Association of beta-blocker dose with serum procollagen concentrations and cardiac response to spironolactone in patients with heart failure.

Abstract

STUDY 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.

DESIGN:

Prospective clinical study.

SETTING:

Two heart failure centers.

PATIENTS:

Eighty-eight spironolactone-naïve patients with heart failure who were taking beta-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 (> 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.

CONCLUSION:

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.

• Authors: Larisa H Cavallari, Kathryn M Momary, Vicki L Groo, Marlos A G Viana, Joseph R Camp, Thomas D Stamos
• Journal: Pharmacotherapy (Pharmacotherapy) Vol. 27 Issue 6 Pg. 801-12 (Jun 2007) ISSN: 0277-0008 [Print] United States
• PMID: 17542763 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adrenergic beta-Antagonists
• Carbazoles
• Diuretics
• Peptide Fragments
• Procollagen
• Propanolamines
• procollagen Type I N-terminal peptide
• procollagen Type III-N-terminal peptide
• Carvedilol
• Spironolactone
• Atenolol
• Metoprolol

Topics

• Adrenergic beta-Antagonists (administration & dosage, pharmacology)
• Adult
• Aged
• Atenolol (administration & dosage, pharmacology)
• Carbazoles (administration & dosage, pharmacology)
• Carvedilol
• Diuretics (administration & dosage, pharmacology)
• Dose-Response Relationship, Drug
• Female
• Fibrosis (physiopathology)
• Heart Failure (drug therapy)
• Humans
• Male
• Metoprolol (administration & dosage, pharmacology)
• Middle Aged
• Peptide Fragments (blood, drug effects, metabolism)
• Procollagen (blood, drug effects, metabolism)
• Propanolamines (administration & dosage, pharmacology)
• Prospective Studies
• Radioimmunoassay
• Spironolactone (administration & dosage, pharmacology)