future of site stable to unstable

Future of PCIStable to Unstable

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

ACS is an Important Manifestation of Atherothrombosis1

1. Cannon CP. J Thromb Thrombolysis 1995; 2: 205–218.

Antithrombotictherapy

Stable angina

UA Non-Q-wave MI

Thrombolysisprimary PCI

Q-wave MI

Minutes– hours

Days–weeks

STEMIUA/NSTEMIAtherothrombosisNew term

Old term

Plaquerupture

UA=unstable angina; NSTEMI=non-ST-segment elevation myocardial infarction; PCI=percutaneous coronary intervention

FOR INTERNAL USE ONLY

AIMS OF TREATMENT

ABOLISH TOTAL ISCHAEMIC BURDEN

PREVENT MI & IMPROVE LV FUNCTION

IMPROVE SURVIVAL

IMPROVE EFFORT TOLERANCE

Current Treatment for Coronary Artery Disease

Current treatment breakdown for 15 million Americans with self-reported coronary artery disease.JACC 2007, 50, 16, 1598

7% 2%

91%

PCI CABG Medical

Reperfusion Rates in UK

Recommendations –Banning et al On behalf of British Card.vasc society Heart 2015

Total PCI 2013 2014 2015 SAD*Centers 404 396 614 868PCI 216817 248152 353346 475575

2013 2014 2015 SAD0

100000

200000

300000

400000

500000

600000

475575

Coronary Intervention Data For The Year 2015

SAD* --Statistically Adjudicated DataRate Of Growth 42.39%

Indication for PCI

Coronary Intervention Data For The Year 2015

Death at 3 years – presentation delay

Maeng,M et al. Am J Cardiol 2010;105:1528 –1534)

Patients randomizedn=611

90% LAD disease41% 2 vessel 58 % 3 vessel

PCIn=205

Medical therapyn=203

CABGn=203

MASS-II 10 year

31.020.7

39.4 40.9 43

13.3

41.957.6 59

25.110.3 10.3

67.0 64

24.1

010203040506070

Death Q-wave MI Revasc Event free angina free

Medical Therapy PCI CABG

Event rate at f-up (%)

p=0.089 p=0.01 p =0.001 p<0.001 p < 0.001

HR for occurrence of composite end-point (Cox regression):

CABG vs MT: 0.43 (0.32-0.56) p=0.001CABG vs PCI: 0.54 (0.4-0.72) p=0.001MT vs PCI: 1.27 (0.99-1.62) p=0.06

MASS-II 10 year

Hueb et al. Circulation 2010;122:949-57

Conclusion: At 10 year follow-up the MASS II trial showed the benefits of CABG and PCI over MT with

regard to several clinical end-points, although with similar rates of overall mortality. CABG

was associated with a higher rate of event free survival.

MASS-II 10 year

BARI -2D

N. Eng. J. Med 360, 2503, 2009

0 1 2 3 4 5 0

Year since Randomization

Surv

ival

(%)

10 20 30 40 50 60 70 80 90

100

P = 0.48

Medical Therapy 89.8

Revascularization89.2

At Risk 1605 1562 1529 1505 1306 863

Survival in PCI Stratum

0 1 2 3 4 5 0


Surv

ival

(%)

10 20 30 40 50 60 70 80 90

100

P = 0.33



At Risk 763 734 718 692 586 333

Survival in CABG Stratum

BARI -2D

N. Eng. J. Med 360, 2503, 2009

0 1 2 3 4 5 0


Even

t Sur

viva

l (%

)

