Observational Study of Cardiovascular Disease. (FOURIER LEGACY)

Long-term Study of LDL-c Lowering With Evolocumab: Observational Follow-up After the FOURIER OUTCOMES Trial.

This observational study will follow participants who completed follow-up in the FOURIER OUTCOMES trial to evaluate the long-term effects of evolocumab treatment. Long-term post-trial (legacy) beneficial effects have been reported with statins, niacin, hypoglycemic therapy and fibrates. Whether similar effects are seen after LDL cholesterol (LDL-c) lowering by PCSK9 inhibition is currently unknown.

Evolocumab therapy causes a profound reduction in LDL cholesterol of approximately 60%. Statins have shown legacy effects over 5 years post-trial, including a 7% reduction in total mortality in meta-analysis and 12% reduction in coronary mortality. It would therefore be hypothesized that additional effects beyond the trial period would be conferred by previous evolocumab treatment. It is also important to assess the long-term safety of prior evolocumab treatment.

Study Overview

• Status: Terminated
• Conditions: Cardiovascular Diseases; Coronary Heart Disease; Cardiovascular Morbidity; Low-density-lipoprotein-type
• Intervention / Treatment: Other: N/A - observational study.

• Study Type: Observational
• Enrollment (Actual): 1137

Contacts and Locations

Study Locations

• Norway
  • Oslo
    • Nydalen, Oslo, Norway, 0424
      • Oslo University Hospital
• United Kingdom
  • London, United Kingdom
    • Imperial College London
• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • TIMI Study Group

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Participants in selected countries who completed the FOURIER OUTCOMES trial, irrespective of non-fatal on-study events during FOURIER OUTCOMES trial, and who agree to take part in the FOURIER LEGACY study following study completion will be enrolled into this trial.

Description

Subjects who completed the FOURIER OUTCOMES trial (defined as attendance at close-out visit irrespective of treatment compliance) will be approached by FOURIER OUTCOMES site investigators and asked about their interest in taking part in this trial.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the potential long-term effect of evolocumab treatment on a composite of CV death, MI, stroke or coronary revascularisation in participants completing participation in the FOURIER OUTCOMES trial.	To evaluate the potential long-term effect of evolocumab treatment on a composite of CV death, MI, stroke or coronary revascularization in patients completing participation in the FOURIER OUTCOMES trial.	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the potential long-term effect of evolocumab treatment on a composite of CV death, MI, stroke or coronary revascularization in patients completing participation in the FOURIER OUTCOMES trial.	To evaluate the potential long-term effect of evolocumab treatment on a composite of CV death, MI, stroke or coronary revascularization in patients completing participation in the FOURIER OUTCOMES trial.	5 years
To evaluate the long-term effect of evolocumab treatment on CV death.	To evaluate the long-term effect of evolocumab treatment on CV death.	5 years
To evaluate the long-term effects of evolocumab treatment on CHD death.	To evaluate the long-term effects of evolocumab treatment on CHD death.	5 years
To evaluate the long-term effect of evolocumab treatment on the individual components of the primary endpoint and any other CV hospitalizations.	To evaluate the long-term effect of evolocumab treatment on the individual components of the primary endpoint and any other CV hospitalizations.	5 years
To evaluate the long-term effect of evolocumab treatment on amputations and peripheral revascularization.	To evaluate the long-term effect of evolocumab treatment on amputations and peripheral revascularization.	5 years
To evaluate the long-term effect of evolocumab treatment in terms of all-cause death (and non-CV, including cancer, death).	To evaluate the long-term effect of evolocumab treatment in terms of all-cause death (and non-CV, including cancer, death).	5 years
To assess the effect modification of use or prescription lipid-lowering treatment classes (statins, cholesterol absorption inhibitors, PCSK9i) administered at FOURIER OUTCOMES trial entry on the outcomes above.	To assess the effect modification of use or prescription lipid-lowering treatment classes (statins, cholesterol absorption inhibitors, PCSK9i) administered at FOURIER OUTCOMES trial entry on the outcomes above.	5 years
To assess the effect modification by baseline characteristics on defined study outcomes above.	To assess the effect modification by baseline characteristics on defined study outcomes above.	5 years

Collaborators and Investigators

• Sponsor: University of Sydney
• Collaborators: University of Oslo; Imperial College London; Amgen; The Thrombolysis in Myocardial Infarction Study Group, Harvard University
• Investigators: Study Chair: Anthony Keech, National Health and Medical Research Council, Australia; Study Chair: Peter Sever, Imperial College London

Study record dates

Study Major Dates

• Study Start (Actual): February 5, 2020
• Primary Completion (Actual): April 26, 2021
• Study Completion (Actual): April 26, 2021

Study Registration Dates

• First Submitted: September 12, 2019
• First Submitted That Met QC Criteria: October 13, 2019
• First Posted (Actual): October 16, 2019

Study Record Updates

• Last Update Posted (Actual): April 8, 2024
• Last Update Submitted That Met QC Criteria: April 4, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Coronary heart disease; Cardiovascular events; Cardiovascular death; Evolocumab; Low density lipoprotein cholesterol (LDL-c); FOURIER OUTCOMES
• Additional Relevant MeSH Terms: Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Heart Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Cardiovascular Diseases
• Other Study ID Numbers: CTC0173

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No