SGC STIMULATOR (BAY 41-8543) FOR THE TREATMENT OF HEART FAILURE WITH REDUCED EJECTION FRACTION (HFREF) AND CARDIO-RENAL SYNDROME

Heart failure with reduced ejection fraction (HFrEF) is considered to be one of the major epidemics of the 21st century. The prognosis and life expectancy is dreadful for patients that develop concurrent impairment of kidney function, so called “cardio-renal syndrome”.

In the present study we investigated the activity of NO-independent sGC stimulator, called BAY 41-8543 (BAY41), in ren-2 transgenic hypertensive rats (TGR) with aorto-caval fistula (ACF)-induced HFrEF. The effectiveness of the BAY41 administered alone (3 mg/kg/day) or combined with an ACE inhibitor (ACEi, Trandolapril, 0.25 mg/kg/day) on the survival rate was investigated for 30 weeks. Blood pressure was measured in separate experiments for 2 weeks.

BAY41 significantly improved the survival in comparison to untreated animals with HFrEF. After 60 days the survival rate of ACF TGR treated with BAY41 was still 50%, while in