Coronary artery disease
Usefulness of Matrix Metalloproteinase-9 Plasma Levels to Identify Patients With Preserved Left Ventricular Systolic Function After Acute Myocardial Infarction Who Could Benefit from Eplerenone

https://doi.org/10.1016/j.amjcard.2012.05.049Get rights and content

We sought to assess possible interactions between eplerenone use and a plasma marker of collagen turnover on prognosis in patients after acute myocardial infarction (AMI) and preserved left ventricular (LV) ejection fraction (≥40%). Three hundred three patients with AMI (58 ± 11 years old, 249 men) and preserved systolic LV function were studied prospectively for 24 months. Plasma levels of matrix metalloproteinase-9 (MMP-9) were assessed on day 7 after AMI. Patients were categorized according to whether (n = 201) or not (n = 102) they received eplerenone (25 mg/day) and their baseline MMP-9 levels using the cut-off level suggested by receiver operating characteristics analysis (12.7 ng/ml). Death from cardiovascular causes, nonfatal reinfarction, hospitalization for unstable angina, and development of heart failure symptoms were considered study end points. Eplerenone use was not associated with better prognosis in the entire study group (p = 0.132). However, a significant beneficial eplerenone effect on outcome was observed in patients with low baseline levels of MMP-9 (event-free survival for eplerenone vs noneplerenone arm 65% vs 35%, p = 0.005). Eplerenone had no effect (p = 0.741) in the subgroup of patients with high baseline MMP-9 levels. In conclusion, in patients after AMI with preserved LV systolic function, low baseline levels of MMP-9 identify a subgroup of patients in whom eplerenone use is associated with a survival benefit.

Section snippets

Methods

The present study was designed as an open-label, randomized, parallel-group, nonplacebo-controlled, clinical study. Consecutive patients with ST-segment elevation AMI were recruited if they fulfilled the following inclusion criteria: (1) AMI 1 day to 7 days before enrollment and no aldosterone antagonist treatment and (2) LV ejection fraction ≥40% by transthoracic echocardiography on day 7 after the index event. Exclusion criteria were use of potassium-sparing diuretics, serum creatinine

Results

From the initial 350 study participants, 47 patients were excluded because of lack of complete (baseline or follow-up) data monitoring criteria or withdrawal of consent (Figure 1). The remaining 303 patients (mean age 58 ± 11 years, 249 men) constituted the study group (201 patients on eplerenone, 102 not on eplerenone treatment). During the study, 27 patients in the eplerenone group (13%) discontinued the study medication. The reported drug discontinuation reasons are shown in Figure 1. In

Discussion

The findings of the present study suggest that in patients after AMI with preserved LV ejection fraction (≥40%), the clinical benefit of eplerenone against death from cardiovascular causes, hospitalization for nonfatal reinfarction or unstable angina, or development of heart failure symptoms may be confined to patients with low baseline MMP-9 levels. Furthermore, use of eplerenone in this subgroup of patients was associated with a significant increase in MMP-9 levels. According to our

References (25)

  • F.G. Spinale

    Matrix metalloproteinases: regulation and dysregulation in the failing heart

    Circ Res

    (2002)
  • R. Mukherjee et al.

    Selective spatiotemporal induction of matrix metalloproteinase-2 and matrix metalloproteinase-9 transcription after myocardial infarction

    Am J Physiol Heart Circ Physiol

    (2006)
  • Cited by (0)

    View full text