Dyslipidemias
Dyslipidemias
References
- 2021 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in Adults — Canadian Journal of Cardiology (Pearson GJ, Thanassoulis G, Anderson TJ, et al.). Can J Cardiol 2021;37(8):1129-1150
- Canadian Cardiovascular Society Position Statement on Familial Hypercholesterolemia: Update 2018 — Canadian Journal of Cardiology (Brunham LR, Ruel I, Aljenedil S, et al.). Can J Cardiol 2018;34(12):1553-1563
- General cardiovascular risk profile for use in primary care: the Framingham Heart Study — Circulation (D'Agostino RB Sr, Vasan RS, Pencina MJ, et al.). Circulation 2008;117(6):743-753
- Primary Prevention of Cardiovascular Disease in Adults: Clinical Decision Support Tool — Canadian Cardiovascular Society. CCS Clinical Tool, April 2026
- Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes — New England Journal of Medicine (Cannon CP, Blazing MA, Giugliano RP, et al.). N Engl J Med 2015;372(25):2387-2397
- Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease — New England Journal of Medicine (Sabatine MS, Giugliano RP, Keech AC, et al.). N Engl J Med 2017;376(18):1713-1722
- Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia — New England Journal of Medicine (Bhatt DL, Steg PG, Miller M, et al.). N Engl J Med 2019;380(1):11-22
- Diagnosis, Prevention, and Management of Statin Adverse Effects and Intolerance: Canadian Working Group Consensus Update (2016) — Canadian Journal of Cardiology (Mancini GBJ, Baker S, Bergeron J, et al.). Can J Cardiol 2016;32(7 Suppl):S35-S65
Clinical Snapshot
Dyslipidemia is an abnormality in the quantity or function of lipids or lipoproteins in the blood — most often an elevation of low-density lipoprotein cholesterol (LDL-C) or another atherogenic lipoprotein (non-HDL-C, apolipoprotein B [ApoB], or lipoprotein(a) [Lp(a)]) — that drives atherosclerotic plaque formation over years to decades. Most dyslipidemia results from an interaction between genetic predisposition and environmental/lifestyle factors, but a meaningful minority is secondary to another condition or medication, and identifying and correcting a secondary cause can eliminate the need for lifelong drug therapy.[1]
The 2021 Canadian Cardiovascular Society (CCS) guideline moved lipid management away from a pure "treat-to-target" model toward a risk-based treatment-threshold approach: rather than treating every patient to the same fixed LDL-C number, the decision to start a statin and the threshold for adding a second agent are both driven by the patient's estimated cardiovascular risk — either because they already have a "statin-indicated condition" (established atherosclerotic disease, diabetes, chronic kidney disease, or severe hypercholesterolemia) or because their calculated Framingham Risk Score (FRS) places them in an intermediate- or high-risk category.[1]
Statins remain the foundation of therapy for essentially every patient who meets a treatment indication, but the growing list of well-tolerated non-statin add-on agents — ezetimibe, PCSK9 inhibitors, bempedoic acid, icosapent ethyl — means more patients than ever can reach target even when statin monotherapy alone is not enough. Pharmacists are well positioned to support long-term adherence, recognize and correctly manage statin-associated muscle symptoms rather than defaulting to simply stopping therapy, and catch dangerous drug interactions — particularly gemfibrozil combined with a statin, and CYP3A4/CYP2C9 inhibitors combined with a CYP-metabolized statin.
Recognize the Condition
Dyslipidemia itself is usually clinically silent — most patients have no symptoms at all, and the abnormality is detected on a screening or incidentally-ordered lipid panel. This is precisely why systematic screening (see Assessment & Diagnosis), rather than waiting for symptoms, is central to management.
Physical findings that suggest a genetic or severe lipid disorder
- Xanthomas — lipid deposits in tendons (especially the Achilles tendon and finger extensors), or eruptive xanthomas over the buttocks/extremities in severe hypertriglyceridemia.
- Xanthelasma — yellowish cholesterol plaques on the eyelids.
- Premature arcus cornealis — a grey-white ring at the corneal margin in a patient under about 45 years of age.
- Lipemia retinalis — creamy-white retinal vessels seen on fundoscopy in severe hypertriglyceridemia.
- Hepatosplenomegaly, which can accompany severe hypertriglyceridemia/chylomicronemia.
Presentations that reflect a complication, not the dyslipidemia itself
- Angina, myocardial infarction, stroke/TIA symptoms, or claudication reflect established atherosclerotic cardiovascular disease (ASCVD) — a statin-indicated condition in its own right.
- Severe, acute abdominal pain in a patient with markedly elevated triglycerides should raise concern for acute pancreatitis secondary to severe hypertriglyceridemia — a medical emergency, not a routine dyslipidemia follow-up issue (see Red Flags & Refer).
Risk Factors
- Abdominal aortic aneurysm.
- Chronic kidney disease (eGFR <60 mL/min/1.73 m²).
- Chronic obstructive pulmonary disease.
- Clinical stigmata of hyperlipidemia — xanthomas, xanthelasmas, premature arcus cornealis.
- Current cigarette smoking.
- Diabetes mellitus.
- Erectile dysfunction.
- Evidence of atherosclerosis on any prior imaging or investigation.
- Family history of dyslipidemia.
- Family history of premature coronary artery disease (first-degree relative: onset before 55 years in men, before 65 years in women).
- HIV infection.
- Hypertension.
- A history of a hypertensive disorder of pregnancy — screen the lipid profile in the late postpartum period.
- Inflammatory diseases — ankylosing spondylitis, inflammatory bowel disease, psoriatic arthritis, rheumatoid arthritis, systemic lupus erythematosus.
- Obesity (BMI >30 kg/m²).
Red Flags & Refer
Refer urgently to a specialized lipid clinic or genetic dyslipidemias clinic, or escalate as a medical emergency where noted:
- Severe hypercholesterolemia — LDL-C ≥95th percentile for age and sex, or LDL-C ≥5 mmol/L in an adult.
- Severe hypertriglyceridemia — triglycerides ≥10 mmol/L, which carries a genuine risk of acute pancreatitis.
- A history of hypertriglyceridemia-induced acute pancreatitis.
- Suspected acute pancreatitis from severe hypertriglyceridemia (severe abdominal pain in a patient with markedly elevated triglycerides) — this needs emergency assessment, not a routine referral.
- Physical or laboratory findings suggesting familial hypercholesterolemia — LDL-C ≥5 mmol/L, tendon xanthomas, or a strong family history of premature coronary artery disease — particularly in a child, since pediatric familial hypercholesterolemia needs specialized management.[2]
- Homozygous familial hypercholesterolemia — needs specialist assessment for LDL apheresis and adjunctive drug therapy (evinacumab, lomitapide).
