Canadian Dyslipidemia Recommendations

Full update July 2023

The FAQ below presents information about the treatment of hyperlipidemia. Use shared decision making to individualize screening, assessment, and treatment. Information is from reference 1 unless otherwise denoted.

Question	Answer/Pertinent Information^1,14
Who should be screened?	Everyone ≥40 years of age. Patients with a history of hypertensive disease in pregnancy, or who are postmenopausal. Family history of hyperlipidemia or early CVD (i.e., in first-degree male relative <55 years of age or first-degree female relative <65 years of age). Adults of any age who have one or more of the following risk factors: physical signs of hyperlipidemia (e.g., xanthoma) diabetes current smoker COPD hypertension HIV obesity (i.e., BMI ≥30 kg/m²) CKD (ACR ≥3 mg/mmol or eGFR <60 mL/min/1.73m²) inflammatory disease (e.g., lupus, psoriatic arthritis, rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease) abdominal aneurysm evidence of ASCVD erectile dysfunction Consider screening all adults of First Nations or South Asian ancestry.
What are the components of screening?	History and physical. Lipid profile, including apoB and non-HDL. Check Lp (a) once (e.g., at baseline only). Non-fasting lipid profile is recommended for most patients (a fasting profile is still suggested for patients with known triglycerides >4.5 mmol/L). Fasting glucose or A1c. eGFR. Also consider ACR in patients with CKD, diabetes, or hypertension.
How is risk assessed and defined?	Assessment Unless the patient has a statin-indicated condition (see below), calculate risk using modified FRS or Cardiovascular Life Expectancy Model. (The calculators are available at https://ccs.ca/calculators-and-forms/ or on the iCCS app from Google Play or App Store.) Recheck every five years in patients 40 to 75 years of age or when patient health status changes such that a change in risk level is expected. Risk levels for primary prevention (primary prevention means patients without a statin-indicated condition, below): high risk: FRS 10-year risk ≥20% intermediate risk: FRS 10-year risk between 10% and 19.9% low risk: FRS 10-year risk <10% Statin-indicated conditions: ASCVD: history of MI, ACS, coronary angiography showing CAD, arterial revascularization, angina, peripheral artery disease, stroke, TIA, carotid disease; CAC >100 Agatston units; abdominal aortic aneurysm >3 cm in diameter or prior repair. diabetes and age ≥40 years, or diabetes ≥15 years’ duration and age ≥30 years, or diabetes with microvascular disease. CKD (eGFR <60 mL/min/1.73m² or ACR ≥3 mg/mmol) ≥3 months’ duration. LDL ≥5 mmol/L or apo B ≥1.45 g/L or non-HDL ≥5.8 mmol/L (e.g., familial hypercholesterolemia). Note: non-HDL or apoB are the preferred indicators, especially if triglycerides are ≥1.5 mmol/L.
When should we treat with pharmacotherapy (i.e., a statin)?	All high-risk patients (FRS 10-year risk ≥20%), and patients with a statin-indicated condition (above) with the following caveat regarding CKD: treat those age ≥50 years and not on dialysis. Intermediate risk level and: LDL ≥3.5 mmol/L or apoB ≥1.05 g/L or non-HDL ≥4.2 mmol/L, or male ≥50 years of age or female ≥60 years of age with one additional risk factor (low HDL, impaired glucose tolerance, high waist circumference, smoker, hypertension), or presence of a risk modifier (e.g., CAC >0 Agatston unit, hs-CRP ≥2 mmol/L, Lp(a) ≥50 g/L, family history of premature CAD). Low risk level and: FRS 5% to 9.9% with LDL ≥3.5 mmol/L or apoB ≥1.05 g/L or HDL ≥4.2 mmol/L, especially with risk modifiers (e.g., CAC >0 Agatston unit, Lp(a) ≥50 g/L, family history of premature CAD). These patients are essentially intermediate-risk patients. Note: non-HDL or apoB are the preferred indicators, especially if triglycerides are >1.5 mmol/L.
What are the recommended treatment goals?	Secondary prevention (ASCVD): LDL <1.8 mmol/L or non-HDL <2.4 mmol/L or apoB <0.7 g/L. Primary prevention: LDL ≤2 mmol/L or apoB ≤0.8 g/L or non-HDL ≤2.6 mmol/L. Very high cholesterol (e.g., familial hypercholesterolemia) without ASCVD: LDL <2.5 mmol/L (or 50% reduction), or apoB <0.85 g/L, or non-HDL <3.2 mmol/L). Note: non-HDL or apoB are the preferred targets, especially if triglycerides are ≥1.5 mmol/L. For patients whose LDL are below thresholds and therapy is being tolerated, it is not generally required to reduce a patient’s statin dose.¹
