Association of β-Blocker Dose with Serum Procollagen Concentrations and Cardiac Response to Spironolactone in Patients with Heart Failure

Study Objective. To determine whether β‐blocker dose influences cardiac collagen turnover and the effects of spironolactone on cardiac collagen turnover in patients with heart failure. Design. Prospective clinical study. Setting. Two heart failure centers. Patients. Eighty‐eight spironolactone‐naïve patients with heart failure who were taking β‐blockers. Intervention. In a subset of 29 patients, spironolactone was started at 12.5 mg/day with the dosage titrated to 25 mg/day if tolerated. Measurements and Main Results. Venous blood samples were collected from each patient. Serum procollagen type I and type III aminoterminal peptides (PINP and PIIINP) were determined by radioimmunoassay and compared between the 25 patients receiving low doses (< 50% of recommended target dose) and the 63 patients receiving high doses (≥ 50% of recommended target dose) of β‐blockers. Patients receiving low‐dose β‐blockers had higher mean ± SD PIIINP concentrations (6.6 ± 3.5 vs 4.9 ± 2.6 μg/L, p=0.03) and tended to have higher PINP concentrations (74.0 ± 44.1 vs 57.1 ± 28.6 μg/L, p=0.10) compared with those receiving high doses. A repeat blood sample was collected from the 29 patients who received spironolactone after 6 months of therapy. Changes in procollagen peptides also were compared in this subset between low‐dose (9 patients) and high‐dose (20 patients) β‐blocker groups. Low β‐blocker doses were associated with greater reductions in concentrations of PINP (median [intraquartile range] −14.3 μg/L [‐9.8 to −19.3 μg/L] vs −2.5 μg/L [5.9 to −9.8 μg/L], p=0.02) and PIIINP (‐1.4 μg/L [‐0.9 to −2.4 μg/L] vs 0.1 μg/L [0.9 to −1.3 μg/L], p=0.045) with spironolactone therapy than high β‐blocker doses. In addition, 100% of the patients in this subset taking low‐dose β‐blockers versus only 35% taking higher doses had reductions in both markers of cardiac fibrosis. Conclusion. Spironolactone may benefit patients with heart failure who cannot tolerate upward titration of β‐blocker dosages, at least in terms of its effects on cardiac remodeling.