<h2>Key Takeaway</h2>
RWE study based on this large, representative, and well-characterised US population cohort that was followed after discharge from ACS hospitalization showed that:
The 5-year event rate for the&nbsp;primary composite endpoint*&nbsp;was&nbsp;33.4%
<ul>
 <li>Highest in subgroups such as&nbsp;MI without revascularization and Thrombolysis In Myocardial Infarction Risk Score for Secondary Prevention (TRS 2oP) ≥4</li>
</ul>
Patients with ACS remain at&nbsp;very high risk&nbsp;of experiencing&nbsp;recurrent CV events,&nbsp;particularly&nbsp;early after discharge
<ul>
 <li>Risk of experiencing the primary composite endpoint was&nbsp;≈6-fold higher immediately after discharge&nbsp;vs ≥1 year after hospital discharge</li>
</ul>
These findings support the potential application of the TRS 2oP for informed decision-making (to multiple stakeholders including payers, regulatory authorities, clinicians and clinical guidelines committees) in clinical management of ACS, identification of patients at highest risk, and development of future guidelines.

<h2>Why This Matters</h2>
Guidelines identified that&nbsp;patients with ACS remain at higher risk&nbsp;for future adverse outcomes.
Evidence from&nbsp;contemporary, representative ACS populations in a clinical practice setting is needed&nbsp;for identifying subgroups and strategies that improve patient outcomes.
This study evaluated a large, representative, well-characterized cohort of patients hospitalized with ACS to better understand recurrent risk and risk predictors in a US clinical practice population.

<h2>Study Design</h2>
This study cohort included patients (N = 594,032) with evidence of an ACS hospitalization (index ACS) from the Optum Research Database between January 1, 2005, and December 30, 2018.
Additional inclusion criteria
<ul>
 <li>Age ≥20 years</li>
 <li>Availability of 1-year baseline data before the index date</li>
 <li>Discharge codes indicative of alive status</li>
</ul>
Exclusion criteria
<ul>
 <li>Patients with a history of heart transplantation</li>
</ul>
Subgroups
<ul>
 <li>Based on index ACS event (MI/UA), revascularization status, and the TRS 2oP</li>
</ul>
Endpoints assessed
<ul>
 <li>Primary composite endpoint:&nbsp;First occurrence of CV death, nonfatal MI, or nonfatal ischemic stroke</li>
 <li>Secondary endpoints:&nbsp;First occurrence of CV death, nonfatal MI, nonfatal ischemic stroke, nonfatal UA hospitalization, and nonfatal elective coronary revascularization, separately and as a composite</li>
</ul>

<h2>Key Results</h2>
Overall,&nbsp;239,234&nbsp;patients were included and were followed up for a median of 1.2 (IQR, 0.4–2.8) years.
<table border="1" cellpadding="10" cellspacing="1">
 <tbody>
 <tr>
 <td style="background-color: rgb(244, 242, 246); width: 25%;">
 Patient-characteristics</td>
 <td>
 •&nbsp;Mean age = 69.2 years •&nbsp;Men =&nbsp;57.2%&nbsp; •&nbsp;As per the 2018 ACC/AHA guidelines,&nbsp;≈97% of the cohort was classified as very high risk</td>
 </tr>
 </tbody>
</table>

<table border="1" cellpadding="1" cellspacing="1" style="width:100%;">
 <tbody>
 <tr>
 <td style="background-color: rgb(244, 242, 246);">
 5-year rates for the primary and secondary endpoints</td>
 </tr>
 </tbody>
</table>

<table border="1" cellpadding="1" cellspacing="1" style="width:100%;">
 <tbody>
 <tr>
 <td style="background-color: rgb(244, 242, 246);">
 Highest rate of the primary endpoint in subgroups</td>
 </tr>
 </tbody>
</table>

<table border="1" cellpadding="10" cellspacing="1" style="width:100%;">
 <tbody>
 <tr>
 <td colspan="2" style="background-color: rgb(244, 242, 246);">
 Risk for primary endpoint 
 (First occurrence of CV death, nonfatal MI, or nonfatal ischemic stroke)</td>
 </tr>
 </tbody>
</table>

a. The instantaneous risk for the primary endpoint was (40.9%) immediately after discharge 
 b. It gradually to ≈6.7% at 1 year of follow-up 
 c. Risk remained gradually after 1 year (≈6.4%)

<h2>Risk Factors Most Strongly Associated† With the Primary Endpoint</h2>

Age ≥65 years

Heart failure

Renal disease stages IV–V

History of Ischemic stroke

An index MI without revascularization

ACS hospitalization in last 12 months

<h2>Limitations</h2>
<ul>
 <li>This analysis might not be representative of the noninsured population, those covered under a public insurance program other than Medicare Advantage, or international populations.</li>
 <li>Claims database captured medications that received only under health plan.</li>
 <li>Clinical trials typically classify patients into ST vs non-ST-segment-elevation MI by electrocardiographic review, which could not be reliably done using claims data.</li>
 <li>Several biomarkers that have shown to offer useful prognostication on top of clinical risk predictors (e.g., TRS 2oP) were not typically collected in a manner that enables their incorporation in this analysis.</li>
 <li>During the identification period (2005–2018), the US changed MI definitions based on biomarkers, which likely affected the classification of MI vs UA in clinical practice over this period.</li>
 <li>Randomized clinical trials used for comparing this study were global trials, whereas this study population represents only patients in the US.</li>
</ul>
*Nonfatal MI, nonfatal ischemic stroke, or cardiovascular death †Hazard ratio, &gt;1.5; P &lt;0.001

Abbreviations

Reference

Event rates and Risk Factors for Recurrent CV Events

DYSLIPIDEMIA

CARDIOLOGY

Lp(a) in clinical practice - Risk estimation and how to reduce its associated risk: A European Atherosclerotic Society consensus statement
Kronenberg F. Oral presentation. Presented at 43rd European Society of Cardiology (ESC) 2022. Kronenberg F, et al. Eur Heart J. 2022.

