Does lowering apoB lower heart disease risk?

controlled trial · 2016

“The corresponding HR for each 27 mg/dL lower apoB was 0.72 (95% CI, 0.60–0.86; P=0.0002; Table 2).”

Reductions in Atherogenic Lipids and Major Cardiovascular Events: A Pooled Analysis of 10 ODYSSEY Trials Comparing Alirocumab With Control. Circulation
Who: Adults with established ASCVD or high cardiovascular risk (including heterozygous familial hypercholesterolemia) with inadequately controlled LDL-C, mostly on maximally tolerated statins
PMID 27777279

pooled analysis · 2010 · landmark

“In these meta-analyses, the size of the proportional reduction in major vascular events is directly proportional to the absolute LDL reduction that is achieved, with further benefit from more intensive statin therapy, even if LDL cholesterol is already lower than 2·0 mmol/L.”

Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet
Who: participants in 26 randomised statin trials: 5 trials of more vs less intensive statin (acute coronary syndrome and stable coronary disease) and 21 trials of statin vs control (including primary prevention, diabetes, haemodialysis, heart failure)
PMID 21067804

controlled trial · 2017 · landmark

“Given these caveats, the magnitude of benefit of evolocumab in reducing the risk of major coronary events, stroke, and urgent coronary revascularization is largely consistent with the benefit seen with statins on a per–millimole-per-liter basis of LDL cholesterol lowering (Fig. S6 in the Supplementary Appendix).”

Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease. N Engl J Med
Who: 27,564 patients aged 40-85 with atherosclerotic cardiovascular disease and LDL >=70 mg/dl on statin therapy
PMID 28304224

controlled trial · 2004 · landmark

“This difference should translate into a 20 percent reduction in clinical events, which is very similar to the 16 percent reduction we observed and suggests that much of the benefit is attributable to the difference in the degree of LDL cholesterol lowering.”

Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med
Who: 4,162 patients hospitalized for an acute coronary syndrome within the preceding 10 days, 349 sites in 8 countries, mean age 58, 22% women
PMID 15007110

controlled trial · 2015 · landmark

“The hazard ratio for clinical benefit per millimole of LDL cholesterol reduction with ezetimibe in IMPROVE-IT was 0.80, as compared with 0.78 observed with statins in the CTT meta-analysis.”

Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes. N Engl J Med
Who: 18,144 patients aged ≥50 hospitalized for acute coronary syndrome within 10 days, LDL 50-125 mg/dL
PMID 26039521

controlled trial · 2018 · landmark

“A composite primary end-point event occurred in 903 patients (9.5%) in the alirocumab group and in 1052 patients (11.1%) in the placebo group (hazard ratio, 0.85; 95% confidence interval [CI], 0.78 to 0.93; P<0.001).”

Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome. N Engl J Med
Who: 18,924 patients aged 40 or older with acute coronary syndrome 1-12 months earlier and LDL-C >=70 mg/dL, non-HDL-C >=100 mg/dL or apoB >=80 mg/dL on high-intensity or maximum tolerated statin
PMID 30403574

pooled analysis · 2016 · landmark

“The RR for major vascular events per 1-mmol/L (38.7-mg/dL) reduction in LDL-C level was 0.77 (95% CI, 0.71-0.84; P < .001) for statins and 0.75 (95% CI, 0.66-0.86; P = .002) for established nonstatin interventions that work primarily via upregulation of LDL receptor expression (ie, diet, bile acid sequestrants, ileal bypass, and ezetimibe) (between-group difference, P = .72).”

Association Between Lowering LDL-C and Cardiovascular Risk Reduction Among Different Therapeutic Interventions: A Systematic Review and Meta-analysis. JAMA
Who: Participants in 49 randomized clinical trials of 9 LDL-C-lowering interventions (mean age 62, 24% women, mean baseline LDL-C 3.16 mmol/L)
PMID 27673306

other primary study · 2020 · landmark

“Circulating lipoprotein lipids cause coronary heart disease (CHD).”

Evaluating the relationship between circulating lipoprotein lipids and apolipoproteins with risk of coronary heart disease: A multivariable Mendelian randomisation analysis. PLoS Med
Who: UK Biobank participants of European descent (mean age 56.9, 54.2% women) for lipid GWAS; CARDIoGRAMplusC4D for CHD outcomes
PMID 32203549

other primary study · 2016 · landmark

“Indeed, when the effects of each PCSK9 score and the individual PCSK9 variants included in these scores were plotted, there was a dose-dependent log-linear association between PCSK9-mediated lower LDL cholesterol levels and the risk of myocardial infarction or death from coronary heart disease (Fig. S3 in the Supplementary Appendix).”

Variation in PCSK9 and HMGCR and Risk of Cardiovascular Disease and Diabetes. N Engl J Med
Who: 112,772 participants from 14 prospective cohort or case-control studies (weighted mean age 59.9), with replication in CARDIoGRAMplusC4D and DIAGRAM consortia
PMID 27959767

trial or observed group · 2019 · landmark

“In this study, triglyceride-lowering LPL variants and LDL-C–lowering LDLR variants were associated with similar lower CHD risk per unit lower level of ApoB-containing lipoproteins.”

Association of Triglyceride-Lowering LPL Variants and LDL-C-Lowering LDLR Variants With Risk of Coronary Heart Disease. JAMA
Who: participants of 63 cohort or case-control studies in North America or Europe (UK Biobank, dbGAP studies, CARDIoGRAMplusC4D), mean age 62.7, 51.4% women
PMID 30694319