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

Author:

Khan Safi U1,Khan Muhammad U1,Valavoor Shahul1,Khan Muhammad Shahzeb2,Okunrintemi Victor3,Mamas Mamas A45,Leucker Thorsten M6,Blaha Michael J6,Michos Erin D6

Affiliation:

1. Department of Medicine, West Virginia University, Morgantown, WV, USA

2. Department of Medicine, John H. Stroger J. Hospital of Cook County, Chicago, IL, USA

3. Department of Internal Medicine, East Carolina University, Greenville, SC, USA

4. Keele Cardiovascular Research Group, Keele University, Stoke-on-Trent, Staffordshire, UK

5. Department of Cardiology, Royal Stoke University Hospital, Stoke-on-Trent, Staffordshire, UK

6. Division of Cardiology, Johns Hopkins School of Medicine, Baltimore, MD, USA

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.

Publisher

Oxford University Press (OUP)

Subject

Cardiology and Cardiovascular Medicine,Epidemiology

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