With the new 2021 European Society of Cardiology recommendations on the prevention of cardiovascular disease, most women are (wrongly?) excluded from statin treatment for primary prevention!

For optimal prevention of cardiovascular disease (CVD), a number of learned societies regularly publish recommendations, whose updates always prompt comments on their applicability in "real life", and comparisons between them. While the epidemiological studies and therapeutic trials selected by the experts are the same, it is the populations with different levels of risk and the organizational model of the various countries that explain the differences between what is proposed by the different societies.

In 2021, the European Society of Cardiology (ESC) recommended a new model for estimating the 10-year risk of cardiovascular events, entitled SCORE 2 (Systematic Coronary Risk Evaluation 2). This involves calculations that take into account various characteristics of the subject, such as age, sex, smoking habits, blood pressure and cholesterol levels, etc., to calculate the probability of developing CVD in a given period. In practice, a 10% 10-year risk level means that out of 100 people with these characteristics, 10 will suffer an accident in the next 10 years in the absence of intervention. Skeptics will point out that, even if we don't intervene, 90 of these 100 subjects will not have an accident, so we're "treating them for nothing". We know that this approach, which takes into account the level of risk, is very important for treating the subjects who are most at risk and who will therefore derive the greatest benefit. The limit is the considerable role played by age in the level of risk, and a strict application of this method leads to young subjects with little risk not being treated within 10 years, and to over-treatment of all elderly subjects who are inevitably at high risk.
The ideal situation would be to have to treat few subjects to avoid many events, in a short space of time and, what's more, with inexpensive treatment! This is generally the case, except in terms of cost, in secondary prevention (i.e. when the patient has already had a cardiovascular or cerebrovascular accident), where the question does not arise, as these patients are at high risk of recurrence and the treatments prescribed are rapidly effective. The problem is more difficult to resolve in primary prevention, where patients are "only at risk" of events (which may only occur a long time later, or perhaps never)... and who, if treated, may present side-effects when the indication could be questionable, with a significant cost of treatment over a prolonged period for a supposed benefit. In short, in addition to the classic benefit/risk ratio, there's also the cost/effectiveness ratio.

According to the ESC 2021 Recommendations, the thresholds for initiating statin-based lipid-lowering treatment are a 10-year CVD risk calculated by SCORE 2 >or = 7.5% between 40 and 49 years of age and > or = 10% between 50 and 69 years of age.

Observational study

To gain a better understanding of the impact of these Recommendations on the population, a cohort study of 66,909 subjects was carried out in Denmark on the general population of Copenhagen, among apparently healthy subjects aged 40 to 69, with an average follow-up of 9.2 years.


Evaluation criteria included statin eligibility according to the Recommendations and the quality of the estimate for predicting the occurrence of CVD events, by comparing the performance of these Recommendations with that of other Recommendations: those of the American College of Cardiology / American Heart Association (ACC/AHA); those of the United Kingdom (National Institute for Health and Care Excellence, NICE); and those of the European Atherosclerosis Society (EAS) / associated with the ESC dating from 2019 since we will be able to compare during this follow-up the number of events actually occurring compared with what had been predicted by the calculation.

Main results

During the follow-up, 2962 non-fatal accidents occurred and 4277 fatalities were observed. The European SCORE 2 model predicted the 10-year CVD event risk better than the models proposed in the USA and the UK. On the other hand, the number of people eligible, i.e. likely to receive statin treatment, was lower. We looked at how many people would be eligible, depending on the Recommendation used. For the European ESC 2021 recommendations, in primary prevention in people aged 40 to 69, 2862 out of 66,909, or just 4%, were eligible, compared with 34% with ACC/AHA (United States), 26% with UK-NICE (United Kingdom) and 20% with the previous 2019 European ESC/EAS Recommendations.

Few women were eligible!

By applying these criteria, the majority of women would not be eligible for statin treatment because the estimate places them at too low a risk level. We come back to the very classic fact of lower CVD risk in women following these calculation models, which is at the root of the erroneous belief of natural protection and hence of a lower level of treatment.

As the number of subjects who can benefit from treatment depends on the threshold chosen, the authors calculated what level should be retained for these Recommendations to match other Recommendations to obtain a similar result: SCORE 2 must be reduced to 5% to match the American Recommendations, to 6% to match those of the UK and to 7% to match the previous 2019 European Recommendations.
An important limitation is that the study was conducted in a low cardiovascular risk country. The recommendations separated the countries into 4 levels with 4 different calculation models (France is in the lowest risk). Denmark is in the low-risk category, which further increases the number of people who need to be treated to avoid an event.

Comments

The 2021 European recommendations have been criticized for strongly encouraging the prescription of drug treatments, by focusing on secondary prevention, with a cholesterol target so low that it will require the use of several drugs to be achieved, including the most recent, which are also the most expensive. We can see that this is not the case for primary prevention, with women in particular, especially younger women, no longer being treated.











In conclusion:
Despite an improved cardiovascular risk prediction model (SCORE 2), the new treatment thresholds proposed by the 2021 European Society of Cardiology Recommendations considerably reduce eligibility for statins in primary prevention in low-risk European countries, particularly women and young subjects. Choosing a single "lower" risk level to trigger the prescription of a statin treatment could enable better prevention of cardiovascular disease, particularly in women.
However, it must be emphasized and reiterated that, irrespective of the level of cardiovascular risk, an LDL cholesterol level of 1.6 g/l constitutes an indication for treatment, whatever the clinical context, and that the LDL cholesterol target of 0.55 g/l for secondary prevention is perfectly valid "whatever the cost".
In this context, the prescription of an appropriate statin remains a fundamental element in the prevention of CVD, including in primary prevention, the most difficult task perhaps being to convince patients to take them...


Reference :
Mortensen MB, Tybjærg-Hansen A, Nordestgaard BG. Statin Eligibility for Primary Prevention of Cardiovascular Disease According to 2021 European Prevention Guidelines Compared With Other International Guidelines. JAMA Cardiol. 2022 Jul 6.