Dyslipidemia

How to read this summary

• Canadian sources come first, US sources second. Each point has a source tag like ^[S1] or ^[U1]. The full list of tags is at the end.
• "WARNING" marks a conflict or an old document. "Unconfirmed" means it could not be verified in the sources used. Never trust an unconfirmed item without checking.
• PEBC follows Canada. When Canada and the US differ, the Canadian answer is the exam answer.
• IMPORTANT (newest guideline): the newest Canadian dyslipidemia guideline found is the 2021 CCS (Canadian Cardiovascular Society) Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in Adults (Can J Cardiol 2021;37:1129-1150). No later full update was found. This summary reads it through the CCS pocket guide posted in 2022 ^[S1] and the journal text ^[S2]. The CCS "at a glance" PDF could not be downloaded completely and was not used.
• WARNING: the Diabetes Canada chapter ^[S3] is from 2018. It says LDL-C (Low-Density Lipoprotein Cholesterol) should be consistently below 2.0 mmol/L in people with diabetes. The 2021 CCS guideline ^{[S1, S2]} does not use one fixed LDL-C target; it uses "treat if statin-indicated" and "add more therapy if LDL-C stays above a threshold". The two agree on direction. Use the CCS 2021 thresholds for add-on therapy.
• Page numbers: S1 uses the printed pocket-guide page number (PDF page = printed page + 3). S2 uses the PDF page of the journal copy. S3 uses the journal page (S178-S185). Drug labels use the monograph section or page.
• Doses and numbers are for exam study, not for real patients.

1. What is dyslipidemia? (too much "bad fat" travelling in the blood)

• Dyslipidemia means unhealthy blood fats: high LDL-C, high non-HDL-C, high ApoB, high triglycerides (TG), high Lp(a), or low HDL-C (High-Density Lipoprotein Cholesterol) ^{[S1 p3-9]}.
• Daily-life picture: blood is a road, and cholesterol travels in "delivery trucks" (lipoproteins). Too many trucks that drop cargo on the walls of the road build up plaque, and the road narrows. That plaque disease is atherosclerosis, and it causes heart attack, stroke and poor leg circulation. These are together called ASCVD (Atherosclerotic Cardiovascular Disease) ^{[S2 p2-3]}.
• Every atherogenic (plaque-forming) truck carries one ApoB (apolipoprotein B) tag. So ApoB counts the trucks. Atherogenic ApoB trucks are VLDL (Very Low-Density Lipoprotein), IDL (Intermediate-Density Lipoprotein), LDL (Low-Density Lipoprotein), chylomicron remnants and Lp(a) (lipoprotein(a)) ^{[S1 p9; S3 p S182]}.
• Non-HDL-C = total cholesterol minus HDL-C. It measures the cholesterol in all the plaque-forming trucks ^{[S1 p9]}.
• ASCVD includes heart attack and acute coronary syndrome, stable angina with proven coronary disease, stroke, TIA (Transient Ischemic Attack), carotid disease, peripheral artery disease (including claudication, or an ankle-brachial index below 0.9), and abdominal aortic aneurysm (aorta wider than 3.0 cm or previous aneurysm surgery) ^{[S1 p8; S2 p2]}.
• "Statin-indicated condition" is a CCS term. It means a condition where a statin is recommended without a risk calculation (see section 3) ^{[S2 p2]}.

1.1 Who to screen and how to test

• Screen all men and women aged 40 or older (women: or postmenopausal). Consider starting earlier in higher-risk ethnic groups such as South Asian or Indigenous people ^{[S1 p3; S2 p3]}.
• Screen at any age with: clinical atherosclerosis, abdominal aortic aneurysm, diabetes, hypertension, current smoking, signs of high lipids (corneal arcus, xanthelasma, xanthoma), family history of premature CVD (relatives: men younger than 55, women younger than 65) or of dyslipidemia, chronic kidney disease (CKD: eGFR 60 or lower, or ACR (albumin-to-creatinine ratio) 3 mg/mmol or higher), obesity (BMI 30 or more), inflammatory diseases (RA, SLE, psoriatic arthritis, ankylosing spondylitis, IBD), HIV, erectile dysfunction, COPD, or a history of a hypertensive disorder of pregnancy ^{[S1 p3; S2 p3]}.
• Blood test: a standard lipid profile (total cholesterol, LDL-C, HDL-C, non-HDL-C, TG), plus fasting glucose or HbA1c (Hemoglobin A1c), eGFR (estimated Glomerular Filtration Rate), and Lp(a) once in a lifetime ^{[S1 p4]}.
• The test can be done non-fasting ^{[S1 p4; S2 p3]}. Daily-life example: you can have the blood test straight after breakfast; only people known to have TG above 4.5 mmol/L need to fast.
• If TG is above 1.5 mmol/L, use non-HDL-C or ApoB instead of LDL-C as the main number (strong recommendation) ^{[S1 p4]}. If TG is above 4.5 mmol/L (known history), measure fasting ^{[S1 p4; S3 p S182]}. Labs do not report a calculated LDL-C when TG is 4.5 mmol/L or higher ^{[S3 p S179]}.
• Lp(a): measure once in a lifetime. If Lp(a) is 50 mg/dL or higher (100 nmol/L or higher), start stronger lifestyle advice and manage other risk factors earlier ^{[S1 p6]}.
• Coronary artery calcium (CAC) scan: may be considered at age 40 or older when risk is intermediate (FRS 10-20%) and the treatment decision is unclear. Not for high-risk people, people already on a statin, or most low-risk people ^{[S1 p5]}. A CAC above 100 AU (Agatston units) is an indication for a statin regardless of FRS ^{[S1 p5]}.

