TUESDAY Hochman Updated

ISCHEMIA Trial
International Study of Comparative

Health Effectiveness with Medical
and Invasive Approaches
Judith S. Hochman, M.D.
Harold Snyder Family Professor of Cardiology

Co-Director, NYU-HHC Clinical and Translational Science Institute
Clinical Chief, The Leon H. Charney Division of Cardiology
Director, Cardiovascular Clinical Research
NYU School of Medicine
Department of Medicine
Cardiovascular Clinical Research Center

Cardiovascular Disease is the #1 cause of death in the US
Major causes of death for men and women, 2019
Prevalence of SIHD in US: 19M

Prevalence of Stable Angina in US: 9.4M
Annual Incidence of Stable Angina in US: 565,000
Benjamin EJ. Circulation. Heart Disease and Stroke Statistics—2019

Update: A Report From the American Heart Association
2
A journey in investigation
Defining the role of revascularization across the spectrum of
ischemic heart disease
Context:
 Prompt reperfusion (PCI or lytics) saves lives early after acute ST elevation
MI. PCI is better than lytics
 An invasive strategy reduces death/MI in high risk non ST elevation acute
coronary syndrome
We asked whether an invasive strategy with coronary
revascularization would be beneficial
 when administered late after acute MI
 in patients with cardiogenic shock complicating ST elevation MI (STEMI)
 in patients with stable CAD but at least moderate inducible ischemia
Stable Ischemia Heart Disease
~500,000 new diagnoses in US each year
How Do We Treat this Person?

• Make the diagnosis
• Medications, lifestyle changes
• Assess risk for having a heart attack or dying
4
Stable Ischemic Heart Disease
Stress test rest exercise
Should a patient with a significantly abnormal stress test be managed with medicines and
lifestyle changes and determine the need for an angiogram based on how they respond or
should they promptly have an angiogram, stents, or surgery?
OR
AND

PCI vs MT alone in Patients With Stable Obstructive CAD
and Myocardial Ischemia: Meta-analysis of RCTs
Selected for >50% statin use in both groups and > 50 % stent use
Subset of patients with ischemia documented (4064 of 5286)
Death MI (non-fatal)
Unplanned Revascularization Angina
Stergiopoulos et al, JAMA Intern Med 2013

Most heart attacks occur on a plaque that does not show a tight blockage on an angiogram
stent
Early
Plaque
Medical therapy
Heart Attack
Blood clot
on ruptured
plaque
Libby. Nature 2002;420:868 .
A paradigm that suggests why randomized trials have not
demonstrated a survival benefit for revascularization in SIHD
Severe Obstruction (angina, no rupture) vs Mild Obstruction (no angina, likely to rupture)
Severe fibrotic plaque Vulnerable plaque
• Severe obstruction • Minor obstruction
• No lipid • Eccentric plaque
• Fibrosis, Ca2+ • Lipid pool
• Thin cap
Plaque rupture
• Acute MI
• Unstable angina
• Sudden death
Exertional angina
• (+) ETT
Pharmacologic stabilization
Revascularization Early identification of high-risk?
Anti-anginal Rx
Courtesy of PH Stone, MD.

Medical therapy has changed
the underlying biology and
natural history of coronary
artery disease

Why do cardiologists often pass up safe,
low-tech treatments for chest pain?
Washington Post, D. Brown, 2/6/12
• COURAGE study had a modest impact. A registry of
26,000 patients in northern New England showed a
reduction in procedures for stable patients from the year
before COURAGE to the years just after it. (21% of all
procedures to 16%)
• However, before COURAGE, 44 % of patients with stable

angina patients getting PCI had fully attempted drug-and-
lifestyle treatment before turning to the procedure. After
COURAGE, it barely changed-- to 45%.
10
Why do cardiologists often pass up safe,
low-tech treatments for chest pain?
Washington Post, D. Brown, 2/6/12
Interviews-
• Many said that patients expect and want interventions.
• Some talked about the fear of lawsuits.
• “They consistently told us that an error of commission was
better than an error of omission,” Redberg said.
• That was echoed in a survey of 500 cardiologists last year in
which a majority said it was “easier to accept” the death of a
patient getting an angioplasty than the death of a patient sent
home without the procedure.
11
Prior Strategy Trials
 Landmark trials (BARI 2D, COURAGE)
• Major contribution
 Considerations to address in further studies
• Eliminate referral bias by randomizing before cardiac catheterization
• Use newer stents and FFR as needed
• Will higher risk patients based on substantial ischemia benefit?