- Dysbetalipoproteinemia requiring combination fibrate-plus-statin therapy, or any patient in whom a fibrate-statin combination is being considered outside the fenofibrate/bezafibrate-with-statin pattern — this combination carries a real risk of severe muscle toxicity.
Assessment & Diagnosis
Who and when to screen
- Screen children with a family history of dyslipidemia or cardiovascular disease.
- Screen men ≥40 years of age.
- Screen women ≥40 years of age, or who are postmenopausal.
- Screen patients of any age who have any of the risk factors listed above (see Risk Factors), irrespective of age.
- Consider earlier screening in patients who are South Asian, First Nations, or recent immigrants — standard risk calculators, including the FRS, have not been validated in these populations, so a reassuringly low calculated score should not be taken at face value. The elevated risk seen in these populations reflects structural inequalities in access to the social determinants of health at least as much as biology, and risk reduction should address both.[1]
- Reassess the (modified) FRS every 5 years in patients 40-75 years of age who are not already in a statin-indicated category.
History
- Past or present cardiovascular disease: angina, aortic aneurysm, claudication, erectile dysfunction, myocardial infarction, revascularization, stroke, or transient ischemic attack.
- Possible secondary causes of dyslipidemia (see below).
- Major cardiovascular risk factors: diabetes, hypertension, smoking.
- A history of severe abdominal pain or acute pancreatitis.
- Family history of premature cardiovascular disease (before 55 years in male relatives, before 65 years in female relatives) and family history of dyslipidemia.
Physical examination
- Waist circumference.
- Bilateral brachial blood pressure.
- Fundoscopy — lipemia retinalis, retinopathy.
- Cardiovascular examination — bruits, peripheral pulses.
- Hepatosplenomegaly.
- Lipid deposits — premature arcus cornealis, xanthomas, xanthelasmas.
Laboratory testing
- Lipid and lipoprotein panel: total cholesterol, triglycerides, HDL-C, and (optionally) ApoB, with calculated LDL-C and non-HDL-C.
- The Friedewald equation (LDL-C = total cholesterol − [HDL-C + triglycerides/2.2]) cannot be used if triglycerides are >4.52 mmol/L, if type III dysbetalipoproteinemia is present, or if chylomicrons are present — the calculated LDL-C will be inaccurate; use a directly measured LDL-C, non-HDL-C, or ApoB instead.
- Use the same laboratory for repeat measurements to avoid assay-to-assay variability.
- Fasting is no longer required for a routine lipid and lipoprotein panel, unless triglycerides are likely to be >4.5 mmol/L.
- Obtain 2 (ideally 3) measurements 4-6 weeks apart to establish a reliable baseline before an initial diagnosis of a dyslipidemic phenotype.
- Measure lipoprotein(a) — Lp(a) — once in a person's lifetime as part of the initial lipid screening; it does not need to be repeated.
- For patients with triglycerides >1.5 mmol/L, use non-HDL-C or ApoB instead of LDL-C as the preferred screening parameter — both correlate more strongly with cardiovascular events than LDL-C in this setting. Non-HDL-C is simply total cholesterol − HDL-C, so it is available even where ApoB testing is not.
- Fasting blood glucose or HbA1c.
- Estimated glomerular filtration rate (eGFR).
- Urine albumin/creatinine ratio — optional, but worth doing in diabetes, hypertension, or eGFR <60 mL/min/1.73 m².
- Additional testing to exclude common secondary causes of dyslipidemia (see below), and baseline liver transaminases and creatine kinase (CK) before starting a statin or fibrate.
Secondary causes of dyslipidemia to rule out
Identifying and correcting a secondary cause can normalize the lipid profile and avoid unnecessary long-term drug therapy.
| Medical conditions | Medications |
|---|---|
| Alcohol excess | Beta-blockers without intrinsic sympathomimetic or alpha-blocking activity |
| Chronic renal failure | Corticosteroids |
| Diabetes / metabolic syndrome | Highly active antiretroviral therapy (HAART) |
| Hypothyroidism | Hormone replacement therapy |
| Nephrotic syndrome | Oral contraceptives |
| Obstructive liver disease | Thiazide diuretics |
| Overweight / obesity | |
| Pregnancy |
Medication-induced dyslipidemia should not, on its own, preclude the use of these medications when they are otherwise clinically indicated — weigh the lipid effect against the reason the medication was prescribed rather than automatically switching.
Cardiovascular risk stratification
Before calculating a risk score, determine whether the patient already has a statin-indicated condition — if so, a statin is recommended regardless of the calculated risk score.
Statin-indicated conditions — a statin is recommended regardless of FRS:
- Atherosclerotic cardiovascular disease — myocardial infarction, any acute coronary syndrome, stable angina, coronary disease documented by angiography (>10% stenosis), stroke, TIA, documented carotid disease, peripheral artery disease, claudication and/or ankle-brachial index <0.9, or abdominal aortic aneurysm (abdominal aorta >3 cm, or previous aneurysm surgery).
- Abdominal aortic aneurysm, independent of the above.
- Diabetes mellitus — age ≥40 years, or ≥15 years' duration with onset at ≥30 years of age (type 1 diabetes), or microvascular complications present.
- Chronic kidney disease — more than 3 months' duration, with albumin-to-creatinine ratio >3 mg/mmol or eGFR <60 mL/min/1.73 m², in a patient ≥50 years of age.
- LDL-C ≥5 mmol/L (or ApoB ≥1.45 g/L, or non-HDL-C ≥5.8 mmol/L), or documented familial hypercholesterolemia or another genetic dyslipidemia — exclude secondary causes first.
Framingham Risk Score (FRS)
If no statin-indicated condition is present, stratify the patient's 10-year cardiovascular risk using the FRS.[3] Add the points for each risk factor below — using the Men or Women columns matching the patient's sex — for a total score, then read the corresponding 10-year risk percentage from the points-to-risk table.
