Combined sympathetic suppression and angiotensin-converting enzyme inhibition in congestive heart failure.

Neurohormonal activation is a pathogenic contributor and prognostic marker in congestive heart failure (CHF). While angiotensin-converting enzyme (ACE) inhibition is now first-line therapy, sympathetic inhibition has only lately been proposed to this aim. Recently, we reported improvement of preload parameters by sympathetic suppression with clonidine. In the present paper we studied the effects of a single oral dose of clonidine 0.15 mg+captopril 6.25 mg combination, compared with captopril 6.15+placebo in a single-blind parallel study on 16 patients with Class III or IV CHF (13 males, 3 females, aged 62 +/- 8 years, with an ejection fraction of 33 +/- 8%). Hemodynamic and hormonal measurements were taken at baseline after a diagnostic cardiac catheterization and again 2 hours after treatment. The results indicate that preload parameters such as RAP, PCWP and MPAP decreased significantly with the combination therapy but not with captopril alone. On the contrary, SVR decreased significantly with both treatments and SVI increased significantly with both-but the latter change was significantly greater with the captopril/clonidine combination than with captopril alone. Suppression of plasma norepinephrine occurred with the combination only (evidently attributable to clonidine), whereas plasma renin activity increased with both regimens, due apparently to captopril. Our results indicate that the combination of clonidine with captopril induces significant improvements in both preload and afterload parameters of CHF and correction of activated neurohormones, suggesting additive hemodynamic and hormonal benefits from the two treatment modalities.