Cholesteryl Ester Transfer Protein Inhibitors and Cardiovascular Outcomes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Cardiovascular events Cholesteryl ester transfer protein inhibitors High-density lipoproteins Low-density lipoproteins Meta-analysis Systematic review

Journal

Cardiology
ISSN: 1421-9751
Titre abrégé: Cardiology
Pays: Switzerland
ID NLM: 1266406

Informations de publication

Date de publication:
2020
Historique:
received: 07 08 2019
accepted: 10 12 2019
pubmed: 17 3 2020
medline: 1 9 2021
entrez: 16 3 2020
Statut: ppublish

Résumé

Cholesteryl ester transfer protein (CETP) inhibitors increase serum high-density lipoprotein cholesterol (HDL-c) concentration; however, their impact on cardiovascular outcomes is not clear. This systematic review examines the effect of CETP inhibitors on serum lipid profiles, cardiovascular events, and all-cause mortality. We searched MEDLINE, Embase, and the Cochrane Library of Clinical Trials for placebo-controlled randomized controlled trials (RCTs) that examined the effect of a CETP inhibitor (dalcetrapib, anacetrapib, evacetrapib, or TA-8995) on all-cause mortality, major adverse cardiovascular events (MACE), or the components of MACE at ≥6 months. Data were pooled using random-effects models. A total of 11 RCTs (n = 62,431) were included in our systematic review; 4 examined dalcetrapib (n = 16,612), 6 anacetrapib (n = 33,682), and 1 evacetrapib (n = 12,092). Compared to dalcetrapib, ana-cetrapib and evacetrapib were more efficacious at raising HDL-c levels (∼100-130 vs. ∼30%). Anacetrapib and evacetrapib also decreased low-density lipoprotein cholesterol (LDL-c) by approximately 30% while dalcetrapib did not affect the LDL-c level. Overall, CETP inhibitors were not associated with the incidence of MACE (pooled relative risk [RR]: 0.97; 95% confidence interval [CI]: 0.91-1.04). CETP inhibitors may decrease the risks of nonfatal myocardial infarction (MI) (RR: 0.93; 95% CI: 0.87-1.00) and cardiovascular death (RR: 0.92; 95% CI: 0.83-1.01), though these trends did not reach statistical significance. CETP inhibitors are not associated with an increased risk of MACE or all-cause mortality. There is a trend towards small reductions in nonfatal MI and cardiovascular death, though the clinical im-portance of such reductions is likely modest.

Sections du résumé

BACKGROUND
Cholesteryl ester transfer protein (CETP) inhibitors increase serum high-density lipoprotein cholesterol (HDL-c) concentration; however, their impact on cardiovascular outcomes is not clear. This systematic review examines the effect of CETP inhibitors on serum lipid profiles, cardiovascular events, and all-cause mortality.
METHODS
We searched MEDLINE, Embase, and the Cochrane Library of Clinical Trials for placebo-controlled randomized controlled trials (RCTs) that examined the effect of a CETP inhibitor (dalcetrapib, anacetrapib, evacetrapib, or TA-8995) on all-cause mortality, major adverse cardiovascular events (MACE), or the components of MACE at ≥6 months. Data were pooled using random-effects models.
RESULTS
A total of 11 RCTs (n = 62,431) were included in our systematic review; 4 examined dalcetrapib (n = 16,612), 6 anacetrapib (n = 33,682), and 1 evacetrapib (n = 12,092). Compared to dalcetrapib, ana-cetrapib and evacetrapib were more efficacious at raising HDL-c levels (∼100-130 vs. ∼30%). Anacetrapib and evacetrapib also decreased low-density lipoprotein cholesterol (LDL-c) by approximately 30% while dalcetrapib did not affect the LDL-c level. Overall, CETP inhibitors were not associated with the incidence of MACE (pooled relative risk [RR]: 0.97; 95% confidence interval [CI]: 0.91-1.04). CETP inhibitors may decrease the risks of nonfatal myocardial infarction (MI) (RR: 0.93; 95% CI: 0.87-1.00) and cardiovascular death (RR: 0.92; 95% CI: 0.83-1.01), though these trends did not reach statistical significance.
CONCLUSIONS
CETP inhibitors are not associated with an increased risk of MACE or all-cause mortality. There is a trend towards small reductions in nonfatal MI and cardiovascular death, though the clinical im-portance of such reductions is likely modest.

Identifiants

pubmed: 32172237
pii: 000505365
doi: 10.1159/000505365
doi:

Substances chimiques

Anticholesteremic Agents 0
Cholesterol Ester Transfer Proteins 0
Cholesterol, HDL 0
Cholesterol, LDL 0

Types de publication

Journal Article Meta-Analysis Research Support, Non-U.S. Gov't Systematic Review

Langues

eng

Sous-ensembles de citation

IM

Pagination

236-250

Informations de copyright

© 2020 S. Karger AG, Basel.

Auteurs

Hossein Taheri (H)

Center for Clinical Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital/McGill University, Montreal, Québec, Canada.
Department of Medicine, McGill University, Montreal, Québec, Canada.

Kristian B Filion (KB)

Center for Clinical Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital/McGill University, Montreal, Québec, Canada.
Department of Medicine, McGill University, Montreal, Québec, Canada.
Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Québec, Canada.

Sarah B Windle (SB)

Center for Clinical Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital/McGill University, Montreal, Québec, Canada.

Pauline Reynier (P)

Center for Clinical Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital/McGill University, Montreal, Québec, Canada.

Mark J Eisenberg (MJ)

Center for Clinical Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital/McGill University, Montreal, Québec, Canada, mark.eisenberg@mcgill.ca.
Department of Medicine, McGill University, Montreal, Québec, Canada, mark.eisenberg@mcgill.ca.
Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Québec, Canada, mark.eisenberg@mcgill.ca.
Division of Cardiology, Jewish General Hospital/McGill University, Montreal, Québec, Canada, mark.eisenberg@mcgill.ca.

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Classifications MeSH