| Age (years) | Points — men | Points — women |
|---|---|---|
| 30-34 | 0 | 0 |
| 35-39 | 2 | 2 |
| 40-44 | 5 | 4 |
| 45-49 | 7 | 5 |
| 50-54 | 8 | 7 |
| 55-59 | 10 | 8 |
| 60-64 | 11 | 9 |
| 65-69 | 12 | 10 |
| 70-74 | 14 | 11 |
| ≥75 | 15 | 12 |
| HDL-C (mmol/L) | Points (men and women) |
|---|---|
| >1.6 | -2 |
| 1.3-1.6 | -1 |
| 1.2-1.29 | 0 |
| 0.9-1.19 | 1 |
| <0.9 | 2 |
| Total cholesterol (mmol/L) | Points — men | Points — women |
|---|---|---|
| <4.1 | 0 | 0 |
| 4.1-5.19 | 1 | 1 |
| 5.2-6.19 | 2 | 3 |
| 6.2-7.2 | 3 | 4 |
| >7.2 | 4 | 5 |
| Systolic BP (mmHg) | Men, untreated | Men, treated | Women, untreated | Women, treated |
|---|---|---|---|---|
| <120 | -2 | 0 | -3 | -1 |
| 120-129 | 0 | 2 | 0 | 2 |
| 130-139 | 1 | 3 | 1 | 3 |
| 140-149 | 2 | 4 | 2 | 5 |
| 150-159 | 2 | 4 | 4 | 6 |
| ≥160 | 3 | 5 | 5 | 7 |
| Risk factor | Points — men | Points — women |
|---|---|---|
| Current smoker | 4 | 3 |
| Not a current smoker | 0 | 0 |
| Diabetes present | Statin-indicated condition — do not calculate FRS points | Statin-indicated condition — do not calculate FRS points |
| No diabetes | 0 | 0 |
| Total points | 10-year risk — men (%) | 10-year risk — women (%) |
|---|---|---|
| -3 or less | <1 | <1 |
| -2 | 1.1 | <1 |
| -1 | 1.4 | 1.0 |
| 0 | 1.6 | 1.2 |
| 1 | 1.9 | 1.5 |
| 2 | 2.3 | 1.7 |
| 3 | 2.8 | 2.0 |
| 4 | 3.3 | 2.4 |
| 5 | 3.9 | 2.8 |
| 6 | 4.7 | 3.3 |
| 7 | 5.6 | 3.9 |
| 8 | 6.7 | 4.5 |
| 9 | 7.9 | 5.3 |
| 10 | 9.4 | 6.3 |
| 11 | 11.2 | 7.3 |
| 12 | 13.3 | 8.6 |
| 13 | 15.6 | 10.0 |
| 14 | 18.4 | 11.7 |
| 15 | 21.6 | 13.7 |
| 16 | 25.3 | 15.9 |
| 17 | 29.4 | 18.5 |
| 18 | >30 | 21.5 |
| 19 | >30 | 24.8 |
| 20 | >30 | 27.5 |
| 21 or more | >30 | >30 |
Modified FRS: if there is a family history of premature cardiovascular disease (onset before 55 years in a male first-degree relative, before 65 years in a female first-degree relative), double the 10-year risk percentage for patients 30-59 years of age without diabetes — this is the "modified Framingham Risk Score" used for treatment decisions.[3]
Treatment Targets
- Reduce the risk of cardiovascular disease.
- Prevent pancreatitis from severe hypertriglyceridemia.
Statin initiation thresholds and LDL-C targets by risk category
Statin-indicated condition
A statin is recommended in essentially all such patients, regardless of FRS. Primary target: LDL-C ≤2 mmol/L, or ≥50% decrease from baseline. Alternate target: ApoB ≤0.8 g/L, or non-HDL-C ≤2.6 mmol/L.
High risk — FRS ≥20%
A statin is recommended in essentially all. Same primary and alternate targets as above.
Intermediate risk — FRS 10-19.9%
A statin is recommended if LDL-C ≥3.5 mmol/L (or non-HDL-C ≥4.2 mmol/L or ApoB ≥1.05 g/L); or, if LDL-C is below that, consider a statin if ApoB ≥1.2 g/L or non-HDL-C ≥4.3 mmol/L, or in men ≥50/women ≥60 years with 1 additional risk factor (low HDL-C, impaired fasting glucose, high waist circumference, smoking, hypertension), or with other risk modifiers present (hsCRP ≥2.0 mg/L, coronary artery calcium score >0 Agatston units, family history of premature coronary artery disease, Lp(a) ≥100 nmol/L [≥50 mg/dL]). Same primary and alternate targets as above.
Low risk — FRS <10%
Statins are generally not indicated, unless LDL-C ≥5 mmol/L (or ApoB ≥1.45 g/L or non-HDL-C ≥5.8 mmol/L), or FRS is 5-9.9% with LDL-C ≥3.5 mmol/L — particularly with other risk modifiers present.
Add-on (escalation) thresholds once a maximally tolerated statin dose has not reached target — 3 tiers by population:
| Population | Consider add-on therapy if |
|---|---|
| ASCVD (secondary prevention) | LDL-C ≥1.8 mmol/L, or non-HDL-C ≥2.4 mmol/L, or ApoB ≥0.70 g/L |
| High-risk primary prevention, diabetes, or chronic kidney disease | LDL-C ≥2 mmol/L, or non-HDL-C ≥2.6 mmol/L, or ApoB ≥0.80 g/L |
| LDL-C ≥5 mmol/L pathway | LDL-C ≥2.5 mmol/L, or <50% LDL-C reduction from baseline, or non-HDL-C ≥3.2 mmol/L, or ApoB ≥0.85 g/L |
Very low LDL-C (<1.30 mmol/L) on treatment is acceptable and safe in high-risk patients, and provides additional cardiovascular benefit — it is not, on its own, a reason to reduce statin intensity.
Choose Initial Treatment
Step 1 — determine if a statin is indicated
Statin-indicated condition present start a statin regardless of FRS: this includes established ASCVD, abdominal aortic aneurysm, diabetes meeting the age/duration/complication criteria, chronic kidney disease meeting the age/eGFR/ACR criteria, and LDL-C ≥5 mmol/L or documented familial hypercholesterolemia (after excluding secondary causes).
No statin-indicated condition calculate the (modified) Framingham Risk Score and stratify into low, intermediate, or high risk, then apply the corresponding threshold from Treatment Targets to decide whether to start a statin.
Step 2 — choose statin intensity
Secondary prevention or very-high cardiovascular risk use a high-intensity statin (atorvastatin 40-80 mg or rosuvastatin 20-40 mg) from the outset; achieving a very low LDL-C is safe and provides additional benefit in this group.[1]
Primary prevention start at the recommended starting dose for the chosen statin and titrate upward to reach the LDL-C/ApoB/non-HDL-C target for the patient's risk category; a patient at particularly high calculated risk may start directly at a high dose.
Step 3 — sequence with lifestyle therapy
Secondary prevention or high-risk primary prevention start lipid-lowering medication at the same time as diet and lifestyle counselling — do not delay statin therapy for a dietary trial in these patients.
Lower-risk primary prevention a 3-month dietary trial (ideally with a registered dietitian, and 2-3 lipid measurements during the trial) is reasonable before starting medication.
