<h2>Main Takeaway</h2>
<ul>
 <li>
 In high-risk patients with severe hypercholesterolemia&nbsp;receiving maximum tolerated dose (MTD) of statins ± lipid-lowering therapies (LLTs):</li>
 <li>Add-on therapy with&nbsp;alirocumab was shown to be generally well tolerated, with the incidence of treatment-emergent adverse events (TEAEs) being similar to those reported in previous trials.</li>
 <li>Treatment with&nbsp;alirocumab reduced low-density lipoprotein cholesterol (LDL-C) levels by over&nbsp;50% from baseline to Week 12; this was sustained throughout the treatment duration (up to 2 years)</li>
</ul>

<h2>Why This Matters</h2>
<ul>
 <li>
 Familial hypercholesterolemia (FH) is associated with&nbsp;increased cardiovascular (CV) risk.</li>
 <li>In clinical practice, despite MTD therapy (with or without ezetimibe),&nbsp;many patients with heterozygous FH (HeFH) fail to attain guideline-recommended LDL-C goals&nbsp;without additional LLTs. Statin intolerance remains a concern in some patients, and discontinuation of statin therapy may cause an increase in CV events</li>
</ul>

<h2>Study Design</h2>
<ul>
 <li>Odyssey apprise (NCT02476006), a real-life European/Canadian, prospective, single-arm, phase 3b, open-label study, duration ≥12 weeks to ≤30 months, evaluated the safety and efficacy of alirocumab (subcutaneous dosing regimen: 75 or 150 mg every 2 weeks, dose adjustment allowed at investigator’s discretion) 
 <ul>
 <li>Alirocumab was administered on top of background MTD statin (rosuvastatin 20 or 40 mg/day, atorvastatin 40 or 80 mg/day, or simvastatin 80 mg/day) ± other LLTs</li>
 </ul></li>
 <li>Eligibility criteria: Patients aged ≥18 years, with HeFH or with non-familial hypercholesterolemia and established coronary heart disease (CHD) or a CHD risk equivalent, and with hypercholesterolemia not adequately controlled with MTD ± LLT</li>
 <li>Primary endpoint: To assess safety parameters including treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs)</li>
 <li>Main secondary (efficacy) endpoint: The percent change in calculated LDL-C from baseline to Week 12</li>
</ul>

<h2>Key Results</h2>
<h3>Safety</h3>
<ul>
 <li>Overall, 994 patients were enrolled and treated, with a mean duration of alirocumab exposure [SD] = 72.4 [42.5] weeks</li>
 <li>Primary endpoint:&nbsp;TEAEs were reported in 712/994 patients
 <ul>
 <li>Four deaths were reported during the on-study period: 2 were during the TEAE period but were not considered as related to alirocumab. Three additional deaths occurred post-study</li>
 <li>45/994 patients permanently discontinued treatment due to a TEAE</li>
 <li>161/994 patients developed TESAEs;&nbsp;9/994 patients were considered to have TESAEs related to alirocumab</li>
 <li>34/994 patients had TEAEs corresponding to AEs of special interest</li>
 </ul></li>
</ul>
<h3>Efficacy</h3>
<ul>
 <li>
 Secondary endpoint: Mean (SD)&nbsp;LDL-C level decreased by 2.6 (1.2) mmol/L&nbsp;from baseline to Week 12 (54.8%; modified intention-to-treat population). This reduction was&nbsp;maintained throughout the study duration</li>
</ul>

<h2>Limitations</h2>
<ul>
 <li>
 The study lacked a comparative control and a treatment bias may exist owing to the open-label design</li>
 <li>Limited applicability of the study findings to other patient populations</li>
 <li>Data on new-onset diabetes and changes in lipoprotein(a) levels were missing</li>
</ul>

Reference

Safety and efficacy of alirocumab in patients with Hypercholesterolemia and high cardiovascular risk in a real-life setting.

Real-life safety and efficacy of Alirocumab - Odyssey apprise study

DYSLIPIDEMIA

CARDIOLOGY

<h2>Odyssey Outcomes: Addition of PCSK9i to background Statin therapy further reduces MACE.</h2>

