Odyssey outcomes - elderly patients results

Odyssey Outcomes: Addition of PCSK9i to background Statin therapy further reduces MACE.
Elderly patients sub-analysis overview
Study outcomes
Primary outcome: composite of death from CHD, nonfatal myocardial infarction, fatal or nonfatal ischemic stroke, or unstable angina requiring hospitalization
Key secondary outcome: all-cause death
All outcomes were adjudicated by physicians who were unaware of the trial-group assignments
*Pre-specified analysis: Age <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
Baseline characteristics by age group
Characteristic | <65 years (n=13,840) | ≥65 years (n=5084) | P-value |
Age (years), mean ± SD | 54.2 ± 6.3 | 70.5 ± 4.7 |
|
Women, n (%) | 2948 (21.3) | 1814 (35.7) | <0.0001 |
Medical history before index ACS, n (%) |
|
|
|
Hypertension | 8390 (60.6) | 3859 (75.9) | <0.0001 |
Diabetes mellitus | 3787 (27.4) | 1657 (32.6) | <0.0001 |
Myocardial infarction | 2499 (18.1) | 1134 (22.3) | <0.0001 |
Percutaneous coronary intervention | 2212 (16.0) | 1029 (20.2) | <0.0001 |
Coronary artery bypass graft | 582 (4.2) | 465 (9.1) | <0.0001 |
Stroke | 337 (2.4) | 274 (5.4) | <0.0001 |
Peripheral artery disease | 428 (3.1) | 331 (6.5) | <0.0001 |
Congestive heart failure | 1800 (13.0) | 1014 (19.9) | <0.0001 |
Index, ACS, n (%) | n=13,818 | n=5075 | <0.0001 |
STEMI | 5039 (36.4) | 1497 (29.4) |
|
Non-STEMI | 6422 (46.4) | 2753 (54.2) |
|
Unstable angina | 2357 (17.0) | 825 (16.2) |
|
PCI or CABG for index ACS, n (%) | 10,201 (73.7) | 3475 (68.4) | <0.0001 |
SD, Standard deviation
Characteristic | <65 years (n=13,840) | ≥65 years (n=5084) | P-value |
The from index ACS to randomization | 3.6 ± 2.8 | 3.8 ± 2.8 | 0.0003 |
Body mass index (kg/m2), mean ± SD | 28.8 ± 4.9 | 27.8 ± 4.6 | <0.0001 |
Renal function |
|
|
|
eGFR (mL/min), mean ± SD | 83.1 ± 18.5 | 70.2 ± 18.2 | <0.0001 |
eGFR <60 mL/min, n (%) | 1,163 (8.4) | 1,377 (27.1) | <0.0001 |
Lipid-lowering drugs at randomization, n (%) |
|
| <0.0001 |
High-intensity | 12,565 (90.8) | 4,246 (83.5) |
|
Low- or moderate-intensity atorvastatin/rosuvastatin | 1,027 (7.4) | 580 (11.4) |
|
No statin | 222 (1.6) | 238 (4.7) |
|
Ezetibime | 408 (2.9) | 142 (2.8) | 0.57 |
eGFR, estimated glomerular filtration rate
Treatment effect by age group: Primary composite outcome

Relative Risk Reduction Hazard Ratio (Alirocumab vs Placebo)
≥65 years: 0.78, 95% CI 0.68-0.91
<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
<65 years: 0.91%, 95% Cl -0.13 to 1.95
Interaction p-value: 0.015
Treatment effect by age group: All cause death

Relative Risk Reduction Hazard Ratio (Alirocumab vs Placebo)
≥65 years: 0.77, 95% CI 0.62-0.95
<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
<65 years: 0.11%, 95% Cl -0.50 to 1.72
Interaction p-value: 0.024
Safety: Adverse events by age group
Adverse Event | Randomized Treatment | Relative Risk (95%CI) Alirocumab vs Placebo | |
| Alirocumab, N (%) | Placebo, N (%) |
|
Any adverse event |
|
|
|
≥65 years | 1,974 (79.0) | 2,042 (79.3) | 1.00 (0.97 -1.02) |
<65 years | 5,191 (74.7) | 5,240 (76.3) | 0.98 (0.96 -1.00) |
Serious adverse event |
|
|
|
≥65 years | 703 (28.1) | 781 (30.3) | 0.93 (0.85 -1.01) |
<65 years | 1,499 (21.6) | 1,569 (22.8) | 0.94 (0.89 -1.00) |
Adverse event leading to discontinuation of treatment |
|
|
|
≥65 years | 121 (4.8) | 128 (5.0) | 0.97 (0.76 -1.24) |
<65 years | 222 (3.2) | 196 (2.9) | 1.12 (0.93 -1.35) |
Neurocognitive disorder |
|
|
|
≥65 years | 52 (2.1) | 65 (2.5) | 0.82 (0.57 -1.18) |
<65 years | 91 (1.3) | 102 (1.5) | 0.88 (0.67 -1.17) |
New-onset diabetes in patients w/o diabetes at baseline |
|
|
|
≥65 years | 156 (9.2) | 167 (9.7) | 0.95 (0.77 -1.17) |
<65 years | 492 (9.7) | 509 (10.2) | 0.95 (0.84 -1.07) |
Hemorrhagic stroke - adjudicated |
|
|
|
≥65 years | 1 (0.0) | 6 (0.2) | 0.17 (0.02 -1.42) |
<65 years | 8 (0.1) | 10 (0.1) | 0.79 (0.31 -2.00) |
Alanine aminotransferase> 3 x upper limit of normal |
|
|
|
≥65 years | 64 (2.6) | 70 (2.8) | 0.94 (0.67 -1.31) |
<65 years | 148 (2.1) | 158 (2.3) | 0.92 (0.74 -1.15) |
Aspartate |
|
|
|
≥65 years | 52 (2.1) | 48 (1.9) | 1.11 (0.75 -1.64) |
<65 years | 108 (1.6) | 118 (1.7) | 0.90 (0.70 -1.17) |
Elderly Patients’ sub-analysis conclusions¹
- Alirocumab demonstrated an effective RRR for primary MACE outcome, and was associated with an effective reduction of all-cause death across age categories
- 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
SD, Standard deviation
- Sinnaeve PR, et al. Eur Heart J. 2020; 41(24):2248-58