Observational study: Revascularization was associated with lower
risk of cardiac death only in those with >10% ischemia on perfusion
5 imaging
N=10,627 no known CAD
146 Cardiac Deaths
4
Medical Rx*
log Hazard Ratio
3
Revasc*
2
*p<0.001
1
0
0 12.5% 25% 32.5% 50%

Source: Hachamovitch Circulation 2003;107:2900-2907. % Ischemic Myocardium

Primary Goals of Treatment in Stable Ischemic
Heart Disease (SIHD)
 To Improve Survival
 To Improve Angina and Quality of Life (QOL)
These goals should govern

management decisions, including
whether and when to revascularize

ISCHEMIA Trial Timeline
Preapproval Request Preapproval Received Last Patient Primary Results

to NHLBI from NHLBI Grant Awarded Randomized Presented at the AHA
May 2009 December 2009 July 2011 January 2018 November 2019
July 2009 February 2010 July 2012 June 2019
Two Study Groups First NHLBI Application First Patient Enrolled Last Patient/Last Visit
Meeting Submission
There is no such thing as a perfect study design!
What are the critical features?
Consensus building
Design #6 Cath done, site
recognizes poss elig
Stable CAD
 ≥10% Ischemia by nuc or similarly high risk ischemia by echo (or ETT)
Provisional
Provisional Consent, phone in patient – all will be registered Consent, phone in,
register
WISDOM arm MAVERIC arm
cath
NO CCTA or Blinded CCTA for high risk cath Require stress test, pt
stress or MD preference Exclude and register LM , enrolled if ischemia
normals, non- criteria met
Exclude and register LM and
normals revascularizable disease
Randomization Randomization, strata by intent PCI or CABG
OMT Revasc + OMT OMT Revasc + OMT
* Overall Composite End Point = Mortality, Nonfatal MI

Composite End Point for each arm: D/MI/Class III-IV HF/ACS hosp
Primary Objective ISCHEMIA
• To determine the optimal initial management

strategy for patients with stable ischemic heart
disease
• Does a routine early invasive management

strategy in patients with coronary artery disease
and significantly abnormal stress test improve
clinical outcomes?
ISCHEMIA Organization
Leadership, Executive, Steering Committees
NIH/NHLBI
NYU School of Medicine
DSMB
Biostatistics Vanderbilt
Clinical Coordinating Center (CCC)

NYU Grossman School of Medicine, NYU Langone Health
Statistical and Data Coordinating Center (SDCC)
Study Chair: Judith Hochman; Study Co-Chair: David Maron (Stanford)
Duke Clinical Research Institute
Associate Director CCC: Harmony Reynolds
ISCHEMIA CKD PI: Sripal Bangalore,
Biorepository Lead: Jeffrey Berger
Economics and Quality of Life Coordinating
OMT Lead: Jonathan Newman
Center (EQOL CC)
Duke Clinical Research Institute
Imaging Coordinating Center and Stress Core Labs Mid-America Heart Institute
(Nuclear, Echo, CMR, ETT)
320 Sites* in 37 Countries Country Leaders/ AROs

Independent Clinical Events Committee
Core Labs St. Louis University
ECG, Angiographic, CCTA Duke Clinical Research Institute

ISCHEMIA design overview
Substantially abnormal:
Moderate or severe ischemia
73% of randomized
patients

Recruitment is challenging in these types of clinical trials
• Bias toward one or the other strategy

• Financial disincentives
• Uncertainty regarding treatment is difficult for patients to
accept

ISCHEMIA Trial
Timeline Overview
Jul 2012 Recruitment Initiated
2012- 2014 Recruitment challenges
Aug 2014 Leadership reviewed precision and power under reduced recruitment
assumptions
Apr 2015 DSMB endorsed the plan to reduce sample size and extend recruitment
by 6 months and follow-up by 6 months
Jun 2017 NHLBI approved Independent Advisory Panel recommendation to
implement the protocol pre-specified change from 2- to 5-component
primary endpoint
Jan 2018 Last Participant Randomized
Jun 2019 Last Participant Last Visit (extended)

