Titration of vasodilator therapy in chronic heart failure according to plasma brain natriuretic peptide concentration: Randomized comparison of the hemodynamic and neuroendocrine effects of tailored versus empirical therapy

Background Most patients with chronic heart failure (CHF) receive the same dose of angiotensin-converting enzyme (ACE) inhibitors because there is cur rently no measure of treatment efficacy. We sought to determine whether tit ration of vasodilator therapy according to plasma brain natriuretic peptide (BNP) concentration may be of value in the individual optimization of vaso dilator therapy in CHF. Methods and Results Twenty patients with mild to moderate CHF receiving sta ble conventional therapy including an ACE inhibitor were randomly assigned to titration of ACE inhibitor dosage according to serial measurement of pla sma BNP concentration (BNP group) or optimal empirical ACE inhibitor therap y (clinical group) for 8 weeks. Only the BNP-driven approach was associated with significant reductions in plasma BNP concentration throughout the dur ation of the study and a significantly greater suppression when compared wi th empiric therapy after 4 weeks [-42.1% (-58.2, -19.7) vs -12.0% (-31.8, 1 3.8), P = .03]. Both treatment strategies were well tolerated and associate d with favorable neurohormonal and hemodynamic effects; however, in compari son between groups, mean heart rate fell (P = .02) and plasma renin activit y rose (P = .03) in the BNP group when compared with the clinical group. Conclusions Plasma BNP concentration may be chronically reduced by tailored vasodilator therapy in CHF. Furthermore, titration of vasodilator therapy according to plasma BNP was associated with more profound inhibition of the renin-angiotensin-aldosterone system and significant fall in heart rate wh en compared with empiric therapy.