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 (months), mean ± SD

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 atorvastatin/rosuvastatin

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
    1. Sinnaeve PR, et al. Eur Heart J. 2020; 41(24):2248-58

MAT-BH-2100544 /V1/JUN2021