LDL-C target attainment in secondary prevention of ASCVD in the United States: barriers, consequences of nonachievement, and strategies to reach goals

References

• Heron M. Deaths: leading causes for 2017. Natl Vital Stat Rep. 2019;68:1–77.
   PubMedGoogle Scholar
• Herrington W, Lacey B, Sherliker P, et al. Epidemiology of atherosclerosis and the potential to reduce the global burden of atherothrombotic disease. Circ Res. 2016;118(4):535–546.
   PubMed Web of Science ®Google Scholar
• Nelson S, Whitsel L, Khavjou O, et al. Projections of cardiovascular disease prevalence and costs: 2015–2035. Technical report. 2016.
   Google Scholar
• Ference BA, Ginsberg HN, Graham I, et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel. Eur Heart J. 2017;38(32):2459–2472.
   PubMed Web of Science ®Google Scholar
• Yusuf S, Joseph P, Rangarajan S, et al. Modifiable risk factors, cardiovascular disease, and mortality in 155 722 individuals from 21 high-income, middle-income, and low-income countries (PURE): a prospective cohort study. Lancet. 2020;395(10226):795–808.
   PubMed Web of Science ®Google Scholar
• Libby P, Buring JE, Badimon L, et al. Atherosclerosis. Nat Rev Dis Primers. 2019;5(1):56.
   PubMed Web of Science ®Google Scholar
• Bentzon JF, Otsuka F, Virmani R, et al. Mechanisms of plaque formation and rupture. Circ Res. 2014;114(12):1852–1866.
   PubMed Web of Science ®Google Scholar
• Ference BA, Graham I, Tokgozoglu L, et al. Reprint of: impact of lipids on cardiovascular health: JACC Health Promotion Series. J Am Coll Cardiol. 2018;72(23, Part B):2980–2995.
   PubMed Web of Science ®Google Scholar
• Abdullah SM, Defina LF, Leonard D, et al. Long-term association of low-density lipoprotein cholesterol with cardiovascular mortality in individuals at low 10-year risk of atherosclerotic cardiovascular disease: results from the Cooper Center Longitudinal Study. Circulation. 2018;138(21):2315–2325.
   PubMed Web of Science ®Google Scholar
• Grundy SM, Stone NJ, Bailey AL, et al. 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. Circulation. 2019;139(25):e1082–e1143.
   PubMed Web of Science ®Google Scholar
• Di Angelantonio E, Gao P, Pennells L, Emerging Risk Factors Collaboration. Lipid-related markers and cardiovascular disease prediction. JAMA. 2012;307(23):2499–2506.
   PubMed Web of Science ®Google Scholar
• Prospective Studies Collaboration. Blood cholesterol and vascular mortality by age, sex, and blood pressure: a meta-analysis of individual data from 61 prospective studies with 55 000 vascular deaths. Lancet. 2007;370(9602):1829–1839.
   PubMed Web of Science ®Google Scholar
• Cohen JC, Boerwinkle E, Mosley TH, et al. Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N Engl J Med. 2006;354(12):1264–1272.
   PubMed Web of Science ®Google Scholar
• Nikpay N, Goel A, Won HH, et al. CARDIoGRAMplusC4D Consortium. A comprehensive 1000 Genomes–based genome-wide association meta-analysis of coronary artery disease. Nat Genet. 2015;47(10):1121–1130. https://www.nature.com/articles/ng.3396#cite
   PubMed Web of Science ®Google Scholar
• Ference BA, Yoo W, Alesh I, et al. Effect of long-term exposure to lower low-density lipoprotein cholesterol beginning early in life on the risk of coronary heart disease: a Mendelian randomization analysis. J Am Coll Cardiol. 2012;60(25):2631–2639.
   PubMed Web of Science ®Google Scholar
• Linsel-Nitschke P, Götz A, Erdmann J, et al. Lifelong reduction of LDL-cholesterol related to a common variant in the LDL-receptor gene decreases the risk of coronary artery disease—a Mendelian randomisation study. PLoS One. 2008;3(8):e2986.
