Determinants of the blood pressure response to the first dose of ACE inhibitor in mild to moderate congestive heart failure.
OBJECTIVE
To investigate the relationship in patients with heart failure between BP response to the first dose of ACE inhibitor and (1) plasma drug concentration and (2) baseline clinical and laboratory variables.


METHODS
We studied individual placebo-corrected BP responses to initiation of treatment with one of a number ACE inhibitor preparations in 132 patients with mild to moderate CHF. Various pharmacokinetic/pharmacodynamic models were compared. We assessed the strength of association between baseline physiological and laboratory variables and the BP response as assessed directly from the AUC(0,10 h) and indirectly from the slope of the PK/PD relationship. Predictive models for response variables were developing using regression analysis.


RESULTS
BP response was primarily related to plasma drug concentration. The association between the fall in BP and baseline variables was weak. The strongest single predictor of BP response was baseline mean arterial pressure (r2 = 5.8%, P = 0.02). The best combinations of predictor variables contained mean arterial pressure, plasma renin activity, creatinine concentration and age (r2 = 14.4%, P = 0.37). When the choice of ACE inhibitor was added, the predictive power of the model increased (r = 23.6%, P < 0.01) but left the majority of the variability in response unexplained.


CONCLUSIONS
The first-dose blood pressure response to ACE inhibition cannot be accurately predicted from baseline pathophysiological variables in patients with mild to moderate CHF. The choice of ACE inhibitor accounts for a small proportion of the variability in response but wide inter-individual variability exists in the response to each treatment.
Murray
L
L
University of Glasgow, Department of Medicine and Therapeutics, Gardiner Institute, Western Infirmary, Scotland.
Squire
I B
IB
Reid
J L
JL
Lees
K R
KR
D000368:Aged; D000369:Aged, 80 and over; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019540:Area Under Curve; D001794:Blood Pressure / Q000187:drug effects*; D004311:Double-Blind Method; D005260:Female; D006333:Heart Failure / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D012044:Regression Analysis
D000806:Angiotensin-Converting Enzyme Inhibitors