SynthesisJAMA2016

Association Between Lowering LDL-C and Cardiovascular Risk Reduction Among Different Therapeutic Interventions: A Systematic Review and Meta-analysis.

Michael G Silverman et al.PubMed ↗Publisher ↗

Statinslooks good hereFewer major vascular events.Correlation only, not a test of it.
Established nonstatin interventions that work primarily via upregulation of LDL receptor expression (ie, diet, bile acid sequestrants, ileal bypass, and ezetimibe)looks good hereFewer major vascular events.Correlation only, not a test of it.
Statins and established nonstatin interventions that work primarily via upregulation of LDL receptor expression combinedlooks good hereFewer major vascular events.Correlation only, not a test of it.
Niacinlooks good hereFewer major vascular events.Correlation only, not a test of it.

What moved togetherboth groups pooled, not the treatment’s effect

Correlation, not cause

Statins went with fewer major vascular events

−0.77−0.84 to −0.71

statins vs per 1-mmol/L reduction in LDL-C level, in statins

As reported

difference −0.77, 95% CI −0.84 to −0.71

Correlation, not cause

Established nonstatin interventions that work primarily via upregulation of LDL receptor expression (ie, diet, bile acid sequestrants, ileal bypass, and ezetimibe) went with fewer major vascular events

−25%−34% to −14%

established nonstatin interventions that work primarily via upregulation of LDL receptor expression (ie, diet, bile acid sequestrants, ileal bypass, and ezetimibe) vs per 1-mmol/L reduction in LDL-C level, in established nonstatin interventions that work primarily via upregulation of LDL receptor expression

Bigger than 6 in 10 on the map

As reported

RR 0.75, 95% CI 0.66–0.86

Correlation, not cause

Statins and established nonstatin interventions that work primarily via upregulation of LDL receptor expression combined went with fewer major vascular events

−23%−25% to −21%

statins and established nonstatin interventions that work primarily via upregulation of LDL receptor expression combined vs per 1-mmol/L reduction in LDL-C level, in 5 therapies combined (statins, diet, bile acid sequestrants, ileal bypass, and ezetimibe)

Bigger than 5 in 10 on the map

As reported

RR 0.77, 95% CI 0.75–0.79

+5 more in the walkthrough ↓

Who was studied, and how

382people in the A Randomized, Double-Blind, Parallel Group Study to Evaluate the Efficacy and Safety of Bempedoic Acid 180 Mg + Ezetimibe 10 Mg Fixed-Dose Combination Compared to Bempedoic Acid, Ezetimibe, and Placebo Alone in Patients Treated With Maximally Tolerated Statin Therapy trial, from 2017

175of them with cardiovascular disease, in this paper

Already taking statins, or nottheir own situation, not assigned

on statins

per 1-mmol/L reduction in LDL-C level

Statins went with fewer major vascular events−0.77

correlation, not a test

Already taking established nonstatin interventions that work primarily via upregulation of LDL receptor expression (ie, diet, bile acid sequestrants, ileal bypass, and ezetimibe), or nottheir own situation, not assigned

on established nonstatin interventions that work primarily via upregulation of LDL receptor expression (ie, diet, bile acid sequestrants, ileal bypass, and ezetimibe)

per 1-mmol/L reduction in LDL-C level

Established nonstatin interventions that work primarily via upregulation of LDL receptor expression (ie, diet, bile acid sequestrants, ileal bypass, and ezetimibe) went with fewer major vascular events−25%

correlation, not a test

the abstract, start to end

… 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) …

… these 5 therapies combined, the RR was 0.77 (95% CI, 0.75-0.79, P < .001) …

… of LDL-C reduction in the trials were 0.94 (95% CI, 0.89-0.99) vs 0.91 (95% CI, 0.90-0.92) for niacin (P = .24); 0.88 (95% CI, 0.83-0.92) vs 0.94 (95% CI, 0.93-0.94) for fibrates (P = .02), which was lower than expected (ie, greater risk reduction); 1.01 (95% CI, 0.94-1.09) vs 0.90 (95% CI, 0.89-0.91) for cholesteryl ester transfer protein inhibitors (P = .002), which was higher than expected (ie, less risk reduction); and 0.49 (95% CI, 0.34-0.71) vs 0.61 …

← favours treatmentfavours comparator →

could be chance

Major vascular eventsstatins vs per 1-mmol/L reduction in LDL-C level, in statins

−0.77−0.84 to −0.71

Major vascular eventsestablished nonstatin interventions that work primarily via upregulation of LDL receptor expression (ie, diet, bile acid sequestrants, ileal bypass, and ezetimibe) vs per 1-mmol/L reduction in LDL-C level, in established nonstatin interventions that work primarily via upregulation of LDL receptor expression

RR 0.750.66–0.86

Major vascular eventsstatins and established nonstatin interventions that work primarily via upregulation of LDL receptor expression combined vs per 1-mmol/L reduction in LDL-C level, in 5 therapies combined (statins, diet, bile acid sequestrants, ileal bypass, and ezetimibe)

RR 0.770.75–0.79

Major vascular eventsniacin vs expected RR based on degree of LDL-C reduction, in niacin

−0.94−0.99 to −0.89

Major vascular eventsexpected RR based on degree of LDL-C reduction vs cholesteryl ester transfer protein inhibitors, in cholesteryl ester transfer protein inhibitors

RR 0.900.89–0.91

Major vascular eventsfibrates vs expected RR based on degree of LDL-C reduction, in fibrates

RR 0.880.83–0.92

Major vascular eventscholesteryl ester transfer protein inhibitors vs expected RR based on degree of LDL-C reduction, in cholesteryl ester transfer protein inhibitors

RR 1.010.94–1.09

Lipidsproprotein convertase subtilisin/kexin type 9 inhibitors vs expected RR based on degree of LDL-C reduction, in proprotein convertase subtilisin/kexin type 9 inhibitors

RR 0.490.34–0.71

StatinsOther lipid agentsDiet, exercise & lifestyleLipids

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634 papers cite itlatest 60 shown

2016

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2024

2025

2026

this paperpooled ittrialcites it

4 trials

NCT03337308phase 3382 enrolled2017 NCT0558963644 enrolled2022 NCT06526013200 enrolled2024 NCT07039123205 enrolled2025

Association Between Lowering LDL-C and Cardiovascular Risk Reduction Among Different Therapeutic Interventions: A Systematic Review and Meta-analysis.

What moved togetherboth groups pooled, not the treatment’s effect

Statins went with fewer major vascular events

Established nonstatin interventions that work primarily via upregulation of LDL receptor expression (ie, diet, bile acid sequestrants, ileal bypass, and ezetimibe) went with fewer major vascular events

Statins and established nonstatin interventions that work primarily via upregulation of LDL receptor expression combined went with fewer major vascular events

Who was studied, and how

Eight numbers in the abstract

Where each one falls

Where it lands on the map

634 papers cite itlatest 60 shown

4 trials