Abstract
Résumé
Definitions
Overview of the Management of Dyslipidemia in Primary Prevention
Screening
Who to screen |
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Men 40 years of age or older; women 40 years of age or older (or postmenopausal) • Consider earlier in ethnic groups at increased risk such as South Asian or indigenous individuals All patients with any of the following conditions, regardless of age • Clinical evidence of atherosclerosis • Abdominal aortic aneurysm • Diabetes mellitus • Arterial hypertension • Current cigarette smoking • Stigmata of dyslipidemia (corneal arcus, xanthelasma, xanthoma) • Family history of premature CVD • Family history of dyslipidemia • CKD (eGFR ≤ 60 mL/min/1.73 m2 or ACR ≥ 3 mg/mmol) • Obesity (BMI ≥ 30) • Inflammatory diseases (RA, SLE, PsA, AS, IBD) • HIV infection • Erectile dysfunction • COPD • History of hypertensive disorder of pregnancy |
How to screen |
---|
For all • History and physical examination • Standard lipid profile: TC, LDL-C, HDL-C, non-HDL-C, TG • FPG or A1c • eGFR • Lipoprotein(a)—once in patient's lifetime, with initial screening Optional • ApoB • Urine ACR (if eGFR <60 mL/min/1.73 m2, hypertension, or diabetes) |
Health behaviour interventions
Pharmacologic treatment

Other statin-indicated conditions

New areas of focus
Overview of the Management of Dyslipidemia in Secondary Prevention
Health behaviour interventions
New areas of focus
PICO Questions, Evidence Review, and New Recommendations
PICO 1: Do pregnancy-related conditions (hypertensive disorders of pregnancy and other related complications) identify women at increased risk of premature CVD warranting lipid screening?
- 1.Among women who have had a pregnancy complication such as hypertensive disorders of pregnancy, gestational diabetes, preterm birth, stillbirth, low birth weight infant, or placental abruption, we recommend screening with a complete lipid panel in the late postpartum period, because these women have a higher risk of premature CVD and stroke with onset 10-15 years after index delivery (Strong Recommendation; Moderate-Quality Evidence).
- 2.We recommend counselling women who have any of these pregnancy-related complications of the increased lifetime risk of ASCVD, and reinforcing the importance of healthy behaviours (ie, maintaining a healthy body weight, 150 weekly minutes of moderate intensity aerobic physical activity, avoiding tobacco consumption, no more than moderate alcohol consumption, stress management, and adopting a healthy dietary pattern, such as the Mediterranean diet (Strong Recommendation; Low-Quality Evidence).
- 3.To assist with decisions about lipid-lowering pharmacotherapy in this patient population, we recommend favouring CV age, over 10-year risk calculators (Strong Recommendation; Low-Quality Evidence).
PICO 2a: Is there evidence to promote non-HDL-C over ApoB or ApoB over non-HDL-C for screening and treatment purposes?
Non-HDL-C or ApoB for predicting CVD risk
PICO 2b: Is there evidence to support measurement of Lp(a) to improve risk stratification and dyslipidemia management in patients with and without previous CV events?
- 5.We recommend measuring Lp(a) level once in a person's lifetime as a part of the initial lipid screening (Strong Recommendation; High-Quality Evidence).
- 6.For all patients in the setting of primary prevention with a Lp(a) ≥ 50 mg/dL (or ≥ 100 nmol/L), we recommend earlier and more intensive health behaviour modification counselling and management of other ASCVD risk factors (Strong Recommendation; Expert Consensus).
PICO 3: In primary prevention, what is the evidence for CAC score to improve risk assessment? Specifically, should low CAC (or CAC = 0) score be used to avoid statin therapy in select individuals?
- Blaha MJ
- Silverman MG
- Budoff MJ
- Villines TC
- Hulten EA
- Shaw LJ
- et al.
- McClelland RL
- Jorgensen NW
- Budoff M
- et al.
- Taylor AJ
- Cerqueira M
- Hodgson JM
- et al.
- 7.We suggest that CAC screening using computed tomography imaging might be considered for asymptomatic adults 40 years of age or older and at intermediate risk (FRS 10%-20%) for whom treatment decisions are uncertain (Strong Recommendation; Moderate-Quality Evidence).
- 8.We recommend that CAC screening using computed tomography imaging not be undertaken for: (1) high-risk individuals; (2) patients receiving statin treatment; or (3) most asymptomatic, low-risk adults (Strong Recommendation; Moderate-Quality Evidence).
