Clinical implications of the log linear association between LDL-C lowering and cardiovascular risk reduction: Greatest benefits when LDL-C >100 mg/dl

Abstract

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.

Higher Serum Triglyceride Can Predict Recurrent Coronary Revascularization Events in Patients Undergoing Percutaneous Coronary Intervention With Baseline LDL-C&lt;55mg/dl

“…Even with low baseline LDL-C, statin therapy improves clinical prognosis [6][7][8][9]. But the bene t is less prominent as compared with high LDL-C, and recurrent vascular events continue to occur [3,4], which suggests other risk factors, rather than LDL-C, are involved in atherosclerosis progression for those patients.…”

“…The higher the baseline LDL-C is, the more bene ts derived from lipid-lowering therapy. Cardiovascular bene ts from intensi ed lipid-lowering therapy are expected less in those with baseline LDL-C < 100 mg/dl [3,4]. Serial intravascular ultrasound analysis also indicates that statin therapy is less effective in inducing coronary plaque regression in patients with low LDL-C [5].…”

LDL-cholesterol lowering efficacy of atorvastatin® in primary prevention. Real-world experience in a developing country; a program based on evidence, personalization, and empowerment

“…Copyright 2021 KEI Journals. All Rights Reserved https://esmed.org/MRA/mra/ the "iconoclasts" of the LDL-centric principle and the benefit of statins 25,26 ; d) attraction to new strategies such as monoclonal antibodies (mAbs) or antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs), many of them still in the research phase and many others, although already approved for clinical use, with inappropriate balances between saving and spending, especially in primary cardiovascular prevention or in patients with LDL-C <100 mg/dL in treatment with statins 27 ; the latter, the main limitation to access these new strategies, even in countries like the United States 28 ; e) and finally, the proliferation of so-called generic and "similar" statins whose therapeutic efficacy is presumed by a single bioequivalence study (generic) or by the active ingredient included in the label (similar), without any other pharmacokinetic or pharmacodynamic evaluation. 29 In addition, the use of some naturopathic products that have been approved by the Federal Commission for the Protection of Sanitary Risks in Mexico.…”

Higher serum triglyceride can predict recurrent coronary revascularization events in patients undergoing percutaneous coronary intervention with baseline LDL-C <55 mg/dL

“…The higher the baseline LDL-C is, the more benefits derived from lipid-lowering therapy. Cardiovascular benefit from intensified LDL-C lowering was expected less in patients with baseline LDL-C <100 mg/dL 3 4. Serial intravascular ultrasound analysis also indicated that statin therapy in inducing coronary plaque regression was less effective in patients with low LDL-C 5.…”