Must remember for the exam: non-fasting lipid tests are fine. TG above 1.5 mmol/L: use non-HDL-C or ApoB. Non-HDL-C = total cholesterol minus HDL-C. Lp(a) once in a lifetime.

Blueprint area: 1A Clinical Care.

2. Risk assessment (how big is the danger?)

• In Canada, risk in primary prevention (no ASCVD yet) is estimated with the modified Framingham Risk Score (FRS) or the Cardiovascular Life Expectancy Model (CLEM), for people aged 40 to 75 ^{[S1 p7]}.
• Repeat the assessment every 5 years, and whenever the person's risk changes (new diabetes, new smoking, new blood pressure problem). Share the result with the patient to support shared decision-making ^{[S1 p7; S2 p3]}.
• WARNING (inside the CCS pocket guide): one box on page 7 also says "repeat screening every 5 years for FRS below 5% or every year for FRS 5% or higher". The text and other pages say every 5 years. This is not tested in the MCQs.
• A first-degree relative with premature CVD roughly doubles the calculated FRS percent in people aged 30-59 without diabetes ^{[S2 p3]}.
• The 10-year FRS bands (CCS) ^{[S1 p8, p12]}:

• Statin-indicated conditions (no calculator needed) ^{[S1 p8, p12; S2 p2-4]}:
• Any ASCVD (including AAA).
• Most people with diabetes: age 40 or older; or age 30 or older with diabetes for 15+ years; or microvascular disease.
• CKD: age 50 or older with eGFR below 60 mL/min/1.73 m2 or ACR above 3 mg/mmol.
• LDL-C 5.0 mmol/L or higher (or ApoB 1.45 g/L or non-HDL-C 5.8 or higher), such as familial hypercholesterolemia (FH) or genetic dyslipidemia.
• Daily-life example: Ms. R is 45, healthy, FRS 4%, LDL-C 3.0. Lifestyle only. Mr. T is 55 with FRS 14% and LDL-C 3.9: intermediate risk plus LDL-C above 3.5, so offer a statin.

Must remember for the exam: FRS or CLEM every 5 years at age 40-75. High risk 20% or more; intermediate 10-19.9% (treat with LDL-C 3.5+, non-HDL-C 4.2+ or ApoB 1.05+ or modifiers); low below 10%. Statin-indicated: ASCVD, most diabetes, CKD 50+, LDL-C 5.0+.

Blueprint area: 1A Clinical Care.

3. When to treat, and what to aim for

• CCS 2021 recommends high-intensity statin therapy plus lifestyle for all people who need a statin in primary prevention, and for all secondary prevention (ASCVD) patients. If a high-intensity statin is not tolerated, use the maximally tolerated dose (strong recommendation) ^{[S1 p10, p12]}.
• Add-on treatment is driven by thresholds measured while on the maximally tolerated statin ^{[S1 p22-23]}:

• Size of the add-on step in ASCVD (pocket guide printed p23): if LDL-C is 1.8-2.2 mmol/L (ApoB 0.70-0.80 g/L, non-HDL-C 2.4-2.9), consider ezetimibe; if LDL-C is above 2.2 (ApoB above 0.80, non-HDL-C above 2.9) or the patient is in the high-benefit list in section 5, consider a PCSK9 inhibitor with or without ezetimibe ^{[S1 p23]}.
• The pocket guide (page 22) shows three columns of thresholds (2.5, 2.0 and 1.8 mmol/L). The assignment of columns to groups above follows recommendations 14-15 of the journal text ^{[S2 p15]} and the primary prevention figure ^{[S1 p20]}. The column-to-group mapping could not be confirmed from the PDF text (it is a figure); where the group is unclear (for example LDL-C 5.0+ or genetic dyslipidemia), check the figure (see Unconfirmed).
• Diabetes Canada 2018 ^{[S3 p S182-S183]}: in people with diabetes who need lipid treatment, start a statin and aim for LDL-C consistently below 2.0 mmol/L or more than a 50% drop from baseline. Alternative targets: ApoB below 0.8 g/L, non-HDL-C below 2.6 mmol/L. TG is not a target of therapy, but below 1.5 mmol/L is considered optimal ^{[S3 p S181]}.
• Do not add a fibrate or niacin only to lower cardiovascular risk when the LDL-C goal is already reached on a statin (strong recommendation, high-quality evidence) ^{[S1 p15; S3 p S182]}.
• Daily-life example: a 62-year-old man with a heart attack years ago has LDL-C 2.0 mmol/L on atorvastatin 80 mg. That is above 1.8, so add ezetimibe 10 mg. If still above 1.8, add a PCSK9 inhibitor.