   PubMed Web of Science ®Google Scholar
• Holmes MV, Asselbergs FW, Palmer TM, et al. Mendelian randomization of blood lipids for coronary heart disease. Eur Heart J. 2015;36(9):539–550.
   PubMed Web of Science ®Google Scholar
• Baigent C, Blackwell L, Emberson J, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010;376(9753):1670–1681.
   PubMed Web of Science ®Google Scholar
• Cannon CP, Blazing MA, Giugliano RP, et al. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med. 2015;372(25):2387–2397.
   PubMed Web of Science ®Google Scholar
• Baigent C, Landray MJ, Reith C, et al. The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial. Lancet. 2011;377(9784):2181–2192.
   PubMed Web of Science ®Google Scholar
• Sabatine MS, Giugliano RP, Keech A, et al. Rationale and design of the further cardiovascular outcomes research with PCSK9 inhibition in subjects with elevated risk trial. Am Heart J. 2016;173:94–101.
   PubMed Web of Science ®Google Scholar
• Sabatine MS, Giugliano RP, Keech AC, et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med. 2017;376(18):1713–1722.
   PubMed Web of Science ®Google Scholar
• Silverman MG, Ference BA, Im K, et al. Association between lowering LDL-C and cardiovascular risk reduction among different therapeutic interventions: a systematic review and meta-analysis. JAMA. 2016;316(12):1289–1297.
   PubMed Web of Science ®Google Scholar
• Boekholdt SM, Arsenault BJ, Mora S, et al. Association of LDL cholesterol, non-HDL cholesterol, and apolipoprotein B levels with risk of cardiovascular events among patients treated with statins: a meta-analysis. JAMA. 2012;307(12):1302–1309.
   PubMed Web of Science ®Google Scholar
• Boekholdt SM, Hovingh GK, Mora S, et al. Very low levels of atherogenic lipoproteins and the risk for cardiovascular events: a meta-analysis of statin trials. J Am Coll Cardiol. 2014;64(5):485–494.
   PubMed Web of Science ®Google Scholar
• Nissen SE, Nicholls SJ, Sipahi I, et al. Effect of very high-intensity statin therapy on regression of coronary atherosclerosis: the ASTEROID trial. JAMA. 2006;295(13):1556–1565.
   PubMed Web of Science ®Google Scholar
• Nicholls SJ, Ballantyne CM, Barter PJ, et al. Effect of two intensive statin regimens on progression of coronary disease. N Engl J Med. 2011;365(22):2078–2087.
   PubMed Web of Science ®Google Scholar
• Nicholls SJ, Puri R, Anderson T, et al. Effect of evolocumab on progression of coronary disease in statin-treated patients: the GLAGOV randomized clinical trial. JAMA. 2016;316(22):2373–2384.
   PubMed Web of Science ®Google Scholar
• Sabatine MS, Wiviott SD, Im K, et al. Efficacy and safety of further lowering of low-density lipoprotein cholesterol in patients starting with very low levels: a meta-analysis. JAMA Cardiol. 2018;3(9):823–828.
   PubMed Web of Science ®Google Scholar
• Robinson JG, Rosenson RS, Farnier M, et al. Safety of very low low-density lipoprotein cholesterol levels with alirocumab: pooled data from randomized trials. J Am Coll Cardiol. 2017;69(5):471–482.
   PubMed Web of Science ®Google Scholar
• Giugliano RP, Wiviott SD, Blazing MA, et al. Long-term safety and efficacy of achieving very low levels of low-density lipoprotein cholesterol: a prespecified analysis of the IMPROVE-IT trial. JAMA Cardiol. 2017;2(5):547–555.
   PubMed Web of Science ®Google Scholar
• Giugliano RP, Pedersen TR, Park JG, et al. Clinical efficacy and safety of achieving very low LDL-cholesterol concentrations with the PCSK9 inhibitor evolocumab: a prespecified secondary analysis of the Fourier trial. Lancet. 2017;390(10106):1962–1971.
   PubMed Web of Science ®Google Scholar
• Gliozzi M, Musolino V, Bosco F, et al. Cholesterol homeostasis: researching a dialogue between the brain and peripheral tissues. Pharmacol Res. 2021;163:105215.
