ASTHMA

RESPIRATORY

Prevalence of Asthma

<p>Dr. Emad Arafa explains the prevalence of severe asthma in Middle East and North Africa, in comparison with the global prevalence.</p>

<h2>Atherosclerotic cardiovascular disease risk assessment: An American Society for Preventive Cardiology clinical practice statement.</h2>
<p>The American Society for Preventive Cardiology (ASPC) offers guidance and tools to assess the risk of atherosclerotic cardiovascular disease (ASCVD), with the goal of enabling specialists to provide suitable treatments to prevent ASCVD events.</p>
<h2>Key Takeaway</h2>
<p>For primary prevention of ASCVD, the first step is to assess cardiovascular risk by determining the global risk score, after which the presence of the following factors can be used to further refine risk estimation:</p>
<ul>
 <li>Traditional risk factors: Age, sex, diabetes, systolic blood pressure, antihypertensive treatment, total cholesterol, low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol, and cigarette smoking</li>
 <li>Risk enhancing factors: Family history of premature ASCVD, sex-specific factors, high-risk ethnicities, primary hypercholesterolemia, metabolic syndrome, chronic inflammatory conditions, and chronic kidney disease</li>
 <li>Female-specific factors: Auto-immune disease, menarche, polycystic ovary syndrome, oral contraceptives, infertility, multiparity, adverse pregnancy outcomes, preeclampsia, gestational diabetes mellitus, early menopause, premature ovarian insufficiency, and vasomotor symptoms</li>
 <li>Inflammatory biomarkers: High sensitivity C-reactive protein (hs-CRP), lipoprotein-associated phospholipase A2, myeloperoxidase, myeloid-related protein 8/14, matrix metalloproteinases, lectin-like oxidized LDL receptor-1, and growth differentiation factor-15</li>
 <li>Other biomarkers: Persistently elevated triglycerides, elevated lipoprotein (a) (Lp[a]) or apolipoprotein B, and low ankle-brachial index (ABI)</li>
 <li>Racial / ethnic factors: Non-Hispanic Black, African American, Asian, etc.</li>
 <li>Social determinants of health: Psychological distress, delayed care due to lack of transport, shortage of food, unemployment, lack of health insurance, inability to pay medical bills, or downward social mobility</li>
 <li>Screening for subclinical atherosclerosis: 
  <ul>
   <li>Carotid intimal-media thickness or established plaque by carotid ultrasound</li>
   <li>Endothelial function by brachial artery reactivity, large vessel (aorta) or small vessel assessment of vascular health</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>
 <li>Nutritional factors, physical activity, and cardiorespiratory fitness levels play vital roles in ASCVD risk assessment and should also be considered.</li>
 <li>For secondary prevention, risk stratification (very high, high, moderate, or low), followed by immediate and intensive risk factor management are essential.</li>
</ul>
<h2>Why This Matters</h2>
<ul>
 <li>To reduce the risk of developing ASCVD, an accurate assessment of the risk is crucial to provide patients with appropriately targeted preventive therapies.</li>
 <li>Without doing a formal risk assessment, a clinician’s estimate can be inaccurate, which can underestimate the actual risk; hence, the use of global risk scores can be beneficial to improve the application of guideline-based therapies.</li>
 <li>Cardiovascular risk assessment forms the basis of preventive cardiology to determine the appropriateness or intensification of preventive therapy.</li>
</ul>
<h2>Clinical recommendations</h2>
<ul>
 <li>For primary prevention, global risk scoring provides a calculation of ASCVD risk from a set of standard office-based risk factors for a stipulated period. 
  <ul>
   <li>Clinicians can then determine the best ways to reduce the risk of developing ASCVD and discuss the same with the patient.</li>
  </ul></li>
 <li>The presence, number, and / or extent of risk enhancing factors as well as severity of inflammatory factors such as hs-CRP and laboratory measures such as Lp(a) levels can help to further refine treatment decision.</li>
 <li>In women, it is crucial to obtain a complete and thorough reproductive history from menarche to menopause, including premature menopause, preeclampsia, and autoimmune disease.</li>
 <li>Certain race / ethnic groups have a higher risk of developing ASCVD, which can help to further refine the use of preventive therapy.</li>
 <li>Social determinants of health may exert independent effects and should be part of the clinician-patient discussion to determine appropriate ways to lower risk.</li>
 <li>Among screening tests for subclinical ASCVD, CAC testing provides considerable improvement of risk reclassification over global risk scoring in most primary prevention groups, including diabetes. 
  <ul>
   <li>Additionally, it can be used to refine decisions on preventive therapy, including on the use of statin and aspirin.</li>
  </ul></li>
 <li>If CAC scoring is unavailable, carotid ultrasound imaging together with carotid plaque assessment may be beneficial for risk assessment.</li>
 <li>The use of ABI is valuable for assessment of peripheral artery disease and can improve risk reclassification beyond global risk scoring.</li>
 <li>In patients with pre-existing ASCVD, more aggressive treatment should be considered for those at the highest risk, based on the history of either multiple high-risk conditions and one major ASCVD event or multiple major events.</li>
 <li>Patients with recurrent ASCVD events within a short period of time represent an extreme risk for further events 
  <ul>
   <li>An even more aggressive risk factor management and intensive treatment should be considered</li>
  </ul></li>
 <li>Clinician-patient discussions on lifestyle management and on the benefits and risks of evidence-based pharmacologic therapies that are essential to lower the risk of developing ASCVD is central to preventive cardiology.</li>
</ul>

