According to the World Health Organization, an estimated 17.9 million people died from CVDs in 2019, representing 32% of all global deaths.1 Of these deaths, 85% were due to myocardial infarction or stroke.1 A CV event is a highly traumatic experience for patients and their families.2 It takes a heavy emotional toll, brings widespread disability and significantly impedes quality of life.3,4

The need is clear: the healthcare community must do more to prevent devastating cardiovascular events in high and very high-risk patients that cause personal, societal and economic trauma!

Reducing risk in very high-risk ASCVD patients requires a HOLISTIC APPROACH and control of all modifiable risk factors, including elevated low-density lipoprotein cholesterol (LDL-C).5
Over 4 million deaths were attributed to elevated LDL-C in 2019.6,12 That’s eight deaths per minute, and many of those could be prevented.

According to the 2019 ESC/EAS Guidelines for the management of dyslipidaemia and the 2023 ESC Guidelines for the management of CVD in patients with diabetes, all ASCVD patients without exceptions are classified as very high-risk and, as such, have very strict LDL-C targets: &lt;1.4 mmol/L (&lt;55 mg/dL) AND ≥50% LDL-C reduction vs. baseline.5,11

DYSLIPIDEMIA

CARDIOLOGY

ACCESS ESC 2019 DYSLIPIDAEMIA GUIDELINES

Yet, less than one third of ASCVD patients had their LDL-C levels within target range, according to the multinational observational SANTORINI study.7 The reasons behind that are numerous, with one of them certainly being underuse of lipid-lowering treatment (LLT), most notably – combined LLT in general and PCSK9 inhibitors in particular.7

ASSESS CV RISK (KEY RISK CALCULATORS FROM THE ESC)

T2DM: from age 50 / LDL-C: 2.9 mmol/L (112 mg/dL) / BP: 130/80 mmHg / HbA1c: 7.0% / TGs: 165 mg/dL / BMI: 29 kg/m2

Complains of transient chest pain and shortness of breath while climbing stairs.

Current medications: Rosuvastatin 40 mg / ezetimibe 10 mg / telmisartan 80 mg / insulin glargine 300 units/mL / metformin 2000 mg / acetylsalicylic acid 100 mg

Patients with combined T2DM and CAD have a 28% higher risk of CV events* compared with those without T2DM8

*cardiovascular death, myocardial infarction or stroke

Smoker / LDL-C:&nbsp;2.9 mmol/L (112 mg/dL) /&nbsp;BP:&nbsp;140/80 mmHg /&nbsp;HbA1c:&nbsp;5.0% /&nbsp;TGs:&nbsp;140 mg/dL /&nbsp;BMI:&nbsp;27 kg/m2

Complained of progressive persistent anginal symptoms, 12 months ago - CTA was performed, 55% obstruction of left anterior descending artery was found, subsequently - severe stenosis was confirmed during a cardiac catheterization, and elective PCI was performed.

Current medications:&nbsp;Rosuvastatin 40 mg / ezetimibe 10 mg / acetysalicylic acid 100 mg / clopidogrel 75 mg

Coronary artery disease (ischemic heart disease) is the leading cause of mortality worldwide, accounting for 16% of all deaths in 20199

Long-term smoker / LDL-C:&nbsp;2.5 mmol/L (98 mg/dL) /&nbsp;BP:&nbsp;130/80 mmHg /&nbsp;T2DM:&nbsp;since age 48 /&nbsp;HbA1c:&nbsp;7.5% /&nbsp;TGs:&nbsp;167 mg/dL /&nbsp;BMI:&nbsp;28 kg/m2

Complains of moderate pain in calves on exertion, which is relieved by rest

Current medications: 
Atorvastatin 80 mg / ezetimibe 10 mg / insulin glargine 300 units/mL / metformin 2000 mg / acetysalicylic acid 100 mg / rivaroxaban 5 mg

Patients with combined T2DM and PAD have a nearly 8x higher risk of CV events compared to those without either condition10

Mission of the healthcare community: to help ASCVD patients avoid the trauma of a 1st&nbsp;event through effective LDL-C control and CV risk reduction

Abbreviations

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Cardiovascular diseases (CVDs) are the leading cause of death globally

<h4>PAD is a common manifestation of atherosclerosis and encompasses all vascular sites, including:1</h4>
<ul>
 <li>Lower extremity arteries</li>
 <li>Carotid artery</li>
 <li>Vertebral artery</li>
 <li>Upper extremity arteries</li>
 <li>Mesenteric artery</li>
 <li>Renal artery</li>
 <li>Aorta</li>
</ul>
New 2024 ESC&nbsp;guidelines for the management of peripheral arterial and aortic diseases (PAAD) show:2

Increased risk of CV events in patients with PAD compared with those without PAD2

Patients with both PAD and T2DM are at a ‘very high’ risk of cardiovascular events2

In a prospective cohort study in Europe, patients with PAD and T2DM had...

