title: Adding the new calcium antagonist mibefradil to patients receiving long-term beta-blocker therapy results in improved antianginal and antiischemic efficacy.
abstract: OBJECTIVE
  The objective of this study was to evaluate the efficacy, tolerability, and safety of mibefradil, a new selective T-type calcium channel blocker, in patients with chronic stable angina pectoris receiving concomitant beta-blocker therapy.
  
  
  METHODS
  This was a multicenter, double-blind, placebo-controlled study.
  
  
  METHODS
  Ninety-five patients receiving a stable dose of beta-blockers, which was not changed for the purpose of the study, were administered either 50 mg mibefradil once daily for 2 weeks, then 100 mg once daily for 2 weeks, or matching placebo. Efficacy was evaluated by treadmill exercise tolerance testing 24 hours after dose and by diary registration of anginal episodes and nitroglycerin consumption.
  
  
  RESULTS
  Two weeks of treatment with 50 mg mibefradil resulted in a significant increase in symptom-limited exercise duration and a significant delay in the onset of persistent 1 mm ST-segment depression (placebo-corrected treatment effect: 23.2 and 51.7 seconds, respectively). Treatment with the 100 mg dose for 2 additional weeks resulted in a larger improvement in treadmill exercise tolerance testing duration and onset of ischemia (placebo-corrected treatment effect: 52.7 and 75.8 seconds, respectively). In addition, a significant decrease in weekly anginal episodes was observed with the 100 mg dose of mibefradil compared with the effect in the placebo group (-53% vs - 12%, p = 0.037).
  
  
  CONCLUSIONS
  The combined treatment of mibefradil and beta-blockers was well tolerated, and the overall incidence of adverse events was no different from that with beta-blockers alone. The results indicate that adding mibefradil to chronic beta-blocker treatment is associated with significant improvement in efficacy, which is not achieved at the expense of tolerability.
authors.affiliation: Cardiovascular Research Foundation, Tel Aviv, Israel.
authors.forename: A
authors.initials: A
authors.lastname: Schneeweiss
authors.forename: I
authors.initials: I
authors.lastname: Kobrin
authors.forename: V
authors.initials: V
authors.lastname: Charlon
authors.forename: A
authors.initials: A
authors.lastname: Caspi
authors.forename: A
authors.initials: A
authors.lastname: Marmor
authors.forename: S
authors.initials: S
authors.lastname: Sclarovsky
authors.forename: L
authors.initials: L
authors.lastname: Reisin
authors.forename: Z
authors.initials: Z
authors.lastname: Schlesinger
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D000787:Angina Pectoris / Q000188:drug therapy*; D001562:Benzimidazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005080:Exercise Test; D005260:Female; D006801:Humans; D008297:Male; D020748:Mibefradil; D008875:Middle Aged; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors
chemical_list: D000319:Adrenergic beta-Antagonists; D001562:Benzimidazoles; D002121:Calcium Channel Blockers; D013764:Tetrahydronaphthalenes; D020748:Mibefradil