Reference

Atherosclerotic Cardiovascular Disease Risk Assessment

DYSLIPIDEMIA

CARDIOLOGY

<h2>Improve prognosis in patients with type 2 diabetes mellitus<br>
  Regulate low-density lipoprotein cholesterol level for those undergoing coronary revascularisation</h2>
<h2>Main takeaway</h2>
<ul>
 <li>Depending on the revascularisation strategy, LDL-C levels yield a differential influence on cardiovascular (CV) outcomes 
  <ul>
   <li>Compared to patients with 1-year LDL-C &lt;70 mg/dl, patients who had 1-year LDL-C ≥100 mg/dl showed a significant increase in long-term cardiovascular risk</li>
   <li>Patients randomised to coronary artery bypass grafting (CABG) group had lower rates of major adverse cardiac or cerebrovascular events (MACCE) versus the optimal medical therapy (OMT) alone group</li>
  </ul></li>
</ul>

<h2>Why this matters</h2>
<ul>
 <li>Guideline-directed management of patients with coronary heart disease (CHD) and type 2 diabetes mellitus (T2DM) includes intensive lifestyle intervention along with aggressive secondary prevention (OMT) and an appropriate revascularisation strategy 
  <ul>
   <li>This analysis highlights the significance of LDL-C control in the first year post-procedure</li>
  </ul></li>
</ul>

<h2>Study design</h2>
<ul>
 <li>Pooled analysis: combined individual patient-level information from 3 federally funded trials (BARI 2D, COURAGE, and FREEDOM)</li>
 <li>4,050 patients with T2DM (mean age = 62.8 ± 8.8 years; female = 27.0%; median follow-up = 3.9 years [after the index 1-year assessment]) were categorised according to LDL-C levels at 1 year following randomisation 
  <ul>
   <li>Key inclusion criteria: all patients with CHD and T2DM from BARI-2D and FREEDOM trials and only patients with T2DM in the COURAGE trial</li>
   <li>Key exclusion criteria: patients with LDL-C &lt;20 mg/dl and triglycerides &gt;400 mg/dl both at baseline and 1 year</li>
   <li>Primary outcome: 4-year rate of the MACCE composite (all-cause mortality, nonfatal myocardial infarction, and nonfatal stroke)</li>
   <li>Secondary outcomes: subsequent revascularisation</li>
  </ul></li>
</ul>

