The Effect of the Concomitant Use of Carvedilol and Spironolactone in Patients With Mild to Moderate Chronic Heart Failure

Takahisa Yamada
Authors: Masatake Fukunami; Hidetaka Kioka; Nobuhiko Makino; Akio Hirata; Kazuaki Kumagai; Tsuyoshi Shimonagata; Takahisa Yamada

Background: Carvedilol and spironolactone have been reported to provide a favorable effect in the treatment of chronic heart failure (CHF). However, no information is available on the effect of the concomitant use of carvedilol and spironolactone (C+S) in patients with CHF.

Methods: We studied 66 patients with radionuclide left ventricular ejection fraction (RI-EF) <0.40 (RI-EF: 31±7%, NYHA class: 2.1±0.7), who were randomized to receive placebo or C (19±3mg/d) in the prospective, double-blind study and followed-up thereafter. At the entry, 17 of 31 patients had received spironolactone (31±11mg/d). Echocardiography, radionuclide angiography and 24 hour Holter monitoring were repeated before and one year after the entry. Plasma concentration of atrial natiruretic peptide (ANP) was also measured before and one year after the entry.

Results: At the entry, there were no significant differences in age, NYHA class, blood pressure, heart rate, left ventricular end-diastolic dimension (LVDd), RI-EF and the content and dose of conventional therapy (angiotensin converting enzyme inhibitors, digoxin and diuretics) among the four groups: C+S (n=17), carvedilol only (n=14), spironolactone only (n=21) and placebo (n=14). LVDd significantly decreased one year after the entry in patients with C+S (60.1±6.7 to 57.5±5.1mm, p<0.05), which was not observed in any other group. Although RI-EF significantly increased one year after the entry in patients with both C+S (31.1±6.4 to 44.2±9.8%) and carvedilol only (32.4±7.3 to 38.1±8.7%), the degree of the improvement in RI-EF was significantly greater in patients with C+S than carvedilol only (13.1±7.9 vs 7±6.2%, p<0.05). Furthermore, there were significant decreases in Lown's grade (4.1±0.8 to 3.6±1.0, p<0.05) and ANP (46.5±33.9 to 26.8±24.5 pg/ml, p<0.05) in patients with C+S, which was not observed in any other group.

Conclusion: The concomitant use of carvedilol and spironolactone would be more effective than the individual use of carvedilol or spironolactone in patients with mild to moderate CHF.