1. Complex Coronary Cases
Supported by:
Abbott Vascular Inc
Boston Scientific Corp
Terumo Vascular Corp
Cardiovascular Science Inc
Abiomed Inc
Chiesi Inc
B.Braun Medical Inc

2. Disclosures Samin K. Sharma, MD, FSCAI, FACC
Speaker’s Bureau – Boston Scientific Co,
Abbott Vascular Inc, ABIOMED, CSI
Annapoorna S. Kini, MD, MRCP, FACC
Nothing to disclose
Sameer Mehta, MD, FACC

3. CCC Live Case # 123 Present Clinical Presentation Patient Demographics
62 yrs, M
Present Clinical Presentation
Cresendo CCS class III angina
for last 3 months
Clinical Variables
Stress MPI revealed ischemia
in anterior, apical & inferior walls
Echo: LVEF 50%
CAD Risk Factors
Hypertension
Hyperlipidemia
NIDDM
+F/H
Medications
Aspirin, ISMN, Amlodipine, Metformin, Glyburide, Pioglitazone, Losartan, Atorvastatin, Synthroid, Omeprazole
Cath: 3 V CAD, 100% prox RCA, 80% calcified prox LAD/D1 bifurcation, 99% diffuse calcified OM2. Syntax score 39 and LVEF 40%. PCI decided after Heart team discussion
Plan: Impella assisted Protected PCI of calcific LAD/D1 bifurcation and LCx-OM2 using rotational atherectomy and multiple DES
contralateral injection

4. AUC 2017: Three-Vessel Disease
Patel et al., J Am Coll Cardiol 2017;69:2212

5. Issues Involving The Case
Key trials from ESC 2019: THEMIS, THEMIS-PCI,
ISAR REACT-5, POPULAR-AGE
COMPLETE Trial of STEMI Strategy

6. Issues Involving The Case
Key trials from ESC 2019: THEMIS, THEMIS-PCI,
ISAR REACT-5, POPular AGE
COMPLETE Trial of STEMI Strategy

8. THEMIS Trial: Background
Patients with both established coronary artery disease and type 2 diabetes mellitus are at increased risk of cardiovascular events.
Platelet-mediated thrombosis is a major mechanism.
Ticagrelor protects against CV events when added to aspirin in acute coronary syndromes and in patients with a history of prior myocardial infarction.
Whether patients with diabetes and stable coronary artery disease without a history of prior MI or stroke also derive benefit from dual antiplatelet therapy with aspirin and ticagrelor is unknown.
Bhatt et al., Clin Cardiol 2019;42:498

9. THEMIS Study Design
Steg et al., N Engl J Med, 2019 Sep 1; Epub ahead of print

10. THEMIS Study: Baseline Characteristics
Steg et al., N Engl J Med, 2019 Sep 1; Epub ahead of print

11. THEMIS Study: History of Disease at Baseline
Steg et al., N Engl J Med, 2019 Sep 1; Epub ahead of print

12. THEMIS Study: Primary Composite Endpoint
Cardiovascular Death, MI, Stroke
Steg et al., N Engl J Med, 2019 Sep 1; Epub ahead of print

13. THEMIS Study: Primary Outcomes at 36 Months%
Steg et al., N Engl J Med, 2019 Sep 1; Epub ahead of print

14. THEMIS Study: Clinical Outcomes
Steg et al., N Engl J Med, 2019 Sep 1; Epub ahead of print

15. THEMIS Study: Primary Efficacy Endpoint
Steg et al., N Engl J Med, 2019 Sep 1; Epub ahead of print

16. THEMIS Study: Safety Outcomes
p<0.001
p=0.005 %
Steg et al., N Engl J Med, 2019 Sep 1; Epub ahead of print

17. THEMIS Study: Bleeding Outcomes
Steg et al., N Engl J Med, 2019 Sep 1; Epub ahead of print

18. THEMIS Study: TIMI Major Bleeding - Subgroups
Steg et al., N Engl J Med, 2019 Sep 1; Epub ahead of print

19. THEMIS Study: Safety Outcomes
Steg et al., N Engl J Med, 2019 Sep 1; Epub ahead of print

20. THEMIS Study: Permanent Treatment Discontinuation
Steg et al., N Engl J Med, 2019 Sep 1; Epub ahead of print

21. THEMIS Study: Primary Composite Endpoint
Cardiovascular Death, MI, Stroke – on Treatment*
* Prespecified analysis with patients censored 3 days after the last dose
Steg et al., N Engl J Med, 2019 Sep 1; Epub ahead of print