<h2>Key results</h2>
<ul>
 <li>Patients with 1-year LDL-C levels ≥100 mg/dl experienced higher 4-year cumulative risk of MACCE 
  <ul>
   <li>17.2% versus 13.3% (70 to &lt;100 mg/dl) versus 13.1% (&lt;70 mg/dl); p = 0.016</li>
  </ul></li>
 <li>Incidence of CV events following a coronary revascularisation procedure or OMT: 
  <ul>
   <li>When comparing CABG with PCI, CABG led to significantly lower rates of MACCE for those with 1-year LDL-C levels: 
    <ul>
     <li>Between 70 and &lt;100 mg/dl: HR: 0.49; 95% CI, 0.31 to 0.79; p = 0.003</li>
     <li>≥100 mg/dl: HR: 0.53; 95% CI, 0.30 to 0.91; p = 0.022</li>
    </ul></li>
   <li>When compared with both OMT and PCI patients, CABG correlated with lower rates of subsequent revascularisation in all 1-year LDL-C strata 
    <ul>
     <li>No difference in subsequent revascularisation rates were observed when comparing PCI with OMT in any of the 1-year LDL-C strata</li>
    </ul></li>
  </ul></li>
</ul>

<h2>Limitations</h2>
<ul>
 <li>There may be a possibility of additional confounders influencing the association between cardiovascular outcomes and both the choice of revascularisation procedure and the LDL-C control rate</li>
 <li>There is a lack of data for adherence to the prescribed therapy</li>
 <li>A systematic analysis was not pursued for lipid lowering therapy during the first year of follow-up</li>
 <li>There could be an occurrence of immortal time bias</li>
</ul>

Regulate LDL-C level for those undergoing coronary revascularization (Diabetic Patients)

<p>Ulf Landmesser<sup>1</sup>, Jennifer McGinniss<sup>2</sup>, Ph. Gabriel Steg<sup>3,4</sup>, Deepak L. Bhatt<sup>5</sup>, Vera A. Bittner<sup>6</sup>, Rafael Diaz<sup>7</sup>, Mirza Dilic<sup>8</sup>, Shaun G. Goodman<sup>9,10</sup>,&nbsp;J. Wouter Jukema<sup>11,12</sup>, Megan Loy<sup>13</sup>, Ivan Pećin<sup>14</sup>, Robert Pordy<sup>15</sup>, Steen H. Poulsen<sup>16</sup>, Michael Szarek<sup>17,18</sup>, Harvey D. White<sup>19</sup>, Gregory G. Schwartz<sup>20</sup>, for the ODYSSEY OUTCOMES Investigators.</p>
<h2>Background and Objectives</h2>
<ul>
 <li>The 2019 ESC/EAS dyslipidemia guidelines lowered LDL-C treatment goals: 
  <ul>
   <li>In patients considered at very high risk (including those with ACS), LDL-C goal of &lt;1.4 mmol/L is recommended together with &gt;50% LDL-C reduction and a lower goal of &lt;1.0 mmol/L may be considered for those with recurrent CV events within 2 years</li>
  </ul></li>
</ul>
<ul>
 <li>This analysis, using the data of ODYSSEY OUTCOMES trial: 
  <ul>
   <li>Examined how many patients not at goal with high-intensity or MTD statin treatment achieved new LDL-C treatment goals with alirocumab, according to baseline LDL-C values</li>
   <li>Projected how many would have achieved the new treatment goals with the use of ezetimibe when added to MTD statin therapy</li>
  </ul></li>
</ul>
<h2>Methods</h2>
<ul>
 <li>This sub analysis of the ODYSSEY OUTCOMES trial (multicentre, double-blind, randomized placebo-controlled trial in 18,924 patients of ≥40 years of age, hospitalized with an ACS 1–12 months before randomization) comprised of 17,589 patients with LDL-C ≥1.4 mmol/L at baseline who did not receive ezetimibe treatment</li>
</ul>
<h2>Key Findings</h2>
<ul>
 <li>94.6% of patients receiving alirocumab achieved LDL-C goal &lt;1.4 mmol/L at ≥1 post-baseline measurement vs. 17.3% patients receiving placebo</li>
 <li>85.2% of patients with recurrent CV events vs 3.5% receiving placebo, can achieve the lower goal (&lt;1.0 mmol/L)</li>
 <li>In contrast, addition of ezetimibe to optimized statin therapy was projected to achieve LDL-C &lt;1.4 mmol/L in only 10.6% of patients at baseline</li>
 <li>Although the statin/ezetimibe combination is more cost effective than the statin/PCSK9i combination, a substantial number of patients will not achieve the LDL-C goal with this combination</li>
</ul>
<h2>Conclusion</h2>
<p>In post ACS patients with residual dyslipidemia despite intensive or MTD statin, adding alirocumab treatment which has been shown to further reduce the risk of MACE and is associated with a reduction in all-cause mortality after ACS, enabled majority of the patients to reach the 2019 ESC guideline targets for LDL-C &lt;1.4 mmol/L (&lt;55 mg/dL) and &lt;1.0 mmol/L (&lt;40 mg/dL) compared to placebo or ezetimibe</p>