Step 4 — add-on therapy when the statin threshold is not met
1st add-on ezetimibe 10 mg daily, once the patient is on a maximally tolerated statin dose and remains above the add-on threshold for their population (see Treatment Targets) — ezetimibe is preferred over a resin as the first add-on agent given better tolerability.[5]
2nd add-on — very-high-risk (established ASCVD or familial hypercholesterolemia) add a PCSK9 inhibitor (evolocumab or alirocumab, or inclisiran as a less-frequently-dosed alternative) when the threshold is still exceeded on a maximally tolerated statin with ezetimibe.[6]
Statin-intolerant patients bempedoic acid is a reasonable option, alone or combined with ezetimibe, since it activates only in the liver and carries a lower risk of muscle-related adverse effects than a statin.
Step 5 — severe hypertriglyceridemia is managed differently
Triglycerides ≥10 mmol/L start a fibrate as first-line pharmacologic therapy (not a statin) to reduce the risk of acute pancreatitis, and refer to a specialized lipid clinic.
Residual hypertriglyceridemia on a statin add icosapent ethyl 2 g PO twice daily in secondary-prevention patients (or primary-prevention patients with diabetes and at least 1 additional cardiovascular risk factor) with fasting triglycerides 1.5-5.6 mmol/L despite maximally tolerated statin therapy.[7]
Non-Pharmacologic Treatment
Diet and lifestyle modification is part of every treatment plan and is never a substitute for medication — lipid-lowering drugs are an adjunct to, not a replacement for, dietary therapy.
Diet
- Dietary patterns associated with an improved lipid profile: DASH, low-glycemic-index/glycemic-load, Mediterranean, Portfolio, or a vegetarian pattern.
- Encourage: nuts (≥30 g/day), legumes (≥4 servings/week up to ≥1 serving/day), olive oil (≥60 mL/day), fruits and vegetables (≥5 servings/day), whole grains (≥3 servings/day), soy protein (≥30 g/day).
- Reduce saturated fat intake (≤10% of energy, or ≤7% of energy for a more intensive approach) and dietary cholesterol (≤300 mg/day, or ≤200 mg/day for a more intensive approach).
- Limit alcohol to 1-2 drinks/day.
- Increase the proportion of mono- and polyunsaturated fat relative to saturated fat.
- Increase total dietary fibre (≥30 g/day), and viscous soluble fibre specifically (≥10 g/day).
- Dietary or nonprescription omega-3 fatty acids (EPA and DHA, 2-4 g/day) lower triglycerides specifically — this is a distinct recommendation from the prescription icosapent ethyl product used for cardiovascular risk reduction (see Drug Tables).
- Plant sterol/stanol supplementation (≥2 g/day) — natural food sources cannot provide this much, so a specific supplement or sterol-enriched food (for example, a fortified margarine or fruit juice) is needed.
Other lifestyle measures
- Weight loss and reduction of abdominal obesity where relevant — a 5-10% reduction in body weight is a reasonable initial goal.
- Physical activity — 30-60 minutes/day of moderate-to-vigorous intensity activity.
- Smoking cessation.
- Sufficient sleep duration (6-8 hours/night).
- Stress management.
Involving a registered dietitian in both the initial assessment and ongoing follow-up is strongly recommended. Framing the discussion around a patient's estimated "cardiovascular age" relative to their actual age can help engage patients in shared decision-making about lifestyle change and treatment.[1]
Nonprescription adjuncts
- Psyllium (10 g/day) can modestly lower LDL-C as an adjunct fibre supplement.
- Omega-3 fatty acid supplements (2-4 g/day) can lower triglycerides in patients with hypertriglyceridemia; doses above 3 g/day from supplements should only be used under a physician's supervision, since high intakes can increase bleeding risk in patients already at elevated bleeding risk. Nonprescription long-chain omega-3 supplementation on its own has not been shown to reduce cardiovascular risk — a different claim from the cardiovascular-outcome evidence behind the prescription product icosapent ethyl.
Apheresis and plasma exchange
Where available, LDL apheresis or plasmapheresis (separation and removal of blood lipids by filtration or centrifugation) may be used in specialized lipid clinics to lower LDL-C in homozygous familial hypercholesterolemia. Plasmapheresis or plasma exchange may also be used to lower triglycerides directly in patients with very severe hypertriglyceridemia.
Pharmacologic Treatment Options
| Drug / intervention | Role | Dose / use | Important adverse effects | Teaching points |
|---|---|---|---|---|
| Atorvastatin (high-intensity) Preferred | 1st-line high-intensity statin — secondary prevention/very-high-risk, or high-risk primary prevention | 40-80 mg PO daily, any time of day | Myalgia; increased CK/transaminases (usually reversible) | Use high-intensity dosing from the outset in secondary prevention rather than starting low and titrating up. |
| Rosuvastatin (high-intensity) Preferred | 1st-line high-intensity statin | 20-40 mg PO daily | Myalgia; increased CK/transaminases | Start at 5 mg/day instead of 10 mg/day in patients of Filipino, Chinese, Japanese, Korean, Vietnamese, or South Asian ancestry, or those on cyclosporine, given higher plasma concentrations. |
| Moderate-intensity statin (e.g., atorvastatin 10-20 mg, simvastatin 20-40 mg, rosuvastatin 5-10 mg) Alternative | Lower-risk primary prevention, where a full high-intensity dose is not required | Per specific statin — see Drug Tables | Myalgia; increased CK/transaminases | Titrate upward if the LDL-C/ApoB/non-HDL-C target for the risk category is not reached. |
| Ezetimibe Preferred | 1st add-on when threshold exceeded on maximally tolerated statin | 10 mg PO daily, any time of day | Generally well tolerated; rare myopathy | Preferred over a resin as the first add-on given better tolerability and lower pill burden. |
| Evolocumab or alirocumab (PCSK9 inhibitor) Special situation | 2nd add-on in very-high-risk patients (ASCVD or familial hypercholesterolemia) | Evolocumab 140 mg SC every 2 weeks or 420 mg SC monthly; alirocumab 75 mg SC every 2 weeks, may increase to 150 mg | Injection-site reactions | Add when threshold is still exceeded on a maximally tolerated statin plus ezetimibe. |
| Inclisiran Special situation | PCSK9-pathway add-on with infrequent dosing | 284 mg SC, repeated at 3 months, then every 6 months | Injection-site reactions | An alternative to the monoclonal-antibody PCSK9 inhibitors when infrequent dosing is an advantage; use influenced by reimbursement. |
| Bempedoic acid Special situation | Statin-intolerant patients (alone or with ezetimibe), or add-on to a statin | 180 mg PO daily | Hyperuricemia/gout; rare tendon rupture | Activated only in the liver, not skeletal muscle — lower myopathy risk than statins, useful specifically for statin intolerance. |
| Fenofibrate Special situation | 1st-line for severe hypertriglyceridemia (TG ≥10 mmol/L) to prevent pancreatitis | Formulation-dependent — see Drug Tables | GI upset, myalgia; increased CK/creatinine | Preferred fibrate for combining with a statin when combination therapy is genuinely needed — never combine gemfibrozil with a statin. |
| Icosapent ethyl Special situation | Add-on for residual hypertriglyceridemia on a statin | 2 g PO twice daily (4 g/day total) | Atrial fibrillation, peripheral edema, constipation | For fasting TG 1.5-5.6 mmol/L despite maximally tolerated statin, in secondary prevention (or primary prevention with diabetes plus ≥1 additional risk factor). |
| Colesevelam Alternative | Add-on, especially in pregnancy or children | 2.5 g PO daily in 1-2 divided doses | Constipation, bloating; increased triglycerides | Best-tolerated resin; separate other medications by 1 hour before or 4 hours after dosing. |
Special Populations
Pregnancy
Total cholesterol and triglycerides rise substantially over the course of a normal pregnancy, and LDL-C and HDL-C also increase by midgestation — routine lipid-profile monitoring during pregnancy is not required except in familial hypercholesterolemia (FH) or familial chylomicronemia syndrome (FCS), where it should continue.