22. THEMIS Study: Limitations
Dose of ticagrelor was changed from 90 mg bid to 60 mg bid during the trial
Though efficacy and bleeding appeared to be consistent between doses
There was a significant increase in major bleeding, including traumatic intracranial bleeding (largely subdural), but not fatal bleeding
Ticagrelor reversal agent under development
Higher rate of treatment discontinuation in the ticagrelor group
On treatment analyses show larger and more robust risk reductions, though with the usual caveats (only applies to adherent patients tolerating therapy)
Subgroups not powered for efficacy
Though better net clinical benefit identified –stay tuned for THEMIS-PCI!
Steg et al., N Engl J Med, 2019 Sep 1; Epub ahead of print

24. Lancet 2019 Sept 1, Epub ahead of print

25. THEMIS-PCI: Background
THEMIS was a randomized, double-blind, placebo-controlled trial of ticagrelor versus placebo, on top of low-dose aspirin (75 to 150 mg) in patients with type 2 diabetes mellitus receiving anti-hyperglycemic medications for at least six months, and with stable CAD.
We hypothesized that THEMIS patients with prior PCI, (who have been previously treated with DAPT), would be the group most likely to have a favorable balance of efficacy and safety.
Bhatt et al., Lancet 2019 Sept 1, Epub ahead of print

26. THEMIS-PCI Study Flow
Bhatt et al., Lancet 2019 Sept 1, Epub ahead of print

27. THEMIS-PCI: Baseline Characteristics
By History of PCI
Bhatt et al., Lancet 2019 Sept 1, Epub ahead of print

28. THEMIS-PCI: Primary Efficacy Endpoint CV Death, MI, Stroke (ITT)
Bhatt et al., Lancet 2019 Sept 1, Epub ahead of print

29. THEMIS-PCI: Efficacy Endpoint (ITT Population)
Bhatt et al., Lancet 2019 Sept 1, Epub ahead of print

30. THEMIS-PCI: Efficacy Endpoint (ITT Population)
History of PCI
No History of PCI %
p=0.01
p=0.02
p=0.03
p=0.68 %
p=0.76
p=0.62
p=0.51
p=0.44
Bhatt et al., Lancet 2019 Sept 1, Epub ahead of print

31. THEMIS-PCI: Bleeding Endpoints
(Safety Population)
History of PCI
No History of PCI %
p<0.0001
p=0.45
p=0.83 %
p<0.0001 p=
p=0.06
Bhatt et al., Lancet 2019 Sept 1, Epub ahead of print

32. THEMIS-PCI: Net Clinical Benefit
All-cause death, MI, Stroke, Fatal bleeding, or Intracranial hemorrhage (ITT)*
*Prespecified definition of Net Clinical Benefit
Bhatt et al., Lancet 2019 Sept 1, Epub ahead of print

33. THEMIS-PCI: Events Prevented or Caused
For 1000 Patients Treated 3 Years with Ticagrelor
Interaction p=0.012*
History of PCI
No History of PCI 20
-20
Benefit
Harm
p= p= p= p= p= p=0.39
Ischemic events prevented
Bleeding
events caused
Net Clinical Benefit*
Ischemic events prevented
Bleeding
events caused
Net Clinical Benefit*
*Prespecified definition of Net Clinical Benefit
Bhatt et al., Lancet 2019 Sept 1, Epub ahead of print

34. THEMIS-PCI: Primary Efficacy Endpoint
(On Treatment)
History of PCI
No History of PCI %
p=0.0003
p=0.06
p=0.003
p=0.15 %
p=0.70
p=0.59
p=0.51
p=0.48
Bhatt et al., Lancet 2019 Sept 1, Epub ahead of print

35. Conclusions
In stable CAD patients with diabetes and prior PCI, Ticagrelor added to aspirin reduced cardiovascular death, MI, stroke, although with increased major bleeding.
This subgroup analysis was Prespecified, pertains to a large, clinically meaningful population, is plausible, and shows a significant interaction for net clinical benefit.
This suggests that long term therapy with Ticagrelor in addition to aspirin is a new option for selected patients with diabetes and a history of PCI who have tolerated antiplatelet therapy, have high ischemic risk, and low bleeding risk.