Abbreviations

References

Achievement of ESC/EAS LDL-C Treatment Goals After an ACS with Statin and Alirocumab

<h2>Key Takeaway</h2>
<p>In clinical practice, PCSK9i (alirocumab or evolocumab) on top of maximum LLT significantly reduced LDL-C levels (by 58%) and improved LDL-C target achievement in patients with heterozygous FH (both in men and women).</p>
<p><strong>LDL-C goals*:</strong></p>
<ul>
 <li>&nbsp;2016 ESC/EAS goals†: Patients with ASCVD = 67%; patients without ASCVD = 80%</li>
 <li>&nbsp;2019 ESC/EAS LDL-C goals‡: VHR patients = 46%; HR patients = 50%</li>
</ul>
<p><strong>Independent predictors for LDL-C goals:</strong>&nbsp;Male gender; smoking; and use of statins + ezetimibe</p>

<h2>Why This Matters</h2>
<ul>
 <li><sup>§</sup>&nbsp;Use of PCSK9i in clinical practice is less frequent (partly due to cost and insurance issues).</li>
 <li>Safeheart&nbsp;registry study assessed the use and efficacy of PCSK9i as well as LDL-C goals attainment in clinical practice setting of FH patients.</li>
</ul>

<h2>Study Design</h2>
<p><strong>Safeheart: Open, Multicenter, Nationwide, Long-term Prospective Study</strong>&nbsp;(N = 433 [Alirocumab = 211; Evolocumab = 222])</p>
<p><strong>Key Inclusion Criteria</strong></p>
<p>Patients with molecular diagnosis of FH (aged ≥20 years) on stable LLT, who received PCSK9i (alirocumab 75/150 mg every 2 or 4 weeks, or evolocumab 140 mg every 2 weeks or 420 mg every 4 weeks) from 2016 to January 2020<sup>¶</sup></p>
<p><strong>Key Exclusion Criteria</strong></p>
<p>Patients who participated in RCTs with PCSK9i before 2016</p>
<p><strong>LDL-C Goals:</strong>&nbsp;Defined and analyzed based on 2016 and 2019 ESC/EAS guidelines</p>

<h2>Key Results</h2>
<p>Overall,&nbsp;<strong>433</strong>&nbsp;patients were included in the analysis</p>
<p>Mean age =&nbsp;<strong>55</strong>&nbsp;years; male =&nbsp;<strong>53%;</strong>&nbsp;history of ASCVD =&nbsp;<strong>39%;</strong>&nbsp;median follow-up =&nbsp;<strong>2.5</strong>&nbsp;years</p>