Occluded
A similar trial with recruitment challenges Artery
Trial
Hypothesis-
• A strategy of late PCI to open
the occluded infarct artery
reduces the first occurrence
of a composite of death,
reinfarction or NYHA class IV
heart failure by 25%
compared to optimal medical
therapy alone
NHLBI funded

GLOBE EDITORIAL: PUNCTURING BALLOONS
DECEMBER 9, 2006
• WHEN RESEARCHERS tried to organize a randomized study
of the benefits of angioplasty for patients who had suffered a
heart attack three days or more before, they ran into a problem.
Many doctors were so convinced of the value of this
procedure, which involves reopening blocked coronary
arteries with tiny balloons and metal stents, that they
thought it would be unethical to assign any patients to the
control group, which would get all the best medicines for
this condition but not the artery-reopening procedure.
• But the researchers persisted, with heavy support from the
National Heart, Lung, and Blood Institute. After four years of
work examining 2,166 patients, they came to an unexpected
conclusion….

Occluded
OAT long term mortality Artery
Trial
• No difference between groups in the primary endpoint (death/MI/Class IV HF) or

• All-cause death,
30
Hazard Ratio*: PCI vs. MED = 0.98, 95% CI (0.78-1.22), p=0.85
25
20
Death (%)
MED
15
PCI
10
0 1 2 3 4 5 6 7 8
Years after Enrollment

At Risk
PCI: 1101 1037 999 963 879 728 518 313 151
MED: 1100 1039 1015 971 906 721 510 289 130
Cardiovascular Clinical Research Center Hochman et al Circulation 2011

GLOBE EDITORIAL: PUNCTURING BALLOONS
DECEMBER 9, 2006
• Much as a federally funded study in 2002 had shown that
hormone replacement therapy for post-menopausal women
brought with it more health problems than benefits, careful
research has again undercut conventional wisdom about a
common medical practice….
• The new study ….. underscores the need for more
independently funded research into the use of drugs,
surgery, and a wide array of devices…..
• This study demonstrates the value of medical research in
which the prime sponsor is the government, not the
pharmaceutical or device industry. Above all, though, it is a
sober reminder that in medicine more can be just more, and not
better.

American Heart Association and American College
of Cardiology Practice Guidelines
European Society of Cardiology Practice Guidelines

Translation to practice guidelines
I IIa IIb III Delayed PCI of totally occluded infacrt artery

> 24 hours post MI in stable patients
Cardiovascular Clinical Research Center O’Gara, et. al., JACC. 2013;61:e78-e140

Back to ISCHEMIA

Study Flow
Screen Failure (3339)
Major Reasons:
• Insufficient ischemia (N = 1350)
Enrolled (8518) • No obstructive CAD (N = 1218)
• Unprotected LMD (N =434)
Randomized (5179)
Study CCTA in 73% of randomized participants
Randomized to INV (2588) Randomized to CON (2591)
Median follow-up 3.2 years (IQR 2.2 to 4.3 Median follow-up 3.2 years (IQR 2.2 to 4.4
years) years)
Proportion of follow-up completed: 99.4% Proportion of follow-up completed: 99.7%
ISCHEMIA
Baseline Characteristics
Characteristic Total INV CON
Clinical
Age at Enrollment (yrs.)
Median 64 (58, 70) 64 (58, 70) 64 (58, 70)
Female Sex (%) 23 23 22
Hypertension (%) 73 73 73
Diabetes (%) 42 41 42
Prior Myocardial Infarction (%) 19 19 19
Ejection Fraction, Median (%) (n=4637) 60 (55, 65) 60 (55, 65) 60 (55, 65)
Systolic Blood Pressure, Median (mmHg) 130 (120, 142) 130 (120, 142) 130 (120, 142)
Diastolic Blood Pressure, Median (mmHg) 77 (70, 81) 77 (70, 81) 77 (70, 81)
LDL Cholesterol, Median (mg/dL) 83 (63, 111) 83 (63, 111) 83 (63, 109.5)
History of Angina 90% 90% 89%
Angina Began or Became More Frequent Over the Past 3 Months 29% 29% 29%
Stress Test Modality
Stress Imaging (%) 75 75 76
Exercise Tolerance Test (ETT) (%) 25 25 24
Median values reported with 25th and 75th percentiles
Hochman JS et al. JAMA Cardiology. 2019 Mar 1;4(3):273-86.