Must remember for the exam: statin first, high intensity. Secondary prevention add-on if LDL-C 1.8+ (non-HDL-C 2.4+, ApoB 0.7+). Other statin-indicated primary prevention: above 2.0. HeFH without ASCVD: 2.5+ or less than 50% fall.

Blueprint area: 1A Clinical Care. Likely exam angle: matching the threshold to the group.

4. Statins (the first-line "factory brakes")

• Statins block HMG-CoA reductase (3-hydroxy-3-methylglutaryl-CoA reductase), the liver enzyme that makes cholesterol. Daily-life picture: the liver is a cholesterol factory, and the statin slows the assembly line, so the liver pulls more LDL out of the blood (teaching picture) ^{[S3 p S182 (mechanism named); Health Canada labels S4-S5 use "HMG-CoA reductase inhibitor"]}.
• Statins lower LDL-C most. They lower TG a little and raise HDL-C a little at higher doses ^{[S3 p S180]}.

4.1 Statin doses (CCS pocket guide, Canada) ^{[S1 p16]}

• The CCS pocket guide marks atorvastatin and rosuvastatin as the high-potency statins ^{[S1 p16]}.
• Health Canada labels:
• Atorvastatin: start 10 or 20 mg daily; 40 mg if more than a 45% LDL-C drop is needed; range 10-80 mg; adjust at 2-4 week intervals. Severe renal impairment (CrCl below 30 mL/min), or renal insufficiency of unknown severity: use the lowest dose, 10 mg ^{[S4 section 4.2]}.
• Rosuvastatin: dose range 5-40 mg; usual start 10 mg; 5 mg for people with predisposing factors for myopathy; adjust at 2-4 week intervals; 40 mg only for severe hypercholesterolemia not controlled on 20 mg, no predisposing factors, and specialist advice recommended when starting 40 mg. Prevention of major cardiovascular events: 20 mg daily ^{[S5 section 4.2]}.
• Switching to rosuvastatin from another statin: start at 10 mg ^{[S5 section 4.2]}.
• Rosuvastatin: morning or evening, with or without food ^{[S5 section 4.4]}. Atorvastatin: any time of the day, preferably in the evening, with or without food, but not with grapefruit juice ^{[S4 section 4.4, section 9.5]}.
• Daily-life example: a patient who always forgets evening pills can take rosuvastatin in the morning with breakfast (atorvastatin is preferably taken in the evening, but any time is allowed).

4.2 Contraindications (Health Canada labels)

• Atorvastatin: hypersensitivity; active liver disease or unexplained persistent transaminases above 3 times the upper limit of normal (ULN); pregnancy and breastfeeding; hepatitis C antivirals (the label lists them as a contraindicated combination); cyclosporine ^{[S4 section 2]}.
• Rosuvastatin: hypersensitivity; active liver disease or unexplained persistent transaminases above 3 times ULN; cyclosporine; sofosbuvir/velpatasvir/voxilaprevir; breastfeeding. Rosuvastatin 40 mg is also contraindicated in Asian patients and in people with predisposing factors for myopathy or rhabdomyolysis ^{[S5 section 2]}.
• Rosuvastatin in Asian patients: start 5 mg once daily, maximum 20 mg daily (about 2-fold higher blood levels) ^{[S5 section 4.2, section 7 Ethnic Origin]}.
• Rosuvastatin in severe renal impairment (CrCl below 30): start 5 mg, maximum 10 mg daily ^{[S5 section 4.2]}. Severe hepatic impairment: do not exceed 20 mg ^{[S5 section 4.2]}.

