cv update 2020 · cv update 2020 ischemia and complete shamir r. mehta md, msc, frcpc, facc, fesc....

CV Update 2020

ISCHEMIA and COMPLETEShamir R. Mehta MD, MSc, FRCPC, FACC, FESC

Director, Interventional CardiologyHamilton Health Sciences

Senior Scientist, Population Health Research InstituteProfessor of Medicine, McMaster University

Disclosures

Research grants from AstraZeneca and Boston Scientific

Scientific Sessions 2019 #AHA19

*Abbreviated Title

International Study Of Comparative Health Effectiveness With Medical And Invasive Approaches (ISCHEMIA):

Cardiovascular Clinical Research Center

Stable PatientModerate or severe ischemia

(determined by site; read by core lab)

CCTA not required, e.g., eGFR 30 to <60 or coronary anatomy previously defined

Blinded CCTA

Core lab anatomy eligible?

RANDOMIZE

Screen failure

Study Design

INVASIVE StrategyOMT + Cath +

Optimal Revascularization

CONSERVATIVE Strategy OMT alone

Cath reserved for OMT failure

NO

YES

Maron DJ, et al. NEJM 2020; 382(15):1395-1407


Mode of RevascularizationFirst Procedure for Those Revascularized in Invasive Group

(80% of INV)

First Procedure Total

PCI 74%• Successful, stent able to be

placed93%

• Of stents placed, drug eluting

98%

First Procedure Total

CABG 26%• Arterial Grafts 93%• IMA 92%

Of the 20% with no revascularization~2/3 had insignificant disease on coronary angiogram

~1/3 had extensive disease unsuitable for any mode of revascularization


0%

5%

10%

15%

20%

25%

30%

0 1 2 3 4 5

Cum

ulat

ive

Inci

denc

e (%

)

Follow-up (years)

CONINV

Adjusted Hazard Ratio = 0.93 (0.80, 1.08)P-value = 0.34

Subjects at Risk

CON 2591 2431 1907 1300 733 293INV 2588 2364 1908 1291 730 271

6 months:Δ = 1.9% (0.8%, 3.0%)

4 years:Δ = -2.2% (-4.4%, 0.0%)

Absolute Difference INV vs. CON

Primary Outcome: CV Death, MI, hospitalization for UA, HF or resuscitated cardiac arrest

15.5%

13.3%



0%

5%

10%

15%

20%

25%

30%

0 1 2 3 4 5

Cum

ulat

ive

Inci

denc

e (%

)

Follow-up (years)

CONINV

Adjusted Hazard Ratio = 0.90 (0.77, 1.06)P-value = 0.21

Subjects at Risk

CON 2591 2453 1933 1325 746 298INV 2588 2383 1933 1314 752 282

6 months:Δ = 1.9% (0.9%, 3.0%)

4 years:Δ = -2.2% (-4.4%, -0.1%)

Absolute Difference INV vs. CON

Major Secondary: CV Death or MI

13.9%

11.7%



All-Cause Death

The probability of at least a 10% relative risk reduction of INV on all-cause mortality is <10%, based on pre-specified Bayesian analysis.

6.4%

6.5%



Myocardial Infarction



Spontaneous MI Types 1, 2, 4b, or 4c MI

Procedural MI Type 4a or 5 MI


Probability of No Angina by Baseline Angina Frequency

n=8 8 67 30 172 140 509 500 850 693 1635

Daily Weekly Monthly None

15%

45%

NNT = ~3

No Difference


Spertus J. NEJM 2020; 382(15):1408-1419


Conclusions

ISCHEMIA is the largest trial of an invasive vs conservative strategy for patients with SIHD

Overall, an initial INV strategy as compared with an initial CON strategy did not demonstrate a reduced risk over median 3.3 years for Primary endpoint - CV death, MI, hospitalization for UA, HF, RCA Major Secondary endpoint - CV death or MI

The probability of at least a 10% benefit of INV on all-cause mortality was <10%, based on pre-specified Bayesian analysis

Available online at NEJM.org

COMPLETETrial Design Exclusion Criteria: Intent to revascularize NCL,

planned surgical revascularization, prior CABG

*Everolimus-eluting stentsstrongly recommended

STEMI WITH MULTIVESSEL CAD AND SUCCESSFUL PCI TO THE CULPRIT LESIONMVD defined as at least one additional non-culprit lesion ≥ 2.5 mm diameter

and ≥70% stenosis or 50-69% with FFR ≤0.80

RANDOMIZATIONStratified 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 ischemia-driven revascularization

KEY SECONDARY OUTCOME: CV death, new MI, IDR, unstable angina, NYHA class IV heart failure

MEDIAN FOLLOW-UP: 3 YEARS

COMPLETE REVASCULARIZATIONRoutine staged PCI* of all suitable non-culprit lesions

with the goal of complete revascularizationN=2000

CULPRIT LESION ONLY REVASCULARIZATIONNo further revascularization of non-culprit lesions,

guideline-directed medical therapy aloneN=2000

Guideline-Directed Medical TherapyASA, 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 12.5-33.5)

Mehta SR et al. Am Heart J 2019; 215:157-166.

