The ODYSSEY OUTCOMES story

KEY POINTS

  • ODYSSEY OUTCOMES was designed to evaluate the long-term efficacy and safety of alirocumab, a PCSK9 inhibitor, as a complementary therapy to maximally tolerated statins in post-ACS patients1

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  • All patients had experienced an ACS event 1-12 months prior to joining the study and had inadequately controlled lipid levels1

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  • 18924 patients across 57 countries (randomized 2012-2017) took part in ODYSSEY OUTCOMES1

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  • ODYSSEY OUTCOMES is the longest PCSK9 inhibitor cardiovascular la outcomes trial to date1

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Footnotes & references

ACS=acute coronary syndrome; PCSK9=proprotein convertase subtilisin/kexin type 9.

  • 1. Schwartz GG, et al. Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome. N Engl J Med. 2018;379(22):2097-2107.
  • Praluent (alirocumab). List B. sanofi-aventis (suisse) sa, 1214 Vernier/GE. A comprehensive information can be found in the professional information on www.swissmedicinfo.ch.

Introduction

Worldwide, cardiovascular disease kills more people than any other disease:1

Those who have already experienced an acute coronary syndrome (ACS) event are at high risk of recurrent cardiovascular events.2, 3

There is a global need for more efficacious ACS management and prevention of further cardiovascular events.4

The ODYSSEY OUTCOMES trial tested the hypothesis that alirocumab, compared with placebo, reduced cardiovascular morbidity and mortality in patients with recent ACS and levels of atherogenic lipoproteins that remain above specified concentrations despite intensive or maximally tolerated statin therapy.5, 6

References

ACS=acute coronary syndrome; PCSK9=proprotein convertase subtilisin/kexin type 9.

  • 1. The top 10 causes of death. Available at: http://www.who.int/en/news-room/fact-sheets/detail/the-top-10-causes-of-death. Accessed: February 2019.
  • 2. Fox KA, et al. Management of acute coronary syndromes. Variations in practice and outcome; findings from the Global Registry of Acute Coronary Events (GRACE). Eur Heart J. 2002; 23(15): 1177-1189.
  • 3. Jernberg T, et al. Cardiovascular risk in post-myocardial infarction patients: nationwide real world data demonstrate the importance of a long-term perspective. Eur Heart J. 2015;36(19):1163-1170.
  • 4. Smith JN, et al. Diagnosis and management of acute coronary syndrome: an evidence-based update. J Am Board Fam Med. 2015;28(2):283-293.
  • 5. Schwartz GG, et al. Effect of alirocumab, a monoclonal antibody to PCSK9, on long-term cardiovascular outcomes following acute coronary syndromes: rationale and design of the ODYSSEY outcomes trial. Am Heart J. 2014;168(5):682-689.
  • 6. Schwartz GG, et al. Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome. N Engl J Med. 2018;379(22):2097-2107.
  • Praluent (alirocumab). List B. sanofi-aventis (suisse) sa, 1214 Vernier/GE. A comprehensive information can be found in the professional information on www.swissmedicinfo.ch.

Study hypothesis and objective

The ODYSSEY OUTCOMES trial tested the hypothesis that treatment with alirocumab (a fully human monoclonal antibody that binds PCSK9) would result in a lower risk of recurrent ischemic cardiovascular events (compared to placebo) in patients who had an ACS in the 1–12 months prior to study enrollment, and who had levels of atherogenic lipoproteins that exceeded specified thresholds despite maximally tolerated statin therapy.1

The primary objective of ODYSSEY OUTCOMES was to evaluate the ability of alirocumab (75 mg or 150 mg) to reduce the incidence of additional cardiovascular events when administered via subcutaneous injection every two weeks, starting in the 1–12 months following an ACS event.2

After 48 months, mean LDL-C levels were 1.7 mmol/L; intention-to-treat and 1.4 mmol/L; on-treatment analysis in alirocumab treated patients and 2.7 mmol/L; intention-to-treat and 2.6 mmol/L; on-treatment analysis in the placebo group. In alirocumab on-treatment analysis, which excluded values measured after discontinuation of alirocumab and after blinded substitution of placebo for alirocumab, LDL-C reduction was 54.7 % lower than the one achieved in placebo.2

View all the end points for ODYSSEY OUTCOMES

View all the statistical considerations for ODYSSEY OUTCOMES

Footnotes & references

ACS=acute coronary syndrome; PCSK9=proprotein convertase subtilisin/kexin type 9.

LDL-C=low-density lipoprotein cholesterol

  • 1. Schwartz GG, et al. Effect of alirocumab, a monoclonal antibody to PCSK9, on long-term cardiovascular outcomes following acute coronary syndromes: rationale and design of the ODYSSEY outcomes trial. Am Heart J. 2014;168(5):682-689.
  • 2. Schwartz GG, et al. Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome. N Engl J Med. 2018;379(22):2097-2107.
  • Praluent (alirocumab). List B. sanofi-aventis (suisse) sa, 1214 Vernier/GE. A comprehensive information can be found in the professional information on www.swissmedicinfo.ch.