Qualifying Stress Test: Core Lab Interpretation
Characteristic Total INV CON
Baseline Inducible Ischemia*

Severe 54% 53% 55%
Moderate 33% 34% 32%
Mild/None 12% 12% 12%
Uninterpretable 1% 1% 1%
*Only severe qualified by ETT

Risk Factor Management
Baseline vs last visit
No between group differences INV vs CON
100 95 95 Baseline Average 100 96 97
90
90 Last Visit Average 90 88
80 80 77
70
70 66 66 70 65
60 59
% AT GOAL
60
% AT GOAL
50
50
41 41
40
40
32
30
30
20 20
20
10
10
0
Any Statin High-Intensity Statin ACE Inhibitor/ARB Among All 0
Participants LDL < 70 mg/dL SBP < 140 mmHg Aspirin or Aspirin Not Smoking High Level of
and on Statin Alternative Medical Therapy
Axis Title
Optimization
High Level of Medical Therapy Optimization is defined as a participant meeting all of the
following goals: LDL < 70 mg/dL and on any statin, systolic blood pressure < 140 mm/Hg, on
aspirin or other antiplatelet or anticoagulant, and not smoking. High level of medical
therapy optimization is missing if any of the individual goals are missing.

Baseline Coronary Artery Anatomy by CCTA
100 100
90 90 87 87
80 80
68 67 70 68
70 70
60 60
50 47
44 50 46 47
40 34 40
29
30 24 30
22
20 20
10 10
1 1
0 0
1 2 ≥3 Left Main Left Anterior Proximal LAD Left Circumflex Right Coronary
Descending Artery
# of Vessels with >50 % Stenosis (%)
Specific Vessels with > 50% Stenosis (%)
N=2982 (% of total) N=3739

Cardiac Catheterization and Revascularization
INVASIVE group CONSERVATIVE group
 Cardiac catheterization - 96%  Low rates of cardiac cath and

 Revascularization feasible and revascularization in CON group
performed - 80%  Indications for cath in CON
 PCI in 74%  Suspected/confirmed event 13.8%
 CABG in 26%  OMT Failure 3.9%
 Non-adherence 8.1%
 Of the ~ 20% with no revascularization  Revascularization in CON at 4 years
 ~ 2/3 had insignificant disease on coronary
not preceded by a primary endpoint
angiogram
 ~1/3 had extensive disease unsuitable for any event - 16%
mode of revascularization

Primary Outcome: CV Death, MI, hospitalization for UA, HF or
Panel A
resuscitatedPrimary
cardiac arrest
Outcome
6 months:
Δ = 1.9% (0.8%, 3.0%)
4 years:
Δ = -2.2% (-4.4%, 0.0%)
Adjusted hazard ratio (HRadj) for invasive vs. conservative: 0.93 (95% confidence interval [CI]: 0.80 to 1.08); ratio of cumulative hazard
rates for invasive vs. conservative over 5 years: 0.89 (95% CI: 0.74 to 1.08).
Panel B
Major Secondary: CV Death or MI
CV Death or MI
6 months:
Δ = 1.9% (0.9%, 3.0%)
4 years:
Δ = -2.2% (-4.4%, -0.1%)
HRadj for invasive vs. conservative: 0.90 [95% CI: 0.77 to 1.06]; ratio of cumulative hazard rates for invasive vs. conservative
over 5 years: 0.85 [95% CI: 0.70 to 1.04]
Myocardial Infarction
HRadj for invasive vs. conservative: 0.92 [95% CI: 0.76 to 1.11]; ratio of cumulative hazard rates for invasive vs. conservative over
5 years: 0.86 [95% CI: 0.69 to 1.07]
Procedural MI Spontaneous MI
HRadj for invasive vs. conservative: 0.67 (95% CI: 0.53 to 0.83); ratio of cumulative average hazard rates for
HRadj for invasive vs. conservative: 2.98 (95% CI: 1.87 to 4.74); ratio of invasive vs. conservative over 5 years: 0.70 (95% CI: 0.54 to 0.92).
cumulative hazard rates for invasive vs. conservative over 5 years: 2.61 (95% CI: Diagnosis of spontaneous MI was defined as Type 1, 2, 4b, or 4c myocardial infarction.
1.61 to 4.22).

