Spironolactone in congestive heart failure refractory to high-dose loop diuretic and low-dose angiotensin-converting enzyme inhibitor

Abstract

Patients with severe congestive heart failure (New York Heart Association [NYHA] functional classes III–IV) often can tolerate only low doses of angiotensin-converting enzyme (ACE) inhibitors because pronounced hypotension caused by additional ACE inhibitor increments may decrease renal perfusion. The use of high-dose loop diuretics is currently advised to overcome diuretic resistance in refractory congestive heart failure (CHF). In a baseline controlled study, we evaluated 21 patients with diuretic resistance and evident fluid retention for the responses to 5 days of double drug therapy consisting of high-dose loop diuretic (10 mg oral bumetanide) in combination with the maximum tolerable dose of an ACE inhibitor (individualized to blood pressure and kidney function). Five patients (24%) showed a gross natriuresis and reduction in excess weight >25% in response to this therapy. The remaining 16 patients (76%) with insufficient responses (i.e., <25% reduction in excess weight) subsequently received 100 mg spironolactone once a day for 7 days in addition to the double therapy. Spironolactone coadministration was highly effective in 13 of 16 patients (81%). Marked natriuresis and diuresis were achieved within the next week of treatment, and CHF symptoms regressed or disappeared. The clinical course was similar in the bumetanide-ACE inhibitor and the bumetanide-ACE inhibitor-spironolactone treatment (triple therapy) groups. Plasma aldosterone was significantly higher (p < 0.05) in the patients who needed spironolactone. The 3 patients who were considered refractory to triple therapy exhibited the highest baseline plasma aldosterone concentrations. In the 13 patients who responded to spironolactone addition, hyperkalemia and azotemia did not occur during the 7 days of treatment, although 1 patient in the spironolactone treatment group developed reversible hyperkalemia and azotemia due to dehydration and decreased effective circulating volume after 8 days of treatment. Plasma aldosterone showed an inverse relation with urinary Na + K + ratio in 24-hour urine samples. Thus, coadministration of spironolactone was shown to be effective in managing CHF refractory to combination therapy with high doses of a loop diuretic and low doses of an ACE inhibitor. The urinary Na + K + ratio appears to be a useful and inexpensive indicator for determining the optimal spironolactone dose.