Effets cardio-vasculaires des antidiabétiques

377

Les complications cardiovasculaires
(CV) représentent aujourd’hui encore la
première cause de décès chez les patients
atteints de diabète de type 2 (DT2). Leur
prévention exige une prise en charge..

Les complications cardiovasculaires
(CV) représentent aujourd’hui encore la
première cause de décès chez les patients
atteints de diabète de type 2 (DT2). Leur
prévention exige une prise en charge de
tous les facteurs de risque.
Si un équilibre glycémique optimal est
bénéfique contre les complications micro-vasculaires et les complications CV,
il ne devient significatif qu’après un
temps de suivi plus long.
Aujourd’hui, face à la multitude de nouveaux anti-hyperglycémiants, la question des effets CV spécifiques des traitements du diabète se pose désormais avec
une acuité croissante.
Metformine
L’étude UKPDS (United Kingdom
Prospective Diabetes Study, étude prospective au Royaume-Uni sur les diabétiques de type 2), qui a suivi 342 patients pendant 10 ans, a révélé que le
groupe traité par metformine a montré
une réduction de 39 % des infarctus du
myocarde et des décès de toute cause.
Cette étude est néanmoins entachée par
le faible nombre de sujets, et par le fait
que y ont participé étaient tous obèses,
ce qui limite les conclusions de l’étude.
De nombreuses analyses rétrospectives
avec de grandes cohortes de patients
ont conclu que la metformine réduisait
l’incidence des événements cardiovasculaires et améliorait la survie indépendamment du contrôle glycémique chez
des patients avec une maladie coronarienne. Malheureusement, ces études
ont souvent comparé la metformine à
un sulfamide hypoglycémiant (SU) et il
reste difficile de savoir si la metformine
diminue les événements cardiovasculaires ou si les SU les augmentent.
Dans une revue systématique portant sur
34 000 patients, les auteurs concluent
que la metformine peut être adminis-
FORMATION CONTINUE
trée sans risque chez des patients avec
une insuffisance cardiaque congestive,
même avec une fraction d’éjection ventriculaire gauche abaissée ou avec une
atteinte rénale, sous réserve de l’adaptation des doses.
En résumé, la metformine demeure
un produit sûr sur le plan cardiovasculaire chez les patients diabétiques
de type 2 et pourrait même réduire la
mortalité et la morbidité cardiovasculaires.
Sulfamides hypoglycémiants (SU)
Depuis l’étude UGDP publiée en 1970,
qui avait retrouvé un effet délétère des
SU de première génération sur la morbi-mortalité CV, les études d’observation vont majoritairement dans le même
sens. Comparativement aux autres anti-hyperglycémiants et notamment à la
metformine, et après multiples ajustements, les SU sont associés à une majoration du risque CV [1]. Le mécanisme
le plus souvent évoqué pour expliquer
ce possible effet délétère des SU est celui d’une altération de l’effet protecteur
du pré-conditionnement ischémique
sur le risque d’infarctus du myocarde
(IDM), en raison de leur rôle inhibiteur
des canaux K+ ATP-sensibles des cellules myocardiques.
L’étude ADVANCE a montré que les
hypoglycémies sévères étaient associées
à une augmentation significative des
événements cardiovasculaires et des décès de cause cardiovasculaire. De nombreuses études rétrospectives, ainsi que
quelques-unes prospectives, ont montré
une augmentation du risque cardiovasculaire chez les patients diabétiques de
type 2 traités par SU, surtout chez ceux
traités par glibenclamide. Toutefois, ceci
n’a pas été démontré dans les études
UKPDS, ADVANCE et ACCORD.
Le SU qui semble le plus sûr en termes
cardiovasculaires est le gliclazide, bien
que les études bien conduites fassent défaut.
En résumé, les études actuelles ne
permettent pas de certifier l’innocuité
cardiovasculaire des SU.
Glinides
Les glinides augmentent la sécrétion
d’insuline et sont généralement de
courte durée d’action, avec une administration juste avant les repas, réduisant
le pic de glycémie postprandiale.
En raison de leur courte durée d’action,
elles sont associées à une prise

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