- 9.We suggest that CAC screening might be considered for a subset of low-risk individuals 40 years of age or older with a family history of premature ASCVD (men 55 years or younger; women 65 years or younger) in addition to identifying known genetic causes of ASCVD such as elevated Lp(a) level or FH (Weak Recommendation; Low-Quality Evidence).
PICO 4: In secondary prevention, what is the most appropriate lipid/lipoprotein threshold for the intensification of therapy?
- Grundy SM
- Stone NJ
- Bailey AL
- et al.
- Giugliano RP
- Peterson TR
- Park G
- et al.
- Gencer B
- Mach F
- Murphy SA
- et al.
- Sabatine M
- Leiter LA
- Wiviott SD
- et al.
- Deedwania P
- Murphy SA
- Scheen A
- et al.
- Bonaca MP
- Nault P
- Giugliano RP
- et al.
Recent acute coronary event (ACS) • Hospitalized index ACS to 52 weeks post index ACS |
Clinically evident ASCVD and any of the following • Diabetes mellitus or metabolic syndrome • Polyvascular disease (vascular disease in ≥ 2 arterial beds) • Symptomatic PAD • Recurrent MI • MI in the past 2 years • Previous CABG surgery • LDL-C ≥ 2.6 mmol/L or heterozygous FH • Lipoprotein(a) ≥ 60 mg/dL (120 nmol/L) |
- 10.We recommend use of high-intensity statin therapy in addition to appropriate health behaviour modifications for all secondary prevention CVD patients. For patients who do not tolerate a high-intensity statins, we recommend the maximally tolerated statin dose (Strong Recommendation; High-Quality Evidence).
- 11.We recommend intensification of lipid-lowering therapy with a PCSK9 inhibitor (evolocumab or alirocumab)—with or without the additional use of ezetimibe—for secondary CV prevention patients shown to derive the largest benefit from PCSK9 inhibitor therapy in whom LDL-C remains ≥ 1.8 mmol/L (or non-HDL-C ≥ 2.4 mmol/L or ApoB ≥ 0.7 g/L) while receiving the maximally tolerated statin dose (Fig. 3; Strong Recommendation; Moderate-Quality Evidence). Secondary prevention patients shown to derive the largest benefit from intensification of statin therapy with PCSK9 inhibitor therapy are defined in Table 3.
- 12.We recommend intensification of lipid-lowering therapy with ezetimibe and/or PCSK9 inhibitor therapy for all secondary prevention CVD patients in whom LDL-C remains ≥ 1.8 mmol/L (or non-HDL-C ≥ 2.4 mmol/L or ApoB ≥ 0.7 g/L) while receiving the maximally tolerated statin dose. (Strong Recommendation; High-Quality Evidence). If ezetimibe is used initially and LDL-C remains ≥ 1.8 mmol/L (or non-HDL-C ≥ 2.4 mmol/L or ApoB ≥ 0.7 g/L) PCSK9 inhibitor therapy is recommended (Strong Recommendation; High-Quality Evidence).
- Giugliano RP
- Peterson TR
- Park G
- et al.

PICO 5: In adults already receiving (or intolerant to) statins, what is the role of nonstatin drugs to reduce CVD risk?
Ezetimibe
PCSK9 inhibitors
Primary prevention
IPE
Other therapies
Ongoing trials
ClinicalTrials.gov. Effect of evolocumab in patients at high cardiovascular risk without prior myocardial infarction or stroke (VERSALIUS-CV). Available at: https://clinicaltrials.gov/ct2/show/NCT03872401. Accessed September 3, 2020.
ClinicalTrials.gov. A randomized trial assessing the effects of inclisiran on clinical outcomes among people with cardiovascular disease (ORION-4). Available at:https://clinicaltrials.gov/ct2/show/NCT03705234. Accessed September 3, 2020.
ClincalTrials.gov. Effect of dalcetrapib vs placebo on CV risk on a genetically defined population with a recent ACS (dal-GenE). Available at: https://clinicaltrials.gov/ct2/show/NCT02525939. Accessed September 3, 2020.
ClinicalTrials.gov. Evaluation of major cardiovascular events in patients with, or at high risk for, cardiovascular disease who are statin intolerant treated with bempedoic acid (ETC-1002) or placebo (CLEAR Outcomes). Available at:https://clinicaltrials.gov/ct2/show/NCT02993406. Accessed September 3, 2020.
