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

Abbreviations

Stem

Practice viva. You are the cardiology registrar in a lipid clinic. The examiner works through risk categories and LDL-C goals, statin intensity, add-on therapy, statin intolerance, Lp(a) and ApoB, and Australian practice. Name the body, year and class for every recommendation you quote.

Branch A — Risk categories and goals

Examiner: How does ESC/EAS set an LDL-C goal, and has that changed recently?^[1][2]

Strong answer:

• ESC/EAS 2019 sets goals by total cardiovascular risk: very high risk in secondary prevention, a 50% or greater reduction from baseline and LDL-C below 1.4 mmol/L (below 55 mg/dL) (Class I, Level A); high risk, a 50% or greater reduction and below 1.8 mmol/L (below 70 mg/dL) (Class I, Level A).^[1]
• Moderate risk: below 2.6 mmol/L (below 100 mg/dL) should be considered (Class IIa, Level A); low risk: below 3.0 mmol/L (below 116 mg/dL) may be considered (Class IIb, Level A).^[1]
• The 2025 focused update says these LDL-C goals have not changed; its new Table 3 uses SCORE2 and SCORE2-OP instead of SCORE for apparently healthy persons (primary prevention) and is intended to replace the 2019 Table 4.^[2]

Follow-up: What does ACC/AHA 2026 do differently in secondary prevention?^[3]

• ACC/AHA 2026 splits clinical ASCVD by very high risk: 2 or more major ASCVD events, or 1 major event plus 2 or more high-risk features.^[3]
• Very high risk: high-intensity statin therapy should be initiated to achieve a 50% or greater reduction, 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).^[3]
• Not at very high risk: high-intensity statin therapy should be initiated to achieve a 50% or greater reduction, LDL-C below 70 mg/dL (1.8 mmol/L) and non-HDL-C below 100 mg/dL, to reduce the risk of recurrent ASCVD events (COR 1, LOE A).^[3]

Follow-up: Can you use SCORE2 to re-estimate risk in a patient already on a statin?^[2]

• No. The 2025 ESC/EAS update says SCORE2 and SCORE2-OP should not be used for people with existing ASCVD or on lipid-lowering therapy, or to re-assess risk with lipid values obtained after starting guideline-recommended therapy.^[2]

Branch B — Statin intensity

Examiner: What do you mean by a high-intensity statin, and which doses qualify?^[1][3]

Strong answer:

• ESC/EAS 2019: the dose of a statin that, on average, reduces LDL-C by 50% or more; moderate intensity reduces it by 30–50%.^[1]
• ACC/AHA 2026 Table 6 lists atorvastatin (40 mg) 80 mg and rosuvastatin 20 mg (40 mg) as high intensity, and atorvastatin 10 mg (20 mg) and rosuvastatin (5 mg) 10 mg as moderate intensity.^[3]
• ACC/AHA 2026 footnotes that individual responses vary, and that the US Food and Drug Administration does not recommend initiation of, or titration to, simvastatin 80 mg because of increased myopathy risk.^[3]

Follow-up: Why not just pick a statin dose and leave it?^[1]

• ESC/EAS 2019 notes considerable interindividual variation in LDL-C reduction with the same dose, and says uptitration of the statin may be required before additional treatments are started.^[1]
• ACC/AHA 2026 says clinicians should perform a lipid profile 4 to 12 weeks after initiation or dose adjustment and every 6 to 12 months thereafter to assess efficacy and adherence (COR 1, LOE A).^[3]

Branch C — Add-on therapy

Examiner: Your very high-risk secondary prevention patient is not at goal on the maximum tolerated statin. What next?^[1]

Strong answer:

• ESC/EAS 2019: combination with ezetimibe is recommended (Class I, Level B); if the goal is still not achieved on a maximum tolerated statin and ezetimibe, a PCSK9 inhibitor is recommended (Class I, Level A).^[1]
• ESC/EAS 2025 adds that bempedoic acid added to the maximally tolerated statin, with or without ezetimibe, should be considered at high or very high risk to achieve the LDL-C goal (Class IIa, Level C).^[2]
• ACC/AHA 2026, very high-risk clinical ASCVD on maximally tolerated statin: ezetimibe and/or a PCSK9 mAb should be added to reach LDL-C below 55 mg/dL and non-HDL-C below 85 mg/dL and reduce the risk of ASCVD events (COR 1, LOE A); adding bempedoic acid is reasonable (COR 2a, LOE B-R), as is adding inclisiran in those unable to tolerate or obtain evolocumab or alirocumab or who strongly prefer less frequent dosing (COR 2a, LOE B-R).^[3]

Follow-up: What does ACC/AHA 2026 say about the evidence base for inclisiran?^[3]

• The ACC/AHA 2026 row footnote says cardiovascular outcomes trials are not completed with inclisiran, that it is approved for LDL-C lowering only, and that it is considered a second-line PCSK9 inhibitor at this time.^[3]
• The 2025 ESC/EAS update says two inclisiran outcome trials are ongoing and expected to report in 2026 and 2027.^[2]
• ORION-10 and ORION-11 used LDL-C end points: inclisiran lowered LDL-C at day 510 by 52.3% and 49.9% versus placebo.^[10]

Follow-up: What outcome-trial evidence supports ezetimibe and the PCSK9 antibodies?^[6][7][8]

