CAD Trial Year in Review Incremental Impact of New Research ABSORB II/III DANAMI-3 IMPROVE-IT MATRIX Chest Pain Choice PCSK9 TUXEDO PROCAT II STICH 10-Year LEADERS-FREE TOTAL SPRINT
Trang 1Coronary Artery Diseases Year in Review
2015-2016
Five Trials That Will Impact Patient Care
Nothing to Disclose Related to this Talk
Gregory W Barsness, MD, FACC, FAHA, FSCAI Consultant, Internal Medicine & Cardiology and Radiology
Director, Mayo Clinic EECP Laboratory Director, Mayo Clinic Cardiac Intensive Care Unit
Mayo Clinic College of Medicine
Rochester, MN, USA
Hanoi, Vietnam, October 9-11, 2016
Trang 2CAD Trial Year in Review
Incremental Impact of New Research
ABSORB II/III DANAMI-3 IMPROVE-IT
MATRIX Chest Pain Choice PCSK9
TUXEDO PROCAT II STICH 10-Year
LEADERS-FREE TOTAL SPRINT
RIDDLE-NSTEMI Early BAMI COSIRA
PEGASUS AVOID ACCELERATE
Trang 3CAD Trial Year in Review
Incremental Impact of New Research
DAPT CULPRIT HOPE-3 ABSORB II/III DANAMI-3 IMPROVE-IT
MATRIX Chest Pain Choice PCSK9 TUXEDO PROCAT II STICH 10-Year LEADERS-FREE TOTAL SPRINT
RIDDLE-NSTEMI Early BAMI COSIRA
PEGASUS AVOID ACCELERATE
Trang 4CAD Trial Year in Review
Incremental Impact of New Research
Trang 6Adjunctive device prior to PCI PCI alone
Thrombus Aspiration in PPCI
Meta-Analysis of Mortality
Bavry AA, et al Eur Heart J 2008
Mechanical thrombectomy
Manual thrombus aspiration
Embolic protection
I I IIa IIa IIa IIb IIb IIb III III III
I I IIa IIa IIa IIb IIb IIb III III III
I IIa IIa IIa IIa IIa IIa IIb IIb IIb IIb IIb IIb III III III III III III
*Weighted Mean 5.0 months
Trang 7AL
TOTAL Trial Flow and Adherence
10,732 enrolled and randomized
Cross-over to Thrombectomy as initial
Trang 8Jolly et al Lancet 2015 Higuma JACC Card Int 2016;8:2002
Trang 9Jolly et al Lancet 2015
Trang 102013 ACC/AHA STEMI Guideline
Thrombus Aspiration in PPCI
I
I I IIa IIa IIa IIb IIb IIb III III III
I I IIa IIa IIa IIb IIb IIb III III III
I IIa IIa IIa IIa IIa IIa IIb IIb IIb IIb IIb IIb III III III III III III
Manual aspiration thrombectomy is reasonable for patients
undergoing PPCI
Trang 112015 ACC/AHA STEMI Guideline
Thrombus Aspiration in PPCI
I
I I IIa IIa IIa IIb IIb IIb III III III
I I IIa IIa IIa IIb IIb IIb III III III
I IIa IIa IIa IIa IIa IIa IIb IIb IIb IIb IIb IIb III III III III III III
Routine aspiration thrombectomy is not useful
I I IIa IIa IIa IIb IIb IIb III III III
I I IIa IIa IIa IIb IIb IIb III III III
I IIa IIa IIa IIa IIa IIa IIb IIb IIb IIb IIb IIb III III III III III III
Trang 13Primary PCI vs Fibrinolysis
Isch
Total stroke
Hem stroke
Major bleed
Death MI Stroke
%
PCI Lysis
Trang 14BMS vs PTCA in AMI
Meta-Analysis of 13 RCT (n=6922)
De Luca et al Int J Card 2007;119:306
Trang 15Previous Deferred Stenting Studies
Adverse Outcome of Stent in PPCI
Tang 87 TIMI frame count ↓ 22%
Cafri 106 thrombotic events ↓ 23%
Pascal 279 MACE-free survival ↑ 15%
Randomised
DEFER-STEMI 101 no-/slow flow ↓ 23%
MIMI 140 MVO (% of LVmass) ↑ 111%**
Trang 16TIMI 0-I TIMI 2-3
To evaluate whether the prognosis of
STEMI patients treated with PPCI can be
improved by deferred stent implantation
flow with stent implantation at 48-72 hrs
Trang 17Primary endpoint
Primary Endpoint Composite: All cause mortality, heart failure hospitalization, re-MI, and TVR
Trang 18612 594 575 403 173 0 Conventional
Number at risk
