Statins in primary prevention of CVD: important but controversial
Statins are important medications that have strong evidence of reducing atherosclerotic CV disease (ASCVD) in patients who have already had a cardiovascular event such as a myocardial infarction, stroke etc. Elevated low-density lipoprotein (LDL) is associated with higher rates of CVD. The benefits of LDL reduction for persons with established CVD are well established. Therefore, in the secondary prevention of ASCVD, statins have been used for a long time with a strong grade of evidence. This is unquestionable. However, there is uncertainty regarding the net benefit-to-risk ratio of using statins to reduce LDL among persons without CVD (primary prevention). When it comes to primary prevention the evidence that statins reduce ASCVD does not have the same grade of evidence and is much less or in some RCTs none.
We normally think that if a drug works to prevent disease, it will work in any setting, primary or secondary. However, evidence from RCTs has been different in the case of statins. We have enough and more patients taking statins before they have had any CV events. Therefore, why is it not possible to have evidence for its effectiveness and efficiency? This is a very reasonable question.
Statins are of high importance in another aspect, ‘financial’. In developed and even developing countries statins are among the top 5 drugs prescribed. Furthermore, it’s one of the most expensive medications around out of the top drugs. In the US about 25 billion dollars are spent on statins annually. There is pharmaceutical pressure for prescribing statins in primary prevention because of the huge numbers and the billions of dollars involved. As it has been shown these pharmaceutical lobbying may even influence guideline makers in many different ways. In 2015 the Chief Medical Office in the UK appointed a committee specifically to study Statins and Tamiflu (Ostelmvir) because of the huge controversies.
Currently, with the generic brands of statins available, the profit considerations will certainly be less for the multinationals.
USPSTF 2022 recommendations – and JAMA Editorial LINK
In summary, the three recommendations will cover what current evidence is there for a statin to be used in primary prevention.
There are additional factors that may be needed consideration other than a 10-year risk calculation using traditional calculators.
The editorial recommends personalized risk discussion and decision-making between the patient and the clinician, especially when 10-year risk estimates are in borderline or intermediate ranges.
- family history of premature ASCVD
- chronic kidney disease
- borderline elevation of LDL-C between 160-189 mg/dL
- presence of the metabolic syndrome
- South Asian ancestry
The intensity of therapy varies with the patient’s risk profile. Those who belong to high-risk primary prevention groups (ie, LDL-C 190 mg/dL, diabetes with end-organ damage, or 10-year ASCVD risk 20%) may derive further benefit from the use of high-intensity statin therapy.
Enrollment in most statin RCTs has been low among women, members of some racial and ethnic groups and individuals from outside the US, limiting the wide generalizability of the findings.
NICE guidelines on Statins
GPs should offer atorvastatin 20mg for the primary prevention of CVD to people who have a 10 per cent or greater risk of developing CVD within the next 10 years. The risk of developing CVD should be estimated using the QRISK2 assessment tool.
However, before offering statins for primary prevention, GPs should discuss the benefits of lifestyle modification, and optimise all other modifiable CVD factors if possible. Patients who may need support to change their lifestyle should be referred to programmes such as exercise referral schemes. They should then be offered the chance to have their risk of CVD assessed again after they have tried to change their lifestyle. Lifestyle adjustments recommended by NICE include being more active, quitting smoking, reducing alcohol intake, eating more healthily and losing weigh