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

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., Leucker, T. M., Blaha, M. J., & 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
• Public URL: https://keele-repository.worktribe.com/output/490436