<h2>Key Takeaway</h2>
In this session, Prof. F. Kronenberg presented the following&nbsp;important highlights&nbsp;from the&nbsp;EAS consensus statement&nbsp;on Lp(a):
<ul>
 <li>A&nbsp;continuous association&nbsp;was found between&nbsp;Lp(a)&nbsp;and&nbsp;major CVD*</li>
 <li>Lp(a) concentration should&nbsp;always be interpreted&nbsp;in the&nbsp;context&nbsp;of: 
 <ul>
 <li>Other risk factors</li>
 <li>Absolute global CV risk</li>
 </ul></li>
 <li>Lp(a) is&nbsp;not considered&nbsp;a risk factor for&nbsp;venous thrombosis,&nbsp;but is a&nbsp;risk factor&nbsp;for&nbsp;ASCVD, AVS, and T2DM&nbsp;(possibly)</li>
 <li>Lp(a) should be&nbsp;measured at least once in adults to identify&nbsp;those with&nbsp;high CV risk</li>
 <li>If Lp(a)&nbsp;concentration is high, consider intensified risk factor management&nbsp;as early as possible by: 
 <ul>
 <li>Lifestyle modifications</li>
 <li>Medications</li>
 </ul></li>
 <li>Specific&nbsp;Lp(a)-lowering therapies&nbsp;are currently in&nbsp;phase 2/3 trials</li>
</ul>

<h2>Why This Matters</h2>
<ul>
 <li>Since the 2010 consensus paper, considerable new evidence from epidemiological and genetic studies on Lp(a) (on causality of CVD) and new findings on outcomes (e.g., AVS and DM) became available.</li>
 <li>Therefore, there was a need for a new consensus statement and for novel recommendations to incorporate Lp(a) in clinical practice.</li>
</ul>

