Primary hypercholesterolemia
Low-density lipoprotein cholesterol (LDL-C) above the target threshold determined by cardiovascular risk. ESC/EAS 2019 targets: below 1.4 mmol/L (very high risk), 1.8 (high), 2.6 (moderate). First-line therapy is a high-intensity statin (atorvastatin 40–80 mg or rosuvastatin 20–40 mg). When the goal is not reached, ezetimibe is added; the next step is a PCSK9 inhibitor.
ICD-10 E78.011 drugs
Also known as: Elevated LDL-C, Hyperlipidemia
Drugs used for this condition
- AEzetimibeSecond line · Selective intestinal cholesterol absorption inhibitorPreferred second-line agent when LDL targets are not met on a maximum-tolerated statin under ESC/EAS 2019. In IMPROVE-IT, adding ezetimibe to simvastatin after acute coronary syndrome reduced cardiovascular events by 6.4% over 7 years, confirming benefit of further LDL lowering. Dose 10 mg once daily with or without food. In statin-intolerant patients, ezetimibe monotherapy is used.
- APitavastatinSecond line · Statin (HMG-CoA reductase inhibitor)Second-line for hypercholesterolemia per ESC/EAS 2019. Advantage over atorvastatin in patients on polytherapy with CYP3A4-metabolized drugs (cyclosporine post-transplant, antiretrovirals, azole antifungals) – fewer interactions. Dose 2–4 mg once daily. In pre-diabetes or T2D, preferred over atorvastatin due to less glycemic impact.
- APravastatinSecond line · Statin (HMG-CoA reductase inhibitor)Second-line for hypercholesterolemia per ESC/EAS 2019 after high-intensity statins (atorvastatin, rosuvastatin). Dose 20–40 mg once daily at bedtime reduces LDL by 30–40%. Preferred in patients on multiple CYP3A4-metabolized drugs (cyclosporine post-transplant, antiretrovirals, antifungals) – pravastatin has no significant interactions. Also in statin intolerance from muscle side effects.
- BBeta-1,3/1,6-D-glucan (yeast or oat)Add-on therapy · Polysaccharide immunomodulator. Oat beta-glucan is a dietary fibre with EFSA-approved cholesterol health claim. Yeast beta-glucan (Wellmune) is a supplement with immunity marketing without EFSA approvalOat beta-glucan is one of the few supplements with an EFSA-approved cardiovascular risk health claim. Meta-analyses of RCTs (Whitehead 2014, AbuMweis 2010) showed that 3 g/day oat beta-glucan for 4–12 weeks lowers total cholesterol by 0.30 mmol/L and LDL by 0.25 mmol/L in mild-to-moderate hypercholesterolaemia. EFSA 2010 approved the official health claim: «consumption of 3 g/day oat beta-glucan lowers blood cholesterol; lowering cholesterol reduces coronary heart disease risk». ESC/EAS 2019 list dietary fibres (including oat beta-glucan) as adjunctive non-pharmacological measure in dyslipidaemia – one serving of oatmeal per day provides ≈3–4 g beta-glucan. Does not replace statins in high or very-high cardiovascular risk (T2DM, prior MI, stroke, familial hypercholesterolaemia). In primary hypercholesterolaemia with LDL ≥4.9 mmol/L or high SCORE2-OP atorvastatin or rosuvastatin with ezetimibe remain first-line, with PCSK9 inhibitors as add-on.
- BLovastatinThird line · HMG-CoA reductase inhibitor (statin)Treats Fredrickson type IIa and IIb primary hypercholesterolaemia. SEC prefers atorvastatin and rosuvastatin for high-intensity statin therapy.
- BPsyllium (Plantago ovata, ispaghula husk)Add-on therapy · Soluble and insoluble fibre from seed husk. AEMPS registered Plantaben and Cenat as medicinal products for chronic constipation and maintenance of normal defecation. ACG 2014 and NICE NG61 IBS 2017 list psyllium as the primary soluble fibrePsyllium is one of the few dietary supplements with confirmed cardiometabolic benefit. EFSA 2010 approved the health claim: «psyllium husk contributes to maintenance of normal blood cholesterol» at minimum 7 g/day. Brown 1999 meta-analysis (8 RCTs) and updated Wei 2009 showed 5–10% LDL reduction on psyllium 7–10 g/day × 8 weeks. FDA in the US allowed a heart-health claim for psyllium from 1998. ACC/AHA in hypercholesterolaemia list statins (atorvastatin, rosuvastatin) first-line; statin intolerance or insufficient effect – ezetimibe, PCSK9 inhibitors (alirocumab, evolocumab), bempedoic acid. Psyllium may be used as adjunct to statin for additional 5–10% LDL reduction but does not replace statin in high cardiovascular risk patients. If psyllium was recommended as a statin substitute in coronary disease, prior myocardial infarction or stroke, consider seeking a second opinion from a cardiologist.
Marketing claims without evidence base
The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.