ClinicalTrials.gov. Pemafibrate to reduce cardiovascular outcomes by reducing triglycerides in patients with diabetes (PROMINENT). Available at: https://clinicaltrials.gov/ct2/show/NCT03071692. Accessed September 3, 2020.
- 13.We recommend the use of IPE to decrease the risk of CV events in patients with ASCVD, or with diabetes and ≥ 1 CVD risk factors, who have an elevated fasting triglyceride level of 1.5-5.6 mmol/L despite treatment with maximally tolerated statin therapy (Strong Recommendation; High-Quality Evidence). Refer to Figure 3.
- 14.We recommend the use of a PCSK9 inhibitor (alirocumab or evolocumab) to lower LDL-C level in patients with heterozygous FH without clinical ASCVD whose LDL-C remains above the target (ie, LDL-C ≥ 2.5 mmol/L or < 50% reduction from baseline; or ApoB ≥ 0.85 mg/dL or non-HDL-C ≥ 3.2 mmol/L) despite maximally tolerated statin therapy with or without ezetimibe therapy (Strong Recommendation; High-Quality Evidence).
- 15.We recommend the use of a PCSK9 inhibitor (alirocumab or evolocumab) for patients with heterozygous FH and ASCVD whose LDL-C remains above the threshold ≥ 1.8 mmol/L (or ApoB ≥ 0.7 mg/dL or non-HDL-C ≥ 2.4 mmol/L) despite maximally tolerated statin therapy, with or without ezetimibe (Strong Recommendation; High-Quality Evidence).
PICO 6: In primary and secondary prevention, what is the evidence for CV benefit of omega-3 from (1) dietary sources; and/or (2) over-the-counter formulations/supplements?
- 16.We do not recommend the use of over-the-counter omega-3 polyunsaturated fatty acid supplements (marketed as natural health products in Canada) to reduce CVD risk (Strong Recommendation; High-Quality Evidence).
Conclusions
Acknowledgements
Appendix. Supplementary materials
References
- 2016 Canadian Cardiovascular Society Guidelines for the management of dyslipidemia for the prevention of cardiovascular disease in the adult.Can J Cardiol. 2016; 32: 1263-1282
- Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study.Lancet. 2004; 364: 937-952
- Primary prevention of coronary heart disease in women through diet and lifestyle.N Engl J Med. 2000; 343: 16-22
- Healthy lifestyle factors in the primary prevention of coronary heart disease among men: benefits among users and nonusers of lipid- lowering and antihypertensive medications.Circulation. 2006; 114: 160-167
- Effect of a dietary portfolio of cholesterol-lowering foods given at 2 levels of intensity of dietary advice on serum lipids in hyperlipidemia: a randomized controlled trial.JAMA. 2011; 306: 831-839
- Diet quality as assessed by the healthy eating index, the alternate healthy eating index, the dietary approaches to stop hypertension score, and health outcomes: a systematic review and meta-analysis of cohort studies.J Acad Nutr Diet. 2015; 115 (780-800.e5)
- Associations of glycemic index and load with coronary heart disease events: a systematic review and meta-analysis of prospective cohorts.J Am Heart Assoc. 2012; 1e000752
- Vegetarian diet, Seventh Day Adventists and risk of cardiovascular mortality: a systematic review and meta-analysis.Int J Cardiol. 2014; 176: 680-686
- Primary prevention of cardiovascular disease with Mediterranean diet.N Engl J Med. 2013; 368: 1279-1290
- Consumption of nuts and legumes and risk of incident ischemic heart disease, stroke, and diabetes: a systematic review and meta- analysis.Am J Clin Nutr. 2014; 100: 278-288
- Fruit and vegetable consumption and mortality from all causes, cardiovascular disease, and cancer: systematic review and dose-response meta-analysis of prospective cohort studies.BMJ. 2014; 349: g4490
- Dietary fibre intake and risk of cardiovascular disease: systematic review and meta-analysis.BMJ. 2013; 347: f6879
- Meta-analysis of the association between whole grain intake and coronary heart disease risk.Am J Cardiol. 2015; 115: 625-629
- Effect of aerobic exercise training on serum levels of high-density lipoprotein cholesterol: a meta-analysis.Arch Intern Med. 2007; 167: 999-1008
- Association between lowering LDL-C and cardiovascular risk reduction among different therapeutic interventions: a systematic review and meta-analysis.JAMA. 2016; 312: 1289-1297
- Cholesterol lowering in intermediate-risk persons without cardiovascular disease.N Engl J Med. 2016; 374: 2021-2031