What lifestyle changes can be recommended?	Lifestyle changes (cornerstone; recommended for all patients): Quit tobacco. Consume a healthy diet: Mediterranean, Portfolio, DASH, low glycemic load, or plant-based dietary patterns, including nuts, beans, olive oil, fruits, vegetables, fibre, and whole grains. Maintain a healthy body weight. Exercise for 150 minutes weekly, at moderate-to-vigorous intensity, and perhaps weight-training twice weekly. Get adequate sleep. Drink alcohol in moderation. Manage stress.
How are statins used to treat dyslipidemia?	Statins are first line for all patients who require pharmacotherapy. High-intensity statins (or max tolerated dose) are used for secondary prevention (ASCVD). The following table shows daily adult statin doses expected to provide similar LDL reduction:⁴
	Statin	Low-intensity statin (expected LDL reduction <30%)	Moderate-intensity statin (expected LDL reduction 30 to <50%)	High-intensity statin (expected LDL reduction ≥50%)
	Atorvastatin	NA	10 to 20 mg	40 to 80 mg
	Fluvastatin	20 to 40 mg	80 mg	NA
	Lovastatin	20 mg	40 to 80 mg	NA
	Pravastatin	10 to 20 mg	40 to 80 mg	NA
	Rosuvastatin	NA	5 to 10 mg	20 to 40 mg
	Simvastatin	10 mg	20 to 40 mg	NA
	In kidney impairment: Atorvastatin dose is 10 mg max, with caution, if CrCl <30 mL/min.⁷ Fluvastatin is NOT recommended if CrCl <30 mL/min.⁸ Lovastatin doses >20 mg should be used with caution if CrCl <30 mL/min.⁹ Pravastatin starting dose is 10 mg in patients with significant kidney impairment.¹⁰ Rosuvastatin starting dose is 5 mg (max 10 mg) if CrCl <30 mL/min/1.73m².¹¹ Simvastatin starting dose is 5 mg, and doses >10 mg should be with caution if CrCl<30 ml/min.¹² In patients with liver impairment: Pravastatin starting dose is 10 mg in significant liver impairment.¹⁰ Rosuvastatin max dose is 20 mg in severe liver impairment.¹¹ In patients of Asian ancestry, the rosuvastatin starting dose is 5 mg (max 20 mg).¹¹
What non-statin treatment options are available?	Ezetimibe: statin add-on for: primary prevention: intermediate risk, high risk, CKD, or diabetes not meeting goal despite maximally tolerated statin dose (first-line add-on; bile acid sequestrant is an alternative but has less evidence). primary prevention: very high cholesterol (e.g., familial hypercholesterolemia) not meeting goal with statin (alternative to PCSK9 inhibitor). secondary prevention (ASCVD): patients with LDL 1.8 to 2.2 mmol/L or apoB 0.7 to 0.8 g/L or non-HDL 2.4 to 2.9 mmol/L despite maximally tolerated statin dose (+/- PCSK9 inhibitor). PCSK9 inhibitor: statin add-on for: secondary prevention (ASCVD): patients with LDL >2.2 mmol/L or apoB >0.8 g/L or non-HDL >2.9 mmol/L despite maximally tolerated statin dose (+/- ezetimibe). See footnote b. primary prevention: very high cholesterol (e.g., familial hypercholesterolemia) not meeting goal despite maximally tolerated statin (alternative to ezetimibe). Icosapent ethyl: consider as a statin add-on for: patients with ASCVD with triglycerides 1.5 to 5.6 mmol/L despite maximally tolerated statin dose. certain high-risk diabetes patients(see footnote a) without ASCVD, but with triglycerides 1.5 to 5.6 mmol/L despite maximally tolerated statin dose. Bile-acid sequestrant: statin add-on for: Primary prevention in CKD or diabetes not meeting goal despite maximally tolerated statin dose (ezetimibe is first-line add-on; bile acid sequestrant has less evidence). Role of niacin or fibrates:² Do NOT add to statin in patients who have achieved LDL goal on a statin. Niacin’s benefit is unclear in patients who do not achieve their LDL goal on a statin, or who have low HDL or high triglycerides. Subgroup analysis suggests fibrate might benefit high-risk patients with low HDL and high triglycerides despite statin. For details about individual agents, see our chart, Non-Statin Lipid-Lowering Agents.
