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Published on: November 10, 2017
Clinical implications of the log linear association between LDL-C lowering and cardiovascular risk reduction:
Jennifer G Robinson1, Manju Bengaluru Jayanna2, C Noel Bairey Merz3
1Division of Cardiology, Department of Epidemiology and Internal Medicine, University of Iowa, Iowa City, IA, United States of America.
Insights
Intensifying LDL-C lowering therapy offers greater cardiovascular risk reduction in patients with LDL-C ≥100 mg/dl. For those with LDL-C <100 mg/dl, alternative risk reduction strategies should be considered alongside LDL-C lowering.
Area of Science:
- Cardiovascular Medicine
- Pharmacology
- Clinical Trials
Background:
- The association between low-density lipoprotein cholesterol (LDL-C) levels and atherosclerotic cardiovascular disease (ASCVD) events follows a log-linear pattern.
- This log-linear relationship is more pronounced in higher-risk patient subgroups within statin versus placebo trials.
Purpose of the Study:
- To update a previous systematic review on the log-linear association between LDL-C and ASCVD events.
- To evaluate how this association influences the magnitude of cardiovascular risk reduction achieved by intensifying LDL-C lowering therapy.
Main Methods:
- A systematic review of MEDLINE/PubMed, ClinicalTrials.gov, and author files (2005-2019) was conducted.
- Subgroup analyses from cardiovascular outcomes trials of statins, ezetimibe, and PCSK9 monoclonal antibodies (mAbs) with ASCVD endpoints were included.
- Data were pooled using random-effects models, and weighted least-squares regression was used to fit linear and log-linear models.
Main Results:
- Ninety-six treatment subgroups from 5 trials were identified.
- A log-linear association between on-treatment LDL-C and ASCVD risk was confirmed, particularly in higher-risk subgroups.
- Greater relative and absolute cardiovascular risk reductions were observed with LDL-C lowering when baseline LDL-C was >100 mg/dl and in extremely high-risk ASCVD patient groups.
Conclusions:
- Intensifying LDL-C lowering therapy is associated with greater cardiovascular and mortality risk reduction in patients with baseline LDL-C ≥100 mg/dl or in extremely high-risk groups.
- When baseline LDL-C is <100 mg/dl, the log-linear relationship suggests considering treatment options beyond further LDL-C lowering for optimal risk reduction.
Background:
The log linear association between on-treatment LDL-C levels and ASCVD events is amplified in higher risk patient subgroups of statin versus placebo trials.
Objectives:
Update previous systematic review to evaluate how the log linear association influences the magnitude of cardiovascular risk reduction from intensifying LDL-C lowering therapy.
Methods:
MEDLINE/PubMED, Clinical trials.gov, and author files were searched from 1/1/2005 through 10/30/2019 for subgroup analyses of cardiovascular outcomes trials of moderate versus high intensity statin, ezetimibe, and PCSK9 mAbs with an ASCVD endpoint (nonfatal myocardial infarction or stroke, cardiovascular death). Annualized ASCVD event rates were used to extrapolate 5-year ASCVD risk for each treatment group reported in subgroup analyses, which were grouped into a priori risk groups according to annualized placebo/control rates of ≥4%, 3-3.9%, or <3% ASCVD risk. Data were pooled using a random-effects model. Weighted least-squares regression was used to fit linear and log-linear models.
Results:
Systematic review identified 96 treatment subgroups from 2 trials of moderate versus high intensity statin, 2 trials of a PCSK9 mAb versus placebo, and 1 trial of ezetimibe versus placebo. A log linear association between on-treatment LDL-C and ASCVD risk represents the association between on-treatment LDL-C levels and ASCVD event rates, especially in higher risk subgroups. Greater relative and absolute cardiovascular risk reductions from LDL-C lowering were observed when baseline LDL-C was >100 mg/dl and in extremely high risk ASCVD patient groups.
Conclusions:
Greater cardiovascular and mortality risk reduction benefits from intensifying LDL-C lowering therapy may be expected in those with LDL-C ≥100 mg/dl, or in extremely high risk patient groups. When baseline LDL-C <100 mg/dl, the log linear association between LDL-C and event rates suggests that treatment options other than further LDL-C lowering should also be considered for optimal risk reduction.
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