Effect of lipid-lowering therapies on lipoprotein(a) levels: a meta-analysis of randomized controlled trials

Lead Investigator: Alberico L. Catapano, IRCCS MultiMedica
Title of Proposal Research: Effect of lipid-lowering therapies on lipoprotein(a) levels: a meta-analysis of randomized controlled trials
Vivli Data Request: 8966
Funding Source: None
Potential Conflicts of Interest: None

Summary of the Proposed Research:

Cardiovascular disease (CVD) is one of the leading causes of death and disability. The prevalence of total CVD cases doubled from 271 million cases in 1990 to 607 million cases in 2020, and the number of CVD deaths steadily rose from 12.1 million cases in 1990 to 19.0 million cases in 2020. Atherosclerosis, a condition where fatty deposits accumulate inside of the arteries and decrease blood flow to the heart muscle, is considered to be the principal driver. Several lipid-lowering therapies (LLTs) were developed for treating this type of disease. But despite administration of the evidence-based therapies, substantial residual risk persists particularly among individuals with known CVDs. Residual cardiovascular (CV) risk has been defined as the risk of CV events that remains despite treatment for or achievement of targets for risk factors such as low-density lipoprotein cholesterol (LDL-C). Several epidemiological studies, Mendelian randomization studies and randomized controlled trials illustrated that lipoprotein(a) [Lp(a)] is a casual risk factor leading to the residual risk in CV prevention. In the attempt of reducing cardiovascular risk, the role of Lp(a) as pharmaceutical target seems to be of great interest. However, no approved therapy for patients with elevated Lp(a) levels is currently available. From this point of view, it is crucial to understand whether available lipid-lowering therapies have an effect also on Lp(a) and how much this could be eventually linked to the reduction of other lipids. According to the Oxford CEBM Levels of Evidence, the systematic reviews and meta-analysis of published randomized controlled trials is considered as the first-level evidence. Since the evidence from literature is conflicting, we will conduct a comprehensive meta-analysis to summarize the data from different sources, provide updated results with increased statistic power and greater accuracy.

Requested Studies:

LTS11717 – Long-term Safety and Tolerability of Alirocumab (SAR236553/REGN727) Versus Placebo on Top of Lipid-Modifying Therapy in High Cardiovascular Risk Patients With Hypercholesterolemia (ODYSSEY Long Term)
Data Contributor: Sanofi
Study ID: NCT01507831

EFC12492 – Efficacy and Safety of Alirocumab (SAR236553/REGN727) Versus Placebo on Top of Lipid-Modifying Therapy in Patients With Heterozygous Familial Hypercholesterolemia Not Adequately Controlled With Their Lipid-Modifying Therapy (ODYSSEY FH I)
Data Contributor: Sanofi
Study ID: NCT01623115

LPS14355 – Efficacy and Safety of Alirocumab Versus Placebo on Top of Maximally Tolerated Lipid Lowering Therapy in Patients With Hypercholesterolemia Who Have Type 1 or Type 2 Diabetes and Are Treated With Insulin (ODYSSEY DM – Insulin)
Data Contributor: Sanofi
Study ID: NCT02585778

LPS14354 – Efficacy and Safety of Alirocumab Versus Usual Care on Top of Maximally Tolerated Statin Therapy in Patients With Type 2 Diabetes and Mixed Dyslipidemia (ODYSSEY DM-Dyslipidemia)
Data Contributor: Sanofi
Study ID: NCT02642159

EFC12732 – Efficacy and Safety of Alirocumab (SAR236553/REGN727) Versus Placebo on Top of Lipid-Modifying Therapy in Patients With Heterozygous Familial Hypercholesterolemia (ODYSSEY HIGH FH)
Data Contributor: Sanofi
Study ID: NCT01617655

EFC11568 – Efficacy and Safety of Alirocumab (SAR236553/REGN727) Versus Placebo on Top of Lipid-Modifying Therapy in Patients With High Cardiovascular Risk and Hypercholesterolemia (ODYSSEY COMBO I)
Data Contributor: Sanofi
Study ID: NCT01644175

EFC13786 – Phase III Study To Evaluate Alirocumab in Patients With Hypercholesterolemia Not Treated With a Statin (ODYSSEY CHOICE II)
Data Contributor: Sanofi
Study ID: NCT02023879

EFC13672 – Efficacy and Safety Evaluation of Alirocumab in Patients With Heterozygous Familial Hypercholesterolemia or High Cardiovascular Risk Patients With Hypercholesterolemia on Lipid Modifying Therapy (ODYSSEY JAPAN)
Data Contributor: Sanofi
Study ID: NCT02107898

EFC14305 – Efficacy and Safety of Alirocumab in Patients With Hypercholesterolemia Not Adequately Controlled With Non-statin Lipid Modifying Therapy or the Lowest Strength of Statin (ODYSSEY-NIPPON)
Data Contributor: Sanofi
Study ID: NCT02584504

EFC14074 – Evaluation of Alirocumab in Addition to Lipid-Modifying Therapy in Patients With High Cardiovascular Risk and Hypercholesterolemia in South Korea and Taiwan
Data Contributor: Sanofi
Study ID: NCT02289963