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Objective To investigate the efficacy and possible mechanism of Guanxining combined with amlodipine in the treatment of hypertension complicating heart failure (HF). Methods Eighty-three patients with hypertension complicating HF were selected as the study subjects. They were divided into control group (41 cases, treated by amlodipine) and observation group (42 cases, treated by Guanxinning combined with amlodipine) by random number table method. We compared the clinical efficacy between the two groups as well as changes of cardiac function (LVEF, LVESd, LVEDd, IVST and NT-proBNP), blood pressure, blood coagulation indexes, vascular endothelial function [endothelin-1, NO, angiotensin Ⅱ (AngⅡ)], and serological indexes [microRNA196a-2 ( miR-196a-2) and soluble factor associated suicide ( sFas )] levels before and after the treatment. Results The total effective rate of the observation group was higher than that of the control group (P<0. 05). After treatment, LVEF and IVST in the observation group were higher than those in the control group while LVESd, LVEDd, systolic blood pressure, diastolic blood pressure, low-shear whole blood viscosity, plasma viscosity and red blood cell aggregation index were lower than those in the control group (P<0. 05). After treatment, the levels of serum NT-proBNP, endothelin-1, AngⅡ, miR-196a-2 and sFas in the observation group were lower than those in the control group while the level of NO was higher than that in the control group (P<0. 05). Conclusion Guanxinning combined with amlodipine is effective in the treatment of hypertension complicated with HF. It could promote the recovery of cardiac function, and improve blood pressure, coagulation function and vascular endothelial function. Its mechanism may be related to the regulation of expression of miR-196a-2 and sFas. [ABSTRACT FROM AUTHOR]