Statins for primary prevention of cardiovascular disease: less enthusiasm?

The US Prevention Services Task Force (USPSTF) has just reiterated its previous recommendations, dating from 2016, for individuals between the ages of 40 and 75, with no known CVD or history of familial hypercholesterolemia, and with LDL cholesterol (LDL-C or bad cholesterol) below 1.9 g/L: - There is a benefit to starting moderate-intensity statin therapy in adults whose 10-year CVD risk is estimated to be 10% (this is still the well-known cardiovascular risk assessment) or higher and in cases of dyslipidemia, diabetes, hypertension, and/or smoking.

- It is less certain but possible to start statin treatment, taking the patient's opinion into account, in cases where the 10-year CV risk is estimated to be between 7.5 and 10% in the presence of a CVD risk factor.

- There is insufficient evidence to establish the benefit/risk ratio of starting statin treatment at age 76 or older, regardless of the estimated 10-year risk.

To analyze these three recommendations in greater depth, the USPSTF reviewed the results of 22 studies involving a total of 90,624 participants followed for an average of three years (only one study involved subjects aged 70 to 82).

Overall, the results show that taking statins leads to a small but statistically significant reduction in the risk of all-cause mortality and the risk of myocardial infarction or ischemic stroke.

This recent finding contradicts that of a previous analysis, dating from 2010, which involved high-CV-risk patients in primary prevention and found no benefit of statins on overall mortality.

Furthermore, in contrast to the 2016 recommendations, the USPSTF no longer recommends the use of low-dose statins only in certain specific situations, as 12 of the 22 studies used moderate doses and it is accepted that the frequency of side effects increases with higher doses.
Finally, these 2022 recommendations acknowledge "uncertainty in individual prescription risk," in contrast to those of 2016. Comments from our expert: At Agir pour le Cœur des Femmes, we also regret that these studies did not include a specific analysis of women, as it is accepted that women up to the age of 75 have a more favorable calculated risk profile than men and therefore the benefit/risk ratio of taking statins is less favorable in women than in men, which is not mentioned in the 2022 USPSTF recommendations.

In addition, it should be noted that the inclusion criteria varied greatly between studies and that subjects not eligible for primary prevention may have been included. There is also a difference between the "statistical" significance of a trial and the actual clinical benefit, particularly for low-risk categories, even though the possibility of side effects remains the same.

Furthermore, the thresholds used to define risk and efficacy levels (5%, 7.5%, or even 10-20%) are arbitrary, sometimes dating back several decades, and do not take into account the impact of changes brought about by better diet, increased physical activity, more effective blood pressure control, and reduced smoking. The assessment of CV risk in many individuals is therefore no longer appropriate. Based on these observational studies, the USPSTF found that statins had no adverse effects on muscles, the liver, new cases of diabetes, cognitive impairment, or cancer. However, in daily practice, the reported "iatrogenic" effects are not so rare, even if muscle disorders are often associated with a nocebo effect (the opposite of the placebo effect). In some observational studies, their frequency is reported at 10%, leading to a reduction in doses or even complete discontinuation of treatment. The risk of developing diabetes is particularly high in individuals who are already "pre-diabetic." These potential adverse effects must be taken into account because these are "healthy" adults. For this reason, the USPSTF, like other major institutions, particularly in Europe, emphasizes the importance of sharing the decision with the patient. It also highlights the potential benefits of stopping statin treatment in people over 75, due to the lower expected benefit in primary prevention and the increased risk of side effects, as people of this age are often on multiple medications. However, the benefits of continuing treatment remain... Finally, it should be noted that nearly $25 billion is spent on statins each year. Could this be one of the keys to the problem? Statins are an "easy" and effective solution for lowering LDL-C, but shouldn't we, for those who are still healthy, create a healthier environment by encouraging physical activity and promoting a more balanced diet? In this sense, the 2022 USPSTF recommendations can be seen as an opportunity to improve the future and epidemiology of CVD. Reference: Habib A.R. et al.: Statins for Primary Cardiovascular Disease Prevention. Time to Crumb Our Enthusiasm. JAMA Intern Med; 2022.