Hospitalization for Unstable Angina
HRadj for invasive vs. conservative: 0.50 (95% CI: 0.27 to 0.91); ratio of cumulative average hazard rates for invasive vs.
conservative over 5 years: 0.48 (95% CI: 0.24 to 0.99).

Hospitalization for Heart Failure
HRadj for invasive vs. conservative: 2.23 (95% CI: 1.38 to 3.61); ratio of cumulative hazard rates for invasive vs. conservative over 5 years:
1.77 (95% CI: 0.95 to 3.28).

Hospitalization for Resuscitated Cardiac Arrest
HRadj for invasive vs. conservative: 1.01 (95% CI: 0.29 to 3.49); ratio of cumulative hazard rates for invasive vs. conservative
over 5 years: 0.92 (95% CI: 0.26 to 3.27).

Net Clinical Benefit: CV Death, MI, UA, HF, RCA, Stroke
Adj HR= 0.95 (0.82,1.10) P-value= 0.50

Cardiovascular Death
HRadj for invasive vs. conservative: 0.87 (95% CI: 0.66 to 1.15); ratio of cumulative hazard rates for invasive vs. conservative over 5
years: 0.80 (95% CI: 0.58 to 1.12).

All-causePanel
Death
C
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.
HRadj for invasive vs. conservative: 1.05 [95% CI: 0.83 to 1.32]; ratio of cumulative hazard rates for invasive vs. conservative
over 5 years: 1.09 [95% CI: 0.82 to 1.45]
Primary endpoint
Pre-specified Important Subgroups
There was no heterogeneity of treatment effect
High degree of medical therapy optimization
N=3739 for Prox LAD Y/N

N=2982 for # diseased vessels
Baseline angina
Total
n = 4617
SAQ-7 Angina Frequency Score
Mean ± SD 81.4 ± 19.6
Median (IQR) 90.0 (70.0, 100.0)
SAQ-7 Angina Frequency Score
Daily/weekly 20%
Monthly 44%
None 36%

Probability of No Angina by Baseline Angina Frequency
No
Difference
45%
NNT = ~3
15%
Daily Weekly Monthly None
n=8 8 67 30 172 140 509 500 850 693 1635

Limitations
 Unblinded trial – no sham procedure
 Based on exclusion criteria, the trial results do not apply to patients with:
 Acute coronary syndromes within 2 months
 Highly symptomatic patients
 Left main stenosis
 LVEF <35%
 Trial findings may not be generalizable to centers with higher procedural

complication rates

Summary
 The curves cross for the primary endpoint and the major secondary
endpoint at approximately 2 years from randomization
 ~2 in 100 higher estimated rate with INV at 6 months
 ~2 in 100 lower estimated rate with INV at 4 years
 Procedural MIs were increased with an invasive strategy

 Spontaneous MIs were reduced with an invasive strategy
 Low all-cause mortality in both groups despite high-risk clinical
characteristics, high-risk ischemia and extensive CAD
 No heterogeneity of treatment effect, including by type of stress test,
severity of ischemia or extent of CAD
 Very low rates of procedure-related stroke and death
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
 Invasive strategy led to greater propori

Conclusions- Quality of Life
• Patients with stable CAD and moderate to severe ischemia had significant,
durable improvements in angina control and quality of life with an invasive
strategy if they had angina (daily/weekly or monthly)
• In patients without angina, an invasive strategy led to minimal symptom or

quality of life benefits, as compared with a conservative strategy
• In patients with angina, shared decision-making should occur to align

treatment with patients’ goals and preferences

Potential Savings
 Cost Estimate1
 Assume 19% of PCI are elective.
 Assume 24% of elective PCI are performed on people without symptoms.
 Assume 500,000 PCI performed annually in the US.
 19% of 500,000 = 95,000 elective PCI are performed annually in US
 24% of 95,000 = 22,800 elective PCI are performed on people without symptoms annually in US.
 Assume $25K/PCI.
 22,800 PCI x $25K per PCI = $570,000,000 ($570M) saved per year if asymptomatic patients
stopped getting PCI.
1Based in part on Faridi et al. Am Heart J 2019;216:53-61.

