Adaptive changes in the acute haemodynamic effects of cilazapril during chronic treatment. Comparison with long-term clinical effect.
OBJECTIVE
To study the adaptive changes in the acute haemodynamic response to ACE inhibition during chronic treatment in CHF.


METHODS
The acute and chronic effects of oral cilazapril (CLZ) treatment, an ACE-inhibitor with prolonged duration on haemodynamic measures (PCWP, PAP, RAP, CI and SVR) and clinical parameters (Quality-of-Life and NYHA class) were investigated in a double-blind, randomised, placebo-controlled trial in CHF. One hundred and thirty five patients (112 completing) in NYHA Classes II-III, on digitalis and diuretic treatment, were randomised after 2 weeks of placebo run-in, to receive either placebo or CLZ 0.5 mg, 1.0 mg or 2.5 mg daily for 12 weeks, followed by 2 week placebo wash-out. Haemodynamic studies, including exercise tests before and 3 h after medication, were performed on the first and last days of treatment. Measurements were performed at rest and at the maximum exercise level.


RESULTS
In ACEI-naive patients oral CLZ 0.5 and 1 mg/d caused a dose dependent decrease in PCWP and diastolic PAP, and a significant reduction of SVR mg. A slight increase in CI was observed in all groups. The maximum effect was observed 3-5 h post dose. After 12 weeks of oral treatment, the acute response was similar but was attenuated relative to the first dose. Exercise tolerance improved in a dose dependent manner. The NYHA classification remained unchanged or improved in the majority of patients. Entry into the 2.5 mg group had to be terminated at an early stage due to severe adverse events observed after the first dose.


CONCLUSIONS
During chronic treatment, the haemodynamic response to oral cilazapril was attenuated, indicating that continued clinical improvement in patients with CHF on CLZ is independent of to its acute haemodynamic effects.
Larsen
J
J
Department of Cardiology, Hvidovre Hospital, University of Copenhagen, Denmark.
Sykulski
R
R
Jensen
G
G
Dössegger
L
L
Trimarco
B
B
Moccetti
T
T
Glogar
D
D
Schelling
A
A
Bosma
A H
AH
D000328:Adult; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D017315:Cilazapril / Q000008:administration & dosage / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006333:Heart Failure / Q000188:drug therapy*; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged
D000806:Angiotensin-Converting Enzyme Inhibitors; D017315:Cilazapril