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Circulation, Vol 68, 803-812, Copyright © 1983 by American Heart Association

ARTICLES

Hemodynamic patterns of response during long-term captopril therapy for severe chronic heart failure

M Packer, N Medina, M Yushak and J Meller

To determine the relationship between the early and late hemodynamic effects of captopril in patients with severe heart failure, we performed serial right heart catheterizations in 51 such patients who were treated with the drug for 2 to 8 weeks. Four hemodynamic patterns of response were observed. Nine patients had minimal responses initially (type I); six failed to improve during long-term treatment, but three showed delayed hemodynamic benefits. Twenty-eight patients had initial beneficial drug effects that were sustained after 48 hr and after 2 to 8 weeks (type II). In seven patients, first doses of captopril produced marked beneficial responses, but these became rapidly attenuated after 48 hr; nevertheless, continued therapy for 2 to 8 weeks was accompanied by spontaneous restoration of the hemodynamic effects of first doses of the drug, i.e., triphasic response (type III). In the remaining seven patients, attenuation of initial response was not reversed by prolonged captopril therapy; hemodynamic variables after 2 to 8 weeks had returned to their pretreatment values, i.e., drug tolerance (type IV). Plasma renin activity was lower in patients with minimal responses (0.6 +/- 0.2 ng/ml/hr) and was higher in patients with triphasic responses (9.4 +/- 2.5 ng/ml/hr) than in patients with types II and IV response patterns (4.4 +/- 0.7 and 2.8 +/- 0.5 ng/ml/hr, respectively; both p less than .05). Although first-dose effects of captopril are frequently sustained, the occurrence of delayed, attenuated, and triphasic responses indicates that a complex and variable relationship may exist between the early and late hemodynamic effects of vasodilator drugs in patients with severe heart failure.

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