CLINICAL RESEARCH: CORONARY ARTERY DISEASE
The angiographic and clinical benefits of mibefradil in the coronary slow flow phenomenon
John F. Beltrame, BSc, BMBS, FRACP, PhD, FESC, FACC*,*,
Stuart P. Turner, BMed, FRACP*,
Sue L. Leslie, RN*,
Patty Solomon, BSc, Dip Maths Stats, PhD ,
Saul B. Freedman, MBBS, FRACP, PhD, FACC and
John D. Horowitz, MBBS, BMed Sci, PhD, FRACP*
* Cardiology Unit, North Western Adelaide Health Service, University of Adelaide, Adelaide, Australia
School of Applied Mathematics and ARC Special Research Centre for Molecular Genetics of Development, University of Adelaide, Adelaide, Australia
Department of Cardiology, Concord Repatriation General Hospital, and Anzac Research Institute, University of Sydney, Sydney, Australia
Manuscript received December 31, 2003;
revised manuscript received March 5, 2004,
accepted March 16, 2004.
* Reprint requests and correspondence: Dr. John F. Beltrame, Cardiology Unit, North Western Adelaide Health Service, The Queen Elizabeth Hospital Campus, 28 Woodville Road, Woodville South SA 5011, Australia.
john.beltrame{at}adelaide.edu.au
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.
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Abbreviations and Acronyms
| | CSFP | = coronary slow flow phenomenon | | CTFC | = corrected TIMI frame count | | ECG | = electrocardiogram | | LAD | = left anterior descending artery | | SF-36 | = Health Outcome Study Short Form-36 | | TIMI | = Thrombolysis In Myocardial Infarction |
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