Neurohormones and oxidative stress in nonischemic cardiomyopathy: relationship to survival and the effect of treatment with amlodipine

OBJECTIVES: The purpose of this study was to assess the effects of amlodipine on neurohormones and oxidative stress in nonischemic cardiomyopathy, and determine the relationship between baseline and posttreatment levels of these markers with survival. BACKGROUND: Neurohormones and oxidative stress are important in the pathophysiology of heart failure. Calcium-channel blockers are associated with poor outcomes in patients with heart failure, in part due to neurohormonal activation. In contrast, amlodipine, a second-generation dihydropyridine, has a more favorable clinical profile. METHODS: In the Prospective Randomized Amlodipine Survival Evaluation 2 (PRAISE-2) trial, a subset of 181 patients with nonischemic cardiomyopathy were randomized to amlodipine (10 mg/day) or placebo. Blood samples were evaluated at baseline, 2 weeks and 26 weeks for norepinephrine, epinephrine, angiotensin II, dopamine, N-terminal pro-atrial natriuretic peptide (Nt-pro-ANP), brain natriuretic peptide (BNP), adrenolutin and malondialdehyde. RESULTS: There was no difference in levels of neurohormones or oxidative stress markers between the amlodipine and placebo groups at the different times. Both Nt-pro-ANP and BNP decreased at 2 weeks and at 26 weeks. Baseline Nt-pro-ANP correlated with survival in multivariate analysis (P =.001). A strong relationship was found between a reduction in BNP at 26 weeks and survival, with a hazard ratio of 0.153 (95% CI 0.051-0.461, P =.017). No relationship was found between markers of oxidative stress and survival. CONCLUSIONS: We conclude that amlodipine does not affect circulating neurohormones and oxidative stress markers in patients with nonischemic cardiomyopathy treated with angiotensin-converting enzyme inhibitors, digoxin and diuretics. In addition, low circulating Nt-pro-ANP and a reduction in BNP over time confers a good prognosis.