Observational Study of Cardiovascular Disease.

Study Overview
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Brief Summary
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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.

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

Conditions
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Cardiovascular Diseases, Cardiovascular Morbidity, Coronary Heart Disease, Low-density-lipoprotein-type

Intervention / Treatment
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* Other: N/A - observational study.


Participation Criteria
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Eligibility Criteria
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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.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Other: N/A - observational study.|N/A - observational study.|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Evolocumab, Cardiovascular events, Coronary heart disease, Cardiovascular death, Low density lipoprotein cholesterol (LDL-c), FOURIER OUTCOMES