Hazard Ratio 0.74 95% CI 0.60-0.91

P=0.004

NNT (median 3 years) = 37

First Co-Primary Outcome: CV Death or New MI

Mehta SR. et al. N Engl J Med 2019

Hazard Ratio 0.51 95% CI 0.43-0.61

P < 0.001

NNT (median 3 years) = 13

2nd Co-Primary Outcome:CV Death, New MI, or IDR


Complete Revasc.N=2016

Culprit Lesion OnlyN=2025 HR (95% CI) P value

N (%) %/year N (%) %/year

Co-Primary Outcomes

CV death or MI 158 (7.8) 2.7 213 (10.5) 3.7 0.74 (0.60-0.91) 0.004

CV death, MI or IDR 179 (8.9) 3.1 339 (16.7) 6.2 0.51 (0.43-0.61) <0.001

Key Secondary OutcomeCV death, MI, IDR,

unstable angina or class IV HF272 (13.5) 4.9 426 (21.0) 8.1 0.62 (0.53-0.72) <0.001

Other Secondary Outcomes

MI 109 (5.4) 1.9 160 (7.9) 2.8 0.68 (0.53-0.86) 0.002

IDR 29 (1.4) 0.5 160 (7.9) 2.8 0.18 (0.12-0.26) <0.001

Unstable Angina 70 (3.5) 1.2 130 (6.4) 2.2 0.53 (0.40-0.71) <0.001

CV death 59 (2.9) 1.0 64 (3.2) 1.0 0.93 (0.65-1.32) 0.68

All-cause Death 96 (4.8) 1.6 106 (5.2) 1.7 0.91 (0.69-1.20) 0.51

Efficacy Outcomes


Meta-analysisCV Death

OR 0.69 [95%CI, 0.48-0.99]; P = 0.05; fixed-effects model OR, 0.74 [95%CI, 0.55-0.99]; P = 0.04

Bainey K. JAMA Cardiol 2020 online first

Endothelium

Lipid-Rich Core

Thick Fibrous Cap

Thin Fibrous Cap

InflammatoryCells

Lumen

Falk E, et al. Circulation. 1995;92:657-671.

Platelets

Stable Unstable (TCFA)

Is the non-culprit lesion more likely to be a stable (active) or unstable (inactive)plaque?

Thrombus

Higher likelihood for MI and DeathLow likelihood of causing MI or Death

OCT COMPLETE: Imaging Protocol

Target 1 (LAD)Obstructive NCL

Target 2 (RCA)Additional vessel

Obstructive or Non-obstructive lesions

Target 3 (LCX)STEMI vessel

If > 50 mm unstented segment

Number of pullbacks / patient (mean): 2.82 Imaged length / patient (mean): 152.5 mm

OCT imaged segment (staged non-culprit PCI procedure)

Example: Inferior STEMI Culprit lesion LCX, Non-culprit lesion LAD

Pinilla-Echeverri N et al. Circ Cardiovasc Int 2020 in press

TCFA (FCT < 65 μm overlying a lipidic plaque)

Yes No

Obs

truc

tive

>70%

DS

Yes

No

n=58 n=92

n=74 n=201

N=425

Classification of non-culprit lesions

TCFA: Thin Cap Fibro AtheromaFCT: Fibrous Cap Thickness

Pinilla-Echeverri N et al. Circ Cardiovasc Int 2020 in press

Results: Prevalence of TCFA (per patient)

OBSTRUCTIVE TCFA Non-TCFA Non-TCFA

NON-OBSTRUTIVE TCFA or Non-TCFA TCFA Non-TCFA

Half of patients had

an obstructive non-

culprit lesion containing

vulnerable plaque

Pinilla-Echeverri N. Circ Cardiovasc Int. 2020, in press

Primary Outcome: Prevalence of TCFA (per lesion)

58/150 74/275 TCFA: Thin Cap Fibro Atheroma

Obstructive non-culprit

lesions are most likely

to be vulnerable

Pinilla-Echeverri N. Circ Cardiovasc Int 2020 in press

COMPLETE and ISCHEMIA

Factor COMPLETE ISCHEMIA

Patient population Acute coronary syndrome (STEMI)1 Stable CAD2

Plaque composition Often unstable plaque morphology (TCFA’s)3

Usually quiescent, stable plaques with low propensity for rupture

Completeness of Revasc >90% complete (SYNTAX score=0)1 Unknown

Complexity of target lesions

Low (SYNTAX NCL score=4.5)1 Unknown. (Ca++, bifurcations, CTO’s common in stable CAD)

Operator Experience High volume STEMI sites Mix of sites

Spontaneous (type 1) MI Clear reduction Clear reduction

Periprocedural MI No difference Clear increaseCV Death Recent meta-analyses shows

reduction with complete revasc.2No difference when taken in context of COURAGE, BARI 2D)

1. Mehta SR. et al. N Engl J Med 2019

2. Bainey K. JAMA Cardiol 2020 online first

cv update 2020 · cv update 2020 ischemia and complete shamir r. mehta md, msc, frcpc, facc, fesc....

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