Statins revisited – appropriate patient selection and management are key

A patient’s absolute CV risk is their likelihood of experiencing a cardiovascular event within a defined period. For Australian guidelines, this is within the next 5 years.^4,7

Assessing risk, using validated Australian CVD risk charts or associated web calculator, is an important first step in determining whether a patient should be prescribed a lipid-modifying medicine or not. The use of an absolute CV calculator can support appropriate treatment options being delivered, leading to improved CV risk management and CV outcomes.⁴ Evidence also indicates that GPs who used absolute risk calculators are more likely to correctly identify risk factors for CVD, compared to those who decided to treat based on individual risk factors.⁸

Guidelines recommend calculating absolute CV risk for patients who are aged 45–74 years and Aboriginal and Torres Strait Islander adults aged 35–74 years, who are not known to have CVD or not already known to be at clinically-determined high risk of CVD (see below).^4,7 Those in the latter group do not need a formal risk calculation as they are already known to be at high risk.

Health professionals should be aware that the predictive value of the risk equation has not been assessed in overweight or obese populations and may underestimate the CVD risk in some groups including socioeconomically disadvantaged groups, people with depression and people aged > 74 years.⁴

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.

Patient non-adherence to lipid-modifying medicines is a key reason for lipid targets not being met and remains a concern in clinical practice. It has been established that up to 67% of patients are non-adherent to statins as prescribed after 12 months.¹⁹ Patients who do not adhere to lipid-modifying medicines have an increased risk of CVD mortality or may be at increased risk of higher all-cause mortality, hospitalisations and revascularisations.¹⁹

Non-adherence can be intentional or unintentional.²⁰ With intentional non-adherence the patient decides to stop or change their agreed treatment regimen, often after balancing the benefits (eg, improved quality of life) against the risks (eg, the adverse effects associated with treatment). When a patient wants to follow the agreed regimen but is prevented by barriers beyond their control, this may be described as unintentional non-adherence. 

The table below outlines some strategies that may help to target and reduce barriers to adherence.²⁰

Review adherence to medicines and lifestyle regularly (eg, at every consultation), especially before changing lipid-modifying medicines,¹⁸ and consider providing resources that explain CVD and statins (eg, print out information from reputable websites). The MedicineWise app may be useful to help remind patients to take their medicine and to refill prescriptions.

Statin-associated muscle symptoms (SAMS) have been reported as a key contributing factor to statin non-adherence – in 65% of former statin users, the main reason for statin non-adherence or discontinuation was onset of side effects, predominantly muscle-related effects.²³

Observational studies in clinical practice have shown SAMS are perceived as a common side effect among people receiving statin therapy (7%-29%).^9,23,24 However, randomised controlled trial data suggests the true incidence of SAMS may not be as high (1%-5%).^25-27 Assessing and confirming the diagnosis of true statin-associated muscle symptoms can help to maximise the benefits of statin therapy for people at high absolute CV risk, and avoid unnecessary medicine changes. 

In 2015, NPS MedicineWise collaborated with clinical experts to develop a SAMS assessment guide and a SAMS management algorithm to support management of patients with suspected muscle symptoms in primary care. Additional materials developed as part of this program include the health professional mediated action plan Staying on track with your statin and a factsheet answering common consumer questions regarding statin medicines.