<h2>Elderly patients sub-analysis overview</h2>
<h3>Study outcomes</h3>
Primary outcome:&nbsp;composite of death from CHD, nonfatal myocardial infarction, fatal or nonfatal ischemic stroke, or unstable angina requiring hospitalization Key secondary outcome:&nbsp;all-cause death 
 All outcomes were adjudicated by physicians who were unaware of the trial-group assignments
*Pre-specified analysis: Age &lt;65 years (n=13,840), age≥65 years (n=5,084). The Cox regression model with age as a continuous variable, randomized treatment and the interaction was used to estimate the event rate at 3 years and HRs comparing alirocumab versus placebo at specific ages to test the interaction between age and treatment with alirocumab
<h2>Baseline characteristics by age group</h2>
<table align="center" border="1" cellpadding="10" cellspacing="1">
 <tbody>
 <tr>
 <td style="width: 51%;">
 Characteristic</td>
 <td style="width: 18%;">
 &lt;65 years (n=13,840)</td>
 <td style="width: 17%;">
 ≥65 years (n=5084)</td>
 <td style="width: 13%;">
 P-value</td>
 </tr>
 <tr>
 <td style="width: 51%;">
 Age (years), mean ± SD</td>
 <td style="width: 18%;">
 54.2 ± 6.3</td>
 <td style="width: 18%;">
 70.5 ± 4.7</td>
 <td style="width: 13%;">
 &nbsp;</td>
 </tr>
 <tr>
 <td style="width: 51%;">
 Women, n (%)</td>
 <td style="width: 18%;">
 2948 (21.3)</td>
 <td style="width: 17%;">
 1814 (35.7)</td>
 <td style="width: 13%;">
 &lt;0.0001</td>
 </tr>
 <tr>
 <td style="width: 51%;">
 Medical history before index ACS, n (%)</td>
 <td style="width: 18%;">
 &nbsp;</td>
 <td style="width: 17%;">
 &nbsp;</td>
 <td style="width: 13%;">
 &nbsp;</td>
 </tr>
 <tr>
 <td style="width: 51%;">
 Hypertension</td>
 <td style="width: 18%;">
 8390 (60.6)</td>
 <td style="width: 17%;">
 3859 (75.9)</td>
 <td style="width: 13%;">
 &lt;0.0001</td>
 </tr>
 <tr>
 <td style="width: 51%;">
 Diabetes mellitus</td>
 <td style="width: 18%;">
 3787 (27.4)</td>
 <td style="width: 17%;">
 1657 (32.6)</td>
 <td style="width: 13%;">
 &lt;0.0001</td>
 </tr>
 <tr>
 <td style="width: 51%;">
 Myocardial infarction</td>
 <td style="width: 18%;">
 2499 (18.1)</td>
 <td style="width: 17%;">
 1134 (22.3)</td>
 <td style="width: 13%;">
 &lt;0.0001</td>
 </tr>
 <tr>
 <td style="width: 51%;">
 Percutaneous coronary intervention</td>
 <td style="width: 18%;">
 2212 (16.0)</td>
 <td style="width: 17%;">
 1029 (20.2)</td>
 <td style="width: 13%;">
 &lt;0.0001</td>
 </tr>
 <tr>
 <td style="width: 51%;">
 Coronary artery bypass graft</td>
 <td style="width: 18%;">
 582 (4.2)</td>
 <td style="width: 17%;">
 465 (9.1)</td>
 <td style="width: 13%;">
 &lt;0.0001</td>
 </tr>
 <tr>
 <td style="width: 51%;">
 Stroke</td>
 <td style="width: 18%;">
 337 (2.4)</td>
 <td style="width: 17%;">
 274 (5.4)</td>
 <td style="width: 13%;">
 &lt;0.0001</td>
 </tr>
 <tr>
 <td style="width: 51%;">
 Peripheral artery disease</td>
 <td style="width: 18%;">
 428 (3.1)</td>
 <td style="width: 17%;">
 331 (6.5)</td>
 <td style="width: 13%;">
 &lt;0.0001</td>
 </tr>
 <tr>
 <td style="width: 51%;">
 Congestive heart failure</td>
 <td style="width: 18%;">
 1800 (13.0)</td>
 <td style="width: 17%;">
 1014 (19.9)</td>
 <td style="width: 13%;">
 &lt;0.0001</td>
 </tr>
 <tr>
 <td style="width: 51%;">
 Index, ACS, n (%)</td>
 <td style="width: 18%;">
 n=13,818</td>
 <td style="width: 17%;">
 n=5075</td>
 <td style="width: 13%;">
 &lt;0.0001</td>
 </tr>
 <tr>
 <td style="width: 51%;">
 STEMI</td>
 <td style="width: 18%;">
 5039 (36.4)</td>
 <td style="width: 17%;">
 1497 (29.4)</td>
 <td style="width: 13%;">
 &nbsp;</td>
 </tr>
 <tr>
 <td style="width: 51%;">
 Non-STEMI</td>
 <td style="width: 18%;">
 6422 (46.4)</td>
 <td style="width: 17%;">
 2753 (54.2)</td>
 <td style="width: 13%;">
 &nbsp;</td>
 </tr>
 <tr>
 <td style="width: 51%;">
 Unstable angina</td>
 <td style="width: 18%;">
 2357 (17.0)</td>
 <td style="width: 17%;">
 825 (16.2)</td>
 <td style="width: 13%;">
 &nbsp;</td>
 </tr>
 <tr>
 <td style="width: 51%;">
 PCI or CABG for index ACS, n (%)</td>
 <td style="width: 18%;">
 10,201 (73.7)</td>
 <td style="width: 18%;">
 3475 (68.4)</td>
 <td style="width: 13%;">
 &lt;0.0001</td>
 </tr>
 </tbody>
</table>
SD, Standard deviation
<table align="center" border="1" cellpadding="10" cellspacing="1">
 <tbody>
 <tr>
 <td style="width: 51%;">
 Characteristic</td>
 <td style="width: 18%;">
 &lt;65 years (n=13,840)</td>
 <td style="width: 18%;">
 ≥65 years (n=5084)</td>
 <td style="width: 13%;">
 P-value</td>
 </tr>
 <tr>
 <td style="width: 51%;">
 The from index ACS to randomization 
 (months), mean ± SD</td>
 <td style="width: 18%;">
 3.6 ± 2.8</td>
 <td style="width: 18%;">
 3.8 ± 2.8</td>
 <td style="width: 13%;">
 0.0003</td>
 </tr>
 <tr>
 <td style="width: 51%;">
 Body mass index (kg/m2), mean ± SD</td>
 <td style="width: 18%;">
 28.8 ± 4.9</td>
 <td style="width: 18%;">
 27.8 ± 4.6</td>
 <td style="width: 13%;">
 &lt;0.0001</td>
 </tr>
 <tr>
 <td style="width: 51%;">
 Renal function</td>
 <td style="width: 18%;">
 &nbsp;</td>
 <td style="width: 18%;">
 &nbsp;</td>
 <td style="width: 13%;">
 &nbsp;</td>
 </tr>
 <tr>
 <td style="width: 51%;">
 eGFR (mL/min), mean ± SD</td>
 <td style="width: 18%;">
 83.1 ± 18.5</td>
 <td style="width: 18%;">
 70.2 ± 18.2</td>
 <td style="width: 13%;">
 &lt;0.0001</td>
 </tr>
 <tr>
 <td style="width: 51%;">
 eGFR &lt;60 mL/min, n (%)</td>
 <td style="width: 18%;">
 1,163 (8.4)</td>
 <td style="width: 18%;">
 1,377 (27.1)</td>
 <td style="width: 13%;">
 &lt;0.0001</td>
 </tr>
 <tr>
 <td style="width: 51%;">
 Lipid-lowering drugs at randomization, n (%)</td>
 <td style="width: 18%;">
 &nbsp;</td>
 <td style="width: 18%;">
 &nbsp;</td>
 <td style="width: 13%;">
 &lt;0.0001</td>
 </tr>
 <tr>
 <td style="width: 51%;">
 High-intensity 
 atorvastatin/rosuvastatin</td>
 <td style="width: 18%;">
 12,565 (90.8)</td>
 <td style="width: 18%;">
 4,246 (83.5)</td>
 <td style="width: 13%;">
 &nbsp;</td>
 </tr>
 <tr>
 <td style="width: 51%;">
 Low- or moderate-intensity atorvastatin/rosuvastatin</td>
 <td style="width: 18%;">
 1,027 (7.4)</td>
 <td style="width: 18%;">
 580 (11.4)</td>
 <td style="width: 13%;">
 &nbsp;</td>
 </tr>
 <tr>
 <td style="width: 51%;">
 No statin</td>
 <td style="width: 18%;">
 222 (1.6)</td>
 <td style="width: 18%;">
 238 (4.7)</td>
 <td style="width: 13%;">
 &nbsp;</td>
 </tr>
 <tr>
 <td style="width: 51%;">
 Ezetibime</td>
 <td style="width: 18%;">
 408 (2.9)</td>
 <td style="width: 18%;">
 142 (2.8)</td>
 <td style="width: 13%;">
 0.57</td>
 </tr>
 </tbody>
</table>