10 20 30 40 50 60 70 80 90

100

P = 0.48



At Risk 1605 1426 1350 1239 1012 593

Freedom from Major Cardiovascular Events in PCI Stratum

0 1 2 3 4 5 0


Even

t Sur

viva

l (%

) 10 20 30 40 50 60 70 80 90

100

P = 0.33



At Risk 763 668 634 568 421 230

Freedom from Major Cardiovascular Events in CABG Stratum

25% decline in PCI for stable angina after COURAGE trial

Circulation: Cardiovascular Quality and Outcomes.2011; 4: 300-305

35,539 Patients underwent assessment

3071 Met eligibility criteria

2287 Consented to participate (74 % of patients with protocol

eligibility)1149 Were assigned to PCI group

46 Did not undergo PCI27 Had a lesion that could not be dilated 1006 Received at least one stent

107 Were lost to follow-up

1149 Were included in the primary analysis

1138 Were assigned to medical-therapy group

97 Were lost to follow-up

1138 Were included in the primary analysis

Enrollment and Outcomes - COURAGE

COURAGE Trial

New Eng-J. Med April 12, 2007

1 2 3 4 5 6 700

0.5

0.6

0.7

0.8

0.9

1.0

Hazard ratio 1.05 ; 95% CI (0.87 – 1.27) ; p = 0.62

PCI

Medical therapy

Years

Surv

ival

Fre

e of

Dea

th fr

omAn

y ca

use

and

myo

card

ial

infa

rctio

n

1 2 3 4 5 6 700

0.5

0.6

0.7

0.8

0.9

1.0

Hazard ratio 1.07 ; 95% CI (0.84 – 1.37) ; p = 0.56

PCI

Medical therapy

Years

Surv

ival

Fre

e of

AC

S

1 2 3 4 5 6 700

0.5

0.6

0.7

0.8

0.9

1.0

Hazard ratio 1.13 ; 95% CI (0.89 – 1.43) ; p = 0.33

PCI

Medical therapy

Years

Surv

ival

Fre

e of

Myo

card

ial

infa

rctio

n

1 2 3 4 5 6 700

0.5

0.6

0.7

0.8

0.9

1.0

Hazard ratio 0.87 ; 95% CI (0.65 – 1.16) ; p = 0.38

PCI

Medical therapy

Years

Ove

rall

surv

ival

COURAGE – Subgroup Analysis


No. of

Event Rate for the PrimaryBaseline Characteristics Patients Hazard Ratio (95 % CI)

Outcome P Value

PCIMedical Therapy

Overall2287 1.05 (0.87-1.27)

0.190.19

Sex

0.03Male1947 1.15 (0.93-1.42)

0.19 0.18Female

338 0.65 (0.40-1.06)

0.18 0.26Myocardial Infarction

0.15Yes

876 0.91 (0.69-1.21)

0.23 0.25No

1371 1.22 (0.93-1.60)

0.17 0.14Extent of CAD

0.65Multi-vessel disease 1581

1.04 (0.84-1.30)0.21

0.21Single-vessel disease 700

1.17 (0.76-1.80)0.15

0.12Smoking

0.71Current

653 1.00 (0.71-1.41)

0.20 0.21Not Current 1631

1.08 (0.86-1.36)0.19

0.18Diabetes

0.33Yes

766 0.99 (0.73-1.32)

0.250.24

No1468 1.20 (0.92-

1.56) 0.17 0.15

CCS angina class

0.730 or I 964 1.01 (0.75-1.38)

0.17 0.20II or III

1371 1.09 (0.85-1.40)

0.20 0.18

0.25 0.50 1.00 1.50 1.75 2.00

PCI Better Medical Therapy Better

COURAGE – Subgroup Analysis


No. of

Event Rate for the PrimaryBaseline Characteristics Patients Hazard Ratio (95 % CI)

Outcome P Value

PCIMedical Therapy

Ejection Fraction

0.72≤ 50 % 406 1.14 (0.77-1.70)

0.28 0.26> 50 %1848 1.05 (0.84-1.32)

0.17 0.16Age

0.62> 65 year 904 1.10 (0.83-1.46)

0.24 0.22≤ 65 year1381 1.00 (0.77-1.32)

0.16 0.16Previous CABG

0.81No

2039 1.04 (0.84-1.29)

0.17 0.17Yes

248 0.98 (0.52-1.82)

0.34 0.29Race

0.43White

1963 1.08 (0.87-1.34)

0.19 0.18Non-white 322 0.87 (0.54-1.42)

0.19 0.24Health care system

0.17Canadian 932 1.27 (0.90-1.78)

0.17 0.14US non-VA 387

0.71 (0.44-1.14)0.15

0.21U.S. VA 968 1.06 (0.80-1.38)

0.22 0.22

0.25 0.50 1.00 1.50 1.75 2.00PCI Better Medical Therapy

Better

Lessons from courage trial • COURAGE trial

concluded that: PCI with OMT did not

provide additional benefit to OMT in patients with SIHD.