   PubMed Web of Science ®Google Scholar
• Giugliano RP, Mach F, Zavitz K, et al. Cognitive function in a randomized trial of evolocumab. N Engl J Med. 2017;377(7):633–643.
   PubMed Web of Science ®Google Scholar
• O’Keefe JH Jr., Cordain L, Harris WH, et al. Optimal low-density lipoprotein is 50 to 70 mg/dl: lower is better and physiologically normal. J Am Coll Cardiol. 2004;43(11):2142–2146.
   PubMed Web of Science ®Google Scholar
• Samaras K, Makkar SR, Crawford JD, et al. Effects of statins on memory, cognition, and brain volume in the elderly. J Am Coll Cardiol. 2019;74(21):2554–2568.
   PubMed Web of Science ®Google Scholar
• Gencer B, Marston NA, Im K, et al. Efficacy and safety of lowering LDL cholesterol in older patients: a systematic review and meta-analysis of randomised controlled trials. Lancet. 2020;396(10263):1637–1643.
   PubMed Web of Science ®Google Scholar
• Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2019;74(10):1376–1414.
   PubMed Web of Science ®Google Scholar
• Collet JP, Thiele H, Barbato E, et al. 2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur Heart J. 2020;42(14):1289–1367.
   Web of Science ®Google Scholar
• Handelsman Y, Jellinger PS, Guerin CK, et al. Consensus statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the management of dyslipidemia and prevention of cardiovascular disease algorithm - 2020 Executive Summary. Endocr Pract. 2020;26(10):1196–1224.
   PubMed Web of Science ®Google Scholar
• Linton MF, Yancey PG, Davies SS, et al. The role of lipids and lipoproteins in atherosclerosis. In: Feingold KR , editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc; 2000.
   Google Scholar
• Dominiczak MH, Caslake MJ. Apolipoproteins: metabolic role and clinical biochemistry applications. Ann Clin Biochem. 2011;48(Pt 6):498–515.
   PubMed Web of Science ®Google Scholar
• Olsson AG, Angelin B, Assmann G, et al. Can LDL cholesterol be too low? Possible risks of extremely low levels. J Intern Med. 2017;281(6):534–553.
   PubMed Web of Science ®Google Scholar
• Luo J, Yang H, Song BL. Mechanisms and regulation of cholesterol homeostasis. Nat Rev Mol Cell Biol. 2020;21(4):225–245.
   PubMed Web of Science ®Google Scholar
• Allen JM, Arnold SV, Lohr NL, et al. Assessing low-density lipoprotein cholesterol risk in secondary prevention patients within the PINNACLE national outpatient registry. Circulation. 2019;140:A12904.
   Web of Science ®Google Scholar
• Menzin J, Aggarwal J, Boatman B, et al. Ezetimibe use and LDL-C goal achievement: a retrospective database analysis of patients with clinical atherosclerotic cardiovascular disease or probable heterozygous familial hypercholesterolemia. J Manag Care Spec Pharm. 2017;23(12):1270–1276.
   PubMed Web of Science ®Google Scholar
• Cannon CP, Khan I, Klimchak AC, et al. Simulation of lipid-lowering therapy intensification in a population with atherosclerotic cardiovascular disease. JAMA Cardiol. 2017;2(9):959–966.
   PubMed Web of Science ®Google Scholar
• Gitt AK, Lautsch D, Ferrières J, et al. Contemporary data on treatment practices for low-density lipoprotein cholesterol in 6794 patients with stable coronary heart disease across the world. Data Brief. 2018;18:1937–1940.
   PubMed Web of Science ®Google Scholar
• Morales C, Plana N, Arnau A, et al. Causes of failure to achieve the low density lipoprotein cholesterol therapeutic target in patients with high and very high vascular risk controlled in lipid and vascular risk units. EROMOT study. Clin Investig Arterioscler. 2018;30(1):1–9.
   PubMed Web of Science ®Google Scholar
• Bruckert E, Parhofer KG, Gonzalez-Juanatey JR, et al. Proportion of high-risk/very high-risk patients in Europe with low-density lipoprotein cholesterol at target according to European guidelines: a systematic review. Adv Ther. 2020;37:1724–1736.