Higher risk of CV events* compared to those with neither PAD nor T2DM3

<h3>Screening for lower-extremity arterial disease (LEAD) is recommended on a regular basis, with clinical assessment and/or ankle-brachial index (ABI) measurement.2,4</h3>

Adapted from Marx N et al. 2023 and Mazzolai L et al. 2024.2,4
a&nbsp;TBI when ABI &gt;1.4. b&nbsp;Further information regarding wound management and exercise training can be found in the 2017 ESC guidelines on the diagnosis and treatment of peripheral arterial diseases. c&nbsp;MRA or CTA when duplex sonography is not sufficient for planning revascularisation.
Patients with PAD, with or without T2DM, are at very high CV risk.1 
 These patients require a holistic multifactorial approach to prevention and management.

<h2>Recommendations for pharmacological LDL-C lowering1</h2>

It is recommended that a high-intensity statin is prescribed up to the highest tolerated dose to reach the goals set for the specific level of risk.

If the goals are not achieved with the maximum tolerated dose of a statin, combination with ezetimibe is recommended.

For secondary prevention, patients at very high risk not achieving their goal on a maximum tolerated dose of a statin and ezetimibe, combination with a PCSK9i is recommended.

Adapted from Mach F et al. 2019 and Mazzolai L et al. 2024.1,2

You should aim to assess your patients response to therapy&nbsp;6–8 weeks from initiation.1

*When compared to those with neither PAD nor T2DM, HRs adjusted for age, gender, BMI, smoking, hypertension, LDL-C, and HDL-C were 1.26 (95% Cl 0.84, 1.91); P=0.267, HR 4.17 (95% Cl 2.97, 5.85); P&lt;0.001, and HR 7.82 (95% Cl 5.49, 11.12); P&lt;0.001 for those with T2DM only, for those with PAD only and for those with the combination of PAD plus T2DM, respectively.3
†Provided the antihypertensive treatment is well tolerated.
‡The term ‘baseline’ refers to the LDL-C level in a person not taking any LDL-C-lowering medication. In people who are taking LDL-C-lowering medication(s), the projected baseline (untreated) LDL-C levels should be estimated, based on the average LDL-C-lowering efficacy of the given medication or combination of medications.1
¥Prevent the first major CV event for your ASCVD patients without prior major CV event.
In a prospective cohort study, cardiovascular events were prospectively recorded over a mean follow-up period of 7.2 ± 2.6 years in 1,049 subjects, encompassing 4 groups: 558 with neither PAD nor diabetes, 153 with T2DM but without PAD, 192 with PAD but without T2DM, and 146 with the combination of PAD and T2DM. 4 PAD patients were defined as those with an ankle brachial index &lt;0.9 or with previous revascularisation of peripheral arteries who underwent routine duplex sonography and in whom PAD was sonographically verified.3
ABI&nbsp;=&nbsp;ankle–brachial index;&nbsp;ASCVD&nbsp;= atherosclerotic cardiovascular disease;&nbsp;BMI&nbsp;= body mass index;&nbsp;CI&nbsp;= confidence interval;&nbsp;CTA&nbsp;= computed tomography angiography;&nbsp;CV&nbsp;= cardiovascular;&nbsp;EAS&nbsp;= European Atherosclerosis Society;&nbsp;ESC&nbsp;= European Society of Cardiology;&nbsp;HbA1c&nbsp;= glycated haemoglobin;&nbsp;HDL-C&nbsp;= high-density lipoprotein cholesterol;&nbsp;HR&nbsp;= hazard ratio;&nbsp;LEAD&nbsp;= lower- extremity artery disease;&nbsp;LDL-C&nbsp;= low-density lipoprotein cholesterol;&nbsp;MRA&nbsp;= magnetic resonance angiography;&nbsp;PAAD&nbsp;= peripheral arterial and aortic disease;&nbsp;PAD&nbsp;= peripheral artery disease;&nbsp;PCSK9i&nbsp;= proprotein convertase subtilisin/kexin type 9 inhibitor;&nbsp;SBP&nbsp;= systolic blood pressure;&nbsp;TBI&nbsp;= toe-brachial index;&nbsp;TcPO2&nbsp;= transcutaneous oxygen pressure;&nbsp;T2DM&nbsp;= type 2 diabetes mellitus;&nbsp;WlfI&nbsp;= Wound, Ischaemia, foot Infection.

