 1 2 3 4 5Follow-up time (years)

4a High risk quartile – lower4b High risk quartile – upper

1 Low risk quartile2 Medium risk quartile3 Medium risk quartile

Invasive group Conservative group

Risk score: age, diabetes, prev MI, smoking, pulse rate, ST depression, angina grade, gender, LBBB, randomised treatment

48.5%

35.4%

6.1%

29.2%

31.3%

6.6%

RITA 3 -10 YRS GRACE SCORE

Prognostic values of Recurrent Ischemia in ACS

Prognostics value of Baseline Troponins in ACSGUSTO-IIA: 30 day mortality

Prognostic value of TN & ECG INACS

B-Type Natriuretic Peptide Predicts Outcomes in Patients with ACS

Inflammatory Markers and long-term Mortality in Acute Coronary Syndrome: FRISC Substudy

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

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) 0.71Death§ 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) <0.001Death 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

Risk criteria mandating invasive strategy in NSTE-ACS2015 ESC Guidelines

NSTEMI NSTEMI 2015

NSTEMI ESC 2015

NSTEMI ESC 2015

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