Abbreviations

<h3>Treatment effect by age group: Primary composite outcome</h3>

Relative Risk Reduction Hazard Ratio (Alirocumab vs Placebo) 
 ≥65 years: 0.78, 95% CI 0.68-0.91 
 &lt;65 years: 0.89, 95% CI 0.80-1.00 
 Interaction p-value: 0.19
Absolute Risk Reduction At 3 years (Placebo - Alirocumab) 
 ≥65 years: 3.88%, 95% Cl 1.74-6.02 
 &lt;65 years: 0.91%, 95% Cl -0.13 to 1.95 
 Interaction p-value: 0.015

<h3>Treatment effect by age group: All cause death</h3>

Relative Risk Reduction Hazard Ratio (Alirocumab vs Placebo) 
 ≥65 years: 0.77, 95% CI 0.62-0.95 
 &lt;65 years: 0.94, 95% CI 0.77-1.15 
 Interaction p-value: 0.46
Absolute Risk Reduction At 3 years (Placebo - Alirocumab) 
 ≥65 years: 2.08%, 95% Cl 0.48-3.67 
 &lt;65 years: 0.11%, 95% Cl -0.50 to 1.72 
 Interaction p-value: 0.024

<h2>Safety: Adverse events by age group</h2>
<table align="center" border="1" cellpadding="10" cellspacing="1">
 <tbody>
 <tr>
 <td style="width: 50px;">
 Adverse Event</td>
 <td colspan="2" rowspan="1" style="width: 28px;">
 Randomized Treatment</td>
 <td style="width: 20%;">
 Relative Risk (95%CI) Alirocumab vs Placebo</td>
 </tr>
 <tr>
 <td style="width: 50px;">
 &nbsp;</td>
 <td style="width: 14px;">
 Alirocumab, N (%)</td>
 <td style="width: 14%;">
 Placebo, N (%)</td>
 <td style="width: 20%;">
 &nbsp;</td>
 </tr>
 <tr>
 <td style="width: 50px;">
 Any adverse event</td>
 <td style="width: 14px;">
 &nbsp;</td>
 <td style="width: 14%;">
 &nbsp;</td>
 <td style="width: 20%;">
 &nbsp;</td>
 </tr>
 <tr>
 <td style="width: 50px;">
 ≥65 years</td>
 <td style="width: 14px;">
 1,974 (79.0)</td>
 <td style="width: 14%;">
 2,042 (79.3)</td>
 <td style="width: 20%;">
 1.00 (0.97 -1.02)</td>
 </tr>
 <tr>
 <td style="width: 50px;">
 &lt;65 years</td>
 <td style="width: 14px;">
 5,191 (74.7)</td>
 <td style="width: 14%;">
 5,240 (76.3)</td>
 <td style="width: 20%;">
 0.98 (0.96 -1.00)</td>
 </tr>
 <tr>
 <td style="width: 50px;">
 Serious adverse event</td>
 <td style="width: 14px;">
 &nbsp;</td>
 <td style="width: 14%;">
 &nbsp;</td>
 <td style="width: 20%;">
 &nbsp;</td>
 </tr>
 <tr>
 <td style="width: 50px;">
 ≥65 years</td>
 <td style="width: 14px;">
 703 (28.1)</td>
 <td style="width: 14%;">
 781 (30.3)</td>
 <td style="width: 20%;">
 0.93 (0.85 -1.01)</td>
 </tr>
 <tr>
 <td style="width: 50px;">
 &lt;65 years</td>
 <td style="width: 14px;">
 1,499 (21.6)</td>
 <td style="width: 14%;">
 1,569 (22.8)</td>
 <td style="width: 20%;">
 0.94 (0.89 -1.00)</td>
 </tr>
 <tr>
 <td style="width: 50px;">
 Adverse event leading to discontinuation of treatment</td>
 <td style="width: 14px;">
 &nbsp;</td>
 <td style="width: 14%;">
 &nbsp;</td>
 <td style="width: 20%;">
 &nbsp;</td>
 </tr>
 <tr>
 <td style="width: 50px;">
 ≥65 years</td>
 <td style="width: 14px;">
 121 (4.8)</td>
 <td style="width: 14%;">
 128 (5.0)</td>
 <td style="width: 20%;">
 0.97 (0.76 -1.24)</td>
 </tr>
 <tr>
 <td style="width: 50px;">
 &lt;65 years</td>
 <td style="width: 14px;">
 222 (3.2)</td>
 <td style="width: 14%;">
 196 (2.9)</td>
 <td style="width: 20%;">
 1.12 (0.93 -1.35)</td>
 </tr>
 <tr>
 <td style="width: 50px;">
 Neurocognitive disorder</td>
 <td style="width: 14px;">
 &nbsp;</td>
 <td style="width: 14%;">
 &nbsp;</td>
 <td style="width: 20%;">
 &nbsp;</td>
 </tr>
 <tr>
 <td style="width: 50px;">
 ≥65 years</td>
 <td style="width: 14px;">
 52 (2.1)</td>
 <td style="width: 14%;">
 65 (2.5)</td>
 <td style="width: 20%;">
 0.82 (0.57 -1.18)</td>
 </tr>
 <tr>
 <td style="width: 50px;">
 &lt;65 years</td>
 <td style="width: 14px;">
 91 (1.3)</td>
 <td style="width: 14%;">
 102 (1.5)</td>
 <td style="width: 20%;">
 0.88 (0.67 -1.17)</td>
 </tr>
 <tr>
 <td style="width: 50px;">
 New-onset diabetes in patients w/o diabetes at baseline</td>
 <td style="width: 14px;">
 &nbsp;</td>
 <td style="width: 14%;">
 &nbsp;</td>
 <td style="width: 20%;">
 &nbsp;</td>
 </tr>
 <tr>
 <td style="width: 50px;">
 ≥65 years</td>
 <td style="width: 14px;">
 156 (9.2)</td>
 <td style="width: 14%;">
 167 (9.7)</td>
 <td style="width: 20%;">
 0.95 (0.77 -1.17)</td>
 </tr>
 <tr>
 <td style="width: 50px;">
 &lt;65 years</td>
 <td style="width: 14px;">
 492 (9.7)</td>
 <td style="width: 14%;">
 509 (10.2)</td>
 <td style="width: 20%;">
 0.95 (0.84 -1.07)</td>
 </tr>
 <tr>
 <td style="width: 50px;">
 Hemorrhagic stroke - adjudicated</td>
 <td style="width: 14px;">
 &nbsp;</td>
 <td style="width: 14%;">
 &nbsp;</td>
 <td style="width: 20%;">
 &nbsp;</td>
 </tr>
 <tr>
 <td style="width: 50px;">
 ≥65 years</td>
 <td style="width: 14px;">
 1 (0.0)</td>
 <td style="width: 14%;">
 6 (0.2)</td>
 <td style="width: 20%;">
 0.17 (0.02 -1.42)</td>
 </tr>
 <tr>
 <td style="width: 50px;">
 &lt;65 years</td>
 <td style="width: 14px;">
 8 (0.1)</td>
 <td style="width: 14%;">
 10 (0.1)</td>
 <td style="width: 20%;">
 0.79 (0.31 -2.00)</td>
 </tr>
 <tr>
 <td style="width: 50px;">
 Alanine aminotransferase&gt; 3 x upper limit of normal</td>
 <td style="width: 14px;">
 &nbsp;</td>
 <td style="width: 14%;">
 &nbsp;</td>
 <td style="width: 20%;">
 &nbsp;</td>
 </tr>
 <tr>
 <td style="width: 50px;">
 ≥65 years</td>
 <td style="width: 14px;">
 64 (2.6)</td>
 <td style="width: 14%;">
 70 (2.8)</td>
 <td style="width: 20%;">
 0.94 (0.67 -1.31)</td>
 </tr>
 <tr>
 <td style="width: 50px;">
 &lt;65 years</td>
 <td style="width: 14px;">
 148 (2.1)</td>
 <td style="width: 14%;">
 158 (2.3)</td>
 <td style="width: 20%;">
 0.92 (0.74 -1.15)</td>
 </tr>
 <tr>
 <td style="width: 50px;">
 Aspartate</td>
 <td style="width: 14px;">
 &nbsp;</td>
 <td style="width: 14%;">
 &nbsp;</td>
 <td style="width: 20%;">
 &nbsp;</td>
 </tr>
 <tr>
 <td style="width: 50px;">
 ≥65 years</td>
 <td style="width: 14px;">
 52 (2.1)</td>
 <td style="width: 14%;">
 48 (1.9)</td>
 <td style="width: 20%;">
 1.11 (0.75 -1.64)</td>
 </tr>
 <tr>
 <td style="width: 50px;">
 &lt;65 years</td>
 <td style="width: 14px;">
 108 (1.6)</td>
 <td style="width: 14%;">
 118 (1.7)</td>
 <td style="width: 20%;">
 0.90 (0.70 -1.17)</td>
 </tr>
 </tbody>
</table>
<h2>Elderly Patients’ sub-analysis conclusions¹</h2>
<ul>
 <li>Alirocumab demonstrated an effective RRR for primary MACE outcome, and was associated with an effective reduction of all-cause death across age categories</li>
 <li>There was a highly significant interaction of treatment effect and age on the absolute reduction of all-cause death, and although adverse events generally were more frequent in older patients, there was no increase occurrence in any of the safety endpoints</li>
</ul>

