Association of beta-blocker dose with serum procollagen concentrations and cardiac response to spironolactone in patients with heart failure.
OBJECTIVE
To determine whether beta-blocker dose influences cardiac collagen turnover and the effects of spironolactone on cardiac collagen turnover in patients with heart failure.


METHODS
Prospective clinical study.


METHODS
Two heart failure centers.


METHODS
Eighty-eight spironolactone-naïve patients with heart failure who were taking beta-blockers.


METHODS
In a subset of 29 patients, spironolactone was started at 12.5 mg/day, with the dosage titrated to 25 mg/day if tolerated.


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 (> or = 50% of recommended target dose) of beta-blockers. Patients receiving low-dose beta-blockers had higher mean +/- SD PIIINP concentrations (6.6 +/- 3.5 vs 4.9 +/- 2.6 microg/L, p=0.03) and tended to have higher PINP concentrations (74.0 +/- 44.1 vs 57.1 +/- 28.6 microg/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) beta-blocker groups. Low beta-blocker doses were associated with greater reductions in concentrations of PINP (median [intraquartile range] -14.3 microg/L [-9.8 to -19.3 microg/L] vs -2.5 microg/L [5.9 to -9.8 microg/L], p=0.02) and PIIINP (-1.4 microg/L [-0.9 to -2.4 microg/L] vs 0.1 microg/L [0.9 to -1.3 microg/L], p=0.045) with spironolactone therapy than high beta-blocker doses. In addition, 100% of the patients in this subset taking low-dose beta-blockers versus only 35% taking higher doses had reductions in both markers of cardiac fibrosis.


CONCLUSIONS
Spironolactone may benefit patients with heart failure who cannot tolerate upward titration of beta-blocker dosages, at least in terms of its effects on cardiac remodeling.
Cavallari
Larisa H
LH
Department of Pharmacy Practice, College of Pharmacy, University of Illinois at Chicago, Illinois 60612-7230, USA. humma@uic.edu
Momary
Kathryn M
KM
Groo
Vicki L
VL
Viana
Marlos A G
MA
Camp
Joseph R
JR
Stamos
Thomas D
TD
D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D001262:Atenolol / Q000008:administration & dosage / Q000494:pharmacology; D002227:Carbazoles / Q000008:administration & dosage / Q000494:pharmacology; D000077261:Carvedilol; D004232:Diuretics / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005355:Fibrosis / Q000503:physiopathology; D006333:Heart Failure / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008790:Metoprolol / Q000008:administration & dosage / Q000494:pharmacology; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood / Q000187:drug effects / Q000378:metabolism*; D011347:Procollagen / Q000097:blood / Q000187:drug effects / Q000378:metabolism*; D011412:Propanolamines / Q000008:administration & dosage / Q000494:pharmacology; D011446:Prospective Studies; D011863:Radioimmunoassay; D013148:Spironolactone / Q000008:administration & dosage / Q000494:pharmacology*
D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D004232:Diuretics; D010446:Peptide Fragments; D011347:Procollagen; D011412:Propanolamines; C047202:procollagen Type I N-terminal peptide; C041876:procollagen Type III-N-terminal peptide; D000077261:Carvedilol; D013148:Spironolactone; D001262:Atenolol; D008790:Metoprolol