   PubMed Web of Science ®Google Scholar
• Wong ND, et al. Prevalence of the American college of Cardiology/American Heart Association statin eligibility groups, statin use, and low-density lipoprotein cholesterol control in US adults using the National Health and Nutrition Examination Survey 2011–2012. J Clin Lipidol. 2016;10(5):1109–1118.
   PubMed Web of Science ®Google Scholar
• Cannon CP, De Lemos JA, Rosenson RS, et al. Use of lipid-lowering therapies over 2 years in GOULD, a registry of patients with atherosclerotic cardiovascular disease in the US. JAMA Cardiol. 2021;6(9):1–9.
   PubMed Web of Science ®Google Scholar
• Nelson AJ, Haynes K, Shambhu S, et al. High-intensity statin use among patients with atherosclerosis in the U.S. J Am Coll Cardiol. 2022;79(18):1802–1813.
   PubMed Web of Science ®Google Scholar
• Lowenstern AM, Li S, Navar AM, et al. Measurement of low-density lipoprotein cholesterol levels in primary and secondary prevention patients: insights from the PALM registry. J Am Heart Assoc. 2018;7(18):e009251.
   PubMed Web of Science ®Google Scholar
• Rodriguez F, Lin S, Maron DJ, et al. Use of high-intensity statins for patients with atherosclerotic cardiovascular disease in the Veterans Affairs Health System: practice impact of the new cholesterol guidelines. Am Heart J. 2016;182:97–102.
   PubMed Web of Science ®Google Scholar
• Navar AM, Wang TY, Li S, et al. Lipid management in contemporary community practice: results from the Provider assessment of lipid management (PALM) registry. Am Heart J. 2017;193:84–92.
   PubMed Web of Science ®Google Scholar
• Bansilal S, Castellano JM, Garrido E, et al. Assessing the impact of medication adherence on long-term cardiovascular outcomes. J Am Coll Cardiol. 2016;68(8):789–801.
   PubMed Web of Science ®Google Scholar
• Toth PP, Granowitz C, Hull M, et al. Long-term statin persistence is poor among high-risk patients with dyslipidemia: a real-world administrative claims analysis. Lipids Health Dis. 2019;18(1):175.
   PubMed Web of Science ®Google Scholar
• Phillips LS, Branch WT, Cook CB, et al. Clinical inertia. Ann Intern Med. 2001;135(9):825–834.
   PubMed Web of Science ®Google Scholar
• Bradley CK, Wang TY, Li S, et al. Patient‐reported reasons for declining or discontinuing statin therapy: insights from the PALM registry. J Am Heart Assoc. 2019;8(7):e011765.
   PubMed Web of Science ®Google Scholar
• Tanner RM, Safford MM, Monda KL, et al. Primary care physician perspectives on barriers to statin treatment. Cardiovasc Drugs Ther. 2017;31(3):303–309.
   PubMed Web of Science ®Google Scholar
• Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk: the task force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS). Eur Heart J. 2020;41(1):111–188.
   PubMed Web of Science ®Google Scholar
• Cosentino F, Grant PJ, Aboyans V, et al. 2019 ESC guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD: the task force for diabetes, pre-diabetes, and cardiovascular diseases of the European Society of Cardiology (ESC) and the European Association for the Study of Diabetes (EASD). Eur Heart J. 2020;41(2):255–323.
   PubMed Web of Science ®Google Scholar
• Parchman ML, Pugh JA, Romero RL, et al. Competing demands or clinical inertia: the case of elevated glycosylated hemoglobin. Ann Fam Med. 2007;5(3):196–201.
   PubMed Web of Science ®Google Scholar
• Spencer-Bonilla G, Chung S, Sarraju A, et al. Statin use in older adults with stable atherosclerotic cardiovascular disease. J Am Geriatr Soc. 2021;69(4):979–985.
   PubMed Web of Science ®Google Scholar
• Zullig LL, Egbuonu-Davis L, Trasy A, et al. Countering clinical inertia in lipid management: expert workshop summary. Am Heart J. 2018;206:24–29.
