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Efficacité et effets indésirables des statines: évidences et polémiques - 15/06/19

Efficacy and side effects of statin therapy: a reappraisal

Doi : 10.1016/S0001-4079(19)30249-3 
Michel Komajda

au nom de la Commission IV (Maladies cardiovasculaires)

 Membre de l’Académie nationale de médecine 

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ABSTRACT

The introduction of statin therapy for the management of hypercholesterolemia was a breakthrough for the prevention of cardio vascular events in this condition and in patients at high cardio vascular risk, especially in people who have an evident cardio vascular disorder such as myocardial infarction or stroke.

However recurrent criticisms raised questions on their efficacy and safety and led a substantial proportion of patients treated by this class of medication to stop their medication.

The purpose of the report of the Académie nationale de médecine is to review evidences for efficacy, adverse effects of statin therapy and to analyze the causes of the « statin crisis » observed in several countries and in particular in France.

Evidence for benefit in the prevention of cardio vascular diseases:

The excess of cholesterol bound to low density lipoproteins is a well defined risk factor of cardio vascular diseases. The evidence derives from epidemiological studies, from the outcomes of familial hypercholesterolemia and from genome wide association studies.

The mechanism of action of statins is linked to the inhibition of the cholesterol synthesis within the liver whereas other effects so called « pleiotropic » play a minimal role if any.

High cholesterol plasma level is one out of other risk factors such as hypertension smoking or diabetes and international guidelines have released scores which allow to determine low, intermediate, high and very high risk subpopulations regarding the occurrence of major cardio vascular events.

The magnitude of the reduction in LDL cholesterol is dependent on the type of statin, the two most powerful being atorvastatin and rosuvastatin and on dosage.

The benefit conferred by statins has recently been evaluated in a large meta-analysis showing that treating 10 000 patients at high cardio vascular risk prevents 1440 major cardio vascular events when LDL cholesterol is lowered by 2mM/L.

Statins are therefore a key treatment in patients at high or very high cardio vascular risk, particularly in secondary prevention.

In patients at low risk statins also reduce the cardio vascular risk but the benefit is counterbalanced by the number of patients needed to treat, cost and side effects.

Pharmaco-economic considerations are also important in this setting.

Therefore there is consensus on the need to treat patients in secondary prevention or in primary prevention at high or very high cardio-vascular risk whereas the decision to treat people in low or intermediate risk categories should be individualized and take into consideration the benefit/risk ratio and cost.

Muscular side effects are the most common adverse effects of statin therapy and are observed in 10-25 % of cases. They most often consist of muscular pain without evidence of muscular damage but in a minority of cases a myositis with necrosis of muscular tissue or a rhabdomyolisis with a risk of acute renal failure can occur. Dosage of Creatine Phospho kinase is recommended upon initiation of therapy and in case of muscular symptoms in order to detect the most severe forms of muscular side effects. Several risk factors have been identified including older age, female gender, alcohol consumption or treatment by colchicine.

Liver toxicity with elevated liver enzymes has also been reported but it is uncommon.

An increase in incident diabetes mellitus has also been reported particularly with rosuvastatin and atorvastatin but it seems to be a class effect and it is dose dependent. The underlying mechanism is unknown and the small increase in cardio vascular risk is offset by the cardio vascular benefit conferred by this therapy.

Finally concerns on the potential risk of cognitive disorders have not been confirmed so far and some studies suggest on the contrary that statin therapy might slow down cognitive decline.

Following several campaigns against statin therapy in France, it has been shown that the number of patients stopping their treatment had increased significantly including patients in secondary prevention, leading to a potential increase in major cardio vascular events.

Several factors can explain why some patients are reluctant to start or continue their treatment:

A general concern about human activities and manufactured products including drugs versus « natural » products.
The loss of trust by the public in institutions and experts
The role of new media and social networks leading to the viral diffusion of biased or fake news.

In conclusion the favorable benefit risk of statin therapy in patients with documented cardio vascular disease or at high risk is well documented and patient education on the benefit and adverse reaction of this class is key in order to restore trust it is in particular of paramount importance to inform patients of the risk induced by treatment interruption.

El texto completo de este artículo está disponible en PDF.

RÉSUMÉ

L’introduction des statines comme traitement des dyslipidémies a révolutionné la prise en charge de cette pathologie et de multiples études randomisées et contrôlées ont confirmé que cette classe thérapeutique réduisait les évènements cardio-vasculaires majeurs en prévention secondaire et en prévention primaire. Cette classe de médicaments est actuellement recommandée par les recommandations internationales afin de réduire le risque cardio-vasculaire en diminuant le taux de LDL cholestérol circulant avec un niveau de preuve très élevé. Cependant une polémique récurrente a alimenté les Interrogations de la population sur l’efficacité et l’innocuité des statines et conduit de nombreux patients à interrompre leur traitement. Ce rapport a pour but d’analyser de manière objective les preuves en faveur de l’efficacité, de l’efficience et des effets indésirables des traitements par statines, mais aussi d’étudier les raisons qui sous-tendent la polémique et les conséquences pour la population des arrêts intempestifs de traitement.

El texto completo de este artículo está disponible en PDF.

Mots clés : Statines, Prévention, Risque cardio-vasculaire, Effets indésirables, Efficacité

Key words : Statins, Orevention, Cardiovascular risk, Side effects, Efficacity


Esquema


 Un rapport exprime une prise de position officielle de l’Académie. L’Académie, saisie dans sa séance du mardi 22 mai 2018, a adopté le texte de ce rapport avec 43 voix pour, 14 voix contre et 19 abstentions.
 Rapport relu et amendé par la Commission IV de l’Académie nationale de médecine.


© 2018  l’Académie nationale de médecine. Publicado por Elsevier Masson SAS. Todos los derechos reservados.
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