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Association aténolol/nif édipine: efficacité et tolérance d’une bithérapie synergique à faibles doses dans le traitement de l’hypertension artérielle

Atenolol/Nifedipine Combination: Efficacy and Tolerability of Low Dose Synergistic Bitherapy for the Treatment of Arterial Hypertension

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Résumé

Les objectifs du traitement de l’hypertension artérielle (HTA) ont été précisés d’après les résultats des grandes enquêtes épidémiologiques. Seule une minorité de patients sous monothérapie atteint et se maintient à un niveau souhaitable de pression artérielle. La pathogénie complexe de l’HTA essentielle, la mise en jeu de contre-régulations nerveuses et humorales, l’hétérogénéité de la réponse individuelle à une classe donnée d’antihypertenseurs, et la survenue d’effets secondaires, expliquent ces échecs et justifient la recherche d’une thérapeutique simple, efficace et bien tolérée par l’association de deux classes d’antihypertenseurs à dose faible. L’association fixe d’aténolol 50mg à la nifédipine à libération prolongée 20mg (A50/N20) permet de bénéficier de l’effet anti-hypertenseur synergique d’un β-bloquant et d’un inhibiteur calcique (dihydropyridine). Plusieurs études en ouvert ou contrôlées en double aveugle ont montré que l’association possédait un effet antihypertenseur plus marqué que ses composants séparés ou que d’autres monothérapies de référence; que l’effet se maintenait au long du nycthémère, notamment au cours des mesures ambulatoires sur 24 heures; que les effets indésirables habituellement observés avec chacune des monothérapies étaient diminués avec l’association de ces deux principes actifs ayant des modes d’action différents et complémentaires; enfin que l’efficacité thérapeutique et la tolérance se maintenaient ou s’amélioraient lors d’études à long terme menées sur 12 mois.

L’association A50/N20 s’inscrit dans la stratégie thérapeutique de l’HTA légère à modérée dès lors qu’une monothérapie de première intention ne répond pas aux critères stricts d’équilibre tensionnel, de tolérance, compromet l’observance par des effets secondaires ou enfin aggrave le fardeau vasculaire par la non prise en compte des facteurs de risque personnels des sujets hypertendus. Dans l’HTA plus sévère l’association A50/N20 peut permettre de remplacer des monothérapies séquentielles ou des associations ne répondant pas aux critères d’efficacité thérapeutique.

Abstract

During recent decades, undeniable progress has been made with regard to the management of arterial hypertension. Larger numbers of patients are aware they have hypertension, receive treatment and benefit from this therapy. Furthermore, significant reductions have been observed in morbidity and mortality resulting from cardiovascular diseases.

The objectives of hypertension treatment have been formulated on the basis of results of extensive epidemiological studies. Only a few patients receiving monotherapy actually achieve and maintain acceptable blood pressure levels. The complex pathogenesis of essential hypertension, the implications of nervous and humoral counter-regulatory effects, the heterogeneous character of individual responses to any given class of antihypertensive treatment and the onset of adverse effects all account for these failures. The search for a simple, effective and well-tolerated treatment based on a low dose combination of 2 classes of antihypertensive agents is consequently legitimate. The fixed combination of atenolol 50mg and sustained release nifedipine 20mg enables patients to benefit from the antihypertensive synergy of a β-blocker and a calcium antagonist (dihydropyridine). Several open-ended or double-blind, controlled studies have shown that this combination produces a more marked antihypertensive effect than the individual components used alone or other reference monotherapies. Furthermore, it has been shown that this effect persists throughout the entire 24-hour period; this has been confirmed by 24-hour blood pressure monitoring. Short and medium term tolerability is significantly improved: the side effects commonly associated with the 2 drugs when used alone are reduced with the combination formulation since the 2 active substances have different and complementary mechanisms of action. In addition, long term studies have shown that therapeutic efficacy and tolerability remain stable and have even been seen to improve over a 12-month period.

The fixed combination of atenolol-nifedipine has a role in strategies for the treatment of mild to moderate hypertension, particularly under the following conditions:

  • —when first-line monotherapy has failed to attain specific clearly defined objectives, including stabilised blood pressure levels together with acceptable tolerability

  • —when patient compliance is jeopardised as a result of undesirable side effects

  • —when the vascular burden is aggravated through lack of attention to individual risk factors in hypertensive patients.

In more serious forms of hypertension, the atenolol-nifedipine combination can replace sequential monotherapies or other combination treatments that have failed to comply with the various criteria of therapeutic efficacy.

Controlling arterial hypertension commonly requires polytherapy with 3 or even 4 different drugs in conjunction with particularly strict rules governing hygiene and diet. The addition of the fixed combination of atenolol-nifedipine simplifies the treatment of patients with arterial hypertension by limiting the daily doses and reducing laboratory monitoring.

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  1. Service d’Endocrinologie et de Médecine Interne, Hôpital Avicenne, 125 rue de Stalingrad, 93000, Bobigny, France

    A. Krivitzky, G. Nguyen, Y. Gaudouen, M. Legrand & R. Cohen

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  1. A. Krivitzky
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  2. G. Nguyen
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  3. Y. Gaudouen
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  4. M. Legrand
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  5. R. Cohen
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Krivitzky, A., Nguyen, G., Gaudouen, Y. et al. Association aténolol/nif édipine: efficacité et tolérance d’une bithérapie synergique à faibles doses dans le traitement de l’hypertension artérielle. Drugs 56 (Suppl 2), 31–43 (1998). https://doi.org/10.2165/00003495-199856002-00004

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