Key result
Intensifying LDL-C lowering therapy provides the greatest relative and absolute cardiovascular risk reductions when baseline LDL-C is >100 mg/dl or in extremely high-risk ASCVD patient groups.
Why the study?
The authors sought to update a systematic review evaluating how the log-linear association between on-treatment LDL-C levels and ASCVD events influences cardiovascular risk reduction from intensifying LDL-C lowering therapy.
Does intensifying LDL-C lowering therapy with high-intensity statins, ezetimibe, or PCSK9 inhibitors reduce ASCVD events in patients with clinical ASCVD?
Systematic Review (n=83,521)
Does intensifying LDL-C lowering therapy with high-intensity statins, ezetimibe, or PCSK9 inhibitors reduce ASCVD events in patients with clinical ASCVD?
Intensifying LDL-C lowering therapy provides the greatest cardiovascular risk reduction benefits in patients with baseline LDL-C >100 mg/dl or those at extremely high ASCVD risk.
Intensify LDL-C lowering in ASCVD patients with baseline >100 mg/dl or extreme risk; reinforces log-linear benefits across therapies.
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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Robinson et al. (2020) conducted a systematic review in Atherosclerotic cardiovascular disease (ASCVD) (n=83,521). Intensifying LDL-C lowering therapy (high intensity statin, ezetimibe, PCSK9 mAbs) vs. Placebo or moderate intensity statin was evaluated on Log-linear association between on-treatment LDL-C and ASCVD event rates. Intensifying LDL-C lowering therapy provides the greatest relative and absolute cardiovascular risk reductions when baseline LDL-C is >100 mg/dl or in extremely high-risk ASCVD patient groups.
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