Statins, ezetimibe, and PCSK9 inhibitors are contraindicated in pregnancy — cholesterol and its synthesis products are important for normal fetal development. Discontinue these agents at least 1 month before stopping contraception in a patient planning pregnancy; if pregnancy occurs while a patient is taking one, stop it immediately, but termination of pregnancy is not warranted on this basis alone, since teratogenicity in humans appears small if present at all. Resins (cholestyramine, colesevelam, colestipol) can be used safely throughout pregnancy and are the treatment of choice when drug therapy for hypercholesterolemia is genuinely needed during pregnancy.
For most patients, interrupting lipid-lowering treatment for the duration of pregnancy has little impact on overall cardiovascular risk unless that risk is very high. In FH specifically, LDL-C monitoring during pregnancy is required, and LDL apheresis can be considered in FH patients with a history of cardiovascular disease or homozygous FH.[2] In familial chylomicronemia syndrome, a very-low-fat diet (<10% of calories from fat) is required even during pregnancy to prevent pancreatitis, with close triglyceride monitoring; plasmapheresis or plasma exchange can be considered, though evidence for this specific use in pregnancy is limited to case reports.
Breastfeeding
Lipid-lowering medications are not recommended during breastfeeding given a lack of safety data — resume statin/ezetimibe/PCSK9-inhibitor therapy after breastfeeding stops, unless overall cardiovascular risk is high enough that resuming sooner is warranted. Resins remain an option during breastfeeding since they act locally in the gut and are not systemically absorbed.
Pediatrics
Statin therapy is recommended for children with heterozygous or homozygous familial hypercholesterolemia, usually starting around 8-10 years of age; the exact LDL-C threshold and age to start require clinical judgment and shared decision-making with the child and family. Refer children with FH to a specialized lipid clinic. Where pediatric dosing is established for a specific statin, it applies to boys and postmenarchal girls 10-17 years of age (see Drug Tables for which statins have established pediatric dosing).
Renal impairment
Monitor more closely for statin adverse effects in patients with moderate-to-severe renal impairment (creatinine clearance <60 mL/min) — several statins need dose adjustment or a lower starting dose in this setting (see Drug Tables). Chronic kidney disease meeting the age/eGFR/ACR criteria is itself a statin-indicated condition (see Assessment & Diagnosis).
Hepatic impairment
Statins and fibrates are contraindicated in active liver disease or unexplained persistent transaminase elevation. Check baseline liver transaminases before starting therapy, and again at 3 months.
Genetic ancestry affecting statin dosing
Patients of Filipino, Chinese, Japanese, Korean, Vietnamese, or South Asian descent have higher circulating concentrations of some statins because of genetic variants in statin-metabolizing enzymes and membrane transporters — start rosuvastatin at 5 mg/day (rather than the usual 10 mg/day starting dose) in these patients.
Older adults
Statin therapy continues to provide benefit in most older adults who meet a treatment indication. Age itself is a risk factor for statin-associated muscle symptoms — see Common Errors to Avoid and Treatment Failure/Next Step for the structured approach to managing this.
Monitoring & Follow-Up
- Check liver transaminases (ALT) at least once, at 3 months after starting or increasing the dose of a statin or fibrate; routine ongoing LFT monitoring beyond this is not required in an asymptomatic patient.
- Check creatine kinase (CK) if myalgia develops — CK is not routinely checked in every asymptomatic patient at baseline or during follow-up.
- For fibrates specifically, also check renal function at 3, 6, and 12 months, then yearly.
- Recheck the lipid panel roughly 6-12 weeks after starting therapy or changing the dose, to confirm the target for the patient's risk category has been reached, then periodically thereafter.
- Allow about 3 months for the lipid profile to stabilize after a major medical event before using it to guide therapy — the exception is acute coronary syndrome, where high-intensity statin therapy is started immediately regardless of the lipid profile at presentation.
- Reassess the (modified) FRS every 5 years in patients 40-75 years of age who are not already in a statin-indicated category.
- Reinforce diet and lifestyle measures at every follow-up visit — these remain part of the plan alongside, not instead of, medication.
- Follow-up for familial hypercholesterolemia and familial chylomicronemia syndrome is more intensive and should involve the specialized lipid clinic managing the patient.
Treatment Failure / Next Step
- Confirm adherence to both the prescribed medication and the non-pharmacologic measures before intensifying pharmacotherapy — nonadherence is a far more common explanation for an unmet target than true treatment failure.
- Look for and correct an unaddressed secondary cause (uncontrolled diabetes, untreated hypothyroidism, nephrotic syndrome, excess alcohol, or an interacting medication) — this can normalize the lipid profile on its own.
- If the current statin is below its maximum tolerated dose or below high intensity in a patient who needs it, increase the dose or switch to a more potent statin (atorvastatin or rosuvastatin).
- If the target is still not met on a maximally tolerated high-intensity statin, add ezetimibe.
- If the target is still not met on a maximally tolerated statin plus ezetimibe in a very-high-risk patient (established ASCVD or familial hypercholesterolemia), add a PCSK9 inhibitor (evolocumab, alirocumab, or inclisiran).
- For genuine statin intolerance with normal CK (myalgia only): weigh the risks and benefits of continuing — options include continuing at the same dose, reducing the dose, switching to a different statin, or — in secondary prevention/very-high-risk patients specifically — trying the same high-intensity statin on alternate days rather than downgrading to a lower-intensity statin.