- Individualized statin benefit for determining statin eligibility in the primary prevention of cardiovascular disease.Circulation. 2016; 133: 1574-1581
- Efficacy and safety of lowering LDL cholesterol in older patients: a systematic review and meta-analysis of randomised controlled trials.Lancet. 2020; 396: 1637-1643
- Stone J Canadian Guidelines for Cardiac Rehabilitation and Cardiovascular Disease Prevention: Translating Knowledge Into Action. 3rd Ed. Canadian Association of Cardiac Rehabilitation, Winnipeg2009
- Pre-eclampsia and risk of cardiovascular disease and cancer later in life: a systematic review and meta-analysis.BMJ. 2007; 335: 974
- Cardiovascular disease-related morbidity and mortality in women with a history of pregnancy complications.Circulation. 2019; 139: 1069-1079
- Recurrent pre-eclampsia and subsequent cardiovascular risk.Heart. 2017; 103: 235-243
- Cardiovascular Health After Maternal Placental Syndrome (CHAMPS): population-based retrospective cohort study.Lancet. 2005; 366: 1797-1803
- Metabolic syndrome after pregnancies complicated by pre-eclampsia or small for gestational age: a retrospective cohort.BJOG. 2015; 122: 1818-1823
- Markers of vascular dysfunction after hypertensive disorders of pregnancy: a systematic review and meta-analysis.Hypertension. 2016; 68: 1447-1458
- Circulating microRNAs implicate multiple atherogenic abnormalities in the long-term cardiovascular sequelae of preeclampsia.Am J Hypertens. 2018; 31: 1093-1097
- 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease. A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.Circulation. 2019; 140: e596-e646
- Hypertensive disorders of pregnancy and subsequent cardiovascular disease: current national and international guidelines and the need for future research.Front Cardiovasc Med. 2019; 6: 55
- The maternal health clinic: a new window of opportunity for early heart disease screening and intervention for women with pregnancy complications.J Obstet Gynaecol Can. 2013; 35: 831-839
- Statins and congenital malformations: cohort study.BMJ. 2015; 350: h1035
- Pregnancy outcomes after maternal exposure to simvastatin and lovastatin.Birth Defects Res A Clin Mol Teratol. 2005; 73: 888-896
- Central nervous system and limb anomalies in case reports of first-trimester statin exposure.N Engl J Med. 2004; 350: 1579-1582
- 2012 update of the Canadian Cardiovascular Society guidelines for the diagnosis and treatment of dyslipidemia for the prevention of cardiovascular disease in the adult.Can J Cardiol. 2013; 29: 151-167
- Atherogenic lipoprotein particles in atherosclerosis.Circulation. 2004; 109 (III2-7)
- Increased small low-density lipoprotein particle number: a prominent feature of the metabolic syndrome in the Framingham Heart Study.Circulation. 2006; 113: 20-29
- A meta-analysis of low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B as markers of cardiovascular risk.Circ Cardiovasc Qual Outcomes. 2011; 4: 337-345
- 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: 1302-1309
- Fasting and nonfasting lipid levels: influence of normal food intake on lipids, lipoproteins, apolipoproteins, and cardiovascular risk prediction.Circulation. 2008; 118: 2047-2056
- Fasting time and lipid levels in a community-based population: a cross-sectional study.Arch Intern Med. 2012; 172: 1707-1710
- Discordance between apolipoprotein B and LDL-cholesterol in young adults predicts coronary artery calcification: the CARDIA study.J Am Coll Cardiol. 2016; 67: 193-201
- Comparison of conventional lipoprotein tests and apolipoproteins in the prediction of cardiovascular disease.Circulation. 2019; 140: 542-552
- Optimal strategies for monitoring lipid levels in patients at risk or with cardiovascular disease: a systematic review with statistical and cost-effectiveness modelling.Health Technol Assess. 2015; 19 (vii-viii): 1-401
- Quantifying atherogenic lipoproteins: current and future challenges in the era of personalized medicine and very low concentrations of LDL cholesterol. A consensus statement from EAS and EFLM.Clin Chem. 2018; 64: 1006-1033
- Quantifying atherogenic lipoproteins for lipid-lowering strategies: consensus-based recommendations from EAS and EFLM.Atherosclerosis. 2020; 294: 46-61
- Lipoprotein (a): coming of age at last.J Lipid Res. 2016; 57: 336-339