• IMPROVE-IT: in 18 144 patients after ACS, simvastatin 40 mg plus ezetimibe 10 mg versus simvastatin plus placebo gave a 7-year primary end-point rate of 32.7% versus 34.7% (hazard ratio 0.936; P=0.016).^[6]
• FOURIER: evolocumab on statin therapy in 27 564 patients with ASCVD and LDL-C 70 mg/dL (1.8 mmol/L) or more reduced LDL-C by 59% versus placebo at 48 weeks (least-squares mean) and the primary end point from 11.3% to 9.8% (hazard ratio 0.85) over a median 2.2 years.^[7]
• ODYSSEY OUTCOMES: alirocumab in 18 924 patients 1 to 12 months after ACS reduced the primary end point from 11.1% to 9.5% (hazard ratio 0.85) over a median 2.8 years.^[8]

Branch D — Statin intolerance

Examiner: A patient says the statin gives him muscle pain. How do you approach it?^[3]

Strong answer:

• ACC/AHA 2026: 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); the discussion should acknowledge the concern, inform the patient of the heightened ASCVD risk of stopping, and provide alternatives to reduce ASCVD risk (COR 1, LOE B-R).^[3]
• ESC/EAS 2019 reports that blinded randomised trials show no, or only a slightly, increased frequency of muscle symptoms with statins, and reports the conclusion of the Anglo-Scandinavian Cardiac Outcomes Trial – Lipid-Lowering Arm (ASCOT-LLA) that a nocebo effect may partly explain the higher frequency in observational studies.^[1]
• With clinical ASCVD, symptoms on the recommended statin intensity (secondary causes excluded) and goals not achieved, ACC/AHA 2026 recommends a reduced statin dose (if tolerable) plus bempedoic acid, ezetimibe or a PCSK9 mAb, alone or in combination, to lower LDL-C and reduce ASCVD risk (COR 1, LOE B-R).^[3]
• ESC/EAS 2025 recommends non-statin therapies with proven cardiovascular benefit, alone or in combination, for patients unable to take statins, to lower LDL-C and reduce the risk of cardiovascular events (Class I, Level A), and bempedoic acid in that group to achieve the LDL-C goal (Class I, Level B).^[2]

Follow-up: When do you stop the statin outright?^[1]

• ESC/EAS 2019: CK must be assessed immediately in patients with muscle pain and weakness, especially older people, and treatment stopped if CK rises above 10 times the upper limit of normal.^[1]
• ESC/EAS 2019 Table 13 adds that with CK at 4 times the upper limit of normal or more but below 10 times, the statin is stopped if symptoms are present, with CK monitored to normalisation before rechallenge with a lower statin dose; with CK below 4 times and persisting muscle symptoms, the statin is stopped and symptoms re-evaluated after 6 weeks.^[1]
• ESC/EAS 2019 describes rhabdomyolysis, with CK elevated 10 times or more (often 40 times or more) the upper limit of normal, as the most severe form of statin-induced muscle damage.^[1]

Branch E — Lp(a) and ApoB

Examiner: Who should have Lp(a) measured, and what do you do with a high value?^[3]

Strong answer:

• ACC/AHA 2026 recommends Lp(a) measurement at least once in all adults for ASCVD risk assessment (COR 1, LOE B-NR); ESC/EAS 2019 says it should be considered at least once in each adult's lifetime, to identify very high inherited levels above 180 mg/dL (above 430 nmol/L) that may carry a lifetime ASCVD risk equivalent to heterozygous FH (Class IIa, Level C).^[3][1]
• 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 levels associated with a greater increase in risk (Class IIa, Level B).^[2]
• ACC/AHA 2026: with elevated Lp(a) (125 nmol/L or more, or 50 mg/dL or more), optimal early control of modifiable cardiovascular risk factors is recommended to reduce ASCVD risk (COR 1, LOE B-NR); with clinical ASCVD and LDL-C and non-HDL-C goals not achieved on maximally tolerated statin, adding a PCSK9 mAb with proven cardiovascular benefit is recommended to achieve the goals and reduce ASCVD risk (COR 1, LOE B-R).^[3]
• ESC/EAS 2025 reports that statins had no effect on Lp(a) concentrations in individual-level data from seven placebo-controlled statin outcome trials, and says whether lowering Lp(a) reduces ASCVD risk has yet to be shown.^[2]

Follow-up: When does ApoB help?^[3]

• ACC/AHA 2026: in adults on lipid-lowering therapy, particularly with ASCVD, cardiovascular-kidney-metabolic syndrome, type 2 diabetes and/or elevated triglycerides, ApoB is reasonable to guide intensification once LDL-C and/or non-HDL-C goals are achieved (COR 2a, LOE B-NR).^[3]
• ESC/EAS 2019 secondary goals by inference: ApoB below 65, below 80 and below 100 mg/dL at very high, high and moderate risk.^[1]

Branch F — Australian practice

Examiner: What would you tell an Australian patient after an ACS about lipids?^[4]

Strong answer:

• NHFA/CSANZ 2025, in people with ACS: before discharge, initiate and continue indefinitely the highest tolerated statin dose unless contraindicated or completely statin intolerant (strong recommendation, high certainty).^[4]
• An initial LDL-C target below 1.4 mmol/L and a reduction of at least 50% from baseline is recommended, with further benefit from treating to the lowest achievable level (consensus); consider adding ezetimibe if LDL-C is suboptimal despite statin therapy or the patient is statin intolerant (weak, moderate certainty); give PCSK9 inhibitors if LDL-C is suboptimal despite maximally tolerated statin and ezetimibe (strong, high certainty).^[4]