Abbreviation

Odyssey outcomes - elderly patients results

<h2>Alirocumab reduces total nonfatal cardiovascular and fatal events the Odyssey Outcomes&nbsp;trial.</h2>
Michael Szarek, Harvey D White, Gregory G Schwartz, Marco Alings, Deepak L Bhatt, Vera A Bittner, Chern-En Chiang, Rafael Diaz, Jay M Edelberg, Shaun G Goodman, Corinne Hanotin, Robert A Harrington, J Wouter Jukema, Takeshi Kimura, Robert Gabor Kiss, Guillaume Lecorps, Kenneth W Mahaffey, Angèle Moryusef, Robert Pordy, Matthew T Roe, Pierluigi Tricoci, Denis Xavier, Andreas M Zeiher, Ph Gabriel Steg, Odyssey Outcomes Committees and Investigators.
<h2>Objective</h2>
This pre-specified analysis determined the extent to which alirocumab reduced total (first and subsequent) nonfatal cardiovascular events and all-cause deaths in Odyssey Outcomes.
<h2>Methods</h2>
The Odyssey Outcomes (Evaluation of Cardiovascular outcomes after an Acute Coronary Syndrome during treatment with Alirocumab) trial compared Alirocumab with placebo, added to high-intensity or maximumtolerated statin treatment, after Acute Coronary Syndrome (ACS) in 18,924 patients. Patients were aged ≥40 years with an ACS 1–12 months before randomization. Qualifying patients had persistent dyslipidemia [LDL-C ≥ 70 mg/dL (1.81 mmol/L), non high-density lipoprotein cholesterol (non-HDL-C) ≥ 100 mg/dL (2.59 mmol/L), or apolipoprotein B ≥ 80 mg/dL] despite treatment with atorvastatin 40–80 mg daily, rosuvastatin 20–40 mg daily, or the maximumtolerated dose of one of these statins.
Participants were randomly assigned (1:1) to receive alirocumab 75 mg or matching placebo subcutaneously every 2 weeks.
<h2>Endpoints</h2>
The primary efficacy endpoint of the study was time to first occurrence of coronary heart disease death, nonfatal myocardial infarction, fatal and nonfatal ischemic stroke, or unstable angina requiring hospitalization. Nonfatal cardiovascular events recorded in the trial included nonfatal primary endpoints, hemorrhagic stroke, heart failure requiring hospitalization, and ischemia-driven coronary revascularization. Events included in the primary analysis of the present report were all-cause death and total nonfatal cardiovascular events.
<h2>Results</h2>
Patients were followed for survival for a median of 2.8 years (quartile 1, quartile 3: 2.3, 3.4 years), consisting of 27,014 patient-years for the alirocumab group and 26,915 patient-years for the placebo group.
With 3,064 first and 5,425 total events, 190 fewer first and 385 fewer total nonfatal cardiovascular events or deaths were observed with alirocumab compared with placebo. Alirocumab reduced total nonfatal cardiovascular events (hazard ratio: 0.87; 95% confidence interval: 0.82 to 0.93) and death (hazard ratio: 0.83; 95% confidence interval: 0.71 to 0.97) in the presence of a strong association between nonfatal and fatal event risk.
<h2>Conclusion</h2>
In patients with ACS, the total number of nonfatal cardiovascular events and deaths prevented with alirocumab was twice the number of first events prevented. Consequently, total event reduction is a more.
comprehensive metric to capture the totality of alirocumab clinical efficacy after ACS.

