Abstract
Lipid-lowering guidelines emphasize shared decision-making between clinicians and
patients, resulting in patients anticipating the degree of response from diet or drug
therapy. Challenging for physicians is understanding the sources of variability complicating
their management decisions, which include non-adherence, genetic considerations, additional
lipid parameters including lipoprotein (a) levels, and rare systemic responses limiting
benefits that result in non-responsiveness to monoclonal antibody injection. In this
narrative review, we focus on the variability of low-density lipoprotein cholesterol
(LDL-C) response to guideline-directed interventions such as statins, ezetimibe, bile
acid sequestrants, fibrates, proprotein/convertase subtilisin-kexin type 9 inhibitors,
and LDL-C-lowering diets. We hypothesize that the variability in individual lipid
responses is multifactorial. We provide an illustrative model with a check list that
can be used to identify factors that may be present in the individual patient.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to The American Journal of MedicineAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.J Am Coll Cardiol. 2019; 73: e285-e350
- Percent reduction in LDL cholesterol following high-intensity statin therapy: potential implications for guidelines and for the prescription of emerging lipid-lowering agents.Eur Heart J. 2016; 37: 1373-1379
- Ezetimibe added to statin therapy after acute coronary syndromes.N Engl J Med. 2015; 372: 2387-2397
- NPC1L1 haplotype is associated with inter-individual variation in plasma low-density lipoprotein response to ezetimibe.Lipids Health Dis. 2005; 4: 16
- A meta-analysis assessing additional LDL-C reduction from addition of a bile acid sequestrant to statin therapy.Am J Med. 2020; 133: 1322-1327
- The effects of bile acid sequestrants on lipid profile and blood glucose concentrations: a systematic review and meta-analysis of randomized controlled trials.Int J Cardiol. 2017; 227: 850-857
- Evolocumab and clinical outcomes in patients with cardiovascular disease.N Engl J Med. 2017; 376: 1713-1722
- Alirocumab and cardiovascular outcomes after acute coronary syndrome.N Engl J Med. 2018; 379: 2097-2107
- Individual cholesterol variation in response to a margarine- or butter-based diet: a study in families.JAMA. 2000; 284: 2740-2747
- Medication adherence: its importance in cardiovascular outcomes.Circulation. 2009; 119: 3028-3035
- Patients and physicians beliefs and practices regarding adherence to cardiovascular medication.JAMA Cardiol. 2016; 1: 470-473
- Association of statin adherence with mortality in patients with atherosclerotic cardiovascular disease.JAMA Cardiol. 2019; 4: 206-213
- Practice-level variation in statin use and low-density lipoprotein cholesterol control in the United States: results from the Patient and Provider Assessment of Lipid Management (PALM) registry.Am Heart J. 2019; 214: 113-124
- Impact of ABCG2 and SLCO1B1 polymorphisms on pharmacokinetics of rosuvastatin, atorvastatin and simvastatin acid in Caucasian and Asian subjects: a class effect?.Eur J Clin Pharmacol. 2015; 71: 341-355
- Genetic determinants of statin-induced low-density lipoprotein cholesterol reduction: the Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial.Circ Cardiovasc Genet. 2012; 5: 257-264
- Lipoprotein(a): a Genetically Determined, Causal, and Prevalent Risk Factor for Atherosclerotic Cardiovascular Disease: a Scientific Statement from the American Heart Association.Arterioscler Thromb Vasc Biol. 2022; 42: e48-e60
- Lp(a) (lipoprotein[a]) concentrations and incident atherosclerotic cardiovascular disease: new insights from a large national biobank.Arterioscler Thromb Vasc Biol. 2021; 41: 465-474
- Use of lipoprotein(a) in clinical practice: a biomarker whose time has come. A scientific statement from the National Lipid Association.J Clin Lipidol. 2019; 13: 374-392
- Statin treatment increases lipoprotein(a) levels in subjects with low molecular weight apolipoprotein(a) phenotype.Atherosclerosis. 2019; 289: 201-205
- Does body fatness modify the association between dietary cholesterol and risk of coronary death? Results from the Chicago Western Electric Study.Arterioscler Thromb. 1992; 12: 755-761
- Statin therapy in patients with cirrhosis.Frontline Gastroenterol. 2015; 6: 255-261
- Intensive versus moderate lipid lowering with statins after acute coronary syndromes.N Engl J Med. 2004; 350: 1495-1504
- Management of dyslipidemia in adult solid organ transplant recipients.J Clin Lipidol. 2019; 13: 231-245
- Effect of bile acid sequestrants on the risk of cardiovascular events: a Mendelian randomization analysis.Circ Cardiovasc Genet. 2015; 8: 618-627
- Assessment of the 1% of patients with consistent < 15% reduction in low-density lipoprotein cholesterol: pooled analysis of 10 phase 3 ODYSSEY alirocumab trials.Cardiovasc Drugs Ther. 2018; 32: 175-180
- Case reports of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition nonresponse.J Clin Lipidol. 2018; 12: 1141-1145
- Inhibition of PCSK9 with evolocumab in homozygous familial hypercholesterolaemia (TESLA Part B): a randomised, double-blind, placebo-controlled trial.Lancet. 2015; 385: 341-350
- Relationship between low-density lipoprotein cholesterol and lipoprotein(a) lowering in response to PCSK9 inhibition with evolocumab.J Am Heart Assoc. 2019; 8e010932
- Unusual responses to PCSK9 inhibitors in a clinical cohort utilizing a structured follow-up protocol.Am J Prev Cardiol. 2020; 1100012
- Association of PCSK9 variants with the risk of atherosclerotic cardiovascular disease and variable responses to PCSK9 inhibitor therapy.Curr Probl Cardiol. 2022; 47101043
- Relation of gemfibrozil treatment and lipid levels with major coronary events: VA-HIT: a randomized controlled trial.JAMA. 2001; 285: 1585-1591
- Effect of fibric acid derivatives on blood lipid and lipoprotein levels.Am J Med. 1987; 83: 44-49
Article Info
Publication History
Published online: July 21, 2022
Publication stage
In Press Journal Pre-ProofFootnotes
Funding: None.
Conflicts of Interest: None of the authors have any relevant conflict of interest disclosures.
Authorship: All authors had access to the data and had a role in writing the manuscript.
Identification
Copyright
© 2022 Elsevier Inc. All rights reserved.
