Dyslipidaemia: low-density lipoprotein cholesterol targets, statin intensity and add-on therapy — structured written assessment

Abbreviations

Short-answer question 1 (10 marks)

Scenario

A 63-year-old man had an MI 18 months ago. He has hypertension and smokes. He takes atorvastatin 80 mg daily, his maximum tolerated dose, and has never taken ezetimibe. His untreated LDL-C before any therapy was 4.0 mmol/L; it is now 2.0 mmol/L (77 mg/dL). He has had no further event. (Practice scenario.)

Questions — question 1

1. State his ESC/EAS risk category and his LDL-C goal under the 2019 ESC/EAS guideline, with class and level, and say whether he meets it. (3)^[2][1]
2. Define high-intensity and moderate-intensity statin therapy as ESC/EAS 2019 and ACC/AHA 2026 do. (2)^[1][3]
3. What are the next two steps on the ESC/EAS 2019 ladder, with their classes? (2)^[1]
4. Is he at very high risk under ACC/AHA 2026, and what do its secondary-prevention rows recommend for him? (3)^[3]

Model answers — question 1

1. Risk: a previous MI is documented ASCVD, which places him at very high risk in ESC/EAS 2025 Table 3 (1 mark).^[2] Goal: in secondary prevention at very high risk, ESC/EAS 2019 recommends an LDL-C reduction of 50% or more from baseline and an LDL-C goal below 1.4 mmol/L (below 55 mg/dL) (Class I, Level A); the 2025 focused update left these goals unchanged (1 mark).^[1][2] Met or not: his LDL-C has fallen from 4.0 to 2.0 mmol/L, a 50% reduction, but 2.0 mmol/L is above 1.4 mmol/L, so he has not met the goal (1 mark).^[1]
2. ESC/EAS 2019: a high-intensity regimen is the dose of a statin that, on average, reduces LDL-C by 50% or more; moderate-intensity therapy is the dose expected to reduce LDL-C by 30–50% (1 mark).^[1] ACC/AHA 2026: high-intensity statin therapy is expected to lower LDL-C by 50% or more, moderate-intensity by 30% to 49% and low-intensity by less than 30% (1 mark).^[3]
3. If the goals are not achieved with the maximum tolerated dose of a statin, combination with ezetimibe is recommended (Class I, Level B) (1 mark).^[1] For secondary prevention, patients at very high risk not achieving their goal on a maximum tolerated dose of a statin and ezetimibe should have a PCSK9 inhibitor added (recommended, Class I, Level A) (1 mark).^[1] Also creditable: ESC/EAS 2019 Table 13 advises rechecking lipids 8 (±4) weeks after each adjustment until the goal is achieved.^[1]
4. Very high risk: ACC/AHA 2026 defines it as 2 or more major ASCVD events, or 1 major event (here, a history of MI other than recent ACS) plus 2 or more high-risk features; he has two, hypertension and current smoking (1 mark).^[3] ACC/AHA 2026, very high risk: high-intensity statin therapy should be initiated to achieve a 50% or greater LDL-C reduction and a goal of LDL-C below 55 mg/dL (1.4 mmol/L) and non-HDL-C below 85 mg/dL (2.2 mmol/L), and to reduce the risk of ASCVD events (COR 1, LOE A) (1 mark).^[3] On maximally tolerated statin, ezetimibe and/or a PCSK9 mAb should be added (chosen by the LDL-C lowering needed and patient preference) to reach those goals and reduce the risk of ASCVD events (COR 1, LOE A); his LDL-C of 77 mg/dL is above 55 mg/dL (1 mark).^[3] Also creditable: adding bempedoic acid, with or without ezetimibe and/or a PCSK9 mAb, to reach those goals and reduce the risk of ASCVD events is reasonable (COR 2a, LOE B-R).^[3]

Short-answer question 2 (10 marks)

Scenario

A 59-year-old woman had PCI for stable angina 2 years ago. Since her rosuvastatin was increased to 20 mg she reports aching in both thighs. Her LDL-C is 2.4 mmol/L (93 mg/dL). Her Lp(a) is 150 nmol/L. (Practice scenario.)

