2023 ESC Guidelines for the management of CVD in patients

with diabetes

Glucose-lowering treatment for patients with type 2 diabetes to

reduce cardiovascular risk based on the presence of
atherosclerotic cardiovascular disease/severe target-organ
damage and 10-year cardiovascular disease risk estimation via
SCORE2-Diabetes.
2023 ESC Guidelines for the management of CVD in patients
with diabetes

Glucose-lowering treatment for patients with type 2 diabetes

and atherosclerotic cardiovascular disease to reduce
cardiovascular risk.
2023 ESC Guidelines for the management of CVD in patients
with diabetes
Recommendations for the management of dyslipidemia in
patients with diabetes
2023 ESC Guidelines for the management of CVD in patients
with diabetes

Recommendations for heart failure treatments in patients

with heart failure with reduced ejection fraction and diabetes
2023 ESC Guidelines for the management of CVD in patients
with diabetes

Recommendations for heart failure treatments in patients

with diabetes and left ventricular ejection fraction over 40%
2023 ESC Guidelines for the management of CVD in patients
with diabetes

Glucose-lowering treatment of patients with heart failure and

type 2 diabetes.
2023 ESC Guidelines for the management of CVD in patients
with diabetes

Pharmacological management to reduce cardiovascular or

kidney failure risk in patients with type 2 diabetes and chronic
kidney disease
 2023 ESC Guidelines for the management of ACS
Developed by the task force on the management of acute coronary
syndromes of the European Society of Cardiology (ESC)

• Following PCI, a default DAPT regimen consisting of a potent

P2Y12 receptor inhibitor (prasugrel or ticagrelor) and aspirin is generally
recommended for 12 months, irrespective of the stent type.

Recommended default antithrombotic therapy regimens in acute coronary syndrome

patients without an indication for oral anticoagulation.
 2023 ESC Guidelines for the management of ACS
Developed by the task force on the management of acute coronary
syndromes of the European Society of Cardiology (ESC)

• DAT (Dual Antithrombotic therapy) with a NOAC (Non-vitamin K antagonist oral

anticoagulant) at the recommended dose for stroke prevention and SAPT (single
antiplatelet therapy) preferably clopidogrel, which was used in >90% of patients
in the major RCTs is recommended as the default strategy for up to 12 months
after up to 1 week of TAT (triple antithrombotic therapy) with NOAC and DAPT
consisting of aspirin and clopidogrel.

Antithrombotic regimens in patients with acute coronary syndrome and an indication for
oral anticoagulation
 2023 ESC Guidelines for the management of ACS
Developed by the task force on the management of acute coronary
syndromes of the European Society of Cardiology (ESC)
 2023 ESC Guidelines for the management of ACS
Developed by the task force on the management of acute coronary
syndromes of the European Society of Cardiology (ESC)

• Alternatives to the default strategy of 12 months DAPT in patients with ACS

include shortening the DAPT duration to 1 or 3–6 months (depending on the
balance of bleeding and ischaemic risks) and de-escalating DAPT from
prasugrel/ticagrelor-based DAPT to clopidogrel-based DAPT.
 2023 ESC Guidelines for the management of ACS
Developed by the task force on the management of acute coronary
syndromes of the European Society of Cardiology (ESC)

Technical aspects of invasive strategies

• Radial access is recommended as the preferred approach in ACS patients
undergoing invasive assessment with or without PCI.
 2023 ESC Guidelines for the management of ACS
Developed by the task force on the management of acute coronary
syndromes of the European Society of Cardiology (ESC)
 2023 Focused Update of the 2021 ESC Guidelines for the
diagnosis and treatment of heart failure

Recommendation for the treatment of patients with symptomatic

heart failure with mildly reduced ejection fraction

Management of patients with heart failure with mildly

reduced ejection fraction
2023 Focused Update of the 2021 ESC Guidelines for the
diagnosis and treatment of heart failure

Recommendation for the treatment of patients with

symptomatic heart failure with preserved ejection fraction

Management of patients with heart failure with preserved

ejection fraction
 2023 Focused Update of the 2021 ESC Guidelines for the
diagnosis and treatment of heart failure

Recommendations for the prevention of heart failure in patients

with type 2 diabetes mellitus and chronic kidney disease

Recommendations for the management of iron

deficiency in patients with heart failure
 How to prevent Stroke and Stroke recurrence in heart failure ?
1. Specific recommendations for prevention strategies often depend on the ischemic
stroke/transient ischemic attack subtype.

2. Management of vascular risk factors remains extremely important in secondary stroke

prevention including diabetes, smoking cessation, lipids and especially hypertension.
Intensive medical management, often performed by multidisciplinary teams, is
usually best with goals of therapy tailored to the individual patient.

3. Lifestyle factors, including healthy diet and physical activity, are important for
preventing a second stroke. Low-salt and Mediterranean diets are recommended for
Stroke risk reduction.

4. Changing patient behaviours such as diet, exercise and medication compliance

requires more than just simple advice or a brochure from their physician.

