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

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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
JournalEuropean Journal of Preventive Cardiology
DOIs
StateAccepted/In press - Jan 1 2019

Fingerprint

Apolipoproteins B
Meta-Analysis
Lipids
LDL Receptors
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Therapeutics
Mortality
Regression Analysis
Cholesterol Ester Transfer Proteins
Fibric Acids
Niacin
Omega-3 Fatty Acids
Therapeutic Uses
Bile Acids and Salts
PubMed
Sample Size
Libraries
Randomized Controlled Trials
Confidence Intervals

Keywords

  • Apolipoprotein B
  • cardiovascular outcomes
  • meta-regression analysis
  • mortality

ASJC Scopus subject areas

  • Epidemiology
  • Cardiology and Cardiovascular Medicine

Cite this

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.

In: European Journal of Preventive Cardiology, 01.01.2019.

Research output: Contribution to journalArticle

@article{9ed98edeec4a4c18ad861a54dc46d34f,
title = "Association of lowering apolipoprotein B with cardiovascular outcomes across various lipid-lowering therapies: Systematic review and meta-analysis of trials",
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.",
keywords = "Apolipoprotein B, cardiovascular outcomes, meta-regression analysis, mortality",
author = "Khan, {Safi U.} and Khan, {Muhammad U.} and Shahul Valavoor and Khan, {Muhammad Shahzeb} and Victor Okunrintemi and Mamas, {Mamas A.} and Leucker, {Thorsten M.} and Blaha, {Michael J.} and Michos, {Erin D.}",
year = "2019",
month = "1",
day = "1",
doi = "10.1177/2047487319871733",
language = "English (US)",
journal = "European Journal of Preventive Cardiology",
issn = "2047-4873",
publisher = "SAGE Publications Ltd",

}

TY - JOUR

T1 - Association of lowering apolipoprotein B with cardiovascular outcomes across various lipid-lowering therapies

T2 - Systematic review and meta-analysis of trials

AU - Khan, Safi U.

AU - Khan, Muhammad U.

AU - Valavoor, Shahul

AU - Khan, Muhammad Shahzeb

AU - Okunrintemi, Victor

AU - Mamas, Mamas A.

AU - Leucker, Thorsten M.

AU - Blaha, Michael J.

AU - Michos, Erin D.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

KW - Apolipoprotein B

KW - cardiovascular outcomes

KW - meta-regression analysis

KW - mortality

UR - http://www.scopus.com/inward/record.url?scp=85073806816&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85073806816&partnerID=8YFLogxK

U2 - 10.1177/2047487319871733

DO - 10.1177/2047487319871733

M3 - Article

C2 - 31475865

AN - SCOPUS:85073806816

JO - European Journal of Preventive Cardiology

JF - European Journal of Preventive Cardiology

SN - 2047-4873

ER -