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Transcript of 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
Year since Randomization
Surv
ival
(%)
10 20 30 40 50 60 70 80 90
100
P = 0.33
Revascularization86.4
Medical Therapy 83.6
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
Year since Randomization
Even
t Sur
viva
l (%
)
10 20 30 40 50 60 70 80 90
100
P = 0.48
Medical Therapy 78.9
Revascularization77.0
At Risk 1605 1426 1350 1239 1012 593
Freedom from Major Cardiovascular Events in PCI Stratum
0 1 2 3 4 5 0
Year since Randomization
Even
t Sur
viva
l (%
) 10 20 30 40 50 60 70 80 90
100
P = 0.33
Revascularization77.6
Medical Therapy 83.6
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
New Eng-J. Med April 12, 2007
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
New Eng-J. Med April 12, 2007
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
PCI PCI 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
PCI PCI No difference
AVERT (10) No difference
PCI PCI 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 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