• The mortality, non fatal myocardial infarction were similar with both the modalities of treatment

N Engl J Med. 2007;356:1503-1516

Summaries of Trials Comparing Medical Therapy Versus PCI for Stable Coronary Artery

Disease Patients

Trial (Ref) Mortality & MI

Angina Relief

QOL

Repeat Revasculariz

ationRITA-2 (7) No

differencePCI PCI PCI

ACME (8) No difference

PCI PCI PCI

ACME-2 (16) No difference

PCI PCI NA

MASS (9) No difference

PCI NA No difference

MASS-II (11) No difference

PCI PCI No difference

AVERT (10) No difference


TIME* No difference

PCI PCI PCI

COURAGE (12)

No difference

No difference

PCI PCI

*TIME Investigators. Lancet 2001;358:951-7MI = myocardial infarction; NA = not available ; PCI = percutaneous coronary intervention; QOL = quality of life

Changes in Geographic Variation in the Use of Percutaneous Coronary

Intervention for Stable Ischemic Heart Disease After Publication of the Clinical

Outcomes Utilizing Revascularization and Aggressive Drug Evaluation

(COURAGE) Trialby Arun V. Mohan, Reza Fazel, Pei-Hsiu Huang, Yu-Chu Shen,

and David Howard

Circ Cardiovasc Qual Outcomes 2014;7:125-130

Decline in the PCI numbers for SIHD and geographic variation

Reasons : • Compelling results of COURAGE trial • Adherence to appropriateness criteria• guidelines• Reimbursement schedules by the insurance

companies• Media attention as regards to the overuse of

the stents

29,000-Deaths Due to Cardiovascular Disease7600 Due t o Cancer !

Dr.James Herrick

A SHORT DISTANCE FROM ITS ORIGIN THE LEFT CORONARY ARTERY WAS COMPLETELY OBLITERATED BY A RED THROMBUS THAT HAD FORMED AT A POINT OF GREAT NARROWING …… THE HOPE FOR THE DAMAGED MYOCARDIUM LIES IN THE DIRECTION OF SECURING A SUPPLY OF BLOOD.

JAMES HERRICK 1912

Angioplasty reduces mortality and morbidity

Primary PCI vs. Thrombolysis in ST-Elevation Myocardial Infarction:Meta-analysis (23 Randomised controlled trials, N=7,739)

Death Nonfatal

MI

Short-term Outcomes (4-6 weeks)

Freq

uenc

y (%

)

P<.0001

P<.0001

P=.0002

P<.0001 PPCI

Thrombolytictherapy

Recurrent

Ischemia

Death, Nonfatal, Reinfarction,or Stroke

Based on Keeley EC, et al. Lancet. 2003;361:13-20.

0

2

4

6

8

10

12

p = 0.003 vs TIMI 0/1

p < 0.0001 vs TIMI 0/1P < 0.0001 vs TIMI 2

9.3%

6.1 %

3.7 %

% M

orta

lity

Reperfusion therapies differ between countries

9286 81 81

75 75 72 70 66 64 5949 45 45

35 33 30 30 28 24 23 19 199 8 5

10 7 2 12

53

15

8 1031

1515

40

3528

2635

30

55

2544

3341

2945

714 12 17 13

20 2515

26 26

10

36 40

15

3039 44

3542

21

52

3748 50

6350

0%10%20%30%40%50%60%70%80%90%

100%

CZ SLO DE CH NO DK PL HR SE HU BE IL IT FIN AT FR SK ES LAT UK BG PO SRB GR TR RO

P-PCI Thrombolysis No reperfusion

P.Widimsky et al. November 19, 2009. Reperfusion therapy for ST elevation acute myocardial infarction in Europe: description of the current situation in 30 countries. Eur. Heart.J.doi:10.1093/eurheartj/ehp492