36. Lancet 2019 Sept 1, Epub ahead of print

37. N Engl J MEd2019 Sep 1. doi: 10. 1056/NEJMe1910813
N Engl J MEd2019 Sep 1. doi: /NEJMe [Epub ahead of print]

39. Onset and Duration of Ticagrelor Cohorts 7, 8, 9, and 10 to Receive 18-g Fixed Dose of PB2452 with Infusion Duration of 8 H, 12 H, 16 H and 16 H Respectively or Placebo
Bhatt et al., N Engl J Med 2019;380:1825

40. Normalization of Platelet Function After Ticagrelor Reversal
Light Transmission Aggregometry
Point-of-Care P2Y12 Platelet-Reactivity Test
VASP Assay
Bhatt et al., N Engl J Med 2019;380:1825

41. TRITON-TIMI 38 Primary Efficacy Outcomes Death, MI, Stroke
PLATO Primary Efficay Outcomes
Death, MI, Stroke
Wiviott et al., N Engl J Med 2007;357:2001
Wallentin et al., N Engl J Med 2009;361:1045

42. PRAGUE-18 Study Flow Chart
The PRAGUE-18 Study Group
N=1,230
Prasugrel
Ticagrelor
N=634
N=596
No information on the combined EP during 365 days*
Without the end-of-treatment data for patients who discontinued the study drugs less than 12 months after randomization
N=0
N=3
FU 365 days
*The combined efficacy endpoint was cv death, MI, or stroke
Motovska et al., J Am Coll Cardiol 2017;71:371

43. PRAGUE-18 Study: Clinical Endpoints
Prasugrel (n=608)
Ticagrelor (n=575) %
Combined Death MI Stroke Def ST Bleeding
ischemic endpoint
(death, MI or stroke)
p=0.50
p=0.93
p=0.54
p=0.42
p=0.61
p=0.77
Motovska et al., J Am Coll Cardiol 2017;71:371

45. ISAR-REACT 5: BACKGROUND
Wiviott et al., N Engl J Med 2007;357:2001
Wallentin et al., N Engl J Med 2009;361:1045

46. 2018 ESC/EACTS Guidelines on Myocardial Revascularization
NSTE-ACS:
STEMI:
Neumann et al., Eur Heart J 2019;40:87

47. ISAR-REACT 5 Trail Design
Schüpke et al., 2019 Sep 1, Epub ahead of print

48. ISAR-REACT 5: Baseline Characteristics (1/2)
Ticagrelor (n=2012)
Prasugrel (n=2006)
Age, yrs
64.5 ± 12.0
64.6 ± 12.1
Women, %
23.8
BMI, kg/m2
27.8 ± 4.6
27.8 ± 4.4
Diabetes, %
- Insulin-treated, %
23.0
7.1
21.4
6.8
Current smoker, %
34.1
33.4
Arterial hypertension, %
71.3
69.1
Hypercholesterolemia, %
58.7
58.1
Prior MI, %
15.5
16.0
Prior PCI, %
22.5
23.1
Prior CABG, %
5.7
6.5
Cardiogenic shock, %
1.5
1.7
Schüpke et al., 2019 Sep 1, Epub ahead of print

49. ISAR-REACT 5: Baseline Characteristics (2/2)
Ticagrelor (n=2012)
Prasugrel (n=2006)
Blood pressure
- Systolic, mmHg
- Diastolic, mmHg
144 ± 25
82 ± 15
143 ± 24
82 ± 14
Heart rate, beats/min
77 ± 16
76 ± 16
Diagnosis at admission, %
- Unstable angina
- NSTEMI
- STEMI
12.4
46.2
41.4
13.0
46.1
40.9
Coronary angiography, %
99.6
99.8
Treatment strategy, %
- PCI
- CABG
- Conservative
- Other
83.5
2.3
14.2
<0.1
84.8
1.8
13.4
0.0
Schüpke et al., 2019 Sep 1, Epub ahead of print

50. ISAR-REACT 5: Angiographic Characteristics Patients with Angiography
Ticagrelor (n=2003)
Prasugrel (n=2001)
Access site, %
- Femoral
- Radial
- Other
62.2
37.3
0.5
63.0
36.5
No. of diseased coronary vessels, %
- No obstructive CAD
- One vessel
- Two vessels
- Three vessels
8.5
30.0
26.0
35.5
8.2
29.1
27.7
35.0
Left ventricular ejection fraction, %
51.6 ± 11.3
52.0 ± 11.2
Schüpke et al., 2019 Sep 1, Epub ahead of print

