title: [Clinical development of therapy with two antihypertensive agents in fixed combination].
abstract: Changing the blood pressure brings counter-regulatory effects into play which may impair the antihypertensive efficacy of treatment targeted at a single blood pressure regulatory factor. Thus, diuretics stimulate the renin angiotensin and catecholamine systems and, in some cases, vasopressin. Arteriolar vasodilators stimulate the sympathetic nervous system and renin-angiotensin system, while blockade of the renin-angiotensin system itself triggers a reactive release of renin which may then serve to restore normal circulating angiotensin II levels. Rational combinations can therefore be developed to neutralize the effects of counter-regulation and achieve blood pressure control at lower drug doses and hence with fewer side-effects. Such combinations can also be prescribed in steadily increasing doses of each drug, to achieve blood pressure control by a process of 3-stage titration. The stringent rules governing the clinical development of such combinations are reviewed: formulation, pharmacokinetics, pilot studies, factorial design, high-risk patients. One advantage of combination therapy is that it enhances compliance, as an entire treatment is contained in a single pack of drugs. A disadvantage is the potential multiplicity of combinations between the five or six major classes of antihypertensive drug.
authors.affiliation: Service de médecine préventive cardiovasculaire, Hôpital Broussais, Paris, France.
authors.forename: I
authors.initials: I
authors.lastname: Ménard
mesh_terms: D000959:Antihypertensive Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*
chemical_list: D000959:Antihypertensive Agents
vernacular_title: Le développement clinique d'une bithérapie antihypertensive en combinaison fixe.