CLINICAL TRIALS REQUIRE TEAMWORK

NYU Cardiovascular Clinical Research Center

ISCHEMIA Research Teams
(of > 350)
ISCHEMIA NYU CCC Staff
Study Timelines
Recruitment began 2012 (ISCHEMIA);2014 (ISCHEMIA-CKD)
ISCHEMIA/ISCHEMIA-CKD Trial Timeline
2017 2018 2019 2020 2021
Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec Jan Feb Mar Apr May Jun Jul Aug
Site Startup Site Closeout/Transition to LTFU

CKD Site Closoeut
Enrollment (to 6 month
Jan 2018) Extension
CKD Enrollment Planned LPLV
6 month
Follow-up Study Visits (to June 2019) Extension
CKD Follow-up Study Visits
6 month DataCleanup,
Data Acquisition and Cleanup Extension Analysis,Final Report
CKD Data Acquistion and Cleanup
AHA
Publications and Presentations Extension
CKD Publications and Presentations
LTFU Planning Long Term Follow-Up

(Dec 2020-2025)

TUESDAY Hochman Updated

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ISCHEMIA Trial

International Study of Comparative

Judith S. Hochman, M.D.

Harold Snyder Family Professor of Cardiology

Cardiovascular Clinical Research Center

Prevalence of SIHD in US: 19M

Benjamin EJ. Circulation. Heart Disease and Stroke Statistics—2019

How Do We Treat this Person?

Cardiovascular Clinical Research Center

Unplanned Revascularization Angina

Stergiopoulos et al, JAMA Intern Med 2013

Cardiovascular Clinical Research Center

Courtesy of PH Stone, MD.

Cardiovascular Clinical Research Center

Cardiovascular Clinical Research Center

• However, before COURAGE, 44 % of patients with stable

Cardiovascular Clinical Research Center

0 12.5% 25% 32.5% 50%

Cardiovascular Clinical Research Center

These goals should govern

Cardiovascular Clinical Research Center

Preapproval Request Preapproval Received Last Patient Primary Results

July 2009 February 2010 July 2012 June 2019

Randomization Randomization, strata by intent PCI or CABG

OMT Revasc + OMT OMT Revasc + OMT

* Overall Composite End Point = Mortality, Nonfatal MI

• To determine the optimal initial management

• Does a routine early invasive management

Clinical Coordinating Center (CCC)

320 Sites* in 37 Countries Country Leaders/ AROs

Cardiovascular Clinical Research Center

Cardiovascular Clinical Research Center

• Bias toward one or the other strategy

Cardiovascular Clinical Research Center

Cardiovascular Clinical Research Center

Cardiovascular Clinical Research Center

Cardiovascular Clinical Research Center

• No difference between groups in the primary endpoint (death/MI/Class IV HF) or

Years after Enrollment

Cardiovascular Clinical Research Center Hochman et al Circulation 2011

Cardiovascular Clinical Research Center

Cardiovascular Clinical Research Center

I IIa IIb III Delayed PCI of totally occluded infacrt artery

Cardiovascular Clinical Research Center O’Gara, et. al., JACC. 2013;61:e78-e140

Cardiovascular Clinical Research Center

Randomized to INV (2588) Randomized to CON (2591)

Hochman JS et al. JAMA Cardiology. 2019 Mar 1;4(3):273-86.

Baseline Inducible Ischemia*

*Only severe qualified by ETT

Hochman JS et al. JAMA Cardiology. 2019 Mar 1;4(3):273-86.

Cardiovascular Clinical Research Center

Hochman JS et al. JAMA Cardiology. 2019 Mar 1;4(3):273-86.

INVASIVE group CONSERVATIVE group

 Cardiac catheterization - 96%  Low rates of cardiac cath and

Cardiovascular Clinical Research Center

Cardiovascular Clinical Research Center

Cardiovascular Clinical Research Center

Cardiovascular Clinical Research Center

Cardiovascular Clinical Research Center

Adj HR= 0.95 (0.82,1.10) P-value= 0.50

Cardiovascular Clinical Research Center

The probability of at least a 10% relative risk reduction of INV on

High degree of medical therapy optimization

N=3739 for Prox LAD Y/N