4.3 Adverse effects and monitoring

• Common worry: muscle pain (myalgia). Rare: myopathy and rhabdomyolysis (muscle breakdown, with kidney injury from myoglobin). Also rare: immune-mediated necrotizing myopathy (muscle weakness that persists after stopping the statin, with anti-HMG-CoA reductase antibodies) and worsening of myasthenia gravis ^{[S5 section 7 Musculoskeletal]}.
• Other effects: small rise in blood sugar and HbA1c; a small rise in new diabetes, but the heart benefit clearly outweighs this ^{[S5 section 7 Plasma Glucose; S3 p S182]}. Liver enzyme rises are usually mild and dose related (below 0.5% of patients with rosuvastatin) ^{[S5 section 7]}.
• Muscle risk factors (Health Canada label, rosuvastatin): personal or family history of muscle disease, previous muscle toxicity with a statin, fibrate or niacin together with the statin, hypothyroidism, alcohol abuse, heavy exercise, age above 70, renal or hepatic impairment, surgery or trauma, frailty ^{[S5 section 7]}. Diabetes Canada adds small body frame, multiple medicines and a lot of grapefruit juice ^{[S3 p S180]}.
• Monitoring (CCS): most lipid-lowering drugs are well tolerated. Check the serum transaminases (ALT) in the first 3 months. Check creatine kinase (CK) if muscle symptoms develop. No routine ALT or CK after that ^{[S1 p24]}.
• Labels: liver tests before starting and then as clinically indicated (atorvastatin) ^{[S4 section 7]}; rosuvastatin: before, 3 months after starting, and if titrated to 40 mg ^{[S5 section 7]}. Lipid recheck 3 to 6 months after starting treatment is advised by Diabetes Canada ^{[S3 p S182]}.
• Stop or reduce when: transaminases stay above 3 times ULN; CK above 10 times ULN, or myopathy diagnosed or suspected; serious liver injury with jaundice; suspected interstitial lung disease; hypersensitivity ^{[S5 section 4.2; S4 section 4.2]}.
• Hold the statin during an acute serious illness that can lead to rhabdomyolysis (sepsis, low blood pressure, major surgery, trauma, uncontrolled seizures) ^{[S5 section 4.2; S4 section 4.2]}.
• Statin intolerance (CCS): check every claimed statin symptom step by step: stop, then restart the same or a different statin, or a lower dose, or a less frequent schedule, to find a tolerated statin-based plan. Do not recommend vitamins, minerals or supplements (for example coenzyme Q10) for statin-related muscle pain (strong recommendation, low-quality evidence) ^{[S1 p13]}.
• Always confirm that there is a real indication for a statin: the benefit usually far outweighs the possible side effects ^{[S1 p13]}.

Must remember for the exam: ALT within 3 months, CK only if symptoms, no routine monitoring after. Stop if CK above 10 times ULN. No supplements for statin muscle pain. Rosuvastatin 40 mg: not for Asian patients.

Blueprint area: 1A Clinical Care. Likely exam angle: myopathy, monitoring.

5. Non-statin add-ons

• Which patients benefit most from adding a PCSK9 inhibitor (secondary prevention, with LDL-C still 1.8+ on a maximally tolerated statin) ^{[S1 p14]}: ASCVD plus any of: recent acute coronary syndrome (hospitalized up to 52 weeks), diabetes or metabolic syndrome, polyvascular disease (2+ arterial beds), symptomatic PAD, recurrent MI, MI in the past 2 years, previous CABG (coronary artery bypass graft), LDL-C 2.6 mmol/L or more or heterozygous FH, or Lp(a) 60 mg/dL (120 nmol/L) or more.
• Step order for ASCVD with LDL-C still 1.8+: ezetimibe and/or PCSK9 inhibitor; if ezetimibe is used first and LDL-C is still 1.8+, then add the PCSK9 inhibitor (strong recommendation) ^{[S1 p14]}.
• Daily-life example: ezetimibe is like closing the side door of the gut so less cholesterol sneaks in; a PCSK9 inhibitor stops the liver's "recycling bin" for LDL receptors from filling up, so more LDL is cleared. (Mechanism wording is a teaching picture, not from the sources.)
• Omega-3 supplements from stores (over-the-counter, natural health products) are not recommended to lower CVD risk (strong recommendation) ^{[S1 p17]}. Only the prescription EPA drug icosapent ethyl showed benefit ^{[S1 p5]}.
• Bile acid sequestrant studies for preventing ASCVD events were inconclusive ^{[S1 p20]}.

Must remember for the exam: ezetimibe 10 mg is the usual first add-on. PCSK9 inhibitors: evolocumab 140 mg every 2 weeks or 420 mg monthly; alirocumab 75-150 mg every 2 weeks or 300 mg every 4 weeks. Bempedoic acid: uric acid, simvastatin limit. Icosapent ethyl: 2 g twice daily with food, bleeding and AF. Gemfibrozil + statin = do not combine.

Blueprint area: 1A Clinical Care. Likely exam angle: choosing the add-on.