   PubMed Web of Science ®Google Scholar
• Yao X, Shah ND, Gersh BJ, et al. Assessment of trends in statin therapy for secondary prevention of atherosclerotic cardiovascular disease in US adults from 2007 to 2016. JAMA Network Open. 2020;3(11):e2025505.
   PubMed Web of Science ®Google Scholar
• Cannon CP, de Lemos JA, Rosenson RS, et al. Getting to an improved understanding of low-density lipoprotein-cholesterol and dyslipidemia management (GOULD): methods and baseline data of a registry of high cardiovascular risk patients in the United States. Am Heart J. 2020;219:70–77.
   PubMed Web of Science ®Google Scholar
• Ramsaran E, Preusse P, Sundaresan D, et al. Adherence to blood cholesterol treatment guidelines among physicians managing patients with atherosclerotic cardiovascular disease. Am J Cardiol. 2019;124(2):169–175.
   PubMed Web of Science ®Google Scholar
• Toth PP, Foody JM, Tomassini JE, et al. Therapeutic practice patterns related to statin potency and ezetimibe/simvastatin combination therapies in lowering LDL-C in patients with high-risk cardiovascular disease. J Clin Lipidol. 2014;8(1):107–116.
   PubMed Web of Science ®Google Scholar
• Adusumalli S, Westover JE, Jacoby DS, et al. Effect of passive choice and active choice interventions in the electronic health record to cardiologists on statin prescribing: a cluster randomized clinical trial. JAMA Cardiol. 2021;6(1):40–48.
   PubMed Web of Science ®Google Scholar
• Maddox TM. Clinical decision support in statin prescription—what we can learn from a negative outcome. JAMA Cardiol. 2021;6(1):48–49.
   PubMed Web of Science ®Google Scholar
• Langer A, Tan M, Goodman SG, et al. GOAL Canada: physician education and support can improve patient management. CJC Open. 2020;2(2):49–54.
   PubMedGoogle Scholar
• Muñoz D, Uzoije P, Reynolds C, et al. Polypill for cardiovascular disease prevention in an underserved population. N Engl J Med. 2019;381(12):1114–1123.
   PubMed Web of Science ®Google Scholar
• Bramlage P, Sims H, Minguet J, et al. The polypill: an effective approach to increasing adherence and reducing cardiovascular event risk. Eur J Prev Cardiol. 2017;24(3):297–310.
   PubMed Web of Science ®Google Scholar
• van Trier TJ, Mohammadnia N, Snaterse M, et al. Lifestyle management to prevent atherosclerotic cardiovascular disease: evidence and challenges. Neth Heart J. 2022;30(1):3–14.
   PubMed Web of Science ®Google Scholar
• Guglielmi V, Bellia A, Pecchioli S, et al. Effectiveness of adherence to lipid lowering therapy on LDL-cholesterol in patients with very high cardiovascular risk: a real-world evidence study in primary care. Atherosclerosis. 2017;263:36–41.
   PubMed Web of Science ®Google Scholar
• De Vera MA, Bhole V, Burns LC, et al. Impact of statin adherence on cardiovascular disease and mortality outcomes: a systematic review. Br J Clin Pharmacol. 2014;78(4):684–698.
   PubMed Web of Science ®Google Scholar
• Maningat P, Gordon BR, Breslow JL. How do we improve patient compliance and adherence to long-term statin therapy? Curr Atheroscler Rep. 2013;15(1):291.
   PubMed Web of Science ®Google Scholar
• Colantonio LD, Huang L, Monda KL, et al. Adherence to high-intensity statins following a myocardial infarction hospitalization among Medicare beneficiaries. JAMA Cardiol. 2017;2(8):890–895.
   PubMed Web of Science ®Google Scholar
• Rodriguez F, Maron DJ, Knowles JW, et al. Association of statin adherence with mortality in patients with atherosclerotic cardiovascular disease. JAMA Cardiol. 2019;4(3):206–213.
   PubMed Web of Science ®Google Scholar
• Serban M-C, Colantonio LD, Manthripragada AD, et al. Statin intolerance and risk of coronary heart events and all-cause mortality following myocardial infarction. J Am Coll Cardiol. 2017;69(11):1386–1395.