Odyssey Outcomes - Total Events Analysis

<h2>Odyssey Outcomes: Addition of PCSK9i to background Statin therapy further reduces MACE</h2>

<h2>Mortality study results</h2>
<h3>Effect of Alirocumab on All-Cause, CV or Non-CV death</h3>

*Stratified by geographic region. †Nominal p-value, as all-cause death followed CHD death and cardiovascular death in tile prespecified hierarchy of main secondary endpoints, the p-value for all-cause death was considered nominal
<h2>All-cause death: All patients vs patients eligible for ≥3 years of follow-up</h2>

*Because all-cause death followed CHD death and CV death in the pre specified hierarchy or main secondary endpoints, the p-value for all-cause death was considered nominal. Alirocumab is associated with lower all-cause death as compared to placebo. Patients were eligible for ≥3 years or follow-up if randomized ≥3 years before the common study end date.
**First year HR 1.01 (95% Cl 0.77, 1.32); for patients eligible for &lt;3 years of follow-up HR 0.96 (95% Cl 0.76, 1.21).
<h2>Post-hoc analysis: All-cause death by baseline LDL-C subgroups</h2>

Relative risk reduction: Pinteraction=0.12
Absolute risk reduction: Pinteraction=0.005
*Based on cumulative incidence, alirocumab is associated with lower all-cause death as compared to placebo
<h2>Mortality study conclusions</h2>
<ul>
 <li>The risk of non-CV death is usually assumed to be independent of risk of CV events, and there is unmodifiable risk by LDL-C lowering</li>
 <li>In the post-hoc, joint semiparametric modelling approach, alirocumab treatment was associated with a favorable effect on risk of nonfatal CV events and was a predictor of non-CV death. The association parameter indicates that these risks are linked</li>
</ul>

Odyssey outcomes - mortality

<h2>Effect of Alirocumab on mortality after Acute Coronary Syndrome. An analysis of the Odyssey Outcomes randomized clinical trial.</h2>
Philippe Gabriel Steg, Michael Szarek, Deepak L. Bhatt, Vera A. Bittner, Marie-France Brégeault, Anthony J. Dalby, Rafael Diaz, Jay M. Edelberg, Shaun G. Goodman, Corinne Hanotin, Robert A. Harrington, J. Wouter Jukema, Guillaume Lecorps, Kenneth W. Mahaffey, Angèle Moryusef, Petr Ostadal, Alexander Parkhomenko, Robert Pordy, Matthew T. Roe, Pierluigi Tricoci, Robert Vogel, Harvey D. White, Andreas M. Zeiher, Gregory G. Schwartz, For the Odyssey Outcomes Committees and Investigators
<h2>Objective</h2>
To better understand the effects of alirocumab on death, this report describes all-cause, cardiovascular, and non-cardiovascular death in participants eligible for ≥3 years of follow-up, the interaction of treatment and baseline LDL-C on death, and the association between nonfatal cardiovascular events and non-cardiovascular death.
<h2>Methods</h2>
Odyssey Outcomes (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Patients were aged ≥40 years with an ACS 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.
Participants were randomly assigned (1:1) to receive alirocumab 75mg or matching placebo subcutaneously every 2 weeks.
<h2>Endpoints</h2>
The primary end point was the composite of death caused by CHD, nonfatal myocardial infarction, ischemic stroke, or unstable angina requiring hospitalization. To control for multiplicity, secondary end points were analyzed in the following prespecified hierarchical sequence to preserve type I error: any CHD event; major CHD event; any cardiovascular event; the composite of all-cause death, nonfatal myocardial infarction, or ischemic stroke; CHD death; cardiovascular death; and all-cause death.
<h2>Results</h2>
Median follow-up was 2.8 (interquartile range, 2.3–3.4) years. Premature treatment discontinuation for reasons other than death or blind switch to placebo because of low LDL-C levels occurred in 1343 (14.2%) patients receiving alirocumab and 1496 (15.8%) patients receiving placebo.
Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and non-cardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for ≥3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and non-cardiovascular deaths (P&lt;0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events (P&lt;0.001) and thereby may have attenuated the number of cardiovascular and non-cardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C ≥100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; P interaction=0.007). In the alirocumab group, all-cause death declined with achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend).
<h2>Conclusion</h2>
Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for ≥3 years, if baseline LDL-C is ≥100 mg/dL, or if achieved LDL-C is low.