Trial population

ODYSSEY OUTCOMES included high-risk patients, all of whom had experienced a previous coronary event, putting them at increased risk of recurrent events and rehospitalization.1,2

All patients had experienced an ACS event 1–12 months prior to joining

the study and had inadequately controlled lipid levels (LDL-C ≥1.8 mmol/L or non-HDL-C ≥2.6 mmol/L, or apolipoprotein B ≥80 mg/dL) despite maximally tolerated statin treatment* for 2–16 weeks.1,2

View the patient inclusion and principal exclusion criteria for ODYSSEY OUTCOMES

Footnotes & references

*Statin treatment consisted of daily atorvastatin (40 or 80 mg), rosuvastatin (20 or 40 mg), or the maximum tolerated dose of either of these statins.

ACS=acute coronary syndrome; non-HDL-C=non–high-density lipoprotein cholesterol.

LDL-C=low-density lipoprotein cholesterol

  • 1. Schwartz GG, et al. Effect of alirocumab, a monoclonal antibody to PCSK9, on long-term cardiovascular outcomes following acute coronary syndromes: rationale and design of the ODYSSEY outcomes trial. Am Heart J. 2014;168(5):682-689.
  • 2. Schwartz GG, et al. Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome. N Engl J Med. 2018;379(22):2097-2107.
  • Praluent (alirocumab). List B. sanofi-aventis (suisse) sa, 1214 Vernier/GE. A comprehensive information can be found in the professional information on www.swissmedicinfo.ch.

Study enrollment

18924 patients across 57 countries took part in ODYSSEY OUTCOMES, randomized at 1315 sites between November 2012 and February 2017.1*

View patient numbers by country

View steering committee and national study leaders

Adapted from Reference 1.

Footnotes & references

* Except in China, patients underwent randomization from November 2012 through November 2015. In China, 613 patients underwent randomization from May 2016 through February 2017.1

1. Schwartz GG, et al. Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome. N Engl J Med. 2018;379(22):2097-2107.

Praluent (alirocumab). List B. sanofi-aventis (suisse) sa, 1214 Vernier/GE. A comprehensive information can be found in the professional information on www.swissmedicinfo.ch.

Study design

Following double-blind randomization, patients subcutaneously self-injected either alirocumab (75 mg initial dose) or matching placebo every 2 weeks.1

The ODYSSEY OUTCOMES trial tested the hypothesis that alirocumab, compared with placebo, reduced cardiovascular morbidity and mortality in patients with recent ACS and levels of atherogenic lipoproteins that remain above specified concentrations despite intensive atorvastatin or rosuvastatin therapy or the maximally tolerated dose of either of these statins.2

Adapted from reference 1.

Footnotes & references

ACS=acute coronary syndrome; LDL-C=low-density lipoprotein cholesterol.

1. Schwartz GG, et al. Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome. N Engl J Med. 2018;379(22):2097-2107.
2. Schwartz GG, et al. Effect of alirocumab, a monoclonal antibody to PCSK9, on long-term cardiovascular outcomes following acute coronary syndromes: rationale and design of the ODYSSEY outcomes trial. Am Heart J. 2014;168(5):682-689.

Follow up

Patients were planned to be followed for up to 5 years, with a minimum follow-up duration of 2 years.*
Patients were followed for a median of 2.8 years (interquartile range 2.3–3.4).1

Footnotes & references

*Except in China, patients underwent randomization from November 2012 through February 2017. In China, 613 patients underwent randomization from May 2016 through February 2017 and were not followed for 2 years, because a lengthy regulatory approval process delayed their random assignment to a trial group until after completion of the randomization process for the rest of the trial cohort.1

ACS=acute coronary syndrome.

1. Schwartz GG, et al. Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome. N Engl J Med. 2018;379(22):2097-2107.

Praluent (alirocumab). List B. sanofi-aventis (suisse) sa, 1214 Vernier/GE. A comprehensive information can be found in the professional information on www.swissmedicinfo.ch.

Treat-to-target approach

Blinded dose adjustments included in the protocol intended to maximize the number of patients in the alirocumab group with LDL-C <1.29 mmol/L, while minimizing the number of patients with sustained levels of LDL-C <0.39 mmol/L.1

If the target LDL-C level was achieved on the 75 mg starting dose, no further dose changes were made. If the initial on-treatment LDL-C level exceeded 1.29 mmol/L at month 1, the dose of alirocumab was blindly up-titrated to 150 mg Q2W at month 2 (it was blindly down-titrated back to 75 mg Q2W if two consecutive LDL-C measurements were <0.65 mmol/L). Patients on the 75 mg Q2W dose were blindly switched to placebo if LDL-C was <0.39 mmol/L on two consecutive measurements.2

Footnotes & references

LDL-C=low-density lipoprotein cholesterol; Q2W=every two weeks.

1. Schwartz GG, et al. Effect of alirocumab, a monoclonal antibody to PCSK9, on long-term cardiovascular outcomes following acute coronary syndromes: rationale and design of the ODYSSEY outcomes trial. Am Heart J. 2014;168(5):682-689.
2. Schwartz GG, et al. Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome. N Engl J Med. 2018;379(22):2097-2107.
Praluent (alirocumab). List B. sanofi-aventis (suisse) sa, 1214 Vernier/GE. A comprehensive information can be found in the professional information on www.swissmedicinfo.ch.