<h2>LDL-C Levels:</h2>
<ul>
 <li><strong>Before PCSK9i:</strong>&nbsp;Median LDL-C =&nbsp;<strong>145</strong>&nbsp;mg/dL (IQR:&nbsp;<strong>125–173</strong>)</li>
 <li><strong>After addition of PCSK9i:</strong>&nbsp;LDL-C levels reduced by&nbsp;<strong>58%</strong>&nbsp;(IQR:&nbsp;<strong>41–70</strong>&nbsp;<strong>[P &lt;0.001]</strong>) in men and women without differences between both PCSK9i&nbsp;<br>
   Median LDL-C =&nbsp;<strong>62</strong>&nbsp;mg/dL (IQR:&nbsp;<strong>44–87</strong>)</li>
</ul>

<h2>LDL-C Goals*</h2>
<ul>
 <li>2016 ESC/EAS goals†: Patients with ASCVD =&nbsp;<strong>67%</strong>; patients without ASCVD =&nbsp;<strong>80%</strong></li>
 <li>2019 ESC/EAS LDL-C goals‡: VHR patients =&nbsp;<strong>46%</strong>; HR patients =&nbsp;<strong>50%</strong></li>
 <li>Higher LDL-C levels before PCSK9i initiation had a significant inverse relationship with goals attainment</li>
</ul>

<h2>Independent Predictors (2019 ESC/EAS LDL-C GOALS)</h2>
<ul>
 <li>Male gender (P = 0.023); smoking (P = 0.041); and use of statins + ezetimibe (P = 0.008)</li>
</ul>

<h2>Limitations</h2>
<ul>
 <li>Study lacked blinding randomization</li>
 <li>Follow-up analysis was not centralize</li>
 <li>In the follow-up analysis, Lp(a) measurement was not available</li>
</ul>
<p data-font="legal">* Without differences between alirocumab or evolocumab.<br><sup>†</sup>&nbsp;LDL-C target below 70 mg/dL and 100 mg/dL, respectively according to 2016 ESC/EAS guidelines.<br><sup>‡</sup>&nbsp;LDL-C goal according to 2019 ESC/EAS guidelines (for VHR patients &lt;55 mg/dL; for HR patients &lt;70 mg/dL).<br><sup>§</sup>&nbsp;International guidelines recommend PCSK9i for patients with FH with substantially higher LDL-C levels despite maximally tolerated statin ± ezetimibe.<br><sup>¶</sup>&nbsp;Kept a stable dose of PCSK9i at least 3 months before the last analysis. PCSK9i eligibility was based on Spanish National Health System reimbursement regulations in FH patients.</p>

Proprotein convertase subtilisin/kexin type 9 inhibitors for heterozygous familial hypercholesterolemia: A clinical practice experience from the Safeheart registry

Clinical practice experience in patients with familial hypercholesterolemia (FH) from the Safeheart registry

<h2>Odyssey Outcomes: Addition of PCSK9i to Background Statin Therapy Further Reduces MACE.</h2>

<h2>Total events study results</h2>
<h3>Study methods</h3>
<ul>
 <li>Prespecified joint semiparametric model that allows for multiple nonfatal events within a given patient</li>
 <li>Separate hazard functions for nonfatal and fatal events</li>
 <li>Association parameter quantifies the strength of the relationship between risk of nonfatal and fatal events; positive value indicates patients at high risk for nonfatal events also at high risk of death</li>
 <li>All analyses conducted according to intention-to-treat, including all patients and adjudicated events from randomization to the common study end date<br>
   &nbsp;</li>
</ul>

<h3>Alirocumab reduced total events</h3>
<p>5,425 total nonfatal CV events or deaths; 77% greater than first events</p>
<p>Among patients with a first nonfatal CV event:</p>
<ul>
 <li>82%* of alirocumab patients and 85% of placebo patients were on assigned treatment; all but four alirocumab patients and three placebo patients continued treatment after first event</li>
 <li>1,261 (48%) had at least one additional event</li>
</ul>