- For CK <10 times the upper limit of normal with muscle symptoms (myositis): stop the statin, monitor CK until it returns to normal, and identify and treat any predisposing factor (see Common Errors to Avoid); once resolved, consider a repeat statin challenge at a lower dose or with an alternate statin, or a nonstatin regimen as an adjunct or replacement.
- For CK >10 times the upper limit of normal: stop the statin immediately, check renal function and urine myoglobin, and treat rhabdomyolysis if diagnosed — then follow the same monitor-and-rechallenge sequence once CK has normalized.
- For residual hypertriglyceridemia (fasting TG 1.5-5.6 mmol/L) despite a maximally tolerated statin in an eligible patient, add icosapent ethyl.
- For persistent severe hypertriglyceridemia (TG ≥10 mmol/L) despite a fibrate, for dysbetalipoproteinemia needing a fibrate-statin combination, or for homozygous familial hypercholesterolemia not reaching target on maximal therapy: refer to a specialized lipid clinic or genetic dyslipidemias clinic.
Common Errors to Avoid
- Calculating LDL-C with the Friedewald equation when triglycerides are >4.52 mmol/L, type III dysbetalipoproteinemia is present, or chylomicrons are present — the result will be inaccurate; use a directly measured LDL-C, non-HDL-C, or ApoB instead.
- Withholding a statin from a patient with diabetes or chronic kidney disease who meets statin-indicated-condition criteria while waiting to calculate an FRS — these conditions bypass the FRS entirely.
- Combining gemfibrozil with a statin — this combination carries the highest myotoxicity risk among the fibrates and should generally be avoided; use fenofibrate or bezafibrate instead if a fibrate-statin combination is genuinely needed.
- Assuming any muscle symptom on a statin is automatically statin-associated without checking CK and considering other causes, and without reviewing the patient's specific predisposing factors and interacting medications.
- Downgrading to a lower-intensity statin at the first sign of intolerance in a secondary-prevention or very-high-risk patient, rather than trying the same high-intensity statin on alternate days first.
- Continuing or starting niacin (nicotinic acid) for dyslipidemia — trial evidence in patients already on optimal statin therapy did not show a benefit from adding niacin, and it is no longer recommended.
- Ordering a fasting lipid panel routinely — fasting is only needed when triglycerides are likely to be >4.5 mmol/L.
- Trusting a reassuringly low FRS in a patient who is South Asian, First Nations, or a recent immigrant — the score has not been validated in these populations and may underestimate true risk.
- Continuing a statin, ezetimibe, or PCSK9 inhibitor right up to the point of conception — stop at least 1 month before a patient planning pregnancy stops contraception.
- Missing familial hypercholesterolemia in a patient with LDL-C ≥5 mmol/L, tendon xanthomas, or a strong family history of premature coronary artery disease — refer to a specialized or genetic lipid clinic rather than simply intensifying standard therapy.
- Treating everyone to the same fixed LDL-C target regardless of risk category — the CCS treatment-threshold approach ties both the decision to treat and the target itself to the patient's statin-indicated-condition/FRS risk category.
Clinical Decision Algorithm
Drug Tables
How to use this table: Doses are adult doses unless otherwise noted, and require patient-specific confirmation, including renal/hepatic adjustment. Select any drug name to open its complete Pharmasist Drug Database page.
HMG-CoA Reductase Inhibitors (Statins)
Statin therapy is classified by expected LDL-C-lowering intensity, which determines which statin and dose is appropriate for a given risk category. Low-intensity: fluvastatin 20-40 mg, lovastatin 20 mg, pravastatin 10-20 mg, simvastatin 5-10 mg. Moderate-intensity: atorvastatin 10-20 mg, fluvastatin 80 mg, lovastatin 40-80 mg, pravastatin 40-80 mg, rosuvastatin 5-10 mg, simvastatin 20-40 mg. High-intensity: atorvastatin 40-80 mg, rosuvastatin 20-40 mg. Use high-intensity therapy preferentially in secondary prevention and very-high-risk patients.
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Atorvastatin | Adults: 10-80 mg PO daily, any time of day Children (10-17y, boys and postmenarchal girls): 10-20 mg PO daily | Increased CK, increased transaminases (usually reversible), mild upper GI disturbances, myalgias (with or without CK elevation), sleep disturbances, headache, rash. Rare: myopathy, rhabdomyolysis, peripheral neuropathy, impotence. | Avoid strong CYP3A4 inhibitors: amiodarone, azole antifungals, cyclosporine, diltiazem, gemfibrozil, grapefruit juice, macrolide antibiotics, protease inhibitors, verapamil. | Start low and titrate to target while monitoring; a high-CV-risk patient may start at a high dose. Check ALT at least once at 3 months; check CK if myalgia develops. Monitor more closely with renal impairment (creatinine clearance under 60 mL/min). Contraindicated in active liver disease, high alcohol consumption, and pregnancy. |
| Fluvastatin | Adults and children (10-17y, boys and postmenarchal girls): 20-80 mg PO daily in 1-2 divided doses (immediate-release capsule) Extended-release (XL) tablet, all ages above: 80 mg PO once daily, any time of day | Increased CK, increased transaminases (usually reversible), mild upper GI disturbances, myalgias (with or without CK elevation), sleep disturbances, headache, rash. Rare: myopathy, rhabdomyolysis, peripheral neuropathy, impotence. | Avoid strong CYP2C9 inhibitors: amiodarone, fluconazole, fluoxetine, fluvoxamine. | Start low and titrate to target while monitoring; a high-CV-risk patient may start at a high dose. Check ALT at least once at 3 months; check CK if myalgia develops. Monitor more closely with renal impairment (creatinine clearance under 60 mL/min). Contraindicated in active liver disease, high alcohol consumption, and pregnancy. |
| Lovastatin | Adults: 20-80 mg PO daily with the evening meal; may be given in 2 divided doses Children: Not established in this reference for routine pediatric use — specialist-directed only | Increased CK, increased transaminases (usually reversible), mild upper GI disturbances, myalgias (with or without CK elevation), sleep disturbances, headache, rash. Rare: myopathy, rhabdomyolysis, peripheral neuropathy, impotence. | Avoid strong CYP3A4 inhibitors: amiodarone, azole antifungals, cyclosporine, diltiazem, gemfibrozil, grapefruit juice, macrolide antibiotics, protease inhibitors, verapamil. | Start low and titrate to target while monitoring; a high-CV-risk patient may start at a high dose. Check ALT at least once at 3 months; check CK if myalgia develops. Monitor more closely with renal impairment (creatinine clearance under 60 mL/min). Contraindicated in active liver disease, high alcohol consumption, and pregnancy. |