Are statins appropriate for patients <40 years of age?	Use shared decision making regarding statin decisions. Review risks, benefits, and alternatives. Share risk assessment results with the patient.² Emphasize lifestyle changes (healthy diet, weight loss, exercise) to meet lipid and other goals as part of a comprehensive CVD risk reduction plan in all patients.² Treat patients who have astatin-indicated condition (see “How is Risk Assessed and Defined?” section above).² For patients without a statin-indicated condition, assess CVD risk if appropriate (see “Who should be screened” section of chart, above). 10-year risk for adults ≥30 years of age can be estimated using the FRS modified to include family history of premature CVD (https://medsquares.com/).² Use this result to help guide statin decisions. MyHealthCheckup (https://myhealthcheckup.com) can be used to calculate 10-year risk and cardiovascular age, and to show patients how various interventions might reduce their CVD risk.²This calculator can also be used as a teaching/discussion tool in patients <30 years of age by putting in “30” as the age.³ In patients who have a strong family history of premature CVD, checking an Lp(a) level might help guide statin decisions.² After estimating risk: Recommend a statin for high-risk patients (e.g., FRS ≥20%).² Advise only lifestyle changes for low-risk patients (e.g., FRS <10%).² Recommend a statin if 10-year risk is 10% to 19%, and LDL is ≥3.5 mmol/L. Consider a statin if LDL <3.5 mmol/L and apoB ≥1.2 g/L, or non-HDL ≥4.3 mmol/L.²
Can pregnant patients take statins?	Although statins have been considered teratogenic, this is based on animal studies. Data from human pregnancies do not consistently suggest that statins cause birth defects; comorbidities confound these studies. Miscarriage risk is unclear, and because statins inhibit cholesterol production, fetal harm remains a concern.⁵ In general, limit statin use during pregnancy to those patients who are very high-risk (e.g., homozygous familial hypercholesterolemia, secondary prevention).^1,5 The safest statin alternatives are bile acid sequestrants because they are not systemically absorbed.⁶ If the decision is made to use a statin in a patient of childbearing potential, a hydrophilic statin (pravastatin, rosuvastatin) may be preferred because they may transfer across the placenta less readily than other statins.¹ In most cases, if a statin is used for primary prevention, advise use of effective contraception, and discontinuation of therapy before planning pregnancy or when pregnancy is discovered.¹ Most patients should stop their statin one to two months before planning a pregnancy, or as soon as they are aware of the pregnancy.^4,5 Statins may pass into breast milk, posing a theoretical risk to the infant.⁵ When making decisions about lipid treatment in patients of childbearing potential, use of cardiovascular age is recommended over 10-year risk calculators.
How should patients ≥75 years of age be managed?	There is good evidence to support statin use for secondary prevention of CVD events in these patients, although a mortality benefit has not been shown.² Statins have not been studied extensively for primary prevention in these patients.²Use of risk estimators (FRS) in these patents may lead to overestimation of risk, and thus inappropriate prescribing of statins.² However, statins should be discussed as part of overall cardiovascular risk reduction in “robust” elderly thought to be at higher CVD risk, because cardiovascular events (e.g., stroke) can lead to significant morbidity.²
How should statin patients be monitored?	Consider US guidelines:⁴ Check transaminases at baseline. Unless the patient has chronic stable liver disease, repeat only if signs/symptoms suggestive of liver toxicity occur. Document any pre-existing muscle symptoms before starting a statin to establish a baseline. If severe muscle symptoms or objective weakness occur, hold the statin and check creatinine kinase. Check fasting lipid panel four to 12 weeks after statin initiation or dosage change, then every three to 12 months. Check adherence to statin and lifestyle interventions if LDL drop is less than expected. In patients with chronic inflammatory disease or HIV, check fasting lipids before and four to 12 weeks after starting a chronic anti-inflammatory drug or antiretroviral. Statins seem to cause a small increase in the risk of diabetes (~0.2% absolute risk per year, depending on statin, dose, and underlying diabetes risk factors). Consider diabetes screening in patients at elevated risk, especially those on a high-intensity statin.¹³
How should statin side effects be managed?	General approach to side effects:² Confirm statin benefit justifies risk. Hold statin and assess, then rechallenge with same or different statin, at same or lower dose or frequency. Look for drug interactions. Emphasize lifestyle modification. Do not treat side effects with supplements. See our FAQ, Statin Muscle Symptoms: Managing Statin Intolerance, for more information.

