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Association of lowering apolipoprotein B with cardiovascular outcomes across various lipid-lowering therapies: Systematic review and meta-analysis of trials

Khan, Safi U; Khan, Muhammad U; Valavoor, Shahul; Khan, Muhammad Shahzeb; Okunrintemi, Victor; Mamas, Mamas A; Leucker, Thorsten M; Blaha, Michael J; Michos, Erin D

Authors

Safi U Khan

Muhammad U Khan

Shahul Valavoor

Muhammad Shahzeb Khan

Victor Okunrintemi

Thorsten M Leucker

Michael J Blaha

Erin D Michos



Abstract

Aims
The effect of therapeutic lowering of apolipoprotein B (apoB) on mortality and major adverse cardiovascular events is uncertain. It is also unclear whether these potential effects vary by different lipid-lowering strategies.

Methods
A total of 29 randomized controlled trials were selected using PubMed, Cochrane Library and EMBASE through 2018. We selected trials of therapies which ultimately clear apolipoprotein B particles by upregulating low-density lipoprotein receptor (LDL-R) expression (statins, ezetimibe, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, bile acid sequestrants) or therapies which reduce apolipoprotein B independent of LDL-R (cholesteryl ester transfer protein inhibitor, fibrates, niacin, omega-3 fatty acids) with sample size of ≥1000 patients and follow-up of ≥1 year. The meta-regression and meta-analyses were constructed using a random effects model.

Results
In 332,912 patients, meta-regression analyses showed relative risks of 0.95 for all-cause mortality (95% confidence interval 0.92–0.99) and 0.93 (0.88–0.98) for cardiovascular mortality for every 10 mg/dL decrease in apolipoprotein B by all interventions combined. Reduction in all-cause mortality was limited to statins (0.92 (0.86–0.98)). For MACE, the relative risk per 10 mg/dL reduction in apolipoprotein B was 0.93 (0.90–0.97) for all therapies combined, with both statin (0.88 (0.83–0.93)) and non-statin therapies (0.96 (0.94–0.99)). which clear apolipoprotein B by upregulating LDL-R showing significant reductions; whereas interventions which lower apolipoprotein B independent of LDL-R did not demonstrate this effect (1.02 (0.81–1.30)).

Conclusion
While both statin and established non-statin therapies (PCSK9 inhibitor and ezetimibe) reduced cardiovascular risk per decrease in apolipoprotein B, interventions which reduce apolipoprotein B independently of LDL-R were not associated with cardiovascular benefit.

Citation

Khan, S. U., Khan, M. U., Valavoor, S., Khan, M. S., Okunrintemi, V., Mamas, M. A., …Michos, E. D. (2020). Association of lowering apolipoprotein B with cardiovascular outcomes across various lipid-lowering therapies: Systematic review and meta-analysis of trials. European Journal of Preventive Cardiology, 27(12), 1255-1268. https://doi.org/10.1177/2047487319871733

Journal Article Type Article
Acceptance Date Aug 3, 2019
Online Publication Date Sep 2, 2019
Publication Date 2020-08
Deposit Date Jun 20, 2023
Journal European Journal of Preventive Cardiology
Print ISSN 2047-4873
Electronic ISSN 2047-4881
Publisher SAGE Publications
Peer Reviewed Peer Reviewed
Volume 27
Issue 12
Pages 1255-1268
DOI https://doi.org/10.1177/2047487319871733
Keywords Cardiology and Cardiovascular Medicine; Epidemiology; Apolipoprotein B; cardiovascular outcomes; mortality; meta-regression analysis