<h2>Key Highlights</h2>
Consensus panel recommendations
<table align="center" border="1" cellpadding="10" cellspacing="1" style="width:100%;">
 <tbody>
 <tr>
 <td colspan="1" rowspan="3" style="background-color: rgb(244, 242, 246); width: 25%;">Lp(a) testing</td>
 <td>To identify individuals at high risk for CVD, Lp(a) should be&nbsp;measured at least once in all adults</td>
 </tr>
 <tr>
 <td>Screening youth with a&nbsp;family history&nbsp;of high Lp(a) or premature ASCVD or a history of stroke without other identifiable risk factors is recommended</td>
 </tr>
 <tr>
 <td>Family&nbsp;cascade screening&nbsp;is recommended for individuals with high Lp(a) with a family history of (very) high Lp(a) or ASCVD or in the settings of FH</td>
 </tr>
 <tr>
 <td colspan="1" rowspan="3" style="background-color: rgb(244, 242, 246); width: 25%;">Lp(a) measurement</td>
 <td>Laboratories should use an Lp(a) assay insensitive to apo(a) isoform and traceable to official reference materials</td>
 </tr>
 <tr>
 <td>
 If available, Lp(a) should be measured in&nbsp;molar units
 If not available, the units that were used for calibrating the assay should be used for reporting</td>
 </tr>
 <tr>
 <td>
 Clinical guidelines should consider using&nbsp;risk thresholds with ‘gray’ zones&nbsp;rather than absolute values to determine risk of CHD:
 <ul>
 <li>Rule-out zone: Very low Lp(a) concentration (&lt;30 mg/dL) and low risk</li>
 <li>Rule-in zone: High Lp(a) concentration (&gt;50 mg/dL) and high risk</li>
 <li>Gray zone: Lp(a) concentration (30–50 mg/dL)</li>
 </ul></td>
 </tr>
 <tr>
 <td colspan="1" rowspan="4" style="background-color: rgb(244, 242, 246); width: 25%;">Managing high Lp(a) concentrations</td>
 <td>For those with high Lp(a), early&nbsp;‘traditional’&nbsp;risk factor management is recommended in the absence of specific Lp(a)-lowering therapies that also considers their absolute CV risk and Lp(a) concentration</td>
 </tr>
 <tr>
 <td>Address all CV risk factors optimally&nbsp;as per guideline recommendations among patients with high Lp(a) concentrations</td>
 </tr>
 <tr>
 <td>Consider&nbsp;lipoprotein apheresis&nbsp;in patients with very high Lp(a) and progressive CVD despite optimal management of risk factors.</td>
 </tr>
 <tr>
 <td>For high Lp(a) concentrations, niacin and “routine aspirin” are&nbsp;not advised</td>
 </tr>
 </tbody>
</table>
Incorporating Lp(a) in risk estimation
<ul>
 <li>Increasing Lp(a) categories causes an&nbsp;incremental increase in absolute risk (AR)&nbsp;of ASCVD</li>
 <li>This increase in AR is&nbsp;measured&nbsp;using&nbsp;estimated baseline absolute lifetime risk†, baseline risk categories based on traditional risk factors (5%, 10%, 15%, 20%, and 25%), and additional risk above the estimated baseline risk caused by the respective Lp(a) concentration categories (7, 30, 50, 75, 100, 150 mg/dL):</li>
</ul>
<table align="center" border="1" cellpadding="10" cellspacing="1">
 <tbody>
 <tr>
 <td style="background-color: rgb(244, 242, 246); text-align: center;">Baseline risk of ASCVD events from traditional risk factors (%)</td>
 <td style="background-color: rgb(244, 242, 246); text-align: center;">Plasma Lp(a) concentration (mg/dL)</td>
 <td style="background-color: rgb(244, 242, 246); text-align: center;">Absolute lifetime 
 risk (%)</td>
 <td style="background-color: rgb(244, 242, 246); text-align: center;">Increase in absolute risk</td>
 </tr>
 <tr>
 <td style="text-align: center;">5</td>
 <td style="text-align: center;">50</td>
 <td style="text-align: center;">50</td>
 <td colspan="1" rowspan="3" style="text-align: center;">≈1.4-fold</td>
 </tr>
 <tr>
 <td style="text-align: center;">15</td>
 <td style="text-align: center;">50</td>
 <td style="text-align: center;">20.9</td>
 </tr>
 <tr>
 <td style="text-align: center;">25</td>
 <td style="text-align: center;">50</td>
 <td style="text-align: center;">34.9</td>
 </tr>
 <tr>
 <td style="text-align: center;">5</td>
 <td style="text-align: center;">150</td>
 <td style="text-align: center;">13.6</td>
 <td colspan="1" rowspan="3" style="text-align: center;">≈2.7-fold</td>
 </tr>
 <tr>
 <td style="text-align: center;">15</td>
 <td style="text-align: center;">150</td>
 <td style="text-align: center;">40.8</td>
 </tr>
 <tr>
 <td style="text-align: center;">25</td>
 <td style="text-align: center;">150</td>
 <td style="text-align: center;">68.1</td>
 </tr>
 <tr>
 <td colspan="4" style="text-align: center;">Absolute risk might be underestimated substantially if Lp(a) concentration is not considered</td>
 </tr>
 </tbody>
</table>
‘Starting age’ of LDL-C lowering
Entire&nbsp;global CV risk&nbsp;can be&nbsp;lowered&nbsp;based on ‘starting age’ of LDL-C lowering
<table align="center" border="1" cellpadding="10" cellspacing="1">
 <tbody>
 <tr>
 <td style="background-color: rgb(244, 242, 246); text-align: center;">Plasma Lp(a) concentration (nmol/L)</td>
 <td style="background-color: rgb(244, 242, 246); text-align: center;">Age of LDL-C lowering (years)</td>
 <td style="background-color: rgb(244, 242, 246); text-align: center;">LDL-C reduction needed (mmol/L)</td>
 </tr>
 <tr>
 <td colspan="1" rowspan="2" style="text-align: center;">120</td>
 <td style="text-align: center;">30</td>
 <td style="text-align: center;">0.4</td>
 </tr>
 <tr>
 <td style="text-align: center;">60</td>
 <td style="text-align: center;">0.8</td>
 </tr>
 <tr>
 <td colspan="1" rowspan="2" style="text-align: center;">320</td>
 <td style="text-align: center;">30</td>
 <td style="text-align: center;">1.2</td>
 </tr>
 <tr>
 <td style="text-align: center;">60</td>
 <td style="text-align: center;">2.3</td>
 </tr>
 <tr>
 <td colspan="3" style="text-align: center;">Starting prevention early is the key</td>
 </tr>
 </tbody>
</table>
Emerging specific Lp(a)-lowering therapies targeting Lp(a) production <a href="https://www.tandfonline.com/doi/full/10.1080/13543784.2020.1757070" target="_blank">(Tromp et al. 2020)</a>
<ul>
 <li>In those with very high Lp(a) level, absolute ASCVD risk is mainly attributable to Lp(a)</li>
 <li>Managing traditional risk factors is important, but not enough</li>
 <li>Specific Lp(a)-lowering therapies are urgently required</li>
</ul>
<table align="center" border="1" cellpadding="10" cellspacing="1">
 <tbody>
 <tr>
 <td style="background-color: rgb(244, 242, 246); text-align: center;">Lp(a)-lowering therapy</td>
 <td style="background-color: rgb(244, 242, 246); text-align: center;">Dosing</td>
 <td style="background-color: rgb(244, 242, 246); text-align: center;">Clinical trial phase</td>
 </tr>
 <tr>
 <td style="text-align: center;">ASO therapy</td>
 <td style="text-align: center;">Monthly</td>
 <td style="text-align: center;">Phase 3 ongoing 
 (results expected in 2025)</td>
 </tr>
 <tr>
 <td style="text-align: center;">Two siRNA technologies</td>
 <td style="text-align: center;">Longer acting</td>
 <td>
 1. Dose-finding study ongoing
 2. Phase 1 trial complete</td>
 </tr>
 </tbody>
</table>
*Defined as composite of first occurrence of fatal or non-fatal MI, fatal or non-fatal MI ischemic stroke, or coronary revascularization (PCI or CABG). †Baseline estimated lifetime risk calculated using JBS3 lifetime risk estimating algorithm.

Footnote

References

ESC Lp(a) in Clinical practice EAS Consensus statement

Statin+ ezetimibe combination therapy vs statin monotherapy in patients with diabetes: a meta‑analysis of randomized controlled trials.
Results from this meta-analysis of randomized controlled trials (RCTs) showed that statin–ezetimibe combination therapy improves levels of low-density lipoprotein cholesterol (LDL-C) and other lipids without increasing the risk of adverse events as compared to statin monotherapy.

<h2>Key Takeaway</h2>
<ul>
 <li>In this meta-analysis of RCTs, comparing the efficacy and safety of statin monotherapy vs statin + ezetimibe combination therapy in patients with diabetes: 
 <ul>
 <li>Statin + ezetimibe therapy significantly improved the lipid parameters vs statin monotherapy (except apolipoprotein [Apo] A1)</li>
 <li>Statin + ezetimibe therapy was associated with a significant decrease in fasting blood glucose (FBG) levels vs statin monotherapy</li>
 <li>In terms of safety: No significant difference was found between the two groups in regard to treatment-related adverse events (TRAEs) and discontinuations due to TRAEs</li>
 </ul></li>
 <li>Overall findings indicate that lipid management with combination therapy vs statin monotherapy, can be considered preferable for the prevention of cardiovascular disease (CVD) or stroke in patients with diabetes</li>
</ul>

