Neither carvedilol nor bisoprolol in maximally tolerated doses has any specific advantage in lowering chronic heart failure oxidant stress: implications for β-blocker selection

Abstract

We hypothesized that abnormal oxidative stress in chronic heart failure (CHF) could be related to endothelial damage and platelet activation, and that the vasodilating beta-blocker carvedilol would have beneficial effects on these processes compared with a selective non-vasodilating cardioselective beta-blocker, bisoprolol. We therefore assessed the effects of introducing carvedilol and bisoprolol in a prospective manner on indices of oxidative stress [lipid hydroperoxides (LHP)], endothelial damage [von Willebrand factor (vWf)], platelet activation (soluble P-selectin) and coagulation (fibrinogen) and their inter-relationships in stable outpatients with CHF in sinus rhythm. We recruited 46 patients [23 male; age 64 +/- 13 years (mean +/- S.D.); range 38-85 years] with CHF. Baseline levels of serum LHP (P<0.002), plasma vWf (P<0.001) and soluble P-selectin (P=0.02), but not fibrinogen (P=0.16), were higher in CHF patients compared with 22 age- and sex-matched healthy controls. After treatment for 2 months, systolic blood pressure fell in both arms of the study (both P<0.01), but there were no statistically significant (defined as P<0.01) decreases in LHP, vWf, fibrinogen or soluble P-selectin levels with either carvedilol or bisoprolol. In conclusion, patients with CHF have increased levels of plasma LHP and vWf, indicating increased oxidative stress and endothelial damage respectively. Contrary to the proposed antioxidative effects of carvedilol, initiating and titrating such therapy did not result in a reduction in levels of LHP in CHF.

Antioxidant activity of carvedilol in cardiovascular disease

“…A fourth comparative trial [74] measured lipid hydroperoxides (LPH) again in chronic HF patients with depressed LVEF (<40%) treated for 2 months with either carvedilol or bisoprolol. Serum LPH levels were determined colorimetrically by the ferrous oxidation of xylenol orange in the presence of the specific hydroperoxide target triphenylphosphine.…”

Plasma indices of endothelial and platelet activation in Rheumatoid Disease: Relationship to cardiovascular co-morbidity

“…In the context of stable heart failure, however, we have previously shown no reduction in sP-sel levels after initiation of treatment with the beta-blockers, bisoprolol and carvedilol [20].…”

Pre-Clinical Investigation of Cardioprotective Beta-Blockers as a Therapeutic Strategy for Preeclampsia

“…Unlike carvedilol, bisoprolol is a second generation beta-1 selective beta-blocker. Despite these differences, carvedilol has not been shown to have benefit over bisoprolol in lowering oxidant stress [ 38 ]. Like carvedilol, bisoprolol has been found to improve endothelial function when used in the context of cardiovascular diseases; these include hypertension and angina [ 74 , 75 ].…”

“…Significantly, women who suffer preeclampsia are at increased risk of future cardiovascular disease, including a 4-fold increased risk of future heart failure [ 33 ]. Like preeclampsia, endothelial dysfunction and end-organ injury are also synonymous with heart failure and are associated with poorer prognosis [ 34 , 35 , 36 , 37 , 38 ]. The vasoactive peptide adrenomedullin (ADM) is a potent vasodilator with implications in both preeclampsia and cardiovascular disease [ 39 , 40 ].…”