- Lipoprotein(a): fasting and nonfasting levels, inflammation, and cardiovascular risk.Atherosclerosis. 2014; 234: 95-101
- Genetic variants associated with Lp(a) lipoprotein level and coronary disease.N Engl J Med. 2009; 361: 2518-2528
- Genetically elevated lipoprotein(a) and increased risk of myocardial infarction.JAMA. 2009; 301: 2331-2339
- Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality.JAMA. 2009; 302: 412-423
- Lipoprotein(a)-lowering by 50 mg/dL (105 nmol/L) may be needed to reduce cardiovascular disease 20% in secondary prevention: a population-based study.Arterioscler Thromb Vasc Biol. 2020; 40: 255-266
- Lipoprotein(a) levels and the risk of myocardial infarction among 7 ethnic groups.Circulation. 2019; 139: 1472-1482
- Lipoprotein (a): impact by ethnicity and environmental and medical conditions.J Lipid Res. 2016; 57: 1111-1125
- Lipoprotein(a), PCSK9 inhibition, and cardiovascular risk.Circulation. 2019; 139: 1483-1492
- Effect of alirocumab on lipoprotein(a) and cardiovascular risk after acute coronary syndrome.J Am Coll Cardiol. 2020; 75: 133-144
- Prognostic value of lipoprotein (a) level in patients with coronary artery disease: a meta-analysis.Lipids Health Dis. 2019; 18: 150
- Causal effect of Lp(a) [lipoprotein(a)] level on ischemic stroke and Alzheimer disease: a Mendelian randomization study.Stroke. 2019; 50: 3532-3539
- Elevated lipoprotein(a) and risk of ischemic stroke.J Am Coll Cardiol. 2019; 74: 54-66
- Lipoprotein(a) levels in patients with abdominal aortic aneurysm.Angiology. 2017; 68: 99-108
- Primary prevention with statins: ACC/AHA risk-based approach versus trial-based approaches to guide statin therapy.J Am Coll Cardiol. 2015; 66: 2699-2709
- Statin use in primary prevention of atherosclerotic cardiovascular disease according to 5 major guidelines for sensitivity, specificity, and number needed to treat.JAMA Cardiol. 2019; 4: 1131-1138
- Statin trials, cardiovascular events, and coronary artery calcification: implications for a trial-based approach to statin therapy in MESA.JACC Cardiovasc Imaging. 2018; 11: 221-230
- Is there a role for coronary artery calcium scoring for management of asymptomatic patients at risk for coronary artery disease?: Clinical risk scores are not sufficient to define primary prevention treatment strategies among asymptomatic patients.Circ Cardiovasc Imaging. 2014; 7 ([discussion: 408]): 398-408
- Impact of coronary artery calcium on coronary heart disease events in individuals at the extremes of traditional risk factor burden: the Multi-Ethnic Study of Atherosclerosis.Eur Heart J. 2014; 35: 2232-2241
- Interplay of coronary artery calcium and risk factors for predicting CVD/CHD mortality: the CAC Consortium.JACC Cardiovasc Imaging. 2020; 13: 1175-1186
- Prevalence and severity of coronary artery disease and adverse events among symptomatic patients with coronary artery calcification scores of zero undergoing coronary computed tomography angiography: results from the CONFIRM (Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter) registry.J Am Coll Cardiol. 2011; 58: 2533-2540
- Race/ethnicity and the prognostic implications of coronary artery calcium for all-cause and cardiovascular disease mortality: the Coronary Artery Calcium Consortium.J Am Heart Assoc. 2018; 7e010471
- 10-Year coronary heart disease risk prediction using coronary artery calcium and traditional risk factors: derivation in the MESA (Multi-Ethnic Study of Atherosclerosis) with validation in the HNR (Heinz Nixdorf Recall) study and the DHS (Dallas Heart Study).J Am Coll Cardiol. 2015; 66: 1643-1653
- Improvements in risk stratification for the occurrence of cardiovascular disease by imaging subclinical atherosclerosis: a systematic review.Heart. 2012; 98: 177-184
- Comparison of novel risk markers for improvement in cardiovascular risk assessment in intermediate-risk individuals.JAMA. 2012; 308: 788-795
- Coronary calcium score and cardiovascular risk.J Am Coll Cardiol. 2018; 72: 434-447
- CAC score improves coronary and CV risk assessment above statin indication by ESC and AHA/ACC primary prevention guidelines.JACC Cardiovasc Imaging. 2017; 10: 143-153
- Reclassification of coronary heart disease risk in a primary prevention setting: traditional risk factor assessment vs. coronary artery calcium scoring.Cardiovasc Diagn Ther. 2019; 9: 214-220