<h2>Nonfatal CV events were associated with Total Mortality</h2>
<p><strong>Table 4</strong> Joint Semiparametric Models</p>
<table border="1" cellpadding="10" cellspacing="1">
 <tbody>
  <tr>
   <td>HR (95%CI)</td>
   <td>p Value</td>
   <td>&nbsp;</td>
  </tr>
  <tr>
   <td>Death and total nonfatal cardiovascular events (n = 5,425)</td>
   <td>&nbsp;</td>
   <td>&nbsp;</td>
  </tr>
  <tr>
   <td>Alirocumab: placebo HR for nonfatal cardiovascular events (n = 2,186 vs. n = 2,513)</td>
   <td>0.87 (0.82-0.93)</td>
   <td>&lt;0.0001</td>
  </tr>
  <tr>
   <td>Alirocumab: placebo HR for fatal events (n = 334 vs. n = 392)</td>
   <td>0.83 (0.71-0.97)</td>
   <td>0.02</td>
  </tr>
  <tr>
   <td>Association between nonfatal cardiovascular and fatal events 2.04 (95% CI: 1.78-2.29)</td>
   <td>-</td>
   <td>&lt;0.0001</td>
  </tr>
  <tr>
   <td>Death and total nonfatal MI, stroke, or UA events (n = 2,999)</td>
   <td>&nbsp;</td>
   <td>&nbsp;</td>
  </tr>
  <tr>
   <td>Alirocumab: placebo HR for nonfatal myocardial infarction, stroke, or unstable angina (n = 1,034 vs. n = 1,239)</td>
   <td>0.84 (0.77-0.91)</td>
   <td>&lt;0.0001</td>
  </tr>
  <tr>
   <td>Alirocumab: placebo HR for fatal events (n = 334 vs. n = 392)</td>
   <td>0.82 (0.68-0.99)</td>
   <td>0.04</td>
  </tr>
  <tr>
   <td>Association between nonfatal and fatal events 3.29 (95% CI: 2.86-3.72)</td>
   <td>&nbsp;</td>
   <td>0.0001</td>
  </tr>
 </tbody>
</table>
<p>In relation to nonfatal events and death risk association, the post-hoc model association parameter was 1.70 (1.44, 1.96), p&lt;0.0001</p>

<h3>Higher baseline LDL-C associated with greater reduction of total events with Alirocumab</h3>
<ul>
 <li>255 fewer total events with alirocumab among 5,629 patients with LDL-C &gt;100 mg/dl at baseline</li>
 <li>130 fewer total events with alirocumab among 13,295 patients with LDL-C</li>
</ul>

<h2>Total events study conclusion</h2>
<ul>
 <li>In the previously reported primary analysis of the study data, the observed 15% relative risk reduction (RRR) in allcause death with alirocumab was considered nominally significant due to the prespecified testing sequence of secondary endpoints</li>
 <li>The joint models showed an associated reduction in non-fatal CV events and was a predictor of non-fatal CV mortality by alirocumab</li>
 <li>The authors in the manuscript conclude that this complementary modelling strategy therefore supports the observation that alirocumab reduced all-cause death in the trial</li>
 <li>They further discuss that reduction in mortality risk may be viewed as a preferred metric to summarise the observed effect of treatment with alirocumab on mortality</li>
</ul>