51. ISAR-REACT 5: Procedural Characteristics
Patients with PCI
Ticagrelor (n=1676)
Prasugrel (n=1701)
Target vessel, %
- Left main
- LAD
- LCx
- RCA
2.2
44.5
20.6
31.0
42.2
20.3
33.5
Drug-eluting stent, %
89.3
90.7
Periprocedural antithrombotic medication, %
- Acetylsalicylic acid
- Unfractionated heparin
- Low molecular weight heparin
- Bivalirudin
- GPllb/llla inhibitor
89.7
94.3
4.4
7.5
13.1
90.1
93.8
3.8
8.3
11.6
Schüpke et al., 2019 Sep 1, Epub ahead of print

52. ISAR-REACT 5: Diagnosis and Drug Therapy at Discharge
Ticagrelor (n=2012)
Prasugrel (n=2006)
Final diagnosis of ACS, %
- Unstable angina
- NSTEMI
- STEMI
91.2
10.3
45.6
44.1
90.5
9.5
44.8
Therapy at discharge, %
- Acetylsalicylic acid
- Ticagrelor
- Prasugrel
- Clopidogrel
- Oral anticoagulant drugs
- Betablocker
- ACE inhibitor/ARB
- Statin
94.5
81.1
1.1
4.6
4.2
83.1
84.0
91.6
94.9
0.7
80.7
5.9
5.1
83.2
85.4
92.6
Schüpke et al., 2019 Sep 1, Epub ahead of print

53. ISAR-REACT 5: Clinical Endpoint at 1 Year%
Schüpke et al., 2019 Sep 1, Epub ahead of print

54. ISAR-REACT 5: Clinical Endpoints at 1 Year
Primary Endpoint
Composite of Death, MI, or Stroke
Safety Endpoint
BARC Type 3-5 Bleeding
Schüpke et al., 2019 Sep 1, Epub ahead of print

55. ISAR-REACT 5: Subgroup Analysis
Schüpke et al., 2019 Sep 1, Epub ahead of print

56. Summary and Conclusions
In ACS patients with or without ST-segment elevation, treatment with Prasugrel as compared with Ticagrelor significantly reduced the composite rate of death, myocardial infarction, or stroke without increase in major bleeding.

57. Randomized Comparison of Clopidogrel vs Ticagrelor
or Prasugrel in Patients of 70 Years or Older with
Non-ST-Elevation Acute Coronary Syndrome
POPular AGE Trial

58. POPular AGE Trial: Background
Roffi et al., Eur Heart J 2016;37:267

59. TRITON-TIMI 38
PLATO

60. Bleeding Risk Major bleeding 5-fold increase in risk of death
“Nuisance” bleeding
frequent
discontinuation P2Y12
inhibitor thrombotic
risk
Eikelboom et al., Circulation 2006;114:774
Roy et al., Am J Cardiol 2008;102:1614

61. Underrepresentation of Elderly in RCTs
Elderly underrepresented
TRITON TIMI 38: 13% ≥ 75 years1
PLATOL 15% ≥ 75 years2
Registry data: ~35% of NSTEMI population is ≥ 75 years3,4
Selective inclusion of elderly in RCT’s
1. Wiviott et al., N Engl J Med 2007;357: De Luca et al., Eur Heart J Acute Cardiovasc Care 2015;4:441
2. Wallentin et al., N Engl J Med 2009;361: Hanssen et al., Heart 2012;98:699

62. Hypothesis
Clopidogrel is superior in reducing bleeding risk and non-inferior in net clinical benefit compared to Ticagrelor/Prasugrel in patients of 70 years or older with non-ST-elevation acute coronary syndrome

63. POPular AGE Trial Design
≥ 70 years with NSTE-ACS R
1:1
Clopidogrel 1dd75
Ticagrelor 2dd90 or Prasugrel 1dd5/10
<72h months
Reloading
Choice Ticagrelor or prasugrel
according to local protocol
Gimbel M, ESC 2019

64. POPular AGE Trial: Primary Endpoint
PLATO major and minor bleeding
Net clinical benefit:
All-cause death, MI, stroke, PLATO major and minor bleeding
Gimbel M, ESC 2019