Time (years)
Conventional Deferred
A
HR: 0.83 [0.56 - 1.24]; P=0.37 All cause mortality
612 580 560 391 167 0 Conventional
Number at risk
Time (years)
Conventional Deferred
C
HR: 0.82 [0.47 - 1.43]; P=0.49 Hospitalisation for heart failure
612 586 554 379 165 0 Conventional
Number at risk
Time (years)
Conventional Deferred
B
HR: 1.1 [0.69 - 1.64]; P=0.77 Recurrent myocardial reinfarction
612 587 561 387 170 0 Conventional
Number at risk
Time (years)
Conventional Deferred
D
HR: 1.7 [1.04 - 2.92]; P=0.03
Unplanned target vessel revascularisation
Components of the Primary Endpoint
Trang 19612 587 561 387 170 0 Conventional
Number at risk
Time (years)
Conventional Deferred
D
HR: 1.7 [1.04 - 2.92]; P=0.03
Unplanned target vessel revascularisation
Components of the Primary Endpoint
Routine deferred stenting was associated with
an increased rate of target vessel revascularisation, mainly due to premature
stent implantation
Bottom Line
Current practice of PPCI is difficult to improve
upon with current technology
DEFER is underpowered: minimal signal (LVEF)
INNOVATION and PRIMACY may add clarity
Prompt reperfusion and (drug-eluting) stent
placement is warranted in PPCI
Trang 21Primary PCI Angiogram
IRA
MVD in 30 - 60% of STEMI Higher mortality than single vessel Culprit lesion PCI improves outcome
Is immediate non-culprit artery PCI indicated?
Trang 22CMR Substudy
3±2d
N=105
CMR Substudy 3±2d
N=98
MPS 6±2 weeks
Of 150 ITT Loss to follow-up n=11
YES
Stratified
Anterior/ non-anterior Sxs <3hours/>3hours
CONSENT
Trang 23The 12-Month Primary Endpoint Composite
Total mortality, re-MI, CHF, ischemia-driven revascularization
Gershlick, et al J Am Coll Cardiol 2015;65:963-972
Trang 2455% MACE reduction with PPCI + Non-IRA lesion(s)
on index admission with no adverse safety signal
compared with IRA-alone
Hard events (death, MI, HF) reduced (5 vs 13%) to same magnitude as repeat revascularisation (4.7% vs 8.2%)
Does not answer primary question of appropriate timing or
identification of suitable lesions for staged PCI
CvLPRIT Conclusions
Gershlick, et al J Am Coll Cardiol 2015;65:963-972
Trang 25Meta-Analysis of Recent Trials of
Complete Revascularization in STEMI
Complete vs Culprit-Only Revascularization
Trang 26Meta-Analysis of Recent Trials of
Complete Revascularization in STEMI
Trang 272013 ACC/AHA/SCAI PCI Guidelines
Management of Patients with STEMI
O’Gara et al: JACC, 2012; Vlaar JACC 2011
I
I I IIa IIa IIa IIb IIb IIb III III III
I I IIa IIa IIa IIb IIb IIb III III III
I IIa IIa IIa IIa IIa IIa IIb IIb IIb IIb IIb IIb III III III III III III
PCI should not be performed in a noninfarct artery at the time of primary PCI in patients without hemodynamic compromise
I
I I IIa IIa IIa IIb IIb IIb III III III
I I IIa IIa IIa IIb IIb IIb III III III
I IIa IIa IIa IIa IIa IIa IIb IIb IIb IIb IIb IIb III III III III III III
Harm
Trang 282015 ACC/AHA/SCAI PCI Guidelines
Management of Patients with STEMI
O’Gara et al: JACC, 2012; Vlaar JACC 2011
I
I I IIa IIa IIa IIb IIb IIb III III III
I I IIa IIa IIa IIb IIb IIb III III III
I IIa IIa IIa IIa IIa IIa IIb IIb IIb IIb IIb IIb III III III III III III
PCI of a noninfarct artery may be considered in select STEMI patients without hemodynamic compromise, either at the time of PPCI or as a
planned staged procedure
I