Odyssey outcomes - total events results

<h2>Optimal utilization of lipid-lowering therapy (LLT) after acute coronary syndrome (ACS)</h2>
<h2>A Position Paper endorsed by the International Lipid Expert Panel (ILEP)</h2>
<h2>Main takeaway</h2>
<p>Recommendations include&nbsp;<strong>a main treatment pathway (diagnosis and stratification/target-driven LLT/support and follow-up)</strong>, along with special pathways for a few specific clinical practice scenarios.</p>
<h2>Why this matters</h2>
<p>This position paper&nbsp;<strong>complements existing guidelines on the management of lipids in patients after ACS</strong>&nbsp;and proposes&nbsp;<strong>practical approaches to improve access/adherence to LLTs</strong>&nbsp;in these patients.</p>
<h2>Key results</h2>
<ul>
 <li>Main pathway for optimal LLT post ACS includes the following: 
  <ul>
   <li>Diagnosis and stratification</li>
   <li>Target-driven LLT: Three stage target-driven approach to LLT 
    <ul>
     <li>In statin-treated patients with LDL-C &lt;100 mg/dL, statin therapy has to be intensified to maximally tolerated dose. In statin-naïve patients with LDL-C &lt;120 mg/dL, high-dose atorvastatin or rosuvastatin treatment should be commenced (&lt;50% reduction to reach target [target LDL-C: &lt;55 mg/dL]; for both the cases).</li>
     <li>In statin-treated patients with LDL-C 100–300 mg/dL or in statin-naïve patients with LDL-C 120–300 mg/dL, maximally tolerated statin therapy should be combined with ezetimibe (50–80% reduction to reach target [target LDL-C: &lt;55 mg/dL]).</li>
     <li>In any patient with LDL-C &gt;300 mg/dL on admission, triple therapy (maximally tolerated statin therapy + ezetimibe + PCSK9i) might be initiated in hospital (&gt;80% reduction to reach target [target LDL-C: &lt;55 mg/dL]).</li>
     <li>After the 4–6 week follow-up visit, treatment should be intensified (as per need), to reach the target LDL-C level; less frequent follow-up is acceptable after reaching the target LDL-C level.</li>
    </ul></li>
   <li>Support and follow-up 
    <ul>
     <li>To maximize adherence to treatment, follow-up, and escalation of LLT, a standardized discharge letter should be used.</li>
    </ul></li>
  </ul></li>
 <li>Treatment recommendations for patients in need of special pathways (as identified during diagnosis and stratification): 
  <ul>
   <li>Patients considered to be at “extremely-high” CV risk: Initial immediate dual LLT should be considered (maximally tolerated statin + ezetimibe [target LDL-C: &lt;40 mg/dL]). A PCSK9i can be prescribed at follow-up, if the target is not met.</li>
   <li>In patients with complete statin intolerance: Treatment should proceed immediately with non-statin LLT; in case of partial statin intolerance, early initiation of additional LLTs + low dose of statin should be considered to attain the LDL-C target of &lt;55 mg/dL.</li>
   <li>If target LDL-C is not attained despite receiving maximally tolerated statin dose and ezetimibe in pre-hospital period: PCSK9i initiation should be considered during hospitalization.</li>
  </ul></li>
</ul>

Optimal use of LLT after ACS

<h2>Polyvascular Disease Sub-analysis Overview</h2>
<h3>Alirocumab in Patients with Polyvascular Disease and Recent Acute Coronary Syndrome</h3>
<h3>Objective</h3>

<p>In this prespecified analysis of the Odyssey Outcomes trial, we investigate the influence of polyvascular disease (PVD) on:</p>
<ul>
 <li>Risks of MACE and death in patients with recent ACS and dyslipidemia despite intensive statin therapy</li>
 <li>The modification of risk by alirocumab</li>
</ul>

<p>For the heterogeneity of alirocumab treatment effed by polyvascular disease category, Cox models were used for interaction terms for relative risk reduction and Gail-Simon tests for AR</p>

<h2>Primary MACE: One, two or three vascular beds</h2>

<p>RRR interaction p=0.40. *In overall population, there were no differences in the incidence of adverse events or laboratory abnormalities between alirocumab and placebo groups, except for local injection-site reactions</p>

<h2>Death: One, two or three vascular beds</h2>

<p>HRs and p-values reflect stratification by geographic region</p>

<h2>Polyvascular disease sub-analysis conclusions</h2>
<ul>
 <li>Increasing risk of death in patients with affected vascular beds remain a challenge for clinicians</li>
 <li>This study demonstrates that PVD is associated with high risk of death, and yet with alirocumab, the corresponding ARR for incidence of death was 0.4% (P-interaction = 0.002)</li>
 <li>Alirocumab, when added to high-intensity statin therapy, was associated with a reduction in mortality in this group of patients</li>
</ul>