   PubMed Web of Science ®Google Scholar
• Boklage SH, Malangone-Monaco E, Lopez-Gonzalez L, et al. Statin utilization patterns and outcomes for patients with acute coronary syndrome during and following inpatient admissions. Cardiovasc Drugs Ther. 2018;32(3):273–280.
   PubMed Web of Science ®Google Scholar
• Newman JD, Alexander KP, Gu X, et al. Baseline predictors of low-density lipoprotein cholesterol and systolic blood pressure goal attainment after 1 year in the ISCHEMIA trial. Circ Cardiovasc Qual Outcomes. 2019;12(11):e006002.
   PubMed Web of Science ®Google Scholar
• Rodriguez F, Olufade TO, Ramey DR, et al. Gender disparities in lipid-lowering therapy in cardiovascular disease: insights from a managed care population. J Womens Health. 2016;25(7):697–706.
   Web of Science ®Google Scholar
• Chang AY, Abou-Arraj NE, Rodriguez F. Interventions to reduce ethnic and racial disparities in dyslipidemia management. Curr Treat Options Cardiovasc Med. 2019;21(5):24.
   PubMedGoogle Scholar
• Ferdinand KC, Senatore FF, Clayton-Jeter H, et al. Improving medication adherence in cardiometabolic disease: practical and regulatory implications. J Am Coll Cardiol. 2017;69(4):437–451.
   PubMed Web of Science ®Google Scholar
• Schultz WM, Kelli HM, Lisko JC, et al. Socioeconomic status and cardiovascular outcomes: challenges and interventions. Circulation. 2018;137(20):2166–2178.
   PubMed Web of Science ®Google Scholar
• Alsan M, Wanamaker M. Tuskegee and the health of black men. Q J Econ. 2018;133(1):407–455.
   PubMed Web of Science ®Google Scholar
• Nanna MG, Navar AM, Zakroysky P, et al. Association of patient perceptions of cardiovascular risk and beliefs on statin drugs with racial differences in statin use: insights from the Patient and Provider Assessment of Lipid Management registry. JAMA Cardiol. 2018;3(8):739–748.
   PubMed Web of Science ®Google Scholar
• Subherwal S, Patel MR, Tang F, et al. Socioeconomic disparities in the use of cardioprotective medications among patients with peripheral artery disease: an analysis of the American College of Cardiology’s NCDR PINNACLE registry. J Am Coll Cardiol. 2013;62(1):51–57.
   PubMed Web of Science ®Google Scholar
• Casula M, Tragni E, Catapano AL. Adherence to lipid-lowering treatment: the patient perspective. Patient Prefer Adherence. 2012;6:805–814.
   PubMed Web of Science ®Google Scholar
• Koh JJK, Cheng RX, Yap YC, et al. Access and adherence to medications for the primary and secondary prevention of atherosclerotic cardiovascular disease in Singapore: a qualitative study. Patient Prefer Adherence. 2018;12:2481–2498.
   PubMed Web of Science ®Google Scholar
• Chen ST, Huang S-T, Shau W-Y, et al. Long-term statin adherence in patients after hospital discharge for new onset of atherosclerotic cardiovascular disease: a population-based study of real world prescriptions in Taiwan. BMC Cardiovasc Disord. 2019;19(1):62.
   PubMed Web of Science ®Google Scholar
• Navar AM, Roe MT, White JA, et al. Medication discontinuation in the IMPROVE-IT trial. Circ Cardiovasc Qual Outcomes. 2019;12(1):e005041.
   PubMed Web of Science ®Google Scholar
• Wood FA, Howard JP, Finegold JA, et al. N-of-1 trial of a statin, placebo, or no treatment to assess side effects. N Engl J Med. 2020;383(22):2182–2184.
   PubMed Web of Science ®Google Scholar
• Abughosh SM, Vadhariya A, Johnson ML, et al. Enhancing statin adherence using a motivational interviewing intervention and past adherence trajectories in patients with suboptimal adherence. J Manag Care Spec Pharm. 2019;25(10):1053–1062.
   PubMed Web of Science ®Google Scholar
• Cohen JD, Aspry KE, Brown AS, et al. Use of health information technology (HIT) to improve statin adherence and low-density lipoprotein cholesterol goal attainment in high-risk patients: proceedings from a workshop. J Clin Lipidol. 2013;7(6):573–609.