Odyssey outcomes - CVOT mortality sub-analysis

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

<h2>CABG Sub-analysis overview</h2>
<h3>Study Design</h3>
<ul>
 <li>Prespecified analysis</li>
 <li>Patients were categorized by coronary artery bypass graft (CABG) status: 
 <ul>
 <li>No CABG (n=16,896)</li>
 <li>CABG after the index ACS but before randomization (index CABG; n=1,025, including n=44 with prior CABG), or</li>
 <li>CABG prior to the index ACS (prior CABG; n=1 ,003)</li>
 </ul></li>
 <li>The primary composite endpoint of MACE encompassed CHD death, nonfatal MI, ischemic stroke, or unstable angina requiring hospitalization 
 <ul>
 <li>The secondary endpoint was all-cause death</li>
 </ul></li>
</ul>
<h2>Baseline demographics and index events</h2>
<table align="center" border="1" cellpadding="10" cellspacing="1">
 <tbody>
 <tr>
 <td style="background-color: rgb(244, 242, 247); width: 39%;">
 No CABG (n=16,896)</td>
 <td style="background-color: rgb(244, 242, 247); width: 16%;">
 Index CABG (n=1,025)</td>
 <td style="background-color: rgb(244, 242, 247); width: 16%;">
 Prior CABG (n=1,003)</td>
 <td style="background-color: rgb(244, 242, 247); width: 16%;">
 P-value</td>
 <td style="background-color: rgb(244, 242, 247); width: 13%;">&nbsp;</td>
 </tr>
 <tr>
 <td style="width: 39%;">
 Age, years, median (Q1, Q3)</td>
 <td style="width: 16%;">
 58 (51, 65)</td>
 <td style="width: 16%;">
 60 (53, 65)</td>
 <td style="width: 16%;">
 63 (57, 70)</td>
 <td style="width: 13%;">
 &lt;0.0001</td>
 </tr>
 <tr>
 <td style="width: 39%;">
 Female, % (n)</td>
 <td style="width: 16%;">
 25.8 (4,354)</td>
 <td style="width: 16%;">
 20.6 (211)</td>
 <td style="width: 16%;">
 19.6 (197)</td>
 <td style="width: 13%;">
 &lt;0.0001</td>
 </tr>
 <tr>
 <td style="width: 39%;">
 Body mass index, kg/m2, median (Q1, Q3)</td>
 <td style="width: 16%;">
 28 (25, 31)</td>
 <td style="width: 16%;">
 28 (25, 31)</td>
 <td style="width: 16%;">
 29 (26, 32)</td>
 <td style="width: 13%;">
 &lt;0.0001</td>
 </tr>
 <tr>
 <td style="width: 39%;">
 Region, % (n)</td>
 <td style="width: 16%;">
 &nbsp;</td>
 <td style="width: 16%;">
 &nbsp;</td>
 <td style="width: 16%;">
 &nbsp;</td>
 <td style="width: 13%;">
 &lt;0.0001</td>
 </tr>
 <tr>
 <td style="width: 39%;">
 Western Europe</td>
 <td style="width: 16%;">
 22.3 (3,767)</td>
 <td style="width: 16%;">
 22.4 (230)</td>
 <td style="width: 16%;">
 17.7 (178)</td>
 <td style="width: 13%;">
 &nbsp;</td>
 </tr>
 <tr>
 <td style="width: 39%;">
 Eastern Europe</td>
 <td style="width: 16%;">
 29.9 (5,049)</td>
 <td style="width: 16%;">
 17.6 (180)</td>
 <td style="width: 16%;">
 20.7 (208)</td>
 <td style="width: 13%;">
 &nbsp;</td>
 </tr>
 <tr>
 <td style="width: 39%;">
 North America</td>
 <td style="width: 16%;">
 13.5 (2,273)</td>
 <td style="width: 16%;">
 24.1 (247)</td>
 <td style="width: 16%;">
 35.0 (351)</td>
 <td style="width: 13%;">
 &nbsp;</td>
 </tr>
 <tr>
 <td style="width: 39%;">
 South America</td>
 <td style="width: 16%;">
 13.6 (2,293)</td>
 <td style="width: 16%;">
 17.6 (180)</td>
 <td style="width: 16%;">
 11.5 (115)</td>
 <td style="width: 13%;">
 &nbsp;</td>
 </tr>
 <tr>
 <td style="width: 39%;">
 Asia</td>
 <td style="width: 16%;">
 13.0 (2,196)</td>
 <td style="width: 16%;">
 5.5 (56)</td>
 <td style="width: 16%;">
 4.1 (41)</td>
 <td style="width: 13%;">
 &nbsp;</td>
 </tr>
 <tr>
 <td style="width: 39%;">
 Rest of the world</td>
 <td style="width: 16%;">
 7.8 (1,318)</td>
 <td style="width: 16%;">
 12.9 (132)</td>
 <td style="width: 16%;">
 11.0 (110)</td>
 <td style="width: 13%;">
 &nbsp;</td>
 </tr>
 <tr>
 <td style="width: 39%;">
 Index event, % (n)</td>
 <td style="width: 16%;">
 &nbsp;</td>
 <td style="width: 16%;">
 &nbsp;</td>
 <td style="width: 16%;">
 &nbsp;</td>
 <td style="width: 13%;">
 &lt;0.0001</td>
 </tr>
 <tr>
 <td style="width: 39%;">
 NSTEMI</td>
 <td style="width: 16%;">
 46.9 (7,913)</td>
 <td style="width: 16%;">
 59.8 (612)</td>
 <td style="width: 16%;">
 64.9 (650)</td>
 <td style="width: 13%;">
 &nbsp;</td>
 </tr>
 <tr>
 <td style="width: 39%;">
 STEMI</td>
 <td style="width: 16%;">
 36.5 (6,156)</td>
 <td style="width: 16%;">
 20.9 (214)</td>
 <td style="width: 16%;">
 16.6 (166)</td>
 <td style="width: 13%;">
 &nbsp;</td>
 </tr>
 <tr>
 <td style="width: 39%;">
 Unstable angina</td>
 <td style="width: 16%;">
 16.6 (2,798)</td>
 <td style="width: 16%;">
 19.3 (198)</td>
 <td style="width: 16%;">
 18.6 (186)</td>
 <td style="width: 13%;">
 &nbsp;</td>
 </tr>
 <tr>
 <td style="width: 39%;">
 Time from index event to randomization, months, median (Q1, Q3)</td>
 <td style="width: 16%;">
 2.6 (1.7, 4.2)</td>
 <td style="width: 16%;">
 3.8 (2.7, 6.8)</td>
 <td style="width: 16%;">
 2.5 (1.7, 4.1)</td>
 <td style="width: 13%;">
 &lt;0.0001</td>
 </tr>
 </tbody>
</table>