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

23

57

33

64

9

32

19

44

30

50

8

7825

9

28

14

41

40

33

26

35

40

29

19

52

3439

22

50

28

48

3035

9

63

3

Percentage of reperfusion therapy utilization in the SFL6 countries, development from 2008 to 2011

No reperfusionTromboPPCI

Bulgaria France Greece Serbia Spain Turkey

2008 2008 2008 2008 2008 20082011 2011 2011 2011 2011 2011

SFL Impact on Access to PPCI

Clin Epidemiol 2016 Jun 6;8:141-9

Trends in Door to Balloon time among patients with STEMI

WORCESTER HEART ATTACK STUDY

Randomized Comparison of Prehospital-Initiated Facilitated PCI vs. Primary PCI in AMI Very

Early After Symptom Onset

Conclusion: Prehospital facilitated PCI does not add a benefit over primary PCI in STEMI patients presenting very early after symptom onset.

139 STEMI pts in a region in Germany characterized by long transfer distances assigned to prehospital tenecteplase or primary PCI.

Thiele H, et al. J Am Coll Cardiol Intv.2011;4:605-614.

Facilitated PCI(n = 69)

Primary PCI(n = 70) P Value

Infarct Size 17.9% 13.7% 0.10

Complete ST Resolution 42.9% 57.7% 0.18

30-Day Death/Reinfarction/CHF 19.8% 13.6% 0.13

30-day AMI Mortality Over Time1995 - 2004

Mortality %

>= 75 yr

65 – 74 yr

< 65 yr

Women<65 Women 65-75 Women >75 Men<65 Men 65-75 Men >75

Uppsala Clinical Research Centre 2005

Impact of Direct Access to Cath Lab on Hospital Mortality for STEMI

7.0

9.4

12.2

0

2

4

6

8

10

12

14

2002 (294) 2003 (449) 6m 2004 (272)

Ortolani P. Eur Heart J 2006;27:1550

Thrombolysis

Primary PCI Primary PCIwith direct access via 118

Policlinico S.Orsola, Bologna - Italy

Mortality reduction over time = 43%

%

ACCESS: in-hospital interventions

ACCESS: reperfusion in STEMI

*94% with stent; 39% with drug-eluting stent

ACCESS: results

• 9732 ACS patients with 1-year follow-up

• Discharge diagnoses:– STEMI 45%– NSTE ACS 52%

• NSTEMI 24%• Unstable angina 28%

Summaries of Trials Comparing Medical Therapy Versus PCI for Stable Coronary Artery

Disease Patients

Trial (Ref) Mortality & MI

Angina Relief

QOL

Repeat Revasculariz

ationRITA-2 (7) No

differencePCI PCI PCI

ACME (8) No difference

PCI PCI PCI

ACME-2 (16) No difference

PCI PCI NA

MASS (9) No difference

PCI NA No difference

MASS-II (11) No difference


AVERT (10) No difference


TIME* No difference

PCI PCI PCI

COURAGE (12)

No difference

No difference

PCI PCI

*TIME Investigators. Lancet 2001;358:951-7MI = myocardial infarction; NA = not available ; PCI = percutaneous coronary intervention; QOL = quality of life

29,000-Deaths Due to Cardiovascular Disease7600 Due t o Cancer !

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

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 INVASIVE TREATMENT-RATIONALE AND TIMING

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

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

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

CONCLUSIONS-1• 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

CONCLUSIONS-2• PCI WILL BE LESS FREQUENTLY PERFORMED

FOR STABLE ISCHEMIC HEART DISEASE• NUMBERS WILL INCREASE DUE TO PRIMARY

PCI OR PHARMACO INVASIVE TREATMENT FOR STEMI

INVASIVE TREATMENT SUPERIOR TO CONSERVATIVE FOR NSTEMI

WILL FURTHER INCREASE THE NUMBERS

future of site stable to unstable

Healthcare