Long-term changes in the response of conductance and resistance coronary vessels to endothelium-dependent and independent vasodilators. A double-blind placebo-controlled study of the effect of a 6-month treatment with cilazapril.
BACKGROUND
The aim of this study was to assess the effect of a 6-month treatment with the inhibitor of the angiotensin-converting enzyme cilazapril on the response of conductance and resistance vessels to endothelium-dependent and independent vasodilators, in a randomized placebo-controlled parallel group single center study.


METHODS
Quantitative angiographic and Doppler flow time-averaged peak velocity measurements were performed in an artery with < 30% diameter stenosis after sequential selective intracoronary injection of papaverine (7 mg), acetylcholine (0.036, 0.36 and 3.6 microg/ml at 2 ml/min) and isosorbide dinitrate. Repeated assessment was performed after a 6-month treatment with cilazapril 20 mg/day or placebo. Thirty-four patients were enrolled in the study undergoing elective percutaneous coronary interventions for stable angina. Main outcome measures were percent differences from baseline and absolute measurements of mean coronary cross-sectional area, coronary flow time-averaged peak velocity and flow resistance in the initial study and at follow-up for the placebo and the treated group.


RESULTS
No significant differences between the placebo and the treated group were observed in the modifications of cross-sectional area after acetylcholine and isosorbide dinitrate and in the response of time-averaged peak velocity to papaverine. After the maximal concentration of acetylcholine a high but statistically not significant increase in flow and a decrease in flow resistance were observed in the treated group (medians: 45% increase vs 4% increase for coronary flow, and 44% decrease vs 1% increase for flow resistance in the cilazapril and in the treated group, respectively, p = NS).


CONCLUSIONS
In patients with coronary artery disease, a 6-month treatment with 20 mg of cilazapril/day did not modify the response to endothelium-independent and dependent vasodilators of epicardial arteries without any significant stenoses but induced a consistent, although not significant, increase in flow and decrease in flow resistance after acetylcholine.
Di Mario
C
C
Division of Cardiology, Thoraxcenter, Erasmus University, Rotterdam, The Netherlands.
Strikwerda
S
S
Gil
R
R
Azar
A
A
Rames
A
A
Serruys
P W
PW
D000109:Acetylcholine / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D017315:Cilazapril / Q000627:therapeutic use*; D003326:Coronary Circulation / Q000187:drug effects*; D003327:Coronary Disease / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007548:Isosorbide Dinitrate / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D010208:Papaverine / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D014665:Vasodilator Agents; D017315:Cilazapril; D010208:Papaverine; D007548:Isosorbide Dinitrate; D000109:Acetylcholine