Key result
Candesartan significantly lowers inflammatory markers and adhesion molecules compared to placebo in CHF.
Why the study?
The long-term effects of Ang II type 1 receptor antagonists on plasma markers of immune activation were unknown in patients with CHF.
Does candesartan cilexetil reduce plasma levels of immune markers and neurohumoral factors in patients with mild to moderate congestive heart failure?
RCT (n=23)
Does candesartan cilexetil reduce plasma levels of immune markers and neurohumoral factors in patients with mild to moderate congestive heart failure?
Treatment with the ARB candesartan cilexetil significantly reduces circulating inflammatory and immune markers while improving the biological action of endogenous natriuretic peptides in patients with mild to moderate heart failure.
OBJECTIVES: To evaluate the effects of an angiotensin (Ang II) type 1 receptor antagonist on immune markers in patients with congestive heart failure (CHF). BACKGROUND: Ang II stimulates production of immune factors via the Ang II type 1 receptor in vitro, and the long-term effects of Ang II type 1 receptor antagonists on plasma markers of immune activation are unknown in patients with CHF. METHODS: Twenty-three patients with mild to moderate CHF with left ventricular dysfunction were randomly divided into two groups: treatment with Ang II type 1 receptor (candesartan cilexetil) (n = 14) or placebo (n = 9). We measured plasma levels of immune factors such as tumor necrosis factor alpha (TNFalpha), interleukin-6 (IL-6), soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1). We also measured plasma levels of the neurohumoral factors such as atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) and cyclic guanosine monophosphate (cGMP), a biological marker of ANP and BNP. RESULTS: Plasma levels of TNFalpha, IL-6, sICAM-1 and sVCAM-1 were increased in the 23 CHF patients compared with normal subjects and significantly decreased after 14 weeks of candesartan cilexetil treatment, but did not change in the placebo group. Plasma levels of BNP, which is a marker of ventricular injury, significantly decreased, and the molar ratio of plasma cGMP to cardiac natriuretic peptides (ANP + BNP) was significantly increased after candesartan cilexetil treatment, but did not change in the placebo group. CONCLUSIONS: These findings suggest that 14 weeks of treatment with an Ang II type 1 receptor antagonist (candesartan cilexetil) decreased plasma levels of the immune markers such as TNFalpha, IL-6, sICAM-1 and sVCAM-1 and that it improved the biological compensatory action of endogenous cardiac natriuretic peptides in patients with mild to moderate CHF.
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Tsutamoto et al. (2000) conducted an RCT in mild to moderate congestive heart failure with left ventricular dysfunction (n=23). Candesartan cilexetil vs. Placebo was evaluated on Plasma levels of immune factors including TNFalpha, IL-6, sICAM-1 and sVCAM-1. Treatment with candesartan cilexetil for 14 weeks significantly decreased plasma levels of TNFalpha, IL-6, sICAM-1, and sVCAM-1 in 23 patients with CHF compared to placebo.
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