<h2>Why This Matters</h2>
<ul>
 <li>Patients with diabetes are at potentially increased risk of morbidity and mortality following atherosclerotic CVD.</li>
 <li>There is no consensus reported yet via a systematic review or meta-analysis for studies comparing the efficacy of statin monotherapy vs combination therapy with ezetimibe in patients with diabetes.</li>
 <li>This meta-analysis was conducted to evaluate and compare the efficacy and safety of statin alone and in combination with ezetimibe in patients with diabetes in RCTs.</li>
</ul>

<h2>Study Design</h2>
<ul>
 <li>Published articles comparing the lipid-lowering effects and safety of statins and ezetimibe in patients with diabetes and dyslipidemia were searched using databases such as the MEDLINE (OVID and PubMed), Embase, and the Cochrane Library</li>
 <li>Inclusion criteria for studies: RCT; administered ezetimibe + statin vs statin only in patients with diabetes; included measurements of lipid concentrations; described safety or toxicity data</li>
 <li>Primary endpoints: Changes in lipid concentrations (changes in LDL-C, high-density lipoprotein cholesterol [HDL-C], total cholesterol, triglycerides, Apo A1, and Apo B levels) • Secondary endpoints: Changes in FBG and glycated hemoglobin (HbA1c) levels</li>
 <li>Safety: TRAEs</li>
</ul>

<h2>Key Results</h2>
<ul>
 <li>Overall, 17 articles were included in this meta-analysis</li>
</ul>
<h3>Effect on lipid parameters</h3>
<ul>
 <li>Changes in LDL-C levels: There was significantly greater reduction in LDL-C levels in combination therapy group vs statin monotherapy group (standard difference in means [SE] = 0.691; 95% confidence interval [CI]: 0.534–0.847)</li>
 <li>Changes in HDL-C levels: There was greater improvement in HDL-C levels in combination therapy group vs statin monotherapy group (SE = 0.280; 95% CI: 0.106–0.453)</li>
 <li>There were significant decreases in the levels of total cholesterol, triglycerides, and Apo B but not of Apo A1 in combination therapy group vs statin monotherapy group (total cholesterol, SE = 0.560; triglyceride, SE = 0.296; Apo B, SE = 0.471; Apo A1, SE = 0.093)</li>
 <li>A significantly higher percentage of patients on combination therapy reached the targeted LDL-C level vs statin monotherapy (odds ratio = 0.478; 95% CI: 0.318–0.718)</li>
</ul>
<h3>Effect on glucose parameters</h3>
<ul>
 <li>Changes in HbA1c levels: No significant difference was identified between the groups (SE = 0.106)</li>
 <li>Changes in FBG levels: Combination treatment significantly reduced FBG levels vs statin monotherapy (SE = 0.190) 
 <ul>
 <li>Based on random-effects model: No significant difference was identified between the groups</li>
 </ul></li>
</ul>
<h3>Effect on adverse events</h3>
<ul>
 <li>Treatment-related adverse events: No significant difference was identified between the groups (relative risk [RR] = 0.774)</li>
 <li>Discontinuations due to TRAEs: No significant difference was identified between the groups (RR = 0.963)</li>
 <li>Alanine aminotransferase levels: No significant difference was identified between the groups (RR = 0.907)</li>
 <li>Other adverse events in both groups: Gastrointestinal-related adverse events, muscle-related adverse events, allergic reaction (generally low incidence rates and varied slightly from study to study)</li>
</ul>

<h2>Limitations</h2>
<ul>
 <li>Since the analysis was based on previous reports, which were not necessarily complete or accurate, analyses of data, including sex, age, duration, or other factors was not possible.</li>
 <li>Outcomes based on overall statistical analysis could vary from the safety or efficacy evaluations in individual patients.</li>
</ul>

Statin/Ezetimibe Combination VS Statin Monotherapy

<h2>Key Takeaway</h2>
In clinical practice, there exist a gap between lipid guidelines and lipid management - use of combination therapy and improving patient adherence should be prioritized
<ul>
 <li>Only half of the patients with CVD received high-intensity statins</li>
 <li>Less than half attained the LDL-C goal in secondary prevention</li>
</ul>
Major reasons for insufficient therapy:
<ul>
 <li>Side effects of LLT</li>
 <li>Poor adherence to medication regimens</li>
 <li>Low use of combination therapies by physicians</li>
</ul>

<h2>Why This Matters</h2>
<ul>
 <li>Extrapolating data from clinical trials of specifically selected populations to usual care in clinical practice is limited.</li>
 <li>Lipid registry-based research is an important tool for evaluating current lipid management in patients at risk of CVD.</li>
</ul>

<h2>Key Highlights</h2>
Various clinical guidelines recommend LLTs for ASCVD prevention
<ul>
 <li>CV event risk remains in high-risk patients with multiple risk factors/established ASCVD</li>
 <li>It is important to quantify accurately if these high-risk patients are receiving guideline-recommended LLTs and attaining optimal recommended LDL-C levels in routine clinicalpractice.</li>
</ul>
Occurrence of ASCVD events§&nbsp;was assessed between hospital discharge for each patient’s index AMI¶and their first fill for a PCSK9i.
<table cellpadding="5" cellspacing="1">
 <tbody>
 <tr>
 <td style="background-color: rgb(244, 242, 246); text-align: center;">Registries of 
 Lipid management</td>
 <td style="background-color: rgb(244, 242, 246); text-align: center;">Study&nbsp;Findings</td>
 </tr>
 <tr>
 <td style="text-align: center;">Euroaspire v</td>
 <td>
 <ul>
 <li>8,261 patients with verified coronary artery events or interventions</li>
 <li>Only half of the patients were prescribed high-intensity lipid-lowering drugs</li>
 <li>Only 8% were prescribed a combination of ezetimibe and statins</li>
 </ul></td>
 </tr>
 <tr>
 <td style="text-align: center;">Da Vinci</td>
 <td>
 <ul>
 <li>2,039 patients with established ASCVD</li>
 <li>42% of patients used high-intensity statins</li>
 <li>&lt; 10% patients used ezetimibe or PCSK9 inhibitors in combination with moderate- or high-intensity statins</li>
 </ul></td>
 </tr>
 <tr>
 <td style="text-align: center;">Dysis&nbsp;II</td>
 <td>
 <ul>
 <li>10,661 patients with either stable coronary heart disease or ACS</li>
 <li>Less than a third of the patients had an LDL-C level&lt;70 mg/dL</li>
 <li>Intensity of LLT was moderate although all patients were at very high risk</li>
 </ul></td>
 </tr>
 <tr>
 <td style="text-align: center;">Gould</td>
 <td>
 <ul>
 <li>5,006 patients with ASCVD</li>
 <li>Median LDL-C level was 90 mg/dL for 2 years</li>
 <li>Only about 40% of secondary prevention patients received high-intensity statins</li>
 <li>Non-statin LDL-C lowering therapies were 10%</li>
 </ul></td>
 </tr>
 <tr>
 <td style="text-align: center;">Palm</td>
 <td>
 <ul>
 <li>5,006 patients with ASCVD</li>
 <li>70% patients had LDL-C levels ≥70 mg/dL at the time of enrollment</li>
 <li>Over half of the secondary prevention patients had either no statin or under-dosed statin</li>
 </ul></td>
 </tr>
 </tbody>
</table>

