title: The addition of mibefradil to chronic hydrochlorothiazide therapy in hypertensive patients is associated with a significant antihypertensive effect.
abstract: OBJECTIVE
  To evaluate the antihypertensive efficacy, tolerability, safety, and dose-response characteristics of the novel calcium antagonist, mibefradil, in combination with a diuretic regimen.
  
  
  METHODS
  A multinational, double-blind, randomised, placebo-controlled, parallel-design trial.
  
  
  METHODS
  Three hundred and seven patients whose mild-to-moderate essential hypertension remained uncontrolled after 4 weeks of treatment with hydrochlorothiazide (HCTZ) 25 mg/day and placebo were randomised to receive combined treatment with HCTZ and once-daily doses of 12.5, 25, 50, or 100 mg of mibefradil or placebo. After 8 weeks of combined treatment, HCTZ was withdrawn and the mibefradil groups continued on their respective doses for an additional 6 weeks.
  
  
  RESULTS
  After 8 weeks, the addition of once-daily doses of mibefradil to the initial HCTZ regimen resulted in clinically relevant, dose-related reductions in sitting diastolic blood pressure (SDBP) and sitting systolic blood pressure (SSBP) at trough, which were significantly greater in the 50 and 100 mg dose groups compared to the placebo group (P < or = 0.003). Placebo-corrected treatment effects on SDBP and SSBP at the end of the combined treatment period relative to baseline were, respectively, -4.1 and -8.0 mm Hg in the 50 mg mibefradil group and -9.5 and -8.0 mm Hg in the 100 mg mibefradil group. Therapeutic response rates to combination mibefradil and HCTZ therapy were high and dose related, reaching 82% for SDBP in the 100 mg group.
  
  
  CONCLUSIONS
  The addition of once-daily doses of 50 or 100 mg of mibefradil to patients whose hypertension is not controlled by HCTZ alone is well tolerated and effective in improving BP control.
authors.affiliation: John Hunter Hospital, Medicine, Newcastle, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Carney
authors.forename: L
authors.initials: L
authors.lastname: Wing
authors.forename: A
authors.initials: A
authors.lastname: Ribeiro
authors.forename: R
authors.initials: R
authors.lastname: Kallwellis
authors.forename: R
authors.initials: R
authors.lastname: Zimlichman
authors.forename: R J
authors.initials: RJ
authors.lastname: Viskoper
authors.forename: D
authors.initials: D
authors.lastname: Mion
authors.forename: I
authors.initials: I
authors.lastname: Kobrin
mesh_terms: D000328:Adult; D000368:Aged; D001562:Benzimidazoles / Q000008:administration & dosage* / Q000009:adverse effects; D002121:Calcium Channel Blockers / Q000008:administration & dosage*; D004232:Diuretics; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage* / Q000009:adverse effects; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D020748:Mibefradil; D008875:Middle Aged; D049993:Sodium Chloride Symporter Inhibitors / Q000008:administration & dosage*; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D001562:Benzimidazoles; D002121:Calcium Channel Blockers; D004232:Diuretics; D049993:Sodium Chloride Symporter Inhibitors; D013764:Tetrahydronaphthalenes; D006852:Hydrochlorothiazide; D020748:Mibefradil