| Pravastatin | Adults: 10-80 mg PO once daily at bedtime Children: Not established in this reference for routine pediatric use — specialist-directed only | Increased CK, increased transaminases (usually reversible), mild upper GI disturbances, myalgias (with or without CK elevation), sleep disturbances, headache, rash. Rare: myopathy, rhabdomyolysis, peripheral neuropathy, impotence. | Not metabolized through the cytochrome P450 pathway — the lowest drug-interaction potential of the commonly used statins. | Start low and titrate to target while monitoring; a high-CV-risk patient may start at a high dose. Check ALT at least once at 3 months; check CK if myalgia develops. Monitor more closely with renal impairment (creatinine clearance under 60 mL/min). Contraindicated in active liver disease, high alcohol consumption, and pregnancy. |
| Rosuvastatin | Adults: 10-40 mg PO daily; initial dose 10 mg/day (5 mg/day in the populations noted in Comments) Children (10-17y, boys and postmenarchal girls): 5-10 mg PO daily | Increased CK, increased transaminases (usually reversible), mild upper GI disturbances, myalgias (with or without CK elevation), sleep disturbances, headache, rash. Rare: myopathy, rhabdomyolysis, peripheral neuropathy, impotence. | Avoid strong CYP2C9 inhibitors: amiodarone, fluconazole, fluoxetine, fluvoxamine. Increased levels with cyclosporine. Reduced levels with concomitant magnesium/aluminum-hydroxide antacids — separate antacid dosing by 2 hours. | Start low and titrate to target while monitoring; a high-CV-risk patient may start at a high dose. Check ALT at least once at 3 months; check CK if myalgia develops. Monitor more closely with renal impairment (creatinine clearance under 60 mL/min). Contraindicated in active liver disease, high alcohol consumption, and pregnancy. Start at 5 mg/day (instead of 10 mg/day) in patients of Filipino, Chinese, Japanese, Korean, Vietnamese, or South Asian ancestry, or those on cyclosporine. |
| Simvastatin | Adults: 10-80 mg PO daily with the evening meal Children (10-17y, boys and postmenarchal girls): 10-40 mg PO daily with the evening meal | Increased CK, increased transaminases (usually reversible), mild upper GI disturbances, myalgias (with or without CK elevation), sleep disturbances, headache, rash. Rare: myopathy, rhabdomyolysis, peripheral neuropathy, impotence. | Avoid strong CYP3A4 inhibitors: amiodarone, azole antifungals, cyclosporine, diltiazem, gemfibrozil, grapefruit juice, macrolide antibiotics, protease inhibitors, verapamil. | Start low and titrate to target while monitoring; a high-CV-risk patient may start at a high dose. Check ALT at least once at 3 months; check CK if myalgia develops. Monitor more closely with renal impairment (creatinine clearance under 60 mL/min). Contraindicated in active liver disease, high alcohol consumption, and pregnancy. The 80 mg dose is discouraged given increased myopathy risk — reserve it for a patient already tolerating it long-term, not for a new start. |
Cholesterol Absorption Inhibitors
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Ezetimibe | Adults and children ≥12y: 10 mg PO once daily, any time of day | Generally well tolerated. Common: back pain, arthralgia, diarrhea, abdominal pain, fatigue, dizziness, headache. Rare: myopathy, rhabdomyolysis, hepatitis, acute pancreatitis, thrombocytopenia. | Low potential for drug interactions. Potential pharmacokinetic interaction with cyclosporine — caution when initiating ezetimibe in a patient receiving cyclosporine, especially with severe renal insufficiency. | Monitor ALT and CK as indicated. Can generally be used in children ≥12 years. Not recommended in moderate-to-severe hepatic impairment. |
Fibrates
Never combine gemfibrozil with a statin — this combination carries the highest myotoxicity risk of the fibrate-statin combinations. Fenofibrate and bezafibrate are the preferred fibrates when a fibrate-statin combination is genuinely needed.
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Bezafibrate | Adults: 400 mg PO once daily with the evening meal (sustained-release) | Upper GI disturbances (nausea, abdominal pain, flatulence), myalgias. Increased bile lithogenicity, increased CK, increased creatinine (not representative of true renal function deterioration). | Caution combining with a statin — potential additive hepatotoxicity and myotoxicity. Monitor INR with concomitant warfarin. Increases ezetimibe levels. Monitor renal function with concomitant cyclosporine. | Check renal function at 3, 6, and 12 months, then yearly. Check ALT at least once at 3 months. Check CK if myalgia develops. Useful in diabetic dyslipidemias. Contraindicated in hepatic impairment, significant renal dysfunction, and pre-existing gallbladder disease. |
| Fenofibrate | Standard formulation: 100 mg PO 2-4 times daily, with meals Microcoated (e.g., Lipidil Supra): 160 mg PO once daily with the largest meal of the day Micronized: 200 mg PO once daily with the largest meal of the day Nanocrystal (e.g., Lipidil EZ): 145 mg PO once daily, with or without food; 48 mg once daily starting dose in renal impairment or the elderly | Upper GI disturbances (nausea, abdominal pain, flatulence), myalgias. Increased bile lithogenicity, increased CK, increased creatinine (not representative of true renal function deterioration). | Caution combining with a statin — potential additive hepatotoxicity and myotoxicity. Monitor INR with concomitant warfarin. | Check renal function at 3, 6, and 12 months, then yearly. Check ALT at least once at 3 months. Check CK if myalgia develops. Useful in diabetic dyslipidemias. Contraindicated in hepatic impairment, significant renal dysfunction, and pre-existing gallbladder disease. |
| Gemfibrozil | Adults: 300-1200 mg/day PO in divided doses twice daily, 30 minutes before meals | Upper GI disturbances (nausea, abdominal pain, flatulence), myalgias. Increased bile lithogenicity, increased CK, increased creatinine (not representative of true renal function deterioration). | Do not use in combination with a statin. May increase repaglinide and rosiglitazone levels (CYP2C8). Monitor INR with concomitant warfarin. | Check renal function at 3, 6, and 12 months, then yearly. Check ALT at least once at 3 months. Check CK if myalgia develops. Useful in diabetic dyslipidemias. Contraindicated in hepatic impairment, significant renal dysfunction, and pre-existing gallbladder disease. |
PCSK9 Inhibitors — Monoclonal Antibodies
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Alirocumab | Initial: 75 mg SC every 2 weeks If required: May increase to 150 mg SC every 2 weeks | Injection-site reactions. | None known. | |
| Evolocumab | Dosing: 140 mg SC every 2 weeks, or 420 mg SC monthly | Injection-site reactions. | None known. |
PCSK9 Inhibitor — Small Interfering RNA (siRNA)
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Inclisiran | Initial: 284 mg SC Repeat: At 3 months, then every 6 months | Injection-site reactions. | None known. | Use influenced by reimbursement. |
