Inpharma 1395 - 12 Jul 2003

Spironolactone pharmacodynamicsin patients with acute MI

Spironolactone prevents left ventricular remodelingand improves left ventricular ejection fraction (LVEF) inpatients with acute myocardial infarction (MI), reportresearchers from Japan.1

Their multicentre, phase II study involved 150 suchpatients who had a first anterior MI and who underwentsuccessful percutaneous coronary intervention (PCI). 75patients received oral spironolactone 25 mg/day for onemonth after PCI; the remaining patients received nosuch treatment (controls). All of the patients wereadministered enalapril 2.5 mg/day from day 1 after onsetof MI. A total of 134 patients were eligible for analysis.

Significantly greater changes from baseline LVEF wereobserved among spironolactone recipients (46% vs53.2%), compared with controls (46.5% vs 51%).However, compared with controls, spironolactonerecipients experienced significantly smaller changesfrom baseline left ventricular end diastolic volume (87.5mL/m2 vs 106.8 mL/m2 and 86.5 mL/m2 vs 90.6 mL/m2),and from baseline plasma levels of procollagen type IIIaminoterminal peptide (0.38 pg/mL vs 0.51 pg/mL and0.39 pg/mL vs 0.43 pg/mL). Transcardiac extraction ofaldosterone was also significantly reduced amongspironolactone recipients, compared with controls. Nosignificant changes in haemodynamic parameters wereobserved among patients from either group.

In an accompanying editorial, Dr bertram Pitt from theUniversity of Michigan Medical Center, US, commentsthat aldosterone blockade (AB) "will be an importantaddition to the current therapy of patients with acutemyocardial infarction. Clearly the risk/benefit of early(day 1) AB after infarction will need to be explored inlarge-scale prospective randomized studies".2

1. Hayashi M, et al. Immediate administration of mineralocorticoid receptorantagonist spironolactone prevents post-infarct left ventricular remodelingassociated with suppression of a marker of myocardial collagen synthesis inpatients with first anterior acute myocardial infarction. Circulation 107:2559-2565, 27 May 2003.

2. Pitt B. Aldosterone blockade in patients with acute myocardial infarction.Circulation 107: 2525-2527, 27 May 2003.

800969044

1

Inpharma 12 Jul 2003 No. 13951173-8324/10/1395-0001/$14.95 Adis © 2010 Springer International Publishing AG. All rights reserved