Statins are the most effective oral lipid-modifying medicines and are the first-line treatment for LDL-C lowering.4 They reduce the risk of cardiovascular events and death for people at high risk of CVD and are effective in both primary and secondary prevention, in men and women, across all age groups.2,4,9
Each 1.0 mmol/L reduction in LDL-C with statin treatment reduces the risk of major vascular events by 20% in primary prevention and 25% in secondary prevention.1 Risk of serious long-term adverse effects associated with use of statins is low.7,10
The AusHEART study suggests that up to 30% of patients at low absolute CV risk are being prescribed a statin.5 However, this group of patients receive the least absolute benefit from lipid-modifying (and BP-lowering) medicines, and harms are likely to outweigh the benefits of treatment in many of them. It is generally recommended not to prescribe lipid-modifying medicines for these patients.4,5,11
Patients identified as high CV risk should be prescribed a lipid-modifying medicine. These patients receive the greatest absolute benefit from statins, and include those who have had a previous CV event (secondary prevention).1,12 Additionally, a modelling study, cited by the National Vascular Disease Prevention Alliance, indicated that treating those at highest absolute risk is potentially more than twice as effective in reducing death from coronary heart disease than treating people with elevated cholesterol levels alone.13,14 Based on meta-analysis data of 27 clinical trials, authors predicted that 5 years of statin therapy that reduces LDL-C by 2.5 mmol/L has the potential to: prevent 100 major vascular events per 1000 people treated in patients with ≥ 20% to < 30% absolute CV risk compared to 12 events per 1000 in patients with <5% risk.1
When lipid modifying medicines are indicated, patients are usually started on a low dose of a statin which is titrated (if necessary) until target lipid levels or maximum tolerated dose (MTD) are achieved.4 In patients who have had a previous CV event, statins are usually started at a higher intensity (dose + potency) with lower LDL-C targets.15-17 The maximum response to a dose can usually be observed within 4 weeks of initiation or dose increase.7 Statin monotherapy should be trialled adequately which involves optimising adherence to medicine and lifestyle changes as well as titrating to MTD. If patients are persistently not meeting targets with optimal monotherapy, consider:7,18
- assessing adherence to medicines and discuss its importance
- increasing the dose or switching to an alternative more potent statin7
- discussing the importance of adherence to lifestyle modifications.
When to add a second-line lipid-modifying medicine
Consider adding a second lipid-modifying medicine if target LDL-C levels are not being achieved with the maximum tolerated dose of a statin.7 Consider ezetimibe or a PCSK9 inhibitor (eg, evolocumab) second-line after statins.7 Ezetimibe is associated with further LDL-C reductions of 20%–25% when added to statin treatment. Therapeutic Guidelines highlights that whilst bile acid binding resins, fibrates and nicotinic acid have been shown to improve lipid abnormalities, there is limited evidence to support adding them to statin treatment to improve cardiovascular outcomes.7
Who needs alternatives to statins?
- Consider non-statin lipid-modifying medicine(s) for:4,7
- those who cannot tolerate a statin (be sure to determine true intolerance)
- those with predominantly elevated triglycerides
- some patients with mixed hyperlipidaemia
- those who need adjuvant treatment because they cannot reach LDL-C targets with the maximum tolerated dose of a statin following an adequate trial.