Icosapent ethyl: medication-treated diabetes patients ≥50 years of age with one additional risk factor: age ≥55 (male) or ≥65 (female) years; smoker or stopped in the past three months; blood pressure ≥140/90 mm Hg or treated; HDL ≤1.04 mmol/L (male) or ≤1.3 mmol/L (female); hs-CRP >3 mg/L; eGFR >30 to <60 mL/min/1.73 m²; albuminuria; retinopathy; ABI <0.9 without claudication symptoms.
PCSK9 inhibitor: patients most likely to benefit are those with a recent ACS within the past year; or MI within two years or recurrent MI; diabetes or metabolic syndrome; vascular disease in more than one arterial bed; symptomatic peripheral artery disease; history of CABG; LDL ≥2.6 mmol/L; heterozygous; familial hypercholesterolemia; Lp(a) ≥60 g/L.

Abbreviations: ABI = ankle brachial index; ACR = albumin:creatinine ratio; ACS = acute coronary syndrome; apoB = apolipoprotein B; ASCVD = atherosclerotic cardiovascular disease; BMI = body mass index; CABG = coronary artery bypass graft; CAC = coronary artery calcium score; CAD = coronary artery disease; COPD = chronic obstructive pulmonary disease; CrCl = creatinine clearance; CVD = cardiovascular disease; eGFR = estimated glomerular filtration rate; FRS = Framingham Risk Score; HDL = high-density lipoprotein cholesterol; HIV = human immunodeficiency virus; hs-CRP = high-sensitivity C-reactive protein; LDL = low-density lipoprotein cholesterol; Lp(a) = lipoprotein (a); MI = myocardial infarction; TIA = transient ischemic attack

Levels of Evidence

In accordance with our goal of providing Evidence-Based information, we are citing the LEVEL OF EVIDENCE for the clinical recommendations we publish.

Level	Definition	Study Quality
A	Good-quality patient-oriented evidence.*	High-quality randomized controlled trial (RCT) Systematic review (SR)/Meta-analysis of RCTs with consistent findings All-or-none study
B	Inconsistent or limited-quality patient-oriented evidence.*	Lower-quality RCT SR/Meta-analysis with low-quality clinical trials or of studies with inconsistent findings Cohort study Case control study
C	Consensus; usual practice; expert opinion; disease-oriented evidence (e.g., physiologic or surrogate endpoints); case series for studies of diagnosis, treatment, prevention, or screening.

*Outcomes that matter to patients (e.g., morbidity, mortality, symptom improvement, quality of life).

[Adapted from Ebell MH, Siwek J, Weiss BD, et al. Strength of Recommendation Taxonomy (SORT): a patient-centered approach to grading evidence in the medical literature. Am Fam Physician 2004;69:548-56. https://www.aafp.org/pubs/afp/issues/2004/0201/p548.html.]

References

Pearson GJ, Thanassoulis G, Anderson TJ, et al. 2021 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in Adults. Can J Cardiol. 2021 Aug;37(8):1129-1150.
Anderson TJ, Grégoire J, Pearson GJ, et al. 2016 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in the Adult. Can J Cardiol. 2016 Nov;32(11):1263-1282.
MyHealthCheckup. http://myhealthcheckup.com. (Accessed June 19, 2023).
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. J Am Coll Cardiol. 2019 Jun 25;73(24):e285-e350. Erratum in: J Am Coll Cardiol. 2019 Jun 25;73(24):3237-3241.
FDA. FDA Drug Safety Communication. FDA requests removal of strongest warning against using cholesterol-lowering statins during pregnancy; still advises most pregnant patients should stop taking statins. July 20, 2021. https://www.fda.gov/media/150774/download. (Accessed June 19, 2023).
Mehta LS, Warnes CA, Bradley E, et al. Cardiovascular Considerations in Caring for Pregnant Patients: A Scientific Statement From the American Heart Association. Circulation. 2020 Jun 9;141(23):e884-e903. Erratum in: Circulation. 2020 Jun 9;141(23):e904. Erratum in: Circulation. 2021 Mar 23;143(12):e792-e793.
Product monograph for Lipitor. Upjohn Canada. Kirkland, QC H9J 2M5. February 2023.
Product monograph for Teva-fluvastatin. Teva Canada. Toronto, ON M1B 2K9. November 2016.
Product monograph for lovastatin. AA Pharma. Vaughan, ON L4K 4N7. February 2021.
Product monograph for Sandoz pravastatin. Sandoz Canada. Boucherville, QC J4B 1E6. April 2021.
Product monograph for Crestor. AstraZeneca Canada. Mississauga, ON L4Y 1M4. June 2022.
Product monograph for Zocor. Organon Canada. Kirkland, QC H9H 4M7. May 2022.
NewmanCB, Preiss D, Tobert JA, et al. American Heart Association Clinical Lipidology, Lipoprotein, Metabolism and Thrombosis Committee, a Joint Committee of the Council on Atherosclerosis, Thrombosis and Vascular Biology and Council on Lifestyle and Cardiometabolic Health; Council on Cardiovascular Disease in the Young; Council on Clinical Cardiology; and Stroke Council. Statin Safety and Associated Adverse Events: A Scientific Statement From the American Heart Association. Arterioscler Thromb Vasc Biol. 2019 Feb;39(2):e38-e81.
Babadagli HE, Barry AR, Thanassoulis G, Pearson GJ. Updated guidelines for the management of dyslipidemia and the prevention of cardiovascular disease in adults by pharmacists. Can Pharm J (Ott). 2023 Apr 21;156(3):117-127.

Cite this document as follows: Clinical Resource, Canadian Dyslipidemia Recommendations. Pharmacist’s Letter/Pharmacy Technician’s Letter/Prescriber Insights. July 2023. [390714]

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