<h2>Barriers to lipid management</h2>
Majority of secondary patients receive inadequate LLT
<ul>
 <li>Guideline-recommended LDL-C goal is not achieved with monotherapy,especially in high-risk patients</li>
</ul>
Data highlight the importance of combination therapies and intensive LLT regimens including greater utilization of non-statin LLTs
Poor adherence of both patients and physicians to LLTs is associated with increased variability in LDL-C levels
<ul>
 <li>Non-statin LLTs (ezetimibe/PCSK9 inhibitor) may be useful for these issues</li>
</ul>
Tailored interventions*based on each patient’s requirements are important
*Such as optimal treatment, simple regimen, education, regular monitoring, and feedback during their treatments

Importance of lipid registries in cardiovascular prevention

This session highlights the place of combination therapies for the management of dyslipidemia in the current guidelines and evaluates the advantages of combination therapy to achieve LDL-C goals as per current guidelines.

<h2>Key Takeaway</h2>
<ul>
 <li>Step-by-step approach requires an optimization of LLT during follow-up that is not observed in real life.</li>
 <li>Early systematic combination therapy:
 <ul>
 <li>Corresponds to a treat-to-target strategy in line with ESC guidelines.</li>
 <li>Is easier to apply in practice than any algorithm.</li>
 <li>Is supported by scientific evidence (<a href="https://www.nejm.org/doi/10.1056/NEJMoa040583?url_ver=Z39.88-2003&amp;rfr_id=ori%3Arid%3Acrossref.org&amp;rfr_dat=cr_pub++0www.ncbi.nlm.nih.gov" target="_blank">Prove It&nbsp;</a>and&nbsp;<a href="https://www.nejm.org/doi/full/10.1056/nejmoa1410489" target="_blank">Improve-it</a>&nbsp;studies)</li>
 <li>Provides the largest decrease in LDL-C with clinical benefits in observational studies.</li>
 <li>Enables early decision on introducing PCSK9 inhibitors.</li>
 </ul></li>
</ul>

<h2>Key Highlights</h2>
<ul>
 <li>The 2019 ESC guidelines for dyslipidemia include risk assessment (low, moderate, high, and very high) and treat-to-target strategy.</li>
 <li>Two strategies for LLT:
 <ul>
 <li>Step-by-step strategy to reach the LDL-C target: Start low–moderate statins, increase LLT intensity, add ezetimibe, and add PCSK9 inhibitor to reach the LDL-C target</li>
 <li>Start with high-intensity statins + ezetimibe and add PCSK9 inhibitor to reach the LDL-C target</li>
 </ul></li>
</ul>
<h3>Real-life results of the step-by-step strategy</h3>
<ul>
 <li><a href="https://www.sciencedirect.com/science/article/abs/pii/S0021915019301509?via%3Dihub" target="_blank">EUROASPIRE V</a>: Included patients with acute coronary artery events or interventions. 
 <ul>
 <li>It was found that only 23% of women had LDL-C &lt;1.8 mmol/L (70 mg/dL) compared to 32% of men.</li>
 <li>At first prescription (discharge), 58% patients were treated with high-intensity statins.</li>
 <li>During follow-up: Among the patients treated with high-intensity statins, there was a decrease in intensity (to low/moderate intensity or no LLT) in 20.8% patients vs an increase in LLT in 11.7% patients.</li>
 <li>As a result, instead of an increase, there was mostly a decrease in low-intensity treatment; hence, the step-by-step approach was not efficient, and only few patients fulfilled this target.</li>
 </ul></li>
</ul>
<h3>Treat-to-target strategy linked to combination LLT</h3>
<ul>
 <li>Percent LDL-C reduction with LLT combination makes it possible to select the appropriate LLT to reach the LDL-C target, according to baseline LLT.</li>
 <li>Example of treat-to-target prescription in a very high-risk patient: 
 <ul>
 <li>Target is &lt;1.4 mmol/L (&lt;55 mg/dL): Cannot be reached with high intensity alone if baseline LDL-C is &gt;3 mmol/L (115 mg/dL) and needs additional effect of ezetimibe.</li>
 <li>Target is &gt;50% decrease in LDL-C: Cannot be reached with high-intensity statin alone; additional effect of ezetimibe is needed.</li>
 </ul></li>
</ul>