65. POPular AGE Trial: Secondary Endpoints
Gimbel M, ESC 2019

66. POPular AGE Trial: Baseline Characteristics
Gimbel M, ESC 2019

67. POPular AGE Trial: Baseline Characteristics
Gimbel M, ESC 2019

68. POPular AGE Trial: Primary Safety Outcomes
PLATO Major and Minor Bleeding
Gimbel M, ESC 2019

69. POPular AGE Trial: Secondary Safety Outcomes%
Gimbel M, ESC 2019

70. POPular AGE Trial: Co-Primary Net Clinical Benefit Outcomes
Death, MI, Stroke, PLATO major and minor bleeding
Gimbel M, ESC 2019

71. POPular AGE Trial: Secondary Efficacy Outcomes
Death, MI, Stroke
Gimbel M, ESC 2019

72. POPular AGE Trial: Subgroup Analysis P-value for interaction
Gimbel M, ESC 2019

73. Conclusions
Compared to Ticagrelor/Prasugrel in the POPular AGE trial we conclude:
Clopidogrel significantly less bleeding
Clopidogrel similar in preventing thrombotic events
Therefore, we consider Clopidogrel the preferred treatment in patients ≥ 70 years with NSTE-ACS

74. Issues Involving The Case
Key trials from ESC 2019: THEMIS, THEMIS-PCI,
ISAR REACT-5, POPULAR-AGE
COMPLETE Trial of STEMI Strategy

75. Randomized Trials of Culprit vs Complete Revascularization in STEMI
PRAMI
(n=465)
CvLPRIT
(n=296)
PRIMULTI
(n=627)
Lesion criteria
> 50% DS
> 70% DS or > 50% DS in 2 views
> 50% DS and FFR <0.80 or > 90% DS
Strategy for non-IRA lesions
Immediate
Immediate or staged within index admission
Staged within index admission
Randomization
After PPCI
“During” PPCI
Age
62 years
65 years
64 years
Bivalirudin or GPIIB/IIIA
79%
83%
97%
Primary endpoint
D/MI/ref ischaemia
D/MI/HF/isch D R
D/MI/isch D R
Result
23% reduced to 9%
(65% Rx effect)
21% reduced to 10%
(55% Rx effect)
22% reduced to 13%
(44% Rx effect)
Early Benefit
Yes
Safe to postpone

76. Culprit Artery – Only Versus Multivessel PCI
COR
LOE
Recommendation
IIb
B-R
PCI of a noninfarct artery may be considered in selected patients with STEMI and multivessel disease who are hemodynamically stable, either at the time of primary PCI or as a planned staged procedure.1
1. Modified recommendation from 2013 Guideline (changed class from III: Harm to IIb and expanded time frame in which multivessel PCI could be performed).

77. COMPLETE TRIAL A Randomized, Comparative Effectiveness Study of
Complete versus Culprit-Only Revascularization Strategies
to Treat Multivessel Disease After Early Percutaneous Coronary
Intervention for ST-Segment Elevation Myocardial Infarction

79. COMPLETE Trial: Primary Objective
In patients presenting with STEMI and multi-vessel coronary artery disease who have undergone culprit-lesion PCI, the objective is:
To determine whether a strategy of routine, staged non-culprit lesion PCI with the goal of complete revascularization is superior to a strategy of culprit lesion-only PCI in reducing the composite of CV death or new MI.

80. COMPLETE Trial Design Mehta et al., Am Heart J 2019; 215:157
Exclusion Criteria: Intent to revascularize NCL,
planned surgical revascularization, prior CABG
*Everolimus-eluting stents
strongly recommended
STEMI with Multivessel CAD and successful PCI to the Culprit Lesion
MVD defined as at least one additional non-culprit lesion ≥ 2.5 mm diameter
and ≥70% stenosis or 50-69% with FFR ≤0.80
RANDOMIZATION
Stratified for intended timing of NCL PCI:
During initial hospitalization or after discharge (max 45 d)
Co-primary Outcomes: 1. Composite of CV death or new MI
2. Composite of CV death, new MI or IDR
Key Secondary Outcome: CV death, new MI, IDR, unstable angina, NYHA class IV heart failure
Median Follow-up: 3 years
Complete Revascularization
Routine staged PCI* of all suitable non-culprit lesions
with the goal of complete revascularization
N=2016
Culprit-Lesion-Only Revascularization
No further revascularization of non-culprit lesions,
guideline-directed medical therapy alone
N=2025
Guideline-Directed Medical Therapy
ASA, P2Y12 inhibitor (Ticagrelor strongly recommended), Statin, BB, ACE/ARB + Risk Factor Modification
Actual Time to study NCL PCI in Complete Group (median)
During initial hospitalization: 1 day (IQR 1-3)
After hospital discharge: 23 days (IQR )
Mehta et al., Am Heart J 2019; 215:157