- ACCF/SCCT/ACR/AHA/ASE/ASNC/NASCI/SCAI/SCMR 2010 appropriate use criteria for cardiac computed tomography. A report of the American College of Cardiology Foundation Appropriate Use Criteria Task Force, the Society of Cardiovascular Computed Tomography, the American College of Radiology, the American Heart Association, the American Society of Echocardiography, the American Society of Nuclear Cardiology, the North American Society for Cardiovascular Imaging, the Society for Cardiovascular Angiography and Interventions, and the Society for Cardiovascular Magnetic Resonance.J Am Coll Cardiol. 2010; 56: 1864-1894
- Diagnostic and prognostic value of absence of coronary artery calcification.JACC Cardiovasc Imaging. 2009; 2: 675-688
- All-cause and cause-specific mortality in individuals with zero and minimal coronary artery calcium: a long-term, competing risk analysis in the Coronary Artery Calcium Consortium.Atherosclerosis. 2020; 294: 72-79
- Coronary artery calcium score improves cardiovascular risk prediction in persons without indication for statin therapy.Atherosclerosis. 2011; 215: 229-236
- Ten-year association of coronary artery calcium with atherosclerotic cardiovascular disease (ASCVD) events: the multi-ethnic study of atherosclerosis (MESA).Eur Heart J. 2018; 39: 2401-2408
- Mortality rates in smokers and nonsmokers in the presence or absence of coronary artery calcification.JACC Cardiovasc Imaging. 2012; 5: 1037-1045
- Significance of a positive family history for coronary heart disease in patients with a zero coronary artery calcium score (from the Multi-Ethnic Study of Atherosclerosis).Am J Cardiol. 2014; 114: 1210-1214
- Coronary artery calcium scoring in low risk patients with family history of coronary heart disease: validation of the SCCT guideline approach in the coronary artery calcium consortium.J Cardiovasc Comput Tomogr. 2019; 13: 21-25
- Determinants of coronary calcium conversion among patients with a normal coronary calcium scan: what is the “warranty period” for remaining normal?.J Am Coll Cardiol. 2010; 55: 1110-1117
- Impact of coronary artery calcium scanning on coronary risk factors and downstream testing the EISNER (Early Identification of Subclinical Atherosclerosis by Noninvasive Imaging Research) prospective randomized trial.J Am Coll Cardiol. 2011; 57: 1622-1632
- The identification of calcified coronary plaque is associated with initiation and continuation of pharmacological and lifestyle preventive therapies: a systematic review and meta-analysis.JACC Cardiovasc Imaging. 2017; 10: 833-842
- Coronary artery calcium and cardiovascular events in patients with familial hypercholesterolemia receiving standard lipid-lowering therapy.JACC Cardiovasc Imaging. 2019; 12: 1797-1804
- Vascular age derived from coronary artery calcium score on the risk stratification of individuals with heterozygous familial hypercholesterolaemia.Eur Heart J Cardiovasc Imaging. 2019; 21: 251-257
- Impact of statins on serial coronary calcification during atheroma progression and regression.J Am Coll Cardiol. 2015; 65: 1273-1282
- Implications of coronary artery calcium testing for treatment decisions among statin candidates according to the ACC/AHA cholesterol management guidelines: a cost-effectiveness analysis.JACC Cardiovasc Imaging. 2017; 10: 938-952
- Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein.N Engl J Med. 2008; 359: 2195-2207
- 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
- Inhibition of PCSK9 with evolocumab in homozygous familial hypercholesterolaemia (TESLA Part B): a randomised, double-blind, placebo-controlled trial.Lancet. 2015; 385: 341-350
- 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: 2459-2472
- Low-density lipoproteins cause atherosclerotic cardiovascular disease: pathophysiological, genetic, and therapeutic insights: a consensus statement from the European Atherosclerosis Society Consensus Panel.Eur Heart J. 2020; 41: 2313-2330
- 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 [erratum in: 2019;139:e1182-6].Circulation. 2019; 139: e1082-e1143
- The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials.Lancet. 2012; 380: 581-590
- Effects of anacetrapib in patients with atherosclerotic vascular disease.N Engl J Med. 2017; 377: 1217-1227
- Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S).Lancet. 1994; 344: 1383-1389
- Ezetimibe added to statin therapy after acute coronary syndromes.N Engl J Med. 2015; 372: 2387-2397
- 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: 1670-1681
- High-dose versus low-dose pitavastatin in Japanese Patients with stable coronary artery disease (REAL-CAD). A randomized superiority trial.Circulation. 2018; 137: 1997-2009
- A comparison of two LDL cholesterol targets after ischemic stroke.N Engl J Med. 2020; 382: 9-19
- ODYSSEY FH I and FH II: 78 week results with alirocumab treatment in 735 patients with heterozygous familial hypercholesterolaemia.Eur Heart J. 2015; 36: 2996-3003
- Very low levels of atherogenic lipoproteins and the risk for cardiovascular events: a meta-analysis of statin trials.J Am Coll Cardiol. 2014; 64: 485-494
- Clinical efficacy and safety of achieving very low LDL-cholesterol concentrations with the PCSK9 inhibitor evolocumab: a prespecified secondary analysis of the Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER) trial.Lancet. 2017; 390: 1962-1971
- Efficacy of evolocumab on cardiovascular outcomes in patients with recent myocardial infarction: a prespecified secondary analysis from the Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER) trial.JAMA Cardiol. 2020; 5: 1-6
- Cardiovascular safety and efficacy of the PCSK9 inhibitor evolocumab in patients with and without diabetes and the effect of evolocumab on glycaemia and risk of new-onset diabetes: a prespecified analysis of the Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER) randomized controlled trial.Lancet Diabetes Endocrinol. 2017; 5: 941-950
- Efficacy and safety of PCSK9 inhibition with evolocumab in reducing cardiovascular events in patients with metabolic syndrome receiving statin therapy: secondary analysis from the Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER) randomized clinical trial.JAMA Cardiol. 2021; 6: 139-147
- 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: 618-628
- Low-density lipoprotein cholesterol lowering with evolocumab and outcomes in patients with peripheral artery disease. Insights from the Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER).Trial. Circulation. 2018; 137: 338-350
- Alirocumab in patients with polyvascular disease and recent acute coronary syndrome. ODYSSEY OUTCOMES Trial.J Am Coll Cardiol. 2019; 74: 1167-1176
- Clinical benefit of evolocumab by severity and extent of coronary artery disease: analysis from Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER).Circulation. 2018; 138: 756-766
- Effects of alirocumab on cardiovascular events after coronary bypass surgery.J Am Coll Cardiol. 2019; 74: 1177-1186
- Effect of alirocumab on lipoprotein(a) and cardiovascular risk after acute coronary syndrome.J Am Coll Cardiol. 2020; 75: 133-144
- Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia.N Engl J Med. 2019; 380: 11-22
- Safety of very low low-density lipoprotein cholesterol levels with alirocumab: pooled data from randomized trials.J Am Coll Cardiol. 2017; 69: 471-482
- Efficacy and safety of PCSK9 monoclonal antibodies.Expert Opin Drug Saf. 2019; 18: 1191-1201
- Low-density lipoprotein cholesterol targeting with pitavastatin + ezetimibe for patients with acute coronary syndrome and dyslipidaemia: the HIJ-PROPER study, a prospective, open-label, randomized trial.Eur Heart J. 2017; 38: 2264-2275
- Monoclonal antibodies for the treatment of hypercholesterolemia: targeting PCSK9.Can J Cardiol. 2016; 32: 1552-1560
- Cardiovascular efficacy and safety of PCSK9 inhibitors: systematic review and meta-analysis including the ODYSSEY OUTCOMES Trial.Can J Cardiol. 2018; 34: 1600-1605
- Efficacy and safety of alirocumab vs ezetimibe in statin-intolerant patients, with a statin rechallenge arm: The ODYSSEY ALTERNATIVE randomized trial.J Clin Lipidol. 2015; 9: 758-769
- Efficacy and tolerability of evolocumab vs ezetimibe in patients with muscle-related statin intolerance: the GAUSS-3 randomized clinical trial.JAMA. 2016; 315: 1580-1590
- PCSK9 inhibition with evolocumab (AMG 145) in heterozygous familial hypercholesterolaemia (RUTHERFORD-2): a randomised, double-blind, placebo-controlled trial.Lancet. 2015; 385: 331-340