6. Drug interactions to know

• Statin and cyclosporine: contraindicated (atorvastatin, rosuvastatin) ^{[S4 section 2; S5 section 2]}.
• Atorvastatin: hepatitis C antivirals contraindicated ^{[S4 section 2]}. Itraconazole: do not exceed atorvastatin 20 mg daily. Letermovir: do not exceed 20 mg daily ^{[S4 section 9.4]}. Clarithromycin (a CYP3A4 inhibitor) raises atorvastatin exposure (AUC ratio about 1.8) ^{[S4 section 9.4]}. Grapefruit juice raises atorvastatin levels, and the label says do not take with grapefruit juice ^{[S4 section 9.5]}.
• Gemfibrozil with atorvastatin: the label says avoid the combination; for fenofibrate, bezafibrate or niacin with atorvastatin, weigh risks and benefits, using lower starting and maintenance doses ^{[S4 section 9.4]}.
• Rosuvastatin has little CYP450 metabolism ^{[S5 section 9.2]}. It is affected by transporters (OATP1B1, BCRP). Protease inhibitors can raise rosuvastatin exposure up to 7-fold ^{[S5 section 9.2]}.
• Rosuvastatin dose limits: clopidogrel, dronedarone, capmatinib, eltrombopag: do not exceed 20 mg; enasidenib: 10 mg; belumosudil, darolutamide: 5 mg ^{[S5 section 9.4]}.
• Rosuvastatin and warfarin (coumarins): INR can rise; check the INR when starting, stopping or changing the rosuvastatin dose ^{[S5 section 9.4]}.
• Rosuvastatin and aluminum/magnesium antacids: antacid can lower rosuvastatin by about 50%; give the antacid 2 hours after rosuvastatin; frequent antacid users should take rosuvastatin at a time when they are unlikely to need an antacid ^{[S5 section 9.4]}.
• Ezetimibe: separate from bile acid sequestrants (2 hours before or 4 hours after). Cyclosporine is listed as a serious interaction. Fibrates other than fenofibrate: combination not recommended; fenofibrate with ezetimibe can cause gallstones ^{[S6 sections 4.2, 7, 9]}.
• Fenofibrate (Lipidil EZ): contraindicated with statins in people with predisposing factors for myopathy; also contraindicated in gallbladder disease, severe renal dysfunction (CrCl below 30), liver insufficiency, pancreatitis, pregnancy and breastfeeding ^{[S10 section 2]}. Warfarin: fenofibrate may raise the INR (see the Atrial Fibrillation summary).
• Bempedoic acid: raises statin levels; contraindicated with simvastatin above 40 mg ^{[S8 section 2]}.
• Icosapent ethyl: more bleeding with aspirin, clopidogrel, warfarin ^{[S9 section 7]}.
• Daily-life example: a patient on atorvastatin 40 mg starts itraconazole for a nail infection. The label limit is 20 mg while on itraconazole, so the pharmacist calls the prescriber.

Must remember for the exam: cyclosporine contraindicated with atorvastatin and rosuvastatin. Gemfibrozil + statin = avoid. Itraconazole: atorvastatin maximum 20 mg. No grapefruit juice with atorvastatin. Rosuvastatin + warfarin: check INR.

Blueprint area: 1A Clinical Care and 1B Distribution (prescription review).

7. Familial hypercholesterolemia (FH)

• FH is an inherited condition with very high LDL-C from birth. LDL-C of 5.0 mmol/L or higher (or ApoB 1.45 g/L+, non-HDL-C 5.8+) is a statin-indicated condition, "familial hypercholesterolemia or genetic dyslipidemia" ^{[S1 p8, p12]}.
• Daily-life example: a 38-year-old with an LDL-C of 6.2 mmol/L, tendon xanthomas, and a father whose heart attack happened at 48 likely has FH. A statin is started even without a risk score.
• For heterozygous FH (HeFH) without ASCVD: add a PCSK9 inhibitor (alirocumab or evolocumab) if LDL-C is 2.5 mmol/L or more or the fall is less than 50%, despite the maximally tolerated statin with or without ezetimibe (strong recommendation) ^{[S1 p15; S2 p15]}.
• For HeFH with ASCVD: add a PCSK9 inhibitor if LDL-C stays at 1.8 mmol/L or more ^{[S1 p15]}.
• Health Canada: evolocumab is indicated for HeFH in adults and in children aged 10 and older who need more LDL-C lowering, and for homozygous FH (HoFH) in adults and children aged 10 and older ^{[S7 section 1]}. Rosuvastatin may be used for HoFH alone or with apheresis ^{[S5 section 1]}. Ezetimibe with a statin is indicated for HoFH ^{[S6 section 1]}.
• Children: atorvastatin is authorized for boys and post-menarchal girls aged 10 to under 18 with HeFH when diet fails and LDL-C stays 4.9 mmol/L or more, or 4.1 or more with a family history of premature CVD or two or more other risk factors; start 10 mg, maximum 20 mg ^{[S4 sections 1.1, 4.2]}. Rosuvastatin for boys and girls at least 1 year post-menarche with HeFH starts at 5 mg, maximum 10 mg ^{[S5 section 4.2]}.
• Specialist referral may be warranted for severe dyslipidemia, genetic lipoprotein disorders, unexplained atherosclerosis, or poor response to drugs ^{[S1 p24]}.