<h3>An innovative lipid-lowering approach to enhance attainment of LDL-C goals</h3>
<ul>
 <li>Real-life application in 270 randomly selected very high-risk patients: 
 <ul>
 <li>Admission LDL-C: 120 ± 47 mg/dL (33% already under statins at admission).</li>
 <li>Compliance with treatment algorithm was 76% despite a discharge treatment with 97% higher intensity statins plus 67% ezetimibe.</li>
 <li>LDL-C target according to the recent guidelines (ESC 2019) was reached in only 46%; even with use of ezetimibe for old patients, this algorithm would have only 56% of patients at this target.</li>
 <li>Hence, giving the systematic combination is much simpler and much more efficient than any algorithm.</li>
 </ul></li>
</ul>
<h3>Early combination: Evidence for high-intensity statin</h3>
<ul>
 <li><a href="https://www.nejm.org/doi/10.1056/NEJMoa040583?url_ver=Z39.88-2003&amp;rfr_id=ori%3Arid%3Acrossref.org&amp;rfr_dat=cr_pub++0www.ncbi.nlm.nih.gov" target="_blank">Prove-it</a>: Trial demonstrated that high-intensity statins were much better than low-intensity statins (LDL-C during study: 62 vs 95 mg/dL: RRR = 16%).</li>
 <li>However, before PCI, the use of high-intensity statin is suggested instead of no or moderate-intensity statins because it is safe for MACE.</li>
</ul>
<h3>Early combination: Evidence for ezetimibe</h3>
<ul>
 <li><a href="https://www.nejm.org/doi/full/10.1056/nejmoa1410489" target="_blank">Improve-it</a>:&nbsp;When added to statin therapy, ezetimibe resulted in incremental lowering of LDL-C levels and improved CV outcomes. 
 <ul>
 <li>Addition of ezetimibe to statin therapy in stable patients who had an ACS and had LDL-C levels within guideline recommendations further lowered the risk of CV events.</li>
 </ul></li>
</ul>
<h3>Early combination: Observational studies</h3>
<ul>
 <li>Swedeheart registry in post-MI patients showed larger LDL-C reduction, and more intensive statin therapy after MI was associated with a reduced hazard of all CV outcomes and all-cause mortality.</li>
 <li>Thus, earlier lowering of LDL-C after an MI conferred the greatest benefits.</li>
</ul>
<h3>Early combination: Timely decision for PCSK9 inhibitors</h3>
<ul>
 <li>Evidence for early PCSK9 inhibitor use: 
 <ul>
 <li>PCSK9i reduces MACE and all-cause mortality immediately after MI. In ODYSSEY outcomes, PCSK9 inhibitor showed 15% RRR in MACE at 33 months.</li>
 <li>In Fourier trial, few patients had recent MI and remote MI; most patients got the advantage of using PCSK9 inhibitor.</li>
 </ul></li>
</ul>

Should we encourage earlier and broader use of combination therapies in dyslipidemia?

Act Now for Your ACS Patients: Optimize Your ACS Pathway

Watch Professor Kausik Ray, a Cardiologist and Professor of Public Health, Imperial College London, presenting ACS initiatives while providing ways to easily implement such methods into clinical practice with the objective to help adopting the 2019 guidelines of ESC/EAS major direction of: Treat aggressively, use combination and start early.

<h2>Key Takeaway</h2>
This simulation study&nbsp;from Da Vinci&nbsp;identified notable differences&nbsp;between the&nbsp;2019 ESC/EAS&nbsp;and&nbsp;2018 ACC/AHA&nbsp;guidelines in their&nbsp;clinical approach to LLT in patients with ASCVD. The study also identified that:
<ul>
 <li>About&nbsp;80–85%&nbsp;of the patients* were on&nbsp;monotherapy based LLT</li>
 <li>Patients&nbsp;achieving 2018 ACC/AHA&nbsp;(&lt;70 mg/dL) vs&nbsp;2019 ESC/EAS&nbsp;(&lt;55 mg/dL) goals were&nbsp;39% vs 19%</li>
 <li>Achievement&nbsp;of&nbsp;LDL−C&nbsp;&lt;70 mg/dL&nbsp;was&nbsp;more likely in patients&nbsp;receiving&nbsp;combination therapy&nbsp;with either&nbsp;ezetimibe&nbsp;or a&nbsp;PCSK9i&nbsp;vs patients on statin monotherapy</li>
 <li>In patients&nbsp;with&nbsp;LDL−C ≥70 mg/dL, to achieve LDL−C levels of&nbsp;&lt;70 mg/dL, &lt;55 mg/dL&nbsp;and&nbsp;&lt;40 mg/dL, median LDL−C reductions&nbsp;of&nbsp;26%,&nbsp;42%&nbsp;and&nbsp;58%&nbsp;would be needed, respectively</li>
 <li>In patients with&nbsp;LDL–C ≥70 mg/dL&nbsp;vs&nbsp;&lt;70 mg/dL, the estimated&nbsp;10–year risk of CV events&nbsp;were&nbsp;32% vs 35%</li>
 <li>Attaining&nbsp;2018 ACC/AHA or 2019 ESC/EAS goals resulted in&nbsp;simulated ARRs&nbsp;of&nbsp;4%&nbsp;and&nbsp;6%, respectively</li>
 <li>For&nbsp;implementation of the guidelines,&nbsp;greater use&nbsp;of&nbsp;combination therapies&nbsp;would be required</li>
 <li>The&nbsp;residual risk&nbsp;among patients with ASCVD&nbsp;receiving statins&nbsp;could be&nbsp;mitigated&nbsp;if&nbsp;2019 ESC/EAS recommendations&nbsp;were&nbsp;achieved‡</li>
 <li>More stringent 2019 ESC/EAS goals&nbsp;are&nbsp;expected&nbsp;to give&nbsp;better health&nbsp;outcomes&nbsp;vs 2018 ACC/AHA approach</li>
</ul>

