Lipid Lowering Therapy

Risk-based framework

Decision to start lipid lowering therapy should be based on CVD Risk calculator

Lipid modifiying therapty is recommended in those at high risk (>15% in 5 yrs) — the risk categories and thresholds themselves have changed; see cardiovascular-risk-assessment for the current 2023 definitions (low <5%, intermediate 5–<10%, high ≥10%)

In pts with moderate or low risk - drug therapy is not recommended initally, though it can be considered at intermediate risk taking reclassification factors and patient preference into account

Drug therapy can be considered if lifestyle modification doesn’t improve risk

A meta-analysis cited in the 2023 guideline found that for every 1.0 mmol/L reduction in LDL cholesterol, the overall risk of major coronary events, coronary revascularisation and stroke fell by about a fifth — the basis for statins remaining first-line regardless of starting LDL level

Target Lipid Levels:

For those on drug therapy

Target of lipid modifiying therapy is LDL-C, which has been shown to have a continuous relationship with CV Risk

For primary prevention, the 2023 guideline remains risk-based rather than target-based — there is no specific LDL-C number to aim for, treatment intensity is guided by overall CVD risk category. For secondary prevention (established CVD), the 2025 NHFA/CSANZ ACS guideline sets an explicit target: LDL-C less than 1.4 mmol/L and at least a 50% reduction from baseline — see acute-coronary-syndromes for the full update. A PCSK9 inhibitor is recommended if this isn’t met on maximally tolerated statin + ezetimibe; PBS-subsidised since a December 2022 expansion of the PBS criteria to a lower LDL-C threshold than before.

If a prescribed statin isn’t tolerated, consider a lower dose, alternate-day dosing, or switching to an alternative statin or non-statin therapy — true statin intolerance is less common than perceived (around 8-10% of patients).

Lifestyle first, then statins

Start a in all patients with high absolute risk of or established CVD.

Patients with low to moderate CVD risk have a smaller benefit from reducing lipid levels

Lifestyle advice should be initally tried, and then statin therapy can be considered if this is not successful

Lifestyle advice:

Weight loss and incraesed physical activity

Dietary changes

Use statins as first-line lipid-modifying therapy to reduce cardiovascular disease (CVD) risk in all patients at high absolute CVD risk or with established CVD (see Cardiovascular disease risk stratification for information about absolute CVD risk). Their efficacy in reducing cardiovascular morbidity and mortality is well established.

Lipoprotein(a)

Lipoprotein(a) (Lp(a)) is an LDL-like particle whose concentrations, mostly genetically determined, are elevated in about one in five people. Lp(a) is a firmly established causal risk factor for coronary artery disease, stroke, peripheral arterial disease and calcific aortic valve stenosis.

Testing

Measuring Lp(a) should be considered in people with ASCVD or aortic valve stenosis, especially if young-onset, familial, unusually severe or progressive. Consider testing in:

• people with a family history of premature ASCVD or of elevated Lp(a)
• people with premature or rapidly progressive aortic stenosis
• people with a very high coronary artery calcium score, diabetes mellitus, familial hypercholesterolaemia or chronic kidney disease
• people in whom LDL-cholesterol lowering is less effective than expected despite good adherence to lipid-lowering therapy (elevated Lp(a) can artefactually raise measured LDL-cholesterol)

Lp(a) typically only needs measuring once, since concentrations vary little with age, diet or currently available medications. Acute inflammation (e.g. post-ACS) can transiently lower concentrations, and fasting is not required. There is no Medicare rebate for Lp(a) testing, though the out-of-pocket cost is typically modest.

Levels and risk

Concentrations above 100 nmol/L are commonly deemed the ASCVD risk cut-off. The relationship between Lp(a) and cardiovascular risk is continuous and independent of other risk factors including LDL-cholesterol. Lp(a) concentrations differ across ancestral groups, with people of African American and South Asian ancestry tending to run higher than Europeans. There are no ancestry-specific testing or management recommendations.

Management

No Lp(a)-lowering therapy is yet licensed, so management targets overall ASCVD risk:

• statins and ezetimibe do not lower Lp(a) concentrations, but lowering LDL-cholesterol reduces the overall ASCVD risk heightened by elevated Lp(a)
• consider intensifying LDL-cholesterol lowering below guideline targets (maximally tolerated statin, ezetimibe, PCSK9 inhibitor) when Lp(a) is raised alongside high or very high ASCVD risk
• PCSK9 inhibitors carry no PBS subsidy specific to elevated Lp(a), but remain an option where they are otherwise PBS-eligible or self-funded
• aspirin may have a role in primary prevention for raised Lp(a), but there is not yet a firm recommendation
• for recurrent ASCVD events despite maximal lipid-lowering therapy with Lp(a) above 200 nmol/L, consider lipoprotein apheresis

Future treatment

Pelacarsen, an Lp(a)-lowering antisense oligonucleotide, is the most progressed agent in ongoing outcomes trials. The results of the Phase III Lp(a)HORIZON secondary prevention study of pelacarsen are expected in late 2026.