DETERMINANTS OF THE BLOOD-PRESSURE RESPONSE TO THE FIRST DOSE OF ACE-INHIBITOR IN MILD-TO-MODERATE CONGESTIVE-HEART-FAILURE

Aims To investigate the relationship in patients with heart failure be tween BP response to the first dose of ACE inhibitor and (1) plasma dr ug concentration and (2) baseline clinical and laboratory variables. M ethods We studied individual placebo-corrected BP responses to initiat ion of treatment with one of a number ACE inhibitor preparations in 13 2 patients with mild to mo derate CHF. Various pharmacokinetic/pharmac odynamic models were compared. We assessed the strength of association between baseline physiological and laboratory variables and the BP re sponse as assessed directly from the AUC(0,10 h) and indirectly from t he slope of the PK/PD relationship. Predictive models for response var iables were developing using regression analysis. Results BP response was primarily related to plasma drug concentration. The association be tween the fall in BP and baseline variables was weak. The strongest si ngle predictor of BP response was baseline mean arterial pressure (r(2 )=5.8%, P= 0.02). The best combinations of predictor variables contain ed mean arterial pressure, plasma renin activity, creatinine concentra tion and age (r(2)=14.4%, P=0.37). When the choice of ACE inhibitor wa s added, the predictive power of the model increased (r(2) = 23.6%, P< 0.01) but left the majority of the variability in response unexplaine d. Conclusions The first-dose blood pressure response to ACE inhibitio n cannot be accurately predicted from baseline pathophysiological vari ables in patients with mild to moderate CHF. The choice of ACE inhibit or accounts for a small proportion of the variability in response but wide inter-individual variability exists in the response to each treat ment.