How will ISCHEMIA-EXTEND change our interpretation of the

ISCHEMIA results?
Determinants of the clinical effect with revascularization on a global scale

Optimal endpoint selection (avoid competing risk)

Sample size

Complete revascularization

Follow-up

Synergism of revascularization and MT startegies

Cardiac mortality endpoint in CV revascularization was showcased in many trials

and meta-analyses
 Revascularization is not associated with a significant increase in non-
cardiac death

2023AHA/ACC/ACCP/ASPC/NLA/PCNA guideline for the management of

patients with Chronic Coronary Disease
Calculus of the benefits of Revascularization + Medical Treatment
(MT)

Final Remarks:
• A prior meta-analysis comparing Revascularization + MT versus MT alone for
stable chronic coronary syndromes demonstrated a reduction in cardiac
death following revascularization with a survival advantage proportional to
both duration of follow-up and magnitude of spontaneous MI reduction.

• A similar cardiac survival benefit was associated with revascularization plus

medication versus medication alone in the ISCHEMIA EXTEND trial.

• Follow-up length, adequate sample size and MV disease are major drivers of
CV benefit and cardiac survival with Revascularization + MT vs MT alone.
Is complete revascularization still the goal in chronic coronary
syndrome interventions?

Complete Revascularization (CR) in CCD : SYNTAX trial

Ischemia: Impact of Completeness of Revascularization

• Anatomic CR: Reverse of all lesions with QCA RVD ≥2.0 mm and QCA
DS≥50%
• Functional CR: Reverse of all lesions with QCA RVD ≥2.0 mm and:
• Localizing FFR/iFR ≤0.80/0.89 plus QCA DS ≥30%, or
• Localizing non-invasive ischemia in the vessel distribution plus QCA
DSA≥50%, or Non-localizing severe ischemia by ETT plus QCA DS≥60%,
or QCA DS ≥70%
ISCHEMIA: Impact of functional completeness of Revascularization
 ISCHEMIA: Impact of Anatomic Completeness of Revascularization

Take home message

• Evidence from non-RCT and RCT show the benefit of CR in STEMI and NSTE-ACS
(reduction in CVD/MI).

• Evidence from non-RCTs points to similar signals in patients with stable CAD but
RCTs are lacking.

• Given the totality of data, “optimal” revascularization in 2023 should aim for
complete revascularization when safely possible unless there are patient and
anatomic factors that preclude it.
 Does silent myocardial ischemia deserve revascularization?

• Silent ischemia worsens prognosis in patients with stable ischemic heart

disease (SIHD).
• Evidence from 2 small randomized controlled trials—one in SIHD,
Asymptomatic Cardiac Ischemia Pilot (ACIP) and one in post MI patients, Swiss
Interventional Study on Silent Ischemia Type II (SWISSI II)—suggests that
revascularization improves survival in patients with silent ischemia

For the ischemia

patients,compared
with MT,
revascularization was
only associated with
decreased incidence
of MACEs.

The relative benefit of revascularization vs MT as function of Ischemia.

Asymptomatic Cardiac Ischemia pilot study (ACIP)

 ISCHEMIA trial : Unanswered questions

• In patients with chronic coronary artery disease undergoing

revascularization, in particular PCI, can reduce the incidence of future
cardiovascular events and relieve angina, The two most widely quoted
trials are COURAGE and ISCHEMIA.

• In both trials revascularization did not reduce the incidence of

cardiovascular death or non-fatal events. In both, revascularization did
relieve angina, particularly in patients with severe pain.

• These data have led to a paradigm shift toward a more nuanced approach
to treating stable ischemic heart disease, with less need for
revascularization except in cases of particularly severe anatomic disease or
unremitting symptoms while on optimal medial therapy.
Results From the Clinical Outcomes Utilizing Revascularization and
Aggressive Drug Evaluation (COURAGE) Trial Nuclear Substudy
 ISCHEMIA trial
(Impact of Completeness of Revascularization on Clinical Outcomes in
Patients With Stable Ischemic Heart Disease Treated With an Invasive
Versus Conservative Strategy) Results

• Ischemia severity was not associated with increased risk after adjustment for CAD
severity. More severe CAD was associated with increased risk.

