The angiographic and clinical benefits of mibefradil in the coronary slow flow phenomenon.
OBJECTIVE
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.
Beltrame
John F
JF
Cardiology Unit, North Western Adelaide Health Service, University of Adelaide, Adelaide, Australia. john.beltrame@adelaide.edu.au
Turner
Stuart P
SP
Leslie
Sue L
SL
Solomon
Patty
P
Freedman
Saul B
SB
Horowitz
John D
JD
D000328:Adult; D015415:Biomarkers / Q000097:blood; D001783:Blood Flow Velocity / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D002097:C-Reactive Protein / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000627:therapeutic use*; D017023:Coronary Angiography; D003327:Coronary Disease / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology*; D003331:Coronary Vessels / Q000000981:diagnostic imaging / Q000503:physiopathology; D018592:Cross-Over Studies; D003971:Diastole / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004452:Echocardiography; D015716:Electrocardiography, Ambulatory; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D020748:Mibefradil / Q000008:administration & dosage / Q000627:therapeutic use*; D008875:Middle Aged; D010349:Patient Compliance; D013223:Statistics as Topic; D013599:Systole / Q000187:drug effects; D016896:Treatment Outcome; D019210:Troponin I / Q000097:blood
D015415:Biomarkers; D002121:Calcium Channel Blockers; D019210:Troponin I; D020748:Mibefradil; D002097:C-Reactive Protein