   PubMed Web of Science ®Google Scholar
• Barankay I, Reese PP, Putt ME, et al. Effect of patient financial incentives on statin adherence and lipid control: a randomized clinical trial. JAMA Network Open. 2020;3(10):e2019429.
   PubMed Web of Science ®Google Scholar
• Nanna MG, Navar AM, Wang TY, et al. 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.
   PubMed Web of Science ®Google Scholar
• Hess GP, Natarajan P, Faridi KF, et al. Proprotein convertase subtilisin/kexin type 9 inhibitor therapy: payer approvals and rejections, and patient characteristics for successful prescribing. Circulation. 2017;136(23):2210–2219.
   PubMed Web of Science ®Google Scholar
• Khera R, Valero-Elizondo J, Okunrintemi V, et al. Association of out-of-pocket annual health expenditures with financial hardship in low-income adults with atherosclerotic cardiovascular disease in the United States. JAMA Cardiol. 2018;3(8):729–738.
   PubMed Web of Science ®Google Scholar
• Khera R, Valero-Elizondo J, Das SR, et al. Cost-related medication nonadherence in adults with atherosclerotic cardiovascular disease in the United States, 2013 to 2017. Circulation. 2019;140(25):2067–2075.
   PubMed Web of Science ®Google Scholar
• Schwartz GG, Steg PG, Szarek M, et al. Alirocumab and cardiovascular outcomes after acute coronary syndrome. N Engl J Med. 2018;379(22):2097–2107.
   PubMed Web of Science ®Google Scholar
• Ray KK, Colhoun HM, Szarek M, et al. Effects of alirocumab on cardiovascular and metabolic outcomes after acute coronary syndrome in patients with or without diabetes: a prespecified analysis of the ODYSSEY OUTCOMES randomised controlled trial. Lancet Diabetes Endocrinol. 2019;7(8):618–628.
   PubMed Web of Science ®Google Scholar
• Karalis DG, Mallya UG, Ghannam AF, et al. Prescribing patterns of proprotein convertase subtilisin-kexin type 9 inhibitors in eligible patients with clinical atherosclerotic cardiovascular disease or heterozygous familial hypercholesterolemia. Am J Cardiol. 2018;121(10):1155–1161.
   PubMed Web of Science ®Google Scholar
• Baum SJ, Toth PP, Underberg JA, et al. PCSK9 inhibitor access barriers—issues and recommendations: improving the access process for patients, clinicians and payers. Clin Cardiol. 2017;40(4):243–254.
   PubMed Web of Science ®Google Scholar
• Knowles JW, Howard WB, Karayan L, et al. Access to nonstatin lipid-lowering therapies in patients at high risk of atherosclerotic cardiovascular disease. Circulation. 2017;135(22):2204–2206.
   PubMed Web of Science ®Google Scholar
• Myers KD, Farboodi N, Mwamburi M, et al. Effect of access to prescribed PCSK9 inhibitors on cardiovascular outcomes. Circ Cardiovasc Qual Outcomes. 2019;12(8):e005404.
   PubMed Web of Science ®Google Scholar
• Cordero A, Rodríguez-Mañero M, Fácila L, et al. Prevention of myocardial infarction and stroke with PCSK9 inhibitors treatment: a metanalysis of recent randomized clinical trials. J Diabet Metab Disord. 2020;19:759–765.
   PubMed Web of Science ®Google Scholar
• Kosmas CE, Muñoz Estrella A, Skavdis A, et al. Inclisiran for the treatment of cardiovascular disease: a short review on the emerging data and therapeutic potential. Ther Clin Risk Manag. 2020;16:1031–1037.
   PubMed Web of Science ®Google Scholar
• Ray KK, Wright RS, Kallend D, et al. Two phase 3 trials of inclisiran in patients with elevated LDL cholesterol. N Engl J Med. 2020;382(16):1507–1519.
   PubMed Web of Science ®Google Scholar
• Novartis Pharmaceuticals Corp. LEQVIO [prescribing information]. 2021.
   Google Scholar