Variable clinical response to long-term angiotensin inhibition in severe heart failure: demonstration of additive benefits of alpha-receptor blockade.
The effects of long-term therapy with captopril (CPT) were studied in 11 patients with severe chronic congestive heart failure (CHF). At initiation of therapy, cardiac index increased from 1.88 +/- 0.56 to 2.12 +/- L/min/m2 (p less than 0.05), while pulmonary capillary wedge pressure decreased from 27.9 +/- 7.2 to 17.8 +/- 7.6 mm Hg (p less than 0.01). This improvement in resting cardiac performance was maintained during maximal exercise; however, maximal oxygen uptake was not acutely increased by CPT. During chronic therapy, 6 of 11 patients showed symptomatic improvements; however, only three of these six patients demonstrated an increase in maximal oxygen uptake, which was measured at an average of 13.2 weeks following initiation of therapy. Five patients did not improve clinically during chronic therapy. In these patients, hemodynamic measurements that had improved initially after CPT returned to baseline values during chronic therapy. The addition of prazosin to chronic CPT therapy elicited a beneficial hemodynamic response in all five patients. Thus, the results of long-term therapy with CPT are variable in patients with severe CHF, and symptomatic improvement does not always correlate with objective measurement of exercise capacity. Combined alpha-adrenergic blockade and angiotensin-converting enzyme inhibition appears safe in patients who failed to exhibit a sustained improvement on CPT alone.