Appropriate primary prevention of cardiovascular disease: does this mean more or less statin use?

Treatment with HMG-CoA reductase inhibitors, commonly known as statins, is beneficial for people at high risk of a cardiovascular event. However, guidelines recommend against routine statin treatment for those with a lower risk.They also recommend waiting until after 45 years of age to assess cardiovascular risk in healthy individuals. Aboriginal and Torres Strait Islander people should be assessed from age 35 years.These recommendations are based on current evidence of who is more likely to benefit from statin treatment.

The absolute risk of developing cardiovascular disease is predictable using risk calculation tools.² Statins are known to reduce this risk in people with existing ischaemic cardiovascular disease, or those at high risk of developing it – defined as more than 15% risk of an event in five years. However it is less clear whether people with a lower cardiovascular risk, benefit from statins.

The number of patients diagnosed with high cholesterol has doubled between 2004 and 2009.³ The focus on single risk factors like cholesterol translates to 27% of adult general practice patients being managed for cholesterol⁴ – three-quarters of them are treated with statins.

Patients and health providers alike tend to focus on cholesterol, perhaps because it is an easy target to test and treat. A possible consequence of this is that statins are the most prescribed of all drugs both in quantity and cost on the Pharmaceutical Benefits Scheme (PBS). There are three individual statins in the top 10 of all prescribed drugs – atorvastatin, simvastatin and rosuvastatin.⁵ Suggestions have been made about both under- and over-prescribing of statins in Australia. Women are far more likely to be treated with statins relative to their risk for cardiovascular disease than men, with the exception of men in the highest socioeconomic group. Rural people are less likely to be treated with a statin.⁶

The term cardiovascular risk refers to the risk of ischaemic disease defined as acute coronary events, angina, stroke, transient ischaemic events, and peripheral vascular disease with or without fatal outcomes. There are multiple modifiable factors that influence the risk of developing cardiovascular disease (Box 1). Modifying these factors can improve morbidity and mortality and includes lifestyle factors such as increasing physical activity and cardiorespiratory fitness, and not smoking.^7,8 If these interventions do not sufficiently reduce the risk of cardiovascular disease, pharmacological interventions may need to be considered.

Generally people under 45 years are likely to have a low risk of cardiovascular disease, as age is one of the biggest determinants of risk, and multiple risk factors are not common in younger people.

A family history of high cholesterol affects 5–20% of the population, depending on how one defines high cholesterol.

This is sometimes confused with familial hypercholesterolaemia (LDL >4.9 mmol/L usually with tendon xanthoma) which affects 1 in 500 (0.2%) people.⁹ This is a high risk condition and results in coronary heart disease or stroke at a young age (under 60 years).

Calculating absolute risk using Framingham data adapted for Australia is well validated, based on multiple factors including cholesterol levels, but is underused.² These tools tend to overestimate the risk in those of European descent but underestimate the risk in high risk groups such as Aboriginal and Torres Strait Islander, Pacific Islander or Indian people. Easy-to-use online tools for calculating cardiovascular risk are shown in Box 2.

Table 1 shows who should have a cardiovascular risk calculation. Conversely, some patients' risk is high enough to not need any risk calculation. These are patients who have had a previous cardiovascular event. It also includes some patients with hypercholesterolaemia, diabetes, hypertension or moderate to severe chronic kidney disease (Box 3).

About 8% of adult patient encounters in general practice involve cholesterol testing but evidence suggests most of these tests do not result in any benefit to patients.^3,10 The Royal Australian College of General Practitioners guidelines for preventive activities in general practice recommend testingadults over 45 years of age for their cholesterol levels every five years (or from 35 years if Aboriginal and Torres Strait Islander).^11,12 Similar recommendations are given by the National Vascular Disease Prevention Alliance (Table 1).²

Most of the evidence about the effect of statins in primary prevention is based on treatment of high-risk males aged 55–65 years.¹³ There is little evidence about benefit in younger age groups. In those at high risk, statins lower ischaemic event rates and all-cause mortality, and are cost-effective. This has not been shown in lower-risk populations.¹⁴

Systematic reviews of trials differ in their conclusions about the benefits of statins in patients who do not have a high risk. When patients with prior cardiovascular disease are excluded, there is no evidence of benefit from statin therapy on all-cause mortality.¹³ This suggests that caution should be used when recommending statins for primary prevention of cardiovascular disease in those at low risk (that is with a risk of cardiovascular disease less than 2% in one year) because of limited benefit and a potential for harm (Table 2).^15,16

In those with moderate to severe chronic kidney disease, statin treatment reduces cardiovascular events but not overall mortality.¹⁷ However, statin treatment of those with less severe chronic kidney disease appears to reduce cardiovascular events and overall mortality.¹⁸

The PBS general statement for using lipid-lowering drugs defines patients at risk who would be expected to benefit from statin therapy. The wording is intended to mirror the absolute cardiovascular disease risk calculation, but is an imperfect match.

It is likely that we are over-prescribing statins to low-risk patients. A focus on single risk factors such as high cholesterol promotes statin treatment. This will not benefit patients unless they have a high risk of cardiovascular disease, and it could result in harm. It is appropriate to assess absolute cardiovascular risk in people aged over 45 years (or from 35 years if Aboriginal and Torres Strait Islander) using tools that integrate multiple risk factors.

Associate professor Smith is a member of the Editorial Advisory Committee of the Australian Medicines Handbook, member of the Advisory Editorial Panel of Australian Prescriber, and an author of the guidelines for preventive activities in general practice.