5. Antithrombotic therapy, including antiplatelet or anticoagulant agents, is

recommended for nearly all patients without contraindications. Dual antiplatelet
therapy is not recommended long-term and short-term dual antiplatelet therapy is
recommended only in very specific patients.

6. Atrial fibrillation remains a common and high-risk condition for second ischemic
stroke. Anticoagulation is usually recommended if the patient has no
contraindications. Heart rhythm monitoring for occult atrial fibrillation is usually
recommended if no other cause of stroke is discovered.

7. Extracranial carotid artery disease is an important and treatable cause of stroke.

Patients with severe stenosis ipsilateral to a nondisabling stroke or transient ischemic
attack who are candidates for intervention should have the stenosis fixed, likely
relatively early after their ischemic stroke

8. Patients with severe intracranial stenosis in the vascular territory of ischemic stroke or
transient ischemic attack should not receive angioplasty and stenting as a first-line
therapy for preventing recurrence. Aggressive medical management of risk factors
and short-term dual antiplatelet therapy are preferred.

9. It is now considered reasonable to percutaneously close patent foramen ovale in

patients who meet each of the following criteria: age 18–60 years, non-lacunar stroke,
no other identified cause and high risk patent foramen ovale features.

10. Patients with embolic stroke of uncertain source should not be treated empirically
with anticoagulants or ticagrelor because it was found to be of no benefit.
 The ABC of integrated Stroke management
• The management of patients with Stroke is often multidisciplinary, involving
various specialities and healthcare professionals

• Putting Patient at the central, requiring a coordinated and uniform approach to

the priorities of post-stroke management, which can be consistently implemented
by different multidisciplinary healthcare professionals, as part of the patient
‘journey’ or ‘patient pathway,’ supported by appropriate education and tele-
medicine approaches.

• Given the need to address the multidisciplinary approach to holistic or integrated

care of patients with heart disease and stroke, the European Society of Cardiology
Council on Stroke convened a Task Force, with the remit to propose a consensus
on Integrated care management for optimizing the management of stroke and
associated heart disease.

• A post-stroke ABC pathway is proposed as a more holistic approach to integrated

stroke care would include three pillars of management :
A: Appropriate Antithrombotic therapy
Appropriate thromboprophylaxis should
be targeted to the underlying
comorbidity

B. Better functional and psychological

status
Requires care packages and
management pathways to be established
and implemented, including tailored
rehabilitation and personalized
appropriately to the patient’s needs

C. Cardiovascular risk factors and

Comorbidity optimization
Integrated care for optimizing the Need to be considered and addressed in
management of stroke and associated heart a holistic manner, with treatment targets
disease: the post-stroke ABC pathway. as per CVD prevention guidelines.

Across the stroke continuum, there is a need for multi-disciplinary collaboration and
coordination of care, including the complex treatment of cardiovascular conditions
with the overarching goal to improve recovery, prevent recurrence and enhance
survival and quality of life for the patient with stroke.
 Gliflozins improve short-term decongestion

Combining SGLT2 inhibitors (SGLT2i) with loop diuretics

• SGLT2 is located in the S1 segment of the nephron's proximal convoluted

tubule.
• It reabsorbs 90% of glucose from the glomerular filtrate. Glucose and sodium
reabsorption are interconnected, powered by the Na/K-ATPase.
• PCT reabsorbs a majority of filtered sodium, making SGLT2 inhibition significant
with loop diuretics.
• Combined use of loop diuretics and SGLT2 inhibitors requires more research.

Use of Diuretics in DAPA-HF

In DAPA-HF, 84% were on a

diuretic

Loop diuretic dose remained

unchanged for most patients up to
18 months.

This was consistent in both

treatment and placebo groups

DAPA-HF and mechanistic study interpretations

• Dapagliflozin recipients often reduced loop diuretic doses over time.

• They were less prone to increase these doses compared to the placebo
group.
• Drug discontinuation was low (3-5%).
• No significant difference in discontinuation between dapagliflozin and
placebo across varying diuretic doses.
• Combined use of SGLT2i and loop diuretics appears well-tolerated.
EMPULSE: Efficacy and safety of SGLT2 inhibition in hospitalized patients with HF

Decongestion and NT-proBNP changes

• EMPA-initiated post-stabilization significantly reduced NT-proBNP levels.

• This reduction was observed by day 15 and maintained till day 90.
• EMPA's effect on NT-proBNP indicates effective decongestion.
• Effective decongestion is linked with reduced neurohormonal activation
and hemodynamic stress.
• A decrease in NP levels post-discharge predicts a lower risk of HF
worsening
Clinical consequences of early Decongestion

• Short-term diuresis from drugs like SGLT2 inhibitors doesn't improve post-
hospitalization heart failure outcomes, even with prolonged use.
• SGLT2 inhibitors' benefits on heart failure after 90 days in the EMPULSE trial
are due to empagliflozin's cardioprotective effects, not its natriuretic effects.
• These benefits align with results from large-scale chronic heart failure trials
with SGLT2 inhibitors initiated within 30 days.
• Similar early benefits are observed with neurohormonal inhibitors that don't
increase urinary sodium excretion.
• Studies show SGLT2 inhibitors' cardioprotective effects in isolated
cardiomyocytes and are seen even without renal tubular SGLT2.

