Calcium antagonists-ACE inhibitors combination therapy: objectives and methodology of clinical development.
The practical objectives of a combination therapy are to obtain a better control of blood pressure (BP), and/or to improve tolerability through the use of lower doses of existing component. The prescription, in a single pill, of an angiotensin-converting enzyme (ACE) inhibitor and a calcium blocker has the theoretical and practical advantages of improving compliance by reducing the number of pills that have to be taken daily and the number of boxes the patient must carry. It also has a pharmacologic rationale mainly based on the buffering by ACE inhibitors of the calcium-blocker-induced stimulations of the renin-angiotensin system and the sympathetic nervous system, and on the reinforcement of the ACE inhibitors antihypertensive effect by the calcium-blocker-induced negative sodium balance. As an argument for such combinations, the neutralization of some dihydropyridines side effects, such as palpitations and edemas, must be addressed. The choice of each component dose is to provide a safe first-line indication and effective and flexible stepped-care treatment. It can only be the result of a complex development program, where BP effect measured at peak and at trough is investigated by the coherent utilization of parallel-group, cross-over, and factorial study designs. Safety studies in high-risk patients enrolled in special controlled trials are necessary.(ABSTRACT TRUNCATED AT 250 WORDS)
Menard
J
J
Service de Médecine Préventive Cardio-Vasculaire, Paris, France.
Bellet
M
M
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D012084:Renin-Angiotensin System / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D002121:Calcium Channel Blockers