81. COMPLETE Trial Flow Diagram
Enrolled and Randomized
N=4041
Assigned to Complete Revascularization
(Staged Non-Culprit Lesion PCI + OMT)
N=2016
Assigned to Culprit Lesion Only Revascularization
(Optimal Medical Therapy Alone)
N=2025
Received Allocated Intervention (n=1881)
Did not receive allocated intervention (n=135)
Within 45 days (n=91)
Crossover to Culprit Lesion only Revasc (n=78)
Patient request (n=24)
Physician decision (n=23)
Non-culprit lesion not significant (n=31)
After 45 days (n=44)
Crossover to Culprit Lesion Only Revasc (n=44)
Patient request (n=7)
Physician decision (n=4)
Non-culprit lesion not significant (n=2)
Non-culprit lesion PCI not completed ≤45 days (n=31)
Lost to Follow-up (n=15)
Withdrew Consent (n=6)
Included in ITT Analysis
(n=2016)
Received Allocated Intervention (n=1634)
Did not receive allocated intervention (n=391)
Within 45 days (n=96)
Met protocol criteria for Complete Revasc (n=60)
Hospitalization for recurrent MI (n=29)
Hospitalization for hemodynamic instability or refractory ischemic heart failure (n=3)
Intractable angina despite OMT and documented evidence of ischemia (n=28)
Did not meet protocol criteria for Complete Revasc (n=36)
Patient request (n=6)
Physician decision (n=30)
After 45 days (n=295)
Met protocol criteria for Complete Revasc (n=138)
Did not meet protocol criteria for Complete Revasc (n=157)
Lost to Follow-up (n=18)
Withdrew Consent (n=3)
(n=2025)
1285 index hospitalization (1 day)
596 after discharge (23 days)
Mehta et al., N Engl J Med 2019 Sept 1 [Epub ahead of print]

82. COMPLETE Trial: Baseline Characteristics
Complete N=2016
Culprit-only N=2025
Age (yrs)
61.6
62.4
Gender (% male)
80.5
79.1
Diabetes (%)
19.1
19.9
Chronic renal insuff. (%)
2.0
2.3
Prior MI (%)
7.3
7.6
Current smoker (%)
40.6
38.9
Hypertension (%)
48.7
50.7
Dyslipidemia (%)
37.9
39.4
Prior PCI (%)
7.0
Prior stroke (%)
3.2
3.1
Hemoglobin A1C
6.3
LDL (mmol/L)
Creatinine (µmol/L)
84.7
85.2
Complete N=2016
Culprit-only N=2025
Sx onset to Culprit PCI (%)
<6 hours
69.4
67.1
6~12 hours
16.1
17.7
>12 hours
14.5
15.3
Discharge Meds (%)
ASA
99.8
99.5
P2Y12 Inhibitor
99.4
99.7
Ticagrelor
64.4
63.3
Prasugrel
9.6
8.3
Clopidogrel
25.6
28.2
Beta blocker
88.1
89.1
ACEi/ARB
85.5
84.6
Statin
98.2
97.2
Mehta et al., N Engl J Med 2019 Sept 1 [Epub ahead of print]