Must remember for the exam: LDL-C 5.0 mmol/L or more = statin-indicated. HeFH without ASCVD: PCSK9 inhibitor if LDL-C stays at 2.5+ (or less than 50% fall). Evolocumab can be used from age 10 in HeFH and HoFH (Health Canada).

Blueprint area: 1A Clinical Care.

8. Triglycerides

• CCS 2021 does not treat TG as a target, but recommends icosapent ethyl for ASCVD patients (or people with diabetes needing medicine, age 50+, with one more risk factor) with TG 1.5-5.6 mmol/L despite a maximally tolerated statin ^{[S1 p5, p15, p23]}.
• The journal text says icosapent ethyl should be preferably reserved for adults aged 45 or older (or 50 or older with one more CVD risk factor) on a maximally tolerated statin with a TG of 1.5-5.6 mmol/L ^{[S2 p15]}.
• The other risk factors in the REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl - Intervention Trial) list include: man 55+ or woman 65+; smoking; hypertension; low HDL-C; hsCRP above 3.0 mg/L; eGFR 30-59; retinopathy; micro- or macroalbuminuria; ABI below 0.9 without claudication ^{[S1 p23]}.
• Health Canada label for Lipitor: high TG is above 2.2 mmol/L; very high is above 5.6 mmol/L, and may need fenofibrate, bezafibrate or niacin with or without the statin ^{[S4 section 4.2]}.
• Diabetes Canada: if fasting TG is above 10.0 mmol/L, use a fibrate to lower pancreatitis risk, while improving blood sugar control, weight, alcohol and refined-carbohydrate intake ^{[S3 p S181, S183]}.
• If TG is high and ApoB or non-HDL-C are also high, a statin is first-line, with a fibrate added later if needed ^{[S3 p S182]}.
• Fenofibrate (Lipidil EZ): adult dose 145 mg daily (elderly or impaired renal function: start 48 mg); maximum 145 mg daily; stop if no significant response in 3 months; do not use in severe renal dysfunction (CrCl below 30), including dialysis ^{[S10 section 4.2, 2]}.
• Pancreatitis is the danger of very high TG. Secondary causes (poor diabetes control, hypothyroidism, alcohol, some drugs) should be treated first ^{[S10 section 4.2; S4 section 4.1]}.
• OTC omega-3 supplements are not recommended for CVD risk; very high doses (4 g/day) lower TG, but fibrates are generally more effective ^{[S1 p17]}.

Must remember for the exam: icosapent ethyl is for TG 1.5-5.6 mmol/L in statin-treated high-risk people. Fasting TG above 10 mmol/L: fibrate (pancreatitis). Do not add fenofibrate or niacin only for heart protection.

Blueprint area: 1A Clinical Care.

9. Lifestyle (the cornerstone)

• Health behaviour change is the foundation of prevention at every risk level; drugs are added to it ^{[S1 p17-18; S2 p3]}.
• Diet: Mediterranean dietary pattern for everyone (strong). Other helpful patterns: Portfolio, DASH (Dietary Approaches to Stop Hypertension), low glycemic index, plant-based; plenty of nuts, legumes, olive oil, fruit, vegetables, fibre and whole grains. The best diet is the one the person will keep eating ^{[S1 p17]}.
• Activity: at least 150 minutes a week of moderate to vigorous aerobic activity, in bouts of 10 minutes or more ^{[S1 p18]}. Adding muscle- and bone-strengthening work 2 days a week may help ^{[S2 p3]}.
• Stop smoking; clinician advice to quit is recommended ^{[S1 p18]}.
• Combine low-risk habits: healthy weight, healthy diet, regular activity, moderate alcohol, 6-8 hours of sleep ^{[S1 p18]}.
• Diabetes Canada adds: energy-restricted diet low in cholesterol, saturated and trans fat and refined carbohydrates; viscous fibre, plant sterols, nuts and soy protein ^{[S3 p S179]}.
• Daily-life example: a 150-minute week is a 30-minute brisk walk on 5 days.

Must remember for the exam: Mediterranean diet, 150 minutes a week, stop smoking. Lifestyle is not replaced by the pill.

Blueprint area: 1A Clinical Care.

