COMBINED SYMPATHETIC SUPPRESSION AND ANGIOTENSIN-CONVERTING ENZYME-INHIBITION IN CONGESTIVE-HEART-FAILURE

Neurohormonal activation is a pathogenic contributor and prognostic ma rker in congestive heart failure (CHF). While angiotensin-converting e nzyme (ACE) inhibition is now first-line therapy, sympathetic inhibiti on has only lately been proposed to this aim. Recently, we reported im provement of preload parameters by sympathetic suppression with clonid ine. 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 c aptopril 6.15 + placebo in a single-blind parallel study on 16 patient s with Class III or IV CHF (13 males, 3 females, aged 62 +/- 8 years, with an ejection fraction of 33 +/- 8%). Hemodynamic and hormonal meas urements were taken at baseline after a diagnostic cardiac catheteriza tion and again 2 hours after treatment. The results indicate that prel oad 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 s ignificantly with both-but the latter change was significantly greater with the captopril/clonidine combination than with captopril alone. S uppression 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 sig nificant improvements in both preload and afterload parameters of CHF and correction of activated neurohormones, suggesting additive hemodyn amic and hormonal benefits from the two treatment modalities.