The angiographic and clinical benefits of mibefradil in the coronary slow flow phenomenon

J Am Coll Cardiol. 2004 Jul 7;44(1):57-62. doi: 10.1016/j.jacc.2004.03.055.

Abstract

Objectives: The aim of the study was to assess the angiographic and clinical benefits of the calcium T-channel blocker, mibefradil, in the coronary slow flow phenomenon (CSFP).

Background: The CSFP is characterized by delayed vessel opacification on angiography (Thrombolysis In Myocardial Infarction [TIMI]-2 flow) in the absence of obstructive epicardial coronary disease and is often associated with recurrent chest pain.

Methods: A total of 10 CSFP patients (46 +/- 9 years) underwent angiography before and 30 min after 50 mg mibefradil; off-line blinded analysis of angiographic data included comparisons of epicardial vessel diameter, TIMI flow grade and TIMI frame count. We also performed a randomized, double-blind, placebo-controlled, cross-over study to examine the long-term efficacy of mibefradil 100 mg/day on the frequency of total angina, prolonged angina (i.e., persisting >20 min) episodes, and sublingual nitrate consumption, during consecutive one-month treatment periods in 20 patients (age 51 +/- 12 years) with the CSFP.

Results: Without changing epicardial vessel diameter or rate-pressure product, mibefradil reduced the number of vessels exhibiting TIMI-2 flow from 18 to 5; furthermore, mibefradil significantly improved the TIMI frame count only in those vessels exhibiting TIMI-2 flow (28 +/- 18%, p < 0.005). Compared with placebo, mibefradil significantly reduced total angina frequency by 56% (p < 0.001), prolonged episodes of angina by 74% (p < 0.001), and sublingual nitrate consumption by 59% (p < 0.01); furthermore, mibefradil improved physical quality of life as assessed by the Health Outcome Study Short Form-36.

Conclusions: These angiographic and clinical improvements produced by mibefradil support a microspastic pathogenesis of the CSFP.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Biomarkers / blood
  • Blood Flow Velocity / drug effects*
  • Blood Pressure / drug effects
  • C-Reactive Protein / metabolism
  • Calcium Channel Blockers / administration & dosage
  • Calcium Channel Blockers / therapeutic use*
  • Coronary Angiography*
  • Coronary Disease / diagnosis
  • Coronary Disease / drug therapy*
  • Coronary Disease / physiopathology*
  • Coronary Vessels / diagnostic imaging
  • Coronary Vessels / physiopathology
  • Cross-Over Studies
  • Diastole / drug effects
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Echocardiography
  • Electrocardiography, Ambulatory
  • Female
  • Heart Conduction System / drug effects
  • Heart Conduction System / metabolism
  • Heart Conduction System / physiopathology
  • Heart Rate / drug effects
  • Humans
  • Male
  • Mibefradil / administration & dosage
  • Mibefradil / therapeutic use*
  • Middle Aged
  • Patient Compliance
  • Statistics as Topic
  • Systole / drug effects
  • Treatment Outcome
  • Troponin I / blood

Substances

  • Biomarkers
  • Calcium Channel Blockers
  • Troponin I
  • Mibefradil
  • C-Reactive Protein