<h2>Why This Matters</h2>
<ul>
 <li>LDL–C recommendations differ between&nbsp;the 2018 ACC/AHA approach&nbsp;and&nbsp;2019 ESC/EAS guidelines&nbsp;for patients with&nbsp;ASCVD.</li>
 <li>The&nbsp;2018 ACC/AHA guidelines&nbsp;recommend targeted reduction&nbsp;LDL–C &lt;70 mg/dL§, in patients at&nbsp;very–high risk.</li>
 <li>The&nbsp;2019 ESC/EAS guidelines&nbsp;recommend a&nbsp;stricter LDL–C goal of &lt;55 mg/dL.</li>
 <li>Using&nbsp;DA VINCI study cohort, the&nbsp;extent of risk that could be mitigated by adopting 2018 ACC/AHA&nbsp;vs&nbsp;2019 ESC/EAS&nbsp;LDL−C recommended approaches was&nbsp;simulated.</li>
</ul>

<h2>Study Design</h2>
This is a simulation study from Da Vinci.&nbsp;The methods and primary outcomes of Da Vinci study can be obtained from the link:&nbsp;<a href="https://www.sciencedirect.com/science/article/pii/S0021915021013083">Da Vinci.</a>
<ul>
 <li>LLT use across the populations</li>
 <li>LDL–C control in patients with established ASCVD and stratified by ASCVD type¶</li>
 <li>Patients with LDL–C &gt;70 mg/dL vs achievement of LDL–C &lt;55 mg/dL</li>
 <li>Patients achieving LDL–C &lt;40 mg/dL</li>
 <li>Implications of current practice and LDL–C goal achievement in future CV risk</li>
</ul>

<h2>Key Results</h2>
Overall,&nbsp;2,039 patients with ASCVD&nbsp;(23% with CAD; 37% with CBD and 40% with PAD)&nbsp;were on stabilized LLT&nbsp;at the time of&nbsp;LDL–C measurement.

<h3 style="text-align: center;">LLT Use in patients with ASCVD</h3>
<table border="1" cellpadding="10" cellspacing="1" style="width:100%;">
 <tbody>
 <tr>
 <td style="background-color: rgb(244, 242, 246); text-align: center;">Type of&nbsp;LLT</td>
 <td style="background-color: rgb(244, 242, 246); text-align: center;">Patients using LLT (%)</td>
 </tr>
 <tr>
 <td>
 Statin monotherapy</td>
 <td style="text-align: center;">Used most frequently</td>
 </tr>
 <tr>
 <td style="text-align: center;">Moderate–intensity statins#&nbsp;as monotherapy</td>
 <td style="text-align: center;">Ranged from&nbsp;40.4%&nbsp;among patients with CAD to&nbsp;48.7%&nbsp;in patients with CBD</td>
 </tr>
 <tr>
 <td style="text-align: center;">High–intensity statins#</td>
 <td style="text-align: center;">CAD: 51.1%;&nbsp;CBD: 39.7%; PAD: 39.1%</td>
 </tr>
 <tr>
 <td style="text-align: center;">Ezetimibe in combination with statins||</td>
 <td style="text-align: center;">CAD: 15.3%;&nbsp;CBD: 6.7%; PAD: 8.2%</td>
 </tr>
 <tr>
 <td style="text-align: center;">PCSK9i in combination with statins and/or ezetimibe||</td>
 <td style="text-align: center;">CAD: 0.4%; CBD: 1.2%; PAD: 1.6%</td>
 </tr>
 </tbody>
</table>

<h3 style="text-align: center;">Proportion of patients achieving LDL–C Levels</h3>

<ul>
 <li>Achievement of an&nbsp;LDL–C level &lt;70 mg/dL&nbsp;was&nbsp;more likely&nbsp;in patients receiving&nbsp;combination therapy with either ezetimibe or a PCSK9i&nbsp;vs patients on statin monotherapy.</li>
 <li>Despite of using PSCK9i infrequently,&nbsp;58% of patients receiving PSCK9i&nbsp;in combination with other LLT have&nbsp;attained LDL–C level of &lt;55 mg/dL.</li>
</ul>

<h3 style="text-align: center;">Residual risk among the patients</h3>
<table border="1" cellpadding="10" cellspacing="1" style="width:100%;">
 <tbody>
 <tr>
 <td style="background-color: rgb(244, 242, 246); text-align: center;">LDL–C Levels</td>
 <td style="background-color: rgb(244, 242, 246); text-align: center;">Patients&nbsp;(%)</td>
 <td style="background-color: rgb(244, 242, 246); text-align: center;">Median&nbsp;(IQR) LDL–C Level</td>
 <td style="background-color: rgb(244, 242, 246); text-align: center;">Median&nbsp;(IQR) Predicted&nbsp;10–year&nbsp;CV risk</td>
 </tr>
 <tr>
 <td style="text-align: center;">≥70 mg/dL</td>
 <td style="text-align: center;">61%</td>
 <td style="text-align: center;">93 (81–115) mg/dL</td>
 <td style="text-align: center;">32% (25–43%)</td>
 </tr>
 <tr>
 <td style="text-align: center;">&lt;70 mg/dL**</td>
 <td style="text-align: center;">39%</td>
 <td style="text-align: center;">56 (46–63) mg/dL</td>
 <td style="text-align: center;">35% (26–46%)</td>
 </tr>
 </tbody>
</table>
<h3 style="text-align: center;">Simulated risk reduction in patients with established&nbsp;ASCVD (LDL–C Level of ≥70 mg/dL)</h3>
<table border="1" cellpadding="10" cellspacing="1" style="width:100%;">
 <tbody>
 <tr>
 <td style="background-color: rgb(244, 242, 246);">LDL–C Levels</td>
 <td style="background-color: rgb(244, 242, 246);">Median&nbsp;10–year&nbsp;CV risk</td>
 <td style="background-color: rgb(244, 242, 246);">Median&nbsp;RRR of&nbsp;CV events</td>
 <td style="background-color: rgb(244, 242, 246);">Median&nbsp;ARR of CV events</td>
 <td style="background-color: rgb(244, 242, 246);">
 Required&nbsp; 
 median&nbsp; 
 reduction&nbsp;in&nbsp; 
 LDL-C</td>
 <td style="background-color: rgb(244, 242, 246);">AR to lower&nbsp;LDL–C levels&nbsp;to 69 mg/dL</td>
 </tr>
 <tr>
 <td style="text-align: center;">&lt;70 mg/dL</td>
 <td style="text-align: center;">28%</td>
 <td style="text-align: center;">14%</td>
 <td style="text-align: center;">4%</td>
 <td style="text-align: center;">26%</td>
 <td style="text-align: center;">24 mg/dL (12–46)</td>
 </tr>
 <tr>
 <td style="text-align: center;">&lt;55 mg/dL</td>
 <td style="text-align: center;">25%</td>
 <td style="text-align: center;">22%</td>
 <td style="text-align: center;">6%</td>
 <td style="text-align: center;">42%</td>
 <td style="text-align: center;">39 mg/dL (27–91)</td>
 </tr>
 <tr>
 <td style="text-align: center;">&lt;40 mg/dL</td>
 <td style="text-align: center;">23%</td>
 <td style="text-align: center;">29%</td>
 <td style="text-align: center;">8%</td>
 <td style="text-align: center;">58%</td>
 <td style="text-align: center;">54 mg/dL (42–76)</td>
 </tr>
 </tbody>
</table>
For additional information about simulated risk reduction, please click on the&nbsp;<a href="http://${link:{uuid:{e3579e13-0af7-4531-bdf0-88d2e3d87092},repository:{dam},path:{/Portal/KSA/Articles/recommendations-for-residual-risk-reduction-in-ascvd/STRATIFIED-BY-ASCVD-TYPE.pdf}}}">hyperlink.</a>