• Invasive management did not lower all-cause mortality at 4 years in any ischemia or
CAD subgroup.
 Presenter’s Approach

• In the ISCHEMIA trial (International Study of Comparative Health Effectiveness With

Medical and Invasive Approaches) of stable ischemic heart disease, severity of
coronary artery disease (CAD), but not ischemia severity, predicted 4-year mortality.

• CAD severity, but not ischemia severity, was independently predictive of 4-year
myocardial infarction risk.

• There was no evidence of a difference between treatment groups in 4-year rates of

mortality, myocardial infarction, or the trial primary or major secondary end point in
any ischemia subgroup.

• In the subgroup with the most severe CAD (n=659), there was no difference
between treatment groups in 4-year mortality rates, but the cardiovascular death or
myocardial infarction rate was lower among participants assigned to the invasive
strategy.
2023 ESC Guidelines for the management of CVD in patients with
Diabetes
Management of CV risk in individuals with diabetes: Case presentation

Recommendations for assessing CVD risk in patients with T2DM

 When and how to use SCORE2-Diabetes?

How did I manage this patient?

• Recommend weight loss and physical activity
• Change simvastatin 40 mg to atorvastatin 80 mg
• Home monitoring of blood pressure
• Echo & CCTA
Dyslipidemia in patients with diabetes
A patient with coronary artery disease and diabetes: Case presentation
On 04/07: The patient was discharged from the hospital, and ASA and Ticagrelor were
prescribed for one year along with Enalapril, Bisoprolol, Omeprazole, and Atorvastatin.
Metformin 500 mg x 2 (same as previously), added Empagliflozin 10 mg
In visit after 6 weeks:
• The patient is stable, does not have any symptoms, has resumed her job
• Up titration of ACEi and BB via CAD nurse
• Vitals: BP 128/75 mmHg, HR 68.BMI 32
• Lab: HBA1c 61 mmol (7.7%), normal liver enzymes
• More regular meals, reduced sugar intake
• Had to lose weight & increase her physical activity level
Coronary revascularization in diabetes: Guideline recommendations
 2023 ESC Guidelines on Cardiomyopathies
Diagnostic approach to cardiomyopathies and the patient pathway

Recommendation for laboratory tests in the diagnosis of cardiomyopathies

Clinical diagnostic workflow of cardiomyopathy
Key aspects in the evaluation and management of
cardiomyopathies
 Recommendation for echocardiographic evaluation in patients with
cardiomyopathy

Recommendations for Cardiac Magnetic Resonance indication in patients

with cardiomyopathy
Recommendations
for computed
tomography and
nuclear imaging

Recommendation
for
left ventricular
assist device
therapy in patients
with
cardiomyopathy
 Recommendations for
genetic counselling and testing in cardiomyopathies
 New concepts in Sudden Death Risk (SCD) stratification in cardiomyopathies

• SCD is a rare event in the short to medium-term

• With aging, the rate of SCD declines.
• Evolution towards an individualized gene-specific SCD prediction approach

• SCD risk stratification:

• Use of available multi-parametric risk models
• Periodic reassessment of SCD risk
• Individualized risk stratification
• Shared decision-making between the healthcare team and the patient
Recommendations for ICD in patients with cardiomyopathy
Advance in cardiomyopathy therapeutics: Phenotype-specific management

Non-dilated left ventricular cardiomyopathy phenotypes and their aetiological correlates

• The identification of an NDLVC phenotype should trigger a

multiparametric approach that leads to a specific aetiological
diagnosis, with implications for clinical treatment.
Oral anticoagulation in patients with AF
 Decision-making in patients eligible for both surgery and
percutaneous coronary intervention

• ACC/AATS/AHA/ASE/ASNC/SCAI/SCCT/STS 2017 appropriate use

criteria for coronary revascularization in patients with stable ischemic
heart disease gives a comparison of different approaches to Coronary
Revascularization in Patients With Stable Ischemic Heart Disease

Appropriate Rarely NOT

Appropriate Appropriate
 Lessons from all trials
Quote to keep in mind by an out-of-the-box thinker
“The absence of a difference does not mean that the difference is absent”
Subgroup analyses, even from large, carefully conducted RCTs, are generally
underpowered
 Take Home Points