83. COMPLETE Trial: Procedural Characteristics
Complete N=2016
Culprit-only N=2025
Index PCI for STEMI
Primary
91.9%
93.1%
Pharmaco-invasive
3.2%
3.0%
Rescue
4.9%
3.9%
Radial access
80.8%
80.7%
Residual diseased vessels 1
76.1%
77.1% ≥2
23.9%
22.9%
NCL location
Left main
0.4%
0.1%
LAD
38.0%
41.2%
Proximal LAD
9.8%
10.4%
Mid LAD
21.7%
23.7%
Circumflex
36.4%
35.6%
RCA
25.3%
23.2%
Complete N=2016
Culprit-only N=2025
NCL diameter
2.8 mm
2.9 mm
Mean NCL stenosis (visual)
79.3%
78.7%
NCL stenosis (visual)
50-69% and FFR<0.80
0.8%
0.6%
70-79%
41.3%
45.1%
80-89%
33.5%
32.6%
90-99%
22.3%
19.7%
100%
2.1%
2.0%
SYNTAX score (Core Lab)
Baseline
16.3
16.0
Culprit lesion specific
8.8
8.6
Non-culprit lesion specific
4.5
Residual (after index PCI)
7.2
7.0
Complete revascularization was achieved in 90.1% after NCL PCI (SYNTAX score = 0)
Mehta et al., N Engl J Med 2019 Sept 1 [Epub ahead of print]

84. COMPLETE Trial: First Co-Primary Outcomes
CV Death or New MI
Mehta et al., N Engl J Med 2019 Sept 1 [Epub ahead of print]

85. COMPLETE Trial: Secondary Co-Primary Outcomes
CV Death, New MI, or IDR
Mehta et al., N Engl J Med 2019 Sept 1 [Epub ahead of print]

86. COMPLETE Trial: Efficacy Outcomes
Complete Revasc. N=2016
Culprit Lesion Only N=2025
HR (95% CI)
P value
N (%)
%/year
Co-Primary Outcomes
CV death or MI
158 (7.8)
2.7
213 (10.5)
3.7
0.74 ( )
0.004
CV death, MI or IDR
179 (8.9)
3.1
339 (16.7)
6.2
0.51 ( )
<0.001
Key Secondary Outcome
CV death, MI, IDR,
unstable angina or class IV HF
272 (13.5)
4.9
426 (21.0)
8.1
0.62 ( )
Other Secondary Outcomes MI
109 (5.4)
1.9
160 (7.9)
2.8
0.68 ( )
0.002
IDR
29 (1.4)
0.5
0.18 ( )
Unstable Angina
70 (3.5)
1.2
130 (6.4)
2.2
0.53 ( )
CV death
59 (2.9)
1.0
64 (3.2)
0.93 ( )
0.68
All-cause Death
96 (4.8)
1.6
106 (5.2)
1.7
0.91 ( )
0.51
Mehta et al., N Engl J Med 2019 Sept 1 [Epub ahead of print]

87. COMPLETE Trial: Efficacy Outcomes%
p=0.68
Mehta et al., N Engl J Med 2019 Sept 1 [Epub ahead of print]

88. COMPLETE Trial: Subtypes of MI
Complete Revasc. N=2016
Culprit Lesion Only N=2025
HR (95% CI)
N (%)
%/year
Subtype of MI
NSTEMI
66 (3.27)
1.11
105 (5.19)
1.78
0.63 ( )
STEMI
43 (2.13)
0.72
53 (2.62)
0.88
0.81 ( )
Universal MI Definition
Type 1
63 (3.13)
1.05
128 (6.32)
2.17
0.49 ( )
Type 2
16 (0.79)
0.26
13 (0.64)
0.21
1.24 ( )
Type 3
4 (0.20)
0.07
1 (0.05)
0.02
4.04 ( )
Type 4a
0.27
8 (0.40)
0.13
2.01 ( )
Type 4b
0.62 ( )
Type 5
1.00 ( )
Mehta et al., N Engl J Med 2019 Sept 1 [Epub ahead of print]

89. COMPLETE Trial: Timing of Non-Culprit Lesion PCI
During or After Index Hospitalization %
p=0.62
130/1349
101/1353
57/663
88/676
CV Death or New MI %
p=0.27
227/1349
113/1353
66/663
112/676
CV Death, New MI, or IDR
Mehta et al., N Engl J Med 2019 Sept 1 [Epub ahead of print]

