ROLE OF CYTOKINES IN THE MECHANISM OF ACTION OF AMLODIPINE - THE PRAISE HEART-FAILURE TRIAL

Objectives. We sought to determine whether the beneficial effects of a mlodipine in heart failure may be mediated by a reduction in tumor nec rosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) levels. We pos tulated that TNF-alpha and IL-6 levels may also have predictive value in patients with congestive heart failure (CHF). Background. The molec ular mechanism for progression of CHF may involve cytokine overexpress ion. The effect of amlodipine on cytokine levels in patients with CHF is unknown. Methods. In the Prospective Randomized Amlodipine Survival Evaluation (PRAISE) trial, we used enzyme-linked immunosorbent assay to measure plasma levels of TNF-alpha in 92 patients and IL-6 in 62 pa tients in New York Heart Association functional classes III and IV ran domized to receive amlodipine (10 mg/day) or placebo. Blood samples we re obtained for cytokine measurement at baseline and at 8 and 26 weeks after enrollment. Results. The baseline amlodipine and placebo groups did not differ in demographics and cytokine levels. Mean (+/-SD) plas ma levels of TNF-alpha were 5.69 +/- 0.32 pg/ml, and those of IL-6 wer e 9.23 +/- 1.26 pg/ml at baseline. These levels were elevated 6 and 10 times, respectively, compared with those of normal subjects (p < 0.00 1). Levels of TNF-alpha did not change significantly over the 26-week period (p = 0.69). However, IL-6 levels were significantly lower at 26 weeks in patients treated with amlodipine versus placebo (p = 0.007 b y the Wilcoxon signed-rank test). An adverse event-CHF or death-occurr ed more commonly in patients with higher IL-6 levels. Conclusions. Aml odipine lowers plasma IL-6 levels in patients with CHF. The beneficial effect of amlodipine in CHF may be due to a reduction of cytokines su ch as IL-6. (C) 1997 by the American College of Cardiology.