PCI is
effective in
reducing
symptoms
Patients
The Optimal In patients and
failing
evaluation of medical with more improving
medical
patient with therapy is advanced quality of life
therapy and
suspected cornerstone disease, and should
with class 3/4
stable of CABG should be a major
symptoms
ischemia management be part of
should be
heart disease and should considered approach in
considered
begins with be the using the suitable
for
presence of frontline Heart team candidates,
revascularizat
symptoms approach approach particularly
-ion
those with
less
advanced
disease.
Antithrombotic therapy: Walking the tightrope between the risk of
ischemia vs. the risk of bleeding

Overview of important clinical trials

Antithrombotic strategies compared to Antithrombotic strategies compared to
short term NMA long term NMA

➢ Compared with aspirin and 12-month ➢ Compared with aspirin, P2Y12

clopidogrel, the greatest mortality monotherapy is associated with lower
reduction was found with ticagrelor MI risk (ticagrelor 90mg best-in-class)
90 mg monotherapy (best-in-class for without risk trade-off.
CV mortality) without bleeding risk ➢ Aspirin and rivaroxaban 2.5mg dual
trade-off followed by rivaroxaban, therapy was the most effective for
clopidogrel, and aspirin triple therapy stroke prevention, with an acceptable
with bleeding risk trade-off. bleeding risk trade-off, in comparison
➢ Dual therapy with aspirin and with aspirin.
prasugrel was associated with lower ➢ The use of aspirin monotherapy as
MI (best-in-class for MI) but higher routine long-term anti-thrombotic
bleeding risk treatment in patients with established
➢ Clopidogrel monotherapy was the CAD does not appear justifiable
only option associated with lower based on the CV and cerebrovascular
bleeding risk (best-in-class for ischemic risk, nor the bleeding risk
bleeding), followed by aspirin and
clopidogrel dual therapy for 3 months
 Post-revascularization noninvasive assessment for ischemia in
asymptomatic chronic coronary syndrome: If and when

• Functional testing has been widely used in clinical practice in chronic coronary artery
disease and in particular after coronary revascularization.
• In several observational studies, more than half of all patients who had undergone
PCI or CABG surgery had functional testing within 2 years after revascularization.

Strategies for follow-up & management after myocardial

revascularization
Key messages of the POST-PCI trial

• The observed number of primary outcome events was lower than expected in
both groups. This might be due to advances in PCI methods and improvements in
CV care over the past years
• In this trial involving high-risk patients who had undergone PCI, routine functional
testing, as compared with standard care, did not result in a lower risk of death, MI,
or hospitalization for UA at 2 years
Conclusion

Contemporary
comprehensive risk
In asymptomatic patients
scores need to be
after myocardial
developed and validated
revascularization,
for MACE in patients with
intensification of Routine functional testing
chronic CAD that would
contemporary guideline- is not recommended
include data from
directed management
noninvasive and/or
and therapy should be
invasive test results,
the first priority
along with clinical risk
factors
 Surprising :
FRAIL-AF - In frail patients with AF, switching to newer anticoagulants raises
bleeding risk

• The FRAIL-AF trial investigated whether switching VKA treatment to NOAC

treatment was superior in terms of major and/or clinically relevant non-
major bleeding complications in frail elderly patients with atrial fibrillation.

• Participants were randomised in a 1:1 ratio to switch from a VKA to a

NOAC or to continue a VKA. The choice of NOAC was left to the discretion
of the treating physician. The follow-up duration was 12 months.

• The mean age was 83 years and 38.8% were women.

• After 163 primary outcome events (101 in the switch arm, 62 in the
continue arm), the trial was stopped for futility on advice from the Data
Safety and Monitoring Board following a prespecified futility analysis.

• The HR for the primary outcome of major or clinically relevant non-major

bleeding was 1.69 (95% confidence interval [CI] 1.23 to 2.32) for switching
to a NOAC relative to continuing a VKA.

• At 1 year, there was a 69% increased risk for bleeding among patients
with frailty syndrome who switched to a NOAC compared with those
who remained on their vitamin K antagonist

• The HR for thromboembolic events was 1.26 (95% CI 0.60 to 2.61).

• The most important take-home message is that switching to NOAC
was associated with more bleeding yet no reduction in stroke in frail
patients with AF.

• The results were very surprising, since historically NOACs have been
shown to be safer in the general population.

• This is especially true for intracerebral bleeding, which is lower in NOACs,

and the elderly are at risk for it.