Odyssey outcomes - PVD results

<h2>Alirocumab in patients with polyvascular disease and recent Acute Coronary Syndrome.</h2>
<p><strong>J Wouter Jukema, Michael Szarek, Laurien E Zijlstra, H Asita de Silva, Deepak L Bhatt, Vera A Bittner, Rafael Diaz, Jay M Edelberg, Shaun G Goodman, Corinne Hanotin, Robert A Harrington, Yuri Karpov, Angèle Moryusef, Robert Pordy, Juan C Prieto, Matthew T Roe, Harvey D White, Andreas M Zeiher, Gregory G Schwartz, P Gabriel Steg, Odyssey Outcomes Committees and Investigators</strong></p>
<h2>Objective</h2>
<p>This pre-specified analysis from ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) determined whether polyvascular disease influenced risks of MACEs and death and their modification by alirocumab in patients with recent ACS and dyslipidemia despite intensive statin therapy.</p>
<h2>Methods</h2>
<p>The trial was a randomized, double-blind, placebo-controlled comparison of alirocumab or placebo in patients with an ACS (myocardial infarction or unstable angina) 1–12months before randomization. Qualifying patients had persistent dyslipidemia [LDL-C≥ 70mg/dL (1.81mmol/L), non-high-density lipoprotein cholesterol (non-HDL-C) ≥ 100mg/dL (2.59mmol/L), or apolipoprotein B≥ 80mg/dL despite treatment with atorvastatin 40–80 mg daily, rosuvastatin 20–40mg daily, or the maximum-tolerated dose of one of these statins.</p>
<p>Participants were randomly assigned (1:1) to receive alirocumab 75mg or matching placebo subcutaneously every 2weeks. In this analysis, 3 subgroups of patients with recent ACS were defined on the basis of the distribution of other evident vascular disease: 1) monovascular disease (CAD without known PAD or CeVD); 2) polyvascular disease in 2 vascular beds (CAD and either PAD or CeVD); and 3) polyvascular disease in 3 vascular beds (CAD with both PAD and CeVD).</p>
<h2>Endpoints</h2>
<p>The primary outcome was a composite of MACE, including death due to coronary heart disease, non-fatal myocardial infarction, ischemic stroke, or unstable angina requiring hospitalization. Death from any cause was a secondary outcome.</p>
<h2>Results</h2>
<p>A total of 18 924 patients underwent randomization; Of these, 9462 were assigned to alirocumab and 9462 to placebo with a median (quartile 1, quartile 3) follow-up of 2.8 years (2.3, 3.4 years). Of 18,924 patients, 17,370 had monovascular (coronary) disease, 1,405 had polyvascular disease in 2 beds (coronary and peripheral artery or cerebrovascular), and 149 had polyvascular disease in 3 beds (coronary, peripheral artery, cerebrovascular). With placebo, the incidence of MACEs by respective vascular categories was 10.0%, 22.2%, and 39.7%. With alirocumab, the corresponding absolute risk reduction was 1.4% (95% confidence interval [CI]: 0.6% to 2.3%), 1.9% (95% CI: -2.4% to 6.2%), and 13.0% (95% CI: -2.0% to 28.0%). With placebo, the incidence of death by respective vascular categories was 3.5%, 10.0%, and 21.8%; the absolute risk reduction with alirocumab was 0.4% (95% CI: -0.1% to 1.0%), 1.3% (95% CI: -1.8% to 4.3%), and 16.2% (95% CI: 5.5% to 26.8%).</p>
<h2>Conclusion</h2>
<p>Patients with recent ACS and dyslipidemia despite intensive statin therapy, polyvascular disease is associated with high risks of MACEs and death. The large absolute reductions in those risks with alirocumab are a potential benefit for these patients.</p>

Odyssey Outcomes - PVD Sub-analysis

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