<h2>Limitations</h2>
<ul>
 <li>Over 90% of patients were white (homogenous ethnicity).</li>
 <li>Simulation might have underestimated CV risk and ARR in very high-risk patients.</li>
 <li>Use of LLT may vary across countries and might not necessarily reflect practice in other regions.</li>
 <li>The study sites might have focused on lipid management and prevention of CV events. Hence, the study findings are likely to present better than average management scenario.</li>
</ul>
For additional details, please refer the source publication&nbsp;<a href="https://link.springer.com/article/10.1007/s10557-022-07343-x#Abs1">Vallejo-Vaz AJ, et al.</a> 
 * Most of the patients with major manifestations of ASCVD 
 † Probably due to additional comorbidities like diabetes, history of smoking and increased use of more potent LLTs including combination therapies. 
 ‡ In a population like Da Vinci cohort § Using 70 mg/dL as a limit to guide additional LLT 
 ¶ As per 2019 ESC/EAS guidelines, all patients are at very–high risk 
 # With or without other LLT || High/moderate/unknown intensity 
 ** Had slightly higher prevalence of risk factors such as a history of smoking and diabetes (50.7%)

ACC/AHA vs ESC/EAS LDL–C recommendations for residual risk reduction in ASCVD: A simulation study from Da Vinci

CAD is defined as the pathological process characterised by atherosclerotic plaque accumulation in the epicardial arteries. It covers different conditions, including:1
<ul>
 <li>Patients with stable angina</li>
 <li>Patients after elective coronary revascularisation procedures, such as percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG)</li>
 <li>Patients with significant coronary disease without prior revascularisation as evidenced by either: 
 <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 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 downloaded by clicking the button

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

Adapted from 2024 ESC CCS Guidelines.4
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.

Patients with PAD,&nbsp;with or without T2DM, are at very&nbsp;high CV risk.1 
 These patients require a&nbsp;holistic multifactorial approach&nbsp;to prevention and management.
Reduce increased levels of causal CV risk factors, such as:5

Target: see below

Target: SBP 120–129 mmHg†

Target is &lt;7.0% (53 mmol/mol)

Reducing LDL-C levels represents the primary target for reducing CV risk5
According to the 2019 ESC/EAS dyslipidemia guidelines, and 2024 ESC chronic coronary syndromes guidelines, all patients with CAD have the following LDL-C goals.4,5
An LDL-C reduction of ≥50% from baseline‡&nbsp;and an&nbsp;LDL-C goal of &lt;55 mg/dL (&lt;1.4 mmol/L)&nbsp;are recommended
For patients at&nbsp;very high CV risk&nbsp;(including those with CAD) not achieving their LDL-C goal on a maximum tolerated dose of statin and ezetimibe, combination&nbsp;with a PCSK9i is recommended.5

Recommendations for pharmacological LDL-C lowering5

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.

Step 1

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

Step 2

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.

Step 3

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

Prevent The 1st&nbsp;Event&nbsp;for your CAD&nbsp;patients with&nbsp;PAD + T2DM¥
*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 CAD: Focus on LDL-C Control

PAD is a common manifestation of atherosclerosis and encompasses all vascular sites, including:1
<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

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

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,&nbsp;with or without T2DM, are at very&nbsp;high CV risk.1 
 These patients require a&nbsp;holistic multifactorial approach&nbsp;to prevention and management.
Reduce increased levels of causal CV risk factors, such as:1

Reducing LDL-C levels represents the primary target for reducing CV risk1
According to the 2019 ESC/EAS dyslipidaemia guidelines, and 2024 ESC chronic coronary syndromes guidelines, all patients with PAD have the following LDL-C goals.1,2
An LDL-C reduction of ≥50% from baseline‡&nbsp;and an&nbsp;LDL-C goal of &lt;55 mg/dL (&lt;1.4 mmol/L)&nbsp;are recommended
For patients at&nbsp;very high CV risk&nbsp;(including those with PAD and T2DM) not achieving their LDL-C goal on a maximum tolerated dose of statin and ezetimibe, combination&nbsp;with a PCSK9i is recommended.1

Recommendations for pharmacological LDL-C lowering1

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

Prevent The 1st&nbsp;Event&nbsp;for your 
 patients with&nbsp;PAD + T2DM¥
*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 PAD and T2D: Focus on LDL-C Control

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