- CArtichoke (Cynara scolymus)Not recommended · Herbal preparation, supplement. In EU – traditional herbal medicinal product (EMA HMPC). In Russia OTC product Hofitol is registeredArtichoke extract is sold for «natural cholesterol lowering» as a statin alternative. Cochrane 2013 reviewed 3 RCTs totalling 262 patients: pooled total cholesterol reduction 17 mg/dL and LDL 23 mg/dL with 1280–1920 mg/day × 6–12 weeks, but quality low, heterogeneity high, hard outcomes (myocardial infarction, stroke, cardiovascular mortality) not assessed. ESC/EAS 2019 in primary hypercholesterolaemia and cardiovascular risk list statins first-line (proven MACE and all-cause mortality reduction), ezetimibe second-line, PCSK9 inhibitors in familial form. SEA 2022 (Spanish Atherosclerosis Society) – same approach. Herbal extracts not included. If artichoke was recommended as a statin substitute in confirmed hypercholesterolaemia and moderate/high cardiovascular risk (SCORE2 ≥5%), consider seeking a second opinion from a cardiologist or lipidologist.
- DEpigallocatechin-3-gallate (EGCG, main green tea polyphenol)Not recommended · Catechin polyphenol from green tea (Camellia sinensis), supplement. EFSA 2018 limited safe dose from supplements to 800 mg/day due to hepatotoxicityEGCG is sold as a «natural cardioprotector» via oxidised LDL reduction and endothelial function improvement. Several meta-analyses showed modest total cholesterol (−5–7 mg/dL) and LDL (−4–6 mg/dL) reduction with catechins 200–800 mg/day, far less than statin effect (30–55% LDL reduction from baseline). ESC dyslipidaemia 2024 at LDL >1.8–3.0 mmol/L (depending on CV risk) lists statins (atorvastatin, rosuvastatin) first-line; green tea extract is not in guidelines. EFSA 2018 warned about EGCG hepatotoxicity at >800 mg/day – relevant when choosing high-dose «cardio complexes». If EGCG was recommended as a statin substitute, consider seeking a second opinion from a cardiologist.
- DGrape seed extract (Vitis vinifera, oligomeric proanthocyanidins)Not recommended · Plant polyphenol complex, supplement. Source of oligomeric proanthocyanidins (OPC), compositionally similar to pycnogenolGrape seed extract is sold as a «natural cardioprotector» and cholesterol-lowering supplement. Feringa 2011 meta-analysis of 9 RCTs in 390 patients showed modest systolic BP reduction (−1.5 mmHg) without significant effect on total cholesterol, LDL or HDL. ESC dyslipidaemia 2024 at LDL >1.8–3.0 mmol/L (depending on CV risk) lists statins (atorvastatin, rosuvastatin) first-line; if not at goal – ezetimibe, PCSK9 inhibitors (alirocumab, evolocumab) or bempedoic acid; grape seed extract is not in guidelines. If grape seed extract was recommended as a statin substitute in primary or familial hypercholesterolaemia, consider seeking a second opinion from a cardiologist.
- DLecithin (soy or sunflower phosphatidylcholine)Not recommended · Phospholipid mixture, dietary supplement. A mass OTC «memory drug» and «hepatoprotector» in Russia. Essentiale (Sanofi, essential phospholipids) is a separate regulated medicine, registered by AEMPS and in Russia for NAFLDLecithin is a mix of phospholipids (mainly phosphatidylcholine) made from soy or sunflower. It is sold as a supplement to lower cholesterol in primary hypercholesterolemia. No convincing benefit has been shown for this use: there is no evidence base supporting a drop in cholesterol or cardiovascular risk. For high cholesterol, statins have proven benefit, along with diet and lifestyle changes, which your doctor selects based on cardiology guidelines. Lecithin is harmless in this role, but do not take it instead of therapy with proven benefit, or you may miss the treatment you need.
- DPterostilbene (dimethyl resveratrol analogue)Not recommended · Plant stilbene, supplement. Natural polyphenol from blueberries, grapes and red sandalwood. Often sold combined with nicotinamide riboside (NR) in longevity complexesPterostilbene is sold as a «natural cardioprotector». Riche 2014 RCT in 80 patients with dyslipidaemia paradoxically showed LDL increase by 10–15% with pterostilbene 250 mg/day × 6–8 weeks vs placebo. No systematic reviews with positive lipid effect. ESC dyslipidaemia 2024 at LDL >1.8–3.0 mmol/L (depending on CV risk) lists statins (atorvastatin, rosuvastatin) first-line; if not at goal – ezetimibe, PCSK9 inhibitors or bempedoic acid; pterostilbene is not in guidelines and may potentially worsen the lipid profile. If pterostilbene was recommended for hypercholesterolaemia, consider seeking a second opinion from a cardiologist.
How to read tiers A–F
Evidence tiers belong to the drug-indication pair, not to the drug as a whole: the same substance can be A for one condition and F for another.
- AStrong evidence – first or second line in international guidelines
- BRecommended in selected cases
- CStudy data contradict each other
- DBenefit not proven, no documented harm
- FDocumented harm, or risk without benefit