I I IIa IIa IIa IIb IIb IIb III III III
I I IIa IIa IIa IIb IIb IIb III III III
I IIa IIa IIa IIa IIa IIa IIb IIb IIb IIb IIb IIb III III III III III III
Trang 30Background:
Cholesterol Lowering
Lowering LDL cholesterol (LDL-C) is a mainstay of
cardiovascular prevention
Supported primarily by statin trials which show
reduction in morbidity and mortality
Previously, no lipid-modifying therapy added to statins has demonstrated a clear clinical benefit
Despite current therapies, patients remain at high risk
Trang 31Patients stabilized post ACS ≤ 10 days
LDL-C 50–125*mg/dL (or 50–100**mg/dL if prior lipid-lowering Rx)
Standard Medical & Interventional Therapy
Ezetimibe / Simvastatin
10 / 40 mg
Simvastatin
40 mg
Follow-up Visit Day 30, every 4 months
Duration: Minimum 2 ½-year follow-up (at least 5250 events)
Primary Endpoint: CV death, MI, hospital admission for UA,
coronary revascularization (≥ 30 days after randomization), or stroke
N=18,144
Uptitrated to Simva 80 mg
if LDL-C > 79 (adapted per FDA label 2011)
Study Design
*3.2mM **2.6mM
Cannon CP AHJ 2008;156:826-32; Califf RM NEJM 2009;361:712-7; Blazing MA AHJ 2014;168:205-12
90% power to detect
~9% difference
Trang 32LDL-C and Lipid Changes
Trang 33Primary Endpoint — ITT
Cardiovascular death, MI, documented unstable angina requiring
rehospitalization, coronary revascularization (≥30 days), or stroke
7-year event rates
NNT= 50
Trang 34HR Simva* EZ/Simva* p-value
Individual Cardiovascular
Endpoints and CVD/MI/Stroke
0.6 1.0 1.4 *7-year
event rates (%)
Trang 35Conclusions
First trial demonstrating incremental clinical benefit when
adding a non-statin agent (ezetimibe) to statin therapy:
Lowering LDL-C with ezetimibe reduces CV events
Even Lower is Even Better (achieved mean LDL-C 53)
Reduced subsequent/total number of events
Further support of the benefit of continuation of intensive lipid therapy after a recurrent CV event
Implications on symptoms, morbidity, prognosis and cost Confirms ezetimibe safety profile - no excess myopathy or CA
Trang 36Impact of LDL Lowering
Lower is Better
Wright and Murphy NEJM 2016:362-4
Trang 37Impact of LDL Lowering
Relative Risk Reduction Across Classes
Silverman, et al JAMA 2016;316(12):1289-1297
Trang 39Timing of Intervention in ACS (TIMACS)
I I IIa IIa IIa IIb IIb IIb III III III
I I IIa IIa IIa IIb IIb IIb III III III
I IIa IIa IIa IIa IIa IIa IIb IIb IIb IIb IIb IIb III III III III III III
*Early intervention (med 14 hrs) **Delayed intervention (med 50 hrs)
Mehta SR et al NEJM 2009;360:2165-2175
Trang 40ABOARD Immediate vs Delay Angio in High-Risk ACS
Trang 41RIDDLE-NSTEMI
Mean 1.4 hrs Mean 61 hrs
Trang 42RIDDLE-NSTEMI Immediate (<2 hr) vs Delayed (2-72 hr)
30-Day Death or MI
13%
4.3%
0 5 10 15 20
Milosivec, et al J Am Coll Cardiol Intv 2016
Trang 43Early Invasive vs Ischemia-Guided Strategy
Selection Factors and Timing Summary
Trang 44What Is the Impact?
Clarification of what not to do in STEMI:
No Routine thrombus aspiration
No Delayed stent implantation
Incomplete guidance on complex issues:
Attempt complete revascularization in patients with STEMI (timing uncertain)
Enhanced knowledge of what to do in ACS:
LDL-lowering hypothesis is alive!
Prompt PCI in NSTE-ACS (akin to STEMI)
Trang 45CP1124540-1
barsness.gregory@mayo.edu
Mayo Clinic Rochester, MN
CAM ON