<h2>Lipid-Lowering Therapy at Randomization and Baseline Laboratory Parameters</h2>
<table align="center" border="1" cellpadding="10" cellspacing="1">
 <tbody>
 <tr>
 <td style="background-color: rgb(244, 242, 247); width: 39%;">
 No CABG (n=16,896)</td>
 <td style="background-color: rgb(244, 242, 247); width: 16%;">
 Index CABG (n=1,025)</td>
 <td style="background-color: rgb(244, 242, 247); width: 16%;">
 Prior CABG (n=1,003)</td>
 <td style="background-color: rgb(244, 242, 247); width: 16%;">
 P-value</td>
 <td style="background-color: rgb(244, 242, 247); width: 13%;">&nbsp;</td>
 </tr>
 <tr>
 <td style="width: 39%;">
 Lipid-lowering therapy at randomization, % (n)</td>
 <td style="width: 16%;">
 &nbsp;</td>
 <td style="width: 16%;">
 &nbsp;</td>
 <td style="width: 16%;">
 &nbsp;</td>
 <td style="width: 13%;">
 &lt;0.0001</td>
 </tr>
 <tr>
 <td style="width: 39%;">
 High-dose atorvastatin or rosuvastatin</td>
 <td style="width: 16%;">
 89.2 (15,077)</td>
 <td style="width: 16%;">
 87.8 (900)</td>
 <td style="width: 16%;">
 83.2 (834)</td>
 <td style="width: 13%;">
 &nbsp;</td>
 </tr>
 <tr>
 <td style="width: 39%;">
 Other lipid-lowering therapy3</td>
 <td style="width: 16%;">
 10.0 (1,690)</td>
 <td style="width: 16%;">
 10.4 (107)</td>
 <td style="width: 16%;">
 13.8 (138)</td>
 <td style="width: 13%;">
 &nbsp;</td>
 </tr>
 <tr>
 <td style="width: 39%;">
 No lipid-lowering therapy</td>
 <td style="width: 16%;">
 0.8 (129)</td>
 <td style="width: 16%;">
 1.8 (18)</td>
 <td style="width: 16%;">
 3.1 (31)</td>
 <td style="width: 13%;">
 &nbsp;</td>
 </tr>
 <tr>
 <td style="width: 39%;">
 Lipid measurements, mg/dL, median (Q1, Q3), unless stated</td>
 <td style="width: 16%;">
 &nbsp;</td>
 <td style="width: 16%;">
 &nbsp;</td>
 <td style="width: 16%;">
 &nbsp;</td>
 <td style="width: 13%;">
 &nbsp;</td>
 </tr>
 <tr>
 <td style="width: 39%;">
 LDL-C</td>
 <td style="width: 16%;">
 86 (73, 103)</td>
 <td style="width: 16%;">
 87 (74, 107)</td>
 <td style="width: 16%;">
 94 (78, 116)</td>
 <td style="width: 13%;">
 &lt;0.0001</td>
 </tr>
 <tr>
 <td style="width: 39%;">
 LDL-C≥100 mg/dL,% (n)</td>
 <td style="width: 16%;">
 28.9 (4,878)</td>
 <td style="width: 16%;">
 32.5 (333)</td>
 <td style="width: 16%;">
 41.7 (418)</td>
 <td style="width: 13%;">
 &lt;0.0001</td>
 </tr>
 <tr>
 <td style="width: 39%;">
 HDL-C</td>
 <td style="width: 16%;">
 42 (36, 50)</td>
 <td style="width: 16%;">
 42 (36, 50)</td>
 <td style="width: 16%;">
 42 (35, 50)</td>
 <td style="width: 13%;">
 0.0166</td>
 </tr>
 <tr>
 <td style="width: 39%;">
 Non-HDL-C</td>
 <td style="width: 16%;">
 114 (99, 136)</td>
 <td style="width: 16%;">
 117 (102, 140)</td>
 <td style="width: 16%;">
 126 (107, 153)</td>
 <td style="width: 13%;">
 &lt;0.0001</td>
 </tr>
 <tr>
 <td style="width: 39%;">
 Triglicerides</td>
 <td style="width: 16%;">
 128 (94, 181)</td>
 <td style="width: 16%;">
 137 (98, 192)</td>
 <td style="width: 16%;">
 139 (102, 195)</td>
 <td style="width: 13%;">
 &lt;0.0001</td>
 </tr>
 <tr>
 <td style="width: 39%;">
 Apoliproprotein B</td>
 <td style="width: 16%;">
 79 (69, 92)</td>
 <td style="width: 16%;">
 82 (70, 96)</td>
 <td style="width: 16%;">
 85 (75, 103)</td>
 <td style="width: 13%;">
 &lt;0.0001</td>
 </tr>
 <tr>
 <td style="width: 39%;">
 Lipoprotein(a)</td>
 <td style="width: 16%;">
 20.3 (6.6, 58.1)</td>
 <td style="width: 16%;">
 27.8 (7.5, 69.0)</td>
 <td style="width: 16%;">
 33.2 (8.1, 79.9)</td>
 <td style="width: 13%;">
 &lt;0.0001</td>
 </tr>
 <tr>
 <td style="width: 39%;">
 Estimated GFR &lt;60 mL/min per 1.73 m2, % (n)</td>
 <td style="width: 16%;">
 12.7 (2138)</td>
 <td style="width: 16%;">
 13.8 (141)</td>
 <td style="width: 16%;">
 25.9 (260)</td>
 <td style="width: 13%;">
 &lt;0.0001</td>
 </tr>
 </tbody>
</table>
ᵃ low-/moderate-dose atorvastatin/rosuvastatin, other statin, any lipid-lowering therapy other than statin.
<h2>Effect of Alirocumab in patients with ACS, Elevated Atherogenic Lipoproteins and Prior CABG</h2>

ᵃ index CABG is CABG between the index ACS event and randomization (including 44 patients with prior CABG); 
 ᵇ Prior CABG is CABG prior to the index ACS event. HRs reflect stratification by geographic region
<h2>CABG Sub-analysis Conclusions</h2>
<ul>
 <li>In this sub-analysis, it was observed that, in a population that has not been fully investigated with regards to the effect of LDL-C lowering therapies, the addition of alirocumab to patients with prior CABG, recent ACS and elevated atherogenic lipoproteins despite intensive statin therapy was associated with consistent relative but greater ARR in MACE and death when compared to patients with an index or no CABG</li>
</ul>