Questions — question 2

1. Which clinical features support a statin-related cause, and what assessment does ACC/AHA 2026 recommend? (3)^[3]
2. How does the frequency of muscle symptoms differ between observational studies and blinded trials, according to ESC/EAS 2019? (2)^[1]
3. If secondary causes are excluded and her goal is not achieved, what does ACC/AHA 2026 recommend, and what do the ESC/EAS 2025 rows say for patients unable to take statins? (3)^[3][2]
4. How do ESC/EAS 2025 and ACC/AHA 2026 interpret her Lp(a), and what does ACC/AHA 2026 recommend for her? (2)^[2][3]

Model answers — question 2

1. ACC/AHA 2026: a statin-related cause is supported by new-onset bilateral, symmetrical, proximal muscle pain or weakness within weeks of starting or increasing the dose of a statin; symptoms typically resolve within a similar period after stopping and may recur on rechallenge (1 mark).^[3] Assessment should include evaluation for secondary causes, and with severe myalgias or weakness, objective measures of muscle strength and CK measurement are recommended to assess severity (COR 1, LOE C-LD) (1 mark).^[3] Risk factors to look for, any three of the 14 in ACC/AHA 2026 Table 24: age 65 years or more, low body mass index, female sex, obesity, hypothyroidism, diabetes, chronic liver disease, chronic kidney disease, alcohol consumption, vigorous exercise, high-dose statin therapy, diseases associated with myalgia or muscle weakness (for example fibromyalgia, polymyalgia rheumatica, polymyositis, primary myopathies), pharmacotherapy affecting statin metabolism, and gene variants affecting statin metabolism (for example SLCO1B1) (1 mark).^[3]
2. ESC/EAS 2019 reports a 10–15% frequency of muscle symptoms among statin-treated individuals in observational studies (1 mark).^[1] ESC/EAS 2019 reports that blinded randomised trials of statins versus placebo show no, or only a slightly, increased frequency of muscle symptoms in statin-allocated groups, and reports the conclusion of the Anglo-Scandinavian Cardiac Outcomes Trial – Lipid-Lowering Arm (ASCOT-LLA) that a nocebo effect may partly explain the difference (1 mark).^[1]
3. ACC/AHA 2026: in adults with clinical ASCVD (her PCI qualifies) who have statin-attributed muscle symptoms on the recommended intensity (secondary causes excluded) and are unable to achieve recommended treatment goals, a reduced statin dose (if tolerable) plus bempedoic acid, ezetimibe or a PCSK9 mAb, alone or in combination, is recommended to lower LDL-C and reduce ASCVD risk (COR 1, LOE B-R) (1 mark).^[3] ACC/AHA 2026 also recommends that the clinician-patient discussion acknowledge her side-effect concerns, inform her of the heightened ASCVD risk associated with statin discontinuation, and provide alternative treatment options to reduce ASCVD risk (COR 1, LOE B-R) (1 mark).^[3] ESC/EAS 2025, for patients unable to take statin therapy: non-statin therapies with proven cardiovascular benefit (ezetimibe, PCSK9 monoclonal antibodies, bempedoic acid), alone or in combination, are recommended to lower LDL-C and reduce the risk of cardiovascular events, the choice being based on the magnitude of additional LDL-C lowering needed (Class I, Level A); bempedoic acid is recommended in these patients to achieve the LDL-C goal (Class I, Level B) (1 mark).^[2]
4. ESC/EAS 2025: Lp(a) above 50 mg/dL (105 nmol/L) should be considered in all adults as a cardiovascular risk-enhancing factor, with higher Lp(a) levels associated with a greater increase in risk (Class IIa, Level B); ACC/AHA 2026 treats 125 nmol/L or more as elevated, so 150 nmol/L is elevated by both (1 mark).^[2][3] ACC/AHA 2026: with clinical ASCVD and elevated Lp(a), if LDL-C and non-HDL-C treatment goals are not achieved on maximally tolerated statin therapy, adding a PCSK9 mAb with proven cardiovascular benefit is recommended (COR 1, LOE B-R) (1 mark).^[3]