Safety, Tolerability, and Effect of Alirocumab in High Cardiovascular Risk Patients With Severe Hypercholesterolemia Not Adequately Controlled With Conventional Lipid-modifying Therapies (ODYSSEY APPRISE)
Source: ClinicalTrials.gov NCT02476006 ↗Summary
Linked Publications
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A subgroup analysis of the ODYSSEY APPRISE study: Safety and efficacy of alirocumab in the Italian cohort.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) |
71.6; 16.2; 0.2; 4.5 | — |
| SECONDARY Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol (LDL-C) at Week 12 |
-54.84 | — |
| SECONDARY Percentage of Participants Reaching Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 12 |
74.6 | — |
| SECONDARY Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 12 |
50.2 | — |
| SECONDARY Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) and/or >=50% Reduction From Baseline in LDL-C at Week 12 |
69.1 | — |
| SECONDARY Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 12 |
-45.89 | — |
| SECONDARY Percent Change From Baseline in Total Cholesterol (Total-C) at Week 12 |
-38.28 | — |
| SECONDARY Percent Change From Baseline in High Density Lipoprotein Cholesterol at Week 12 |
4.37 | — |
| SECONDARY Percent Change From Baseline in Triglycerides at Week 12 |
-8.28 | — |
| SECONDARY Assessment of Participant's Acceptability of Self-Injection Using Self Injection Assessment Questionnaire (SIAQ): Feeling About Injections, Self Confidence, Satisfaction With Self-Injections |
8.6; 9.1; 9.1; 9.2; 9.2; 9.2 | — |
| SECONDARY Assessment of Participant's Acceptability of Self-Injection Using Self Injection Assessment Questionnaire (SIAQ): Self Image, Injection-Site Reactions, Ease of Use |
9.4; 9.4; 9.4; 9.3; 9.4; 9.3 | — |
Eligibility Criteria
Inclusion criteria
Either A, B, C, D, or E below and not adequately controlled with a maximally tolerated dose of statin with or without other LMTs, all at stable doses for at least 4 weeks prior to the screening visit (Week-3):
A. Participants suffering from heterozygous familial hypercholesterolemia (heFH) with LDL-C concentrations greater than or equal to (>=)160 mg/dL (4.14 millimoles per liter [mmol/L]) despite treatment.
B. Participants suffering from heFH with LDL-C concentrations >=130 mg/dL (3.36 mmol/L) despite treatment and two or more CV risk factors among this list:
- LDL-C greater than (>) 250 milligrams per deciliter (mg/dL) (6.46 mmol/L) at the time of the familial hypercholesterolemia (FH) diagnosis (before treatment).
- Family history of premature-onset coronary heart disease (CHD; first-degree male relative with onset before age 55 years; first-degree female relative with onset before age 65 years).
- Metabolic syndrome.
- HDL-C less than ( 140/90 mmHg or drug treatment).
- Lipoprotein a (Lp[a]) >=50 mg/dL (1.78 µmol/L).
- Tendon xanthoma.
C. Participants suffering from heFH with LDL-C concentrations >=130 mg/dL (3.36 mmol/L) despite treatment and one of the following characteristics:
- Established CHD or other cardiovascular disease (CVD; history of acute myocardial infarction, ischemic stroke, peripheral arterial disease, coronary or peripheral arterial revascularization, stable or unstable angina, transient ischemic attack, carotid artery stenosis >=50 percent (%), or aortic abdominal aneurysm).
- Drug-treated type 2 diabetes mellitus or type 1 with target organ damage.
- Family history of first- or second-degree relative with very premature onset CHD (first- or second-degree male relative with onset before age 45; first- or second-degree female relative with onset before age 55).
D. Non-FH participants suffering from established CHD or other CVD (history of acute myocardial infarction (MI), ischemic stroke, peripheral arterial disease, coronary or peripheral arterial revascularization, stable or unstable angina, transient ischemic attack, carotid artery stenosis >=50%, or aortic abdominal aneurysm) and with LDL-C concentrations >=130 mg/dL (3.36 mmol/L).
E. Participants suffering from progressive CVD (coronary artery disease, or peripheral arterial occlusive disease or cerebrovascular disease as documented clinically or by imaging techniques, with a subsequent CV event [acute MI, ischemic stroke, ischemia-driven revascularization, unstable angina, transient ischemic attack] occurring despite stable doses of maximally tolerated LMT) with LDL-C concentrations >=100 mg/dL (2.59 mmol/L).
Exclusion criteria
Not on a stable dose of LMT (including statin) for at least 4 weeks prior to the screening visit (Week -3) and from screening to enrollment.
Use of a fibrate other than fenofibrate within 4 weeks of the screening visit (Week-3) or between screening and enrollment.
Daily doses above atorvastatin 80 mg, rosuvastatin 40 mg, or simvastatin 40 mg (except for participants on simvastatin 80 mg for more than one year, who were eligible).
Use of statin other than simvastatin, atorvastatin, or rosuvastatin prior to the screening visit (Week-3) or between screening and enrollment, except when there was a documented reason for intolerance to the above mentioned potent statins (in which case the use of a different statin was allowed).
Fasting serum TG >400 mg/dL (>4.52 mmol/L) at the screening visit (Week -3). Uncontrolled hypertension (>180 mmHg systolic and/or >110 mmHg diastolic at randomization visit).
New York Heart Association Class III or IV congestive heart failure persisting despite treatment.
History of hemorrhagic stroke. Liver transaminases >3 times the upper limit of normal. Laboratory evidence of current hepatitis B or C infection. Creatine kinase >3 times the upper limit of normal. Estimated glomerular filtration rate <30 mL/min/1.73 m^2. Pregnant or breastfeeding woman or with childbea
Data sourced from ClinicalTrials.gov (NCT02476006) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.