Odyssey outcomes - CABG results

<h2>Alirocumab and Cardiovascular outcomes after Acute Coronary Syndrome.</h2>
Gregory G Schwartz, P Gabriel Steg, Michael Szarek, Deepak L Bhatt, Vera A Bittner, Rafael Diaz, Jay M Edelberg, Shaun G Goodman, Corinne Hanotin, Robert A Harrington, J Wouter Jukema, Guillaume Lecorps, Kenneth W Mahaffey, Angèle Moryusef, Robert Pordy, Kirby Quintero, Matthew T Roe, William J Sasiela, Jean-François Tamby, Pierluigi Tricoci, Harvey D White, Andreas M Zeiher, Odyssey Outcomes Committees and Investigators
<h3>Objective</h3>
The aim of this study is to test the hypothesis that treatment with alirocumab, a fully human monoclonal antibody to PCSK9, would result in a lower risk of recurrent ischemic cardiovascular events than placebo among patients who had an acute coronary syndrome within the preceding 1 to 12 months and who have levels of atherogenic lipoproteins that exceed specified thresholds despite statin therapy at a high-intensity dose or at the maximum tolerated dose.
<h3>Endpoints</h3>
The primary end point was a composite of death from coronary heart disease, nonfatal myocardial infarction, fatal or nonfatal ischemic stroke, or unstable angina requiring hospitalization.
Prespecified main secondary end points were any coronary heart disease event (death from coronary heart disease, nonfatal myocardial infarction, unstable angina requiring hospitalization, or an ischemia-driven coronary revascularization procedure); major coronary heart disease event (death from coronary heart disease or nonfatal myocardial infarction); any cardiovascular event (death from cardiovascular causes, nonfatal ischemic stroke, nonfatal myocardial infarction, unstable angina requiring hospitalization, or an ischemia-driven coronary revascularization procedure); a composite of death from any cause, nonfatal myocardial infarction, or nonfatal ischemic stroke; death from coronary heart disease; death from cardiovascular causes; and death from any cause.
<h3>Methods</h3>
A multicenter, randomized, double-blind, placebo-controlled trial involving 18,924 patients who had an acute coronary syndrome 1 to 12 months earlier, had a low-density lipoprotein (LDL) cholesterol level of at least 70 mg per deciliter (1.8 mmol per liter), a non−high-density lipoprotein cholesterol level of at least 100 mg per deciliter (2.6 mmol per liter), or an apolipoprotein B level of at least 80 mg per deciliter, and were receiving statin therapy at a high-intensity dose or at the maximum tolerated dose.
Patients were randomly assigned to receive alirocumab subcutaneously at a dose of 75 mg (9462 patients) or matching placebo (9462 patients) every 2 weeks. The dose of alirocumab was adjusted under blinded conditions to target an LDL cholesterol level of 25 to 50 mg per deciliter (0.6 to 1.3 mmol per liter).
<h3>Results</h3>
The median duration of follow-up was 2.8 years. A composite primary end-point event occurred in 903 patients (9.5%) in the alirocumab group and in 1052 patients (11.1%) in the placebo group (hazard ratio, 0.85; 95% confidence interval [CI], 0.78 to 0.93; P&lt;0.001). A total of 334 patients (3.5%) in the alirocumab group and 392 patients (4.1%) in the placebo group died (hazard ratio, 0.85; 95% CI, 0.73 to 0.98). The absolute benefit of alirocumab with respect to the composite primary end point was greater among patients who had a baseline LDL cholesterol level of 100 mg or more per deciliter than among patients who had a lower baseline level.
Among the main secondary end points, the risks of any coronary heart disease event, major coronary heart disease events, any cardiovascular event, and a composite of death from any cause, nonfatal myocardial infarction, or nonfatal ischemic stroke were lower among patients treated with alirocumab than among those who received placebo. A total of 334 patients (3.5%) in the alirocumab group and 392 patients (4.1%) in the placebo group died (hazard ratio, 0.85; 95% CI, 0.73 to 0.98).
The incidence of adverse events was similar in the two groups, with the exception of local injection-site reactions (3.8% in the alirocumab group vs. 2.1% in the placebo group).
<h3>Conclusion</h3>
Among patients who had a previous acute coronary syndrome and who were receiving high-intensity statin therapy, the risk of recurrent ischemic cardiovascular events was lower among those who received alirocumab than among those who received placebo.

NEJM Odyssey outcomes

Key Learnings in Dyslipidemia by Prof. Kausik Ray - 2021 EAS Congress

Acquire profound insights into the realm of Dyslipidemia through the discerning perspective of Prof. Kausik Ray, the Director of the Imperial Center of Cardiovascular Disease Prevention and Deputy Director of the Imperial Clinical Trial Unit at Imperial College London. Prof. Ray offers a comprehensive review of the key takeaways from the 2021 EAS Congress.
Engage in in-depth conversations and analysis surrounding this vital subject matter. Join Prof. Ray in delving into the substantial findings unveiled during this enlightening event, ensuring you remain in the loop of the latest developments in Dyslipidemia management.

<h2>Odyssey Outcomes: Addition of PCSK9i to background Statin therapy further reduces MACE.</h2>
<h2>Study Design¹</h2>

<h2>Major Primary endpoints¹</h2>
<h3>The primary endpoint was a composite of:</h3>
<ul>
 <li>Death from coronary heart disease</li>
 <li>Nonfatal myocardial infarction</li>
 <li>Fatal or nonfatal ischemic stroke</li>
 <li>Unstable angina requiring hospitalization.</li>
</ul>
<h2>Major Secondary efficacy Endpoints²</h2>
<h3>Tested in the following hierarchical sequence:</h3>
<ul>
 <li>CHD event: CHD death, nonfatal MI, unstable angina requiring hospitalization, or ischaemia-driven coronary revascularization*</li>
 <li>Major CHD event: CHD death or nonfatal MI</li>
 <li>CV event: CV death, nonfatal CHD event, or nonfatal ischaemic stroke</li>
 <li>All-cause death, nonfatal MI, nonfatal ischaemic stroke</li>
 <li>CHD death</li>
 <li>CV death</li>
 <li>All-cause death</li>
</ul>
*Revascularization performed because of recurrent ACS, new or progressive symptoms of myocardial ischemia or new or progressive abnormalities on functional testing, except revascularization due to restenosis at a prior coronary intervention site.
<h2>Odyssey Outcomes: Addition of PCSK9i to background Statin therapy further reduces MACE</h2>

Safety: Incidence or adverse events and laboratory abnormalities was similar in the alirocumab group and the placebo group, apart from local injection-site reaction (3.8% in alirocumab group vs 2.1% in the placebo group, p&lt;0.001).
ᵃ Primary efficacy endpoint (a composite of death from CHD, nonfatal MI, fatal or nonfatal ischaemic stroke, or unstable angina requiring hospitalization)

<h2>Primary MACE, All-cause death and safety</h2>

<h2>Safety</h2>
Similar incidence of adverse events and laboratory abnormalities in the alirocumab group and the placebo group, except for local injection-site reactions (3 .8% in the alirocumab group vs 2.1% in the placebo group, p&lt;0.001)¹
*Nominal p-value; ᵃBased on cumulative incidence; bp-interaction value for ARR &lt;0.001 in post-hoc analysis

*Nominal p-value 
 †Based on cumulative incidence

<h2>Primary Analysis Conclusions¹</h2>
<ul>
 <li>The primary results show that, compared with placebo in patients with recent ACS, alirocumab 75 or 150 mg SC twice a week targeting LDL-C levels 25-50 mg/dl reduced MACE, MI*, ischemic stroke* and was associated with a lower rate of all-cause death</li>
 <li>Among patients with ACS and baseline LDL-C &gt;100 mg/dl, alirocumab was well tolerated, reduced MACE by 24% (absolute risk reduction [ARR] 3.4%), and was associated with a lower rate of all-cause death compared with placebo</li>
</ul>
*Nominally significant as per hierarchical testing.

References

Odyssey outcomes

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