90. COMPLETE Trial: Main Pre-Defined
Subgroup Analyses
Mehta et al., N Engl J Med 2019 Sept 1 [Epub ahead of print]

91. COMPLETE Trial: Safety and Other Outcomes
Complete Revasc. N=2016
Culprit Lesion Only N=2025
HR (95% CI)
P value
N (%)
%/year
Stroke
38 (1.9)
0.6
29 (1.4)
0.5
1.31 ( )
0.27
Stent thrombosis
26 (1.3)
0.4
19 (0.9)
0.3
1.38 ( )
0.28
All cause death or new MI
194 (9.6)
3.3
251 (12.4)
4.3
0.77 ( )
0.006
Major bleeding
58 (2.9)
1.0
44 (2.2)
0.7
1.33 ( )
0.15
Contrast-associated acute kidney
injury*
30 (1.5) -
1.59 ( )
0.11
NYHA class IV heart failure
56 (2.8)
0.9
1.04 ( )
0.83
Clinically non-significant bleeding
32 (1.6)
27 (1.3)
1.19 ( )
0.50
Mehta et al., N Engl J Med 2019 Sept 1 [Epub ahead of print]

92. Conclusions
In patients with STEMI and multi-vessel coronary artery disease:
Compared with culprit-lesion-only PCI, routine non-culprit lesion PCI with the goal of complete revascularization:
Reduced CV death or new MI by 26% (P=0.004), NNT = 37
Reduced CV death, new MI or IDR by 49% (P<0.001), NNT = 13
The benefit of complete revascularization was similar in those undergoing non-culprit lesion PCI during the index hospitalization (median 1 day) and several weeks after hospital discharge (median 3 weeks)
There were no significant differences in bleeding, stent thrombosis, AKI or stroke

95. MV PCI in STEMI: Will COMPLETE Trial Change the STEMI Guidelines?
STEMI: Complete Revascularization
2016 I
IIa
IIb
III B
2019? I
IIa
IIb
III C

97. CULPRIT-SHOCK Trial: Primary Endpoints
All-Cause Mortality or Renal Replacement Therapy at 1 Year
All-Cause Mortality at 30 Days
Relative Risk (95% CI) 0.87 ( ); P=0.048
59.5%
52.0%
Days since randomization
Thiele et al., N Engl J Med 2017;377:2419
Thiele et al., N Engl J Med 2018;379:1699

98. C B CULPRIT-SHOCK Trial: MV PCI in Shock Guideline Evolution
ESC STEMI Guidelines 2017 → Revascularization Guidelines 2018
STEMI (NSTEMI), Cardiogenic Shock
2017 I
IIa
IIb
III B
2018 I
IIa
IIb
III C
Ibanez et al., Eur Heart J 2018;39:119;
Neumann et al. Eur Heart J 2019;40:87

99. 2019 ESC Trials Revolutionary / significant observation
Widespread acceptance
Change in clinical practice
Ticagrelor in DM without prior PCI:
Ticagrelor in prior PCI+DM, Clopidogrel in elderly:
Prasugrel in ACS, Complete Revas in STEMI:
Final result  BETTER INTERVENTION/SURVIVAL

100. Take Home Message: Recent interventional trials from ESC 2019 and COMPLETE trial of STEMI strategy
RCT evaluating the extended role of ticagrelor in diabetic pts with stable CAD failed to show any benefit largely due to higher bleeding. However prior PCI subgroup had net clinical benefit and no increased bleeding. Also elderly pts (>70yrs) with ACS has better outcomes with clopidogrel vs more potent P2Y12 inhibitors and hence should be the first line therapy.
The strategy of complete revascularization (done 1 day or 3 weeks later) has shown to be superior to culprit vessel only PCI in STEMI pts with MV CAD as shown in the large randomized COMPLETE Trial. I believe, time has now come to change the STEMI guidelines to make MV PCI as ACC Class I indication in MV STEMI pts.

101. Question # 1 The correct answer is D
THEMIS trial evaluated Ticagrelor vs placebo in all following clinical subset except;
Diabetes
Prior PCI
Stable CAD
Prior MI in <1 year
E. Absence of stroke
The correct answer is D

102. Question # 2 The correct answer is C
POPular AGE trial compared the following scenario except;
Pts with Unstable angina
Pts >70yrs age
Pts with STEMI
Clopidogrel vs Ticagrelor/Prasugrel
Pts with NSTEMI
The correct answer is C

103. Question # 3 The correct answer is B
Following are the results of COMPLETE trial of STEMI strategy except:
A. Lower death and MI in complete revsc gp vs culprit only
B. Significantly lower death in complete revas gp vs culprit only
C. Lower IDR in completer revasc gp vs culprit only
D. Similar bleeding rates between complete revasc vs culprit only
E. Similar stroke rates between complete revas vs culprit only
The correct answer is B