ATP-Citrate Lyase (ACL) Inhibitor
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Bempedoic acid | Adults: 180 mg PO once daily | Hyperuricemia/gout, rare tendon rupture, anemia. | Increases statin plasma levels — monitor for statin adverse effects when combined. | Activated only in the liver, not skeletal muscle, giving a lower myopathy risk than statins — a useful option specifically for statin-intolerant patients. |
Angiopoietin-like Protein 3 (ANGPTL3) Inhibitor
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Evinacumab | Adults: 15 mg/kg IV over 60 minutes, every 4 weeks | Dizziness, nausea, infusion reactions (including reports of anaphylaxis). | None known. | Indicated as adjunctive therapy in homozygous familial hypercholesterolemia. |
Microsomal Triglyceride Transfer Protein Inhibitor
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Lomitapide | Initial: 5 mg PO daily for 2 weeks Titration: May increase to 10 mg daily if GI effects are tolerated, then increase further at 4-week intervals Maximum: 60 mg PO daily | GI effects (diarrhea, nausea, vomiting), chest pain, fatigue. | Avoid moderate or strong CYP3A4 inhibitors (e.g., ketoconazole). Increases statin plasma levels. | Indicated as adjunctive therapy in adult homozygous familial hypercholesterolemia. Take with a fat-soluble vitamin supplement. Regular liver-test monitoring recommended. |
Omega-3 Fatty Acid Derivative (prescription)
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Icosapent ethyl | Adults: 2 g PO twice daily (4 g/day total) | Atrial fibrillation, constipation, peripheral edema. Possible allergic reactions in patients allergic to fish or shellfish. | Increased bleeding risk combined with an anticoagulant or antiplatelet agent. | Safety in triglycerides ≥10 mmol/L has not been determined. Not the same product as nonprescription fish oil — see Non-Pharmacologic Treatment. |
Resins (Bile Acid Sequestrants)
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Cholestyramine | Adults: 4 g PO 2-3 times daily before meals; maximum 24 g/day in 3 divided doses Children: 240 mg/kg/day PO; maximum 16 g/day in 3 divided doses | Common (>10%): constipation, bloating, abdominal fullness, flatulence, increased triglycerides, increased transaminases (reversible). Rare: hyperchloremic acidosis, cholecystitis, cholelithiasis, pancreatitis, malabsorption syndrome, GI bleeding, peptic ulceration. | Give other medications 1 hour before or 4-6 hours after the resin to limit reduced absorption in the GI tract. | Start with once-daily dosing to improve tolerability. Recommend a high-fibre diet and high water intake to minimize constipation. Long-term or high-dose use can impair absorption of fat-soluble vitamins and folic acid. Safe to use to lower cholesterol and LDL-C in pregnancy and in children. Contraindicated in biliary obstruction, dysbetalipoproteinemia, and triglycerides >3.4 mmol/L. Powder may be mixed with juice, soup, or applesauce; add granules to at least 90 mL of fluid. Some formulations contain phenylalanine — caution in phenylketonuria. |
| Colesevelam | Adults: 2.5 g PO daily in 1-2 divided doses (tablets); maximum 4.375 g/day | Common (>10%): constipation, bloating, abdominal fullness, flatulence, increased triglycerides, increased transaminases (reversible). Rare: hyperchloremic acidosis, cholecystitis, cholelithiasis, pancreatitis, malabsorption syndrome, GI bleeding, peptic ulceration. | Give other medications 1 hour before or 4-6 hours after the resin to limit reduced absorption in the GI tract. | Start with once-daily dosing to improve tolerability. Recommend a high-fibre diet and high water intake to minimize constipation. Long-term or high-dose use can impair absorption of fat-soluble vitamins and folic acid. Safe to use to lower cholesterol and LDL-C in pregnancy and in children. Contraindicated in biliary obstruction, dysbetalipoproteinemia, and triglycerides >3.4 mmol/L. |
| Colestipol | Granules: 5 g PO 2-3 times daily before meals; maximum 30 g/day Tablets: 2 g PO 1-2 times daily; maximum 16 g/day | Common (>10%): constipation, bloating, abdominal fullness, flatulence, increased triglycerides, increased transaminases (reversible). Rare: hyperchloremic acidosis, cholecystitis, cholelithiasis, pancreatitis, malabsorption syndrome, GI bleeding, peptic ulceration. | Give other medications 1 hour before or 4-6 hours after the resin to limit reduced absorption in the GI tract. | Start with once-daily dosing to improve tolerability. Recommend a high-fibre diet and high water intake to minimize constipation. Long-term or high-dose use can impair absorption of fat-soluble vitamins and folic acid. Safe to use to lower cholesterol and LDL-C in pregnancy and in children. Contraindicated in biliary obstruction, dysbetalipoproteinemia, and triglycerides >3.4 mmol/L. Powder may be mixed with juice, soup, or applesauce; add granules to at least 90 mL of fluid. Some formulations contain phenylalanine — caution in phenylketonuria. |
Agents no longer recommended
Niacin (nicotinic acid) lowers triglycerides and LDL-C and raises HDL-C at high doses, but randomized trial evidence in patients already on optimal statin therapy did not show additional cardiovascular benefit from adding niacin. Niacin is no longer recommended in the management of dyslipidemia.
Nonprescription Adjuncts
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Psyllium | Dosing: 10 g/day | GI bloating, flatulence. | May reduce absorption of other drugs if taken at the same time — separate dosing. | Adjunct fibre supplement with a modest LDL-C-lowering effect. |
| Omega-3 fatty acids (nonprescription fish oil) | Dosing: 2-4 g/day (EPA and DHA) for triglyceride-lowering | GI upset, fishy aftertaste; bleeding risk at higher doses. | Additive bleeding risk with an anticoagulant or antiplatelet agent at higher doses. | Lowers triglycerides in hypertriglyceridemia. Doses above 3 g/day from supplements should be physician-supervised. Not the same product as prescription icosapent ethyl, and nonprescription supplementation on its own has not shown a cardiovascular risk reduction. |
| Plant sterols/stanols | Dosing: ≥2 g/day | Generally well tolerated. | None significant. | Taken as a dietary supplement or sterol-enriched food (for example, a fortified margarine). Natural food sources alone cannot provide an effective dose. |
Evidence note: Drug inventory, dosing, adverse effects, and interactions reflect standard Canadian practice, cross-checked against the current Canadian Cardiovascular Society dyslipidemia guideline[1] and the Canadian statin-intolerance consensus update for the statin-associated-muscle-symptom guidance.[8]
Professional reference only. Apply clinical judgment and verify patient-specific decisions against current authoritative guidance and product information.