Safi U Khan
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
Muhammad U Khan
Shahul Valavoor
Muhammad Shahzeb Khan
Victor Okunrintemi
Mamas Mamas m.mamas@keele.ac.uk
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 |
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