Approach for patients with peripheral artery disease (PAD) + T2DM: focus on LDL-C control


<h4>CAD is defined as the pathological process characterised by atherosclerotic plaque accumulation in the epicardial arteries. It covers different conditions, including:1</h4>
<ul>
 <li>Patients with stable angina 
 &nbsp;</li>
 <li>Patients after elective coronary revascularisation procedures, such as percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) 
 &nbsp;</li>
 <li>Patients with significant coronary disease without prior revascularisation as evidenced by either: 
 &nbsp; 
 <ul>
 <li>≥70% stenosis of at least one coronary artery</li>
 <li>≥50% stenosis of the left main coronary artery</li>
 <li>Three-vessel obstructive (&gt;70%) disease</li>
 </ul></li>
</ul>

Ischaemic heart disease accounts for&nbsp;16% of all deaths worldwide.2*

The presence of T2DM alongside CAD was shown to increase the risk of a CV event by 28% vs those without diabetes in the CLARIFY study.3
Diabetes is a well-established risk factor for ischaemic heart disease, and CAD accounts for 40–80% of deaths in patients with T2DM.1

New 2024 ESC guidelines for the management of chronic coronary syndromes have been published recently and can be <a href="https://www.escardio.org/Guidelines/Clinical-Practice-Guidelines/Dyslipidaemias-Management-of" target="_blank">downloaded here</a>

<h3>These guidelines present the following steps for management of chronic coronary syndrome (CCS), including CAD4</h3>

a&nbsp;High–risk CAD: obstructive CAD at high risk of adverse events by CCTA: ≥50% stenosis of the left main stem; three–vessel disease with severe stenoses (≥70% diameter stenosis); single- or two– vessel disease including the proximal LAD with severe stenoses. Consider functional imaging or invasive investigation.
Patients with CAD, with or without T2DM, are at&nbsp;very high CV risk.5&nbsp;These patients require a&nbsp;holistic multifactorial approach&nbsp;to prevention and management.

<h2>Recommendations for pharmacological LDL-C lowering5</h2>

Adapted from Vrints et al. 2024 and Mach et al. 20204,5

You should aim to assess your patients response to therapy&nbsp;6–8 weeks from initiation.5

*The term stable ischaemic heart disease often is used synonymously with chronic CAD and encompasses a variety of conditions that result in a mismatch between myocardial oxygen supply and demand.6
†Provided the antihypertensive treatment is well tolerated.
‡The term ‘baseline’ refers to the LDL-C level in a person not taking any LDL-C-lowering medication. In people who are taking LDL-C-lowering medication(s), the projected baseline (untreated) LDL-C levels should be estimated, based on the average LDL-C-lowering efficacy of the given medication or combination of medications.5
¥Prevent the first major CV event for your CAD and T2DM patients without prior major CV event.
CLARIFY is an observational registry of patients with chronic coronary syndromes, taking place across 45 countries from 2009 to 2010; follow-up was 5 years. Chronic coronary syndromes were defined by ≥1 of the following criteria: prior myocardial infarction, evidence of coronary stenosis &gt;50%, proven symptomatic myocardial ischaemia, or prior revascularisation procedure.3
ANOCA&nbsp;= angina with non-obstructive coronary arteries;&nbsp;CABG&nbsp;= coronary artery bypass graft;&nbsp;CAD&nbsp;= coronary artery disease;&nbsp;CCS&nbsp;= chronic coronary syndromes;&nbsp;CCTA&nbsp;= coronary computed tomography angiography;&nbsp;CMR&nbsp;= cardiac magnetic resonance;&nbsp;CV&nbsp;= cardiovascular;&nbsp;EAS&nbsp;= European Atherosclerosis Society;&nbsp;ECHO&nbsp;= echocardiography;&nbsp;ESC&nbsp;= European Society of Cardiology;&nbsp;FFR&nbsp;= fractional flow reserve;&nbsp;HbA1c&nbsp;= glycated haemoglobin;&nbsp;ICFT&nbsp;= invasive coronary functional testing;&nbsp;iFR&nbsp;= instantaneous wave-free ratio;&nbsp;INOCA&nbsp;= ischaemia with non-obstructed coronary arteries;&nbsp;LAD&nbsp;= left anterior descending artery;&nbsp;LDL-C&nbsp;= low-density lipoprotein cholesterol;&nbsp;LV&nbsp;= left ventricular;&nbsp;PCI&nbsp;= percutaneous coronary intervention;&nbsp;PCSK9i&nbsp;= proprotein convertase subtilisin/kexin type 9 inhibitor;&nbsp;PET&nbsp;= positron emission tomography;&nbsp;SBP&nbsp;= systolic blood pressure;&nbsp;SPECT&nbsp;= single-photon emission computed tomography;&nbsp;T2DM&nbsp;= type 2 diabetes mellitus.

Approach for patients with coronary artery disease (CAD): focus on LDL-C control

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Cardiovascular diseases (CVDs) are the leading cause of death globally

Approach for patients with peripheral artery disease (PAD) + T2DM: focus on LDL-C control

Approach for patients with coronary artery disease (CAD): focus on LDL-C control