Take home message for the AHF patients

• Early decongestion is related to earlier improvements in QoL. Dyspnea and

oedema are unpleasant symptoms to live with.

• No detrimental kidney effects when combining IV loop diuretics and SGLT2i &
earlier clinical benefits associated with early use of SGLT2i may be seen (as
compared to starting those agents later).

• There is still relatively limited clinical trial data regarding the safety and
efficacy of SGLT2i in AHF, namely for patients with diuretic resistance and/or
advanced CKD (largest RCT had 530 patients, mean eGFR 50-55, 10% or less
with eGFR <30mL/min/1.73m2) .
What are the unmet needs for lipid-lowering in the population?

Statin discontinuation is a major challenge in lipid lowering therapy

Studies have shown that upto 50% of patients discontinued
their statin within < 2 years.

96.6% - Adherence in ODYSSEY APPRISE study

The better adherence, the more patients on the LDL-C target
 Steps to consider in case of Statin Intolerance
Step 1

Carefully evaluate CVD risk

Start optimal statin/lipid lowering therapy

Always use the “lower the better for longer” and the “earlier on LDL-C the better
strategies”

Always consider high intensity statin therapy or upfront combination therapy if

indicated

If SAMS occurs: Confirm with approved definition, Evaluate risk factors; optimize
management of the condition that may occur; Exclude nocebo/placebo effect.

Always follow the existing recommendations to treat SI/SAMS patients

SI – Statin Intolerance; SAMS - Statin-Associated Muscle Symptoms

Step 2
1. Educate your patient (use PLIP
algorithm) 2. (Re)check symptoms
and introduce optimal lifestyle
changes (use MEDS algorithm) 3.
Carefully evaluate CVD risk and set
the LDL-C target.
1. Use SLAP algorithm 2. Always
consider FDC therapy to improve
adherence
3. Consider BA (40-50% reduction)
and FDC of BA and EZE (75%
reduction with low to moderate
statins)

Use immediate therapy with

ezetimibe (up to 20% reduction),
bempedoic acid (20- 25%), and
preferably upfront combination
therapy (FDC) of ezetimibe and
bempedoic acid (40%)
Use innovative therapies, alone or
in the combination
(60-80% LDL-C reduction)

SLAP - Switch statins, Lower dose, Alternate day dosing, Polypharmacy

 New Therapies to lower LDL-C: How to choose?

Interventions to reduce LDL-C

Lifestyle

Statin+/-Ezetimibe

Not at goal/intolerant/non-adherent

Bempedoic acid*, PCSK9 MoAb* inhibitors,

Inclisiran, Obicetrapib, Evinacumab
*Therapies shown to decrease CV events

Bempedoic acid (BA) - Inhibits ATP- citrate lyase upstream of HMG-CoA in the
cholesterol biosynthetic pathway. Prodrug, the isozyme converting BA into an active
form is not present in skeletal muscle. Activates AMP-activated protein kinase.
PCSK9 inhibitors MoAbs- Both FOURIER and ODYSSEY demonstrated positive
cardiovascular outcomes. FOURIER suggests Evolocumab benefits patients with
>2MIs, multivessel disease, PAD, recent recurrent MI (<2yr ago), and high Lp(a).
ODYSSEY indicates Alirocumab's advantage for patients with LDL over 100, high
Lp(a), and multiple vascular CABG

Inclisiran - A small interfering RNA that binds to PCSK9 m-RNA in hepatocytes,

blocking PCSK9’s translation and production.
The addition of GaINAc increases liver-specific uptake. Twice yearly dosing ORION
1-12 studies exploring efficacy and safety

Inclisiran and CV events

Evinacumab:
• In the phase 3 EIPSE study, Evinacumab, targeting ANGPTL3, showed significant
lipid reductions: 47% in LDL-C, 40% in apoB, and 55% in triglycerides among 65
participants.
• Administered at 15g/kg every four weeks, no major safety concerns arose.

Obiceptrapib

• In dyslipidemia patients on high-intensity statins, the combination of

Obicetrapib and 10 mg ezetimibe resulted in a 63% reduction in LDL-C.
Are triglycerides and triglyceride-rich lipoproteins still relevant?

Remnant cholesterol are

Strongly Not always Not 'much

associated assocaited more'
with CV risk with CV atherogenic
increase benefit than LDL-C
(Observation (Prominant (Prominenet
al data) study study)

Triglyceride and remnant cholesterol:

• Very important to estimate absolute CV risk in patients

Triglyceride-rich particle number and /or apoB:

• More reliable as surrogate in intervention studies targeting CV

benefit
 Why measure Lp(a) and what to do about it?

Consensus panel recommendations for managing high Lp(a) concentrations

• In the absence of specific Lp(a) lowering therapies, early ‘traditional’ risk
factor management is recommended for individuals with elevated Lp(a),
taking into account their absolute CV risk and Lp(a) level.
• Lipoprotein apheresis can be considered in patients with very high Lp(a)
and progressive CVD despite optimal management of risk factors.
• Specific Lp(a)- lowering therapies are in clinical trial stages.