10. Special populations

10.1 Diabetes

• Most people with diabetes are statin-indicated (age 40+, or 30+ with 15 years of diabetes, or microvascular disease) ^{[S1 p8]}.
• Diabetes Canada: statin first, aim for LDL-C below 2.0 mmol/L or more than 50% fall; ApoB below 0.8 g/L or non-HDL-C below 2.6 as alternates ^{[S3 p S182-S183]}.
• Lipid profile at diagnosis; if no treatment, repeat every 1 to 3 years based on risk; 3-6 months after treatment starts ^{[S3 p S182]}.
• Ezetimibe or evolocumab may be added when the person has clinical CVD and is not at goal ^{[S3 p S183]}. Fibrates or niacin are not added just for extra protection once the LDL-C goal is met ^{[S3 p S183]}.
• Statins slightly raise the chance of new diabetes, but the heart benefit is larger ^{[S3 p S182]}.
• Typical diabetic pattern: high TG, low HDL-C, small dense LDL particles ^{[S3 p S178]}.

10.2 Chronic kidney disease (CKD)

• Age 50 or older with CKD not on dialysis and not a kidney transplant: a statin, or a statin plus ezetimibe (the SHARP study used simvastatin 20 mg plus ezetimibe 10 mg) ^{[S1 p11]}.
• Dialysis-dependent CKD: suggest not starting lipid-lowering therapy; continue it if the patient is already on it at dialysis start (conditional recommendations). Kidney transplant: suggest a statin ^{[S1 p11]}.
• Dose cautions: atorvastatin lowest dose (10 mg) in severe renal impairment; rosuvastatin starts at 5 mg and does not exceed 10 mg if CrCl is below 30 ^{[S4 section 4.2; S5 section 4.2]}. Fenofibrate is contraindicated at CrCl below 30 ^{[S10 section 2]}.

10.3 Pregnancy and breastfeeding

• Canada (labels): atorvastatin is contraindicated in pregnancy and breastfeeding ^{[S4 section 2]}. Rosuvastatin is not recommended in pregnancy, to be stopped as soon as pregnancy is recognized, and is contraindicated in breastfeeding ^{[S5 sections 2, 7.1.1]}. Bempedoic acid is contraindicated in pregnancy and breastfeeding ^{[S8 section 2]}. Fenofibrate is contraindicated in pregnancy and breastfeeding ^{[S10 section 2]}. Evolocumab: stop if pregnant when used for primary hyperlipidemia (because statins are stopped); for homozygous FH use only if the benefit justifies the risk ^{[S7 section 7.1.1]}.
• CCS 2021 ^{[S2 p7]}: in women of reproductive age, use an effective birth control method, stop the statin before a planned pregnancy or at an unplanned positive pregnancy test, and resume after delivery when breastfeeding is finished. CCS suggests hydrophilic statins (pravastatin, rosuvastatin) over lipophilic ones (atorvastatin, lovastatin, simvastatin) in women who may become pregnant. Consider referral to obstetrical medicine.
• A history of a hypertensive disorder of pregnancy (preeclampsia) raises later ASCVD risk, so these women should be screened ^{[S1 p3; S2 p2]}.
• US (extra, see section 12): in July 2021 the FDA asked to remove the strongest pregnancy warning for statins ^[U1].

10.4 Older adults

• Risk calculators apply to ages 40-75 ^{[S1 p7]}.
• Over 75: statins have good evidence for some outcomes in secondary prevention, but no mortality benefit has been shown. For primary prevention in people over 75, evidence is lacking because they were not studied much. For robust older people at higher risk, discuss the role of a statin ^{[S1 p7]}.
• Age is a muscle-risk factor: rosuvastatin label says age over 70 ^{[S5 section 7]}; atorvastatin label says over 65 ^{[S4 section 7]}. The labels differ, so write "over 65 to 70". No rosuvastatin dose change is needed for age alone ^{[S5 section 4.2]}. Ezetimibe needs no dose change in older adults ^{[S6 section 4.2]}. Fenofibrate: start 48 mg in the elderly ^{[S10 section 4.2]}.

10.5 Other

• Asian patients: rosuvastatin maximum 20 mg (40 mg contraindicated) ^[S5].
• Hepatic impairment: rosuvastatin maximum 20 mg in severe impairment; ezetimibe not recommended in moderate or severe impairment; active liver disease contraindicates statins ^{[S5 section 4.2; S6 section 4.2; S4 section 2]}.

Must remember for the exam: diabetes 40+ = statin; CKD 50+ not on dialysis = statin or statin plus ezetimibe; pregnancy: stop statin (Canada labels contraindicate atorvastatin); rosuvastatin 40 mg not for Asian patients.

Blueprint area: 1A Clinical Care.

11. Counselling points (what to tell the patient)

• Take the statin every day, even if you feel well; high cholesterol has no symptoms. Daily-life example: like brushing teeth, the benefit comes from the habit ^{[S1 p13]}.
• Report unexplained muscle pain, tenderness, weakness, especially with fever or feeling unwell, to the pharmacist or doctor ^{[S5 section 7 Musculoskeletal]}.
• Atorvastatin: no grapefruit juice. Rosuvastatin: any time of day, with or without food ^{[S4 section 9.5; S5 section 4.4]}.
• Tell all health professionals that you take a lipid-lowering medicine ^{[S5 section 7 General]}.
• Women who could become pregnant: use effective contraception; call your prescriber right away if pregnant ^{[S2 p7; S4 section 4.2]}.
• Do not take two doses to make up for a missed rosuvastatin dose: take the missed dose when remembered, unless the next dose is almost due ^{[S5 section 4.5]}.
• Ezetimibe: any time of day, same time daily; separate from bile acid sequestrants (2 hours before or 4 hours after) ^{[S6 section 4.2]}.
• Evolocumab: let it come to room temperature for at least 30 minutes (the automated mini-doser: 45 minutes), do not shake, rotate sites (arm, thigh, abdomen) ^{[S7 section 4.4]}.
• Bempedoic acid: swallow whole; report joint pain or swelling (gout) and tendon pain; avoid in pregnancy ^{[S8 sections 4.4, 7]}.
• Icosapent ethyl: with food, swallow whole; tell the pharmacist about fish or shellfish allergy, blood thinners, and irregular heartbeat history ^{[S9 sections 4.1, 4.4, 7]}.
• Fenofibrate: lipid response should be seen in 3 months; swallow tablet whole ^{[S10 section 4]}.
• Lifestyle: Mediterranean-style diet, 150 minutes of activity a week, quit smoking ^{[S1 p17-18]}.
• Do not use vitamins or supplements for statin muscle pain ^{[S1 p13]}. Do not buy over-the-counter omega-3 pills to protect the heart ^{[S1 p17]}.

Must remember for the exam: grapefruit with atorvastatin, muscle pain reporting, pregnancy advice, injection technique for PCSK9 inhibitors.

Blueprint area: 1A Clinical Care and 1B Distribution (counselling and dispensing).

12. Label vs guideline, and Canada vs US (none of these points is tested in the MCQs)

• PEBC follows Canada: use the Health Canada label for dose and contraindication questions, and the CCS 2021 guideline for choice of therapy and thresholds.

13. Quick quiz (study yourself)

1. A 56-year-old man, FRS 15%, LDL-C 3.8 mmol/L, no diabetes. Which group is he in, and what is advised?
2. After a heart attack, LDL-C is 2.1 mmol/L on atorvastatin 80 mg. What is the next step?
3. What is the first add-on for most people who miss the LDL-C threshold on a statin?
4. How soon should ALT be checked after starting a statin, and is routine CK needed?
5. Which lipid-lowering drug is contraindicated with cyclosporine?
6. Which fibrate should not be combined with a statin?
7. Name two things that rise with bempedoic acid that need monitoring or caution.
8. What is the TG range in which icosapent ethyl is recommended in statin-treated high-risk people?
9. Name two reasons why rosuvastatin 40 mg is restricted in Canada.
10. What is the lifestyle activity target per week?

Answers: 1. Intermediate risk with LDL-C above 3.5: offer a high-intensity statin. 2. Add ezetimibe (threshold 1.8 mmol/L); then a PCSK9 inhibitor if still 1.8 or more. 3. Ezetimibe 10 mg. 4. Within 3 months; CK only if muscle symptoms. 5. Atorvastatin and rosuvastatin (both). 6. Gemfibrozil. 7. Uric acid (gout) and simvastatin dose limit. 8. 1.5-5.6 mmol/L. 9. Contraindicated in Asian patients and in people with predisposing factors for myopathy; specialist advice at initiation. 10. At least 150 minutes of moderate to vigorous aerobic activity.

Unconfirmed items

• The CCS "Dyslipidemia at a Glance" PDF (2021) downloaded only in part and could not be opened. The CCS website chapters returned figures with little text. The journal text was read from a saved copy of the published article.
• The pocket-guide threshold figure (page 22) was read from PDF text only; the column-to-group assignment follows the journal recommendations.
• Praluent (alirocumab) Health Canada label was not retrieved; alirocumab doses come from the CCS pocket guide only. Lipidil EZ was used for fenofibrate; Lipidil Supra and Micro labels were not read. Simvastatin, pravastatin, lovastatin, fluvastatin and pitavastatin labels were not read.
• Statin intensity lists beyond atorvastatin and rosuvastatin (simvastatin, pravastatin, lovastatin, fluvastatin) were not confirmed.
• The CCS FH diagnostic criteria and the 2018 CCS FH position statement were not opened.
• The CCS text says ApoB thresholds in "mg/dL" in two sentences; the pocket guide tables use g/L. This summary uses g/L.
• US points came from secondary summaries only. FDA, ACC/AHA full documents were not opened.
• Doses are for exam study only, not for real patients. Not affiliated with or endorsed by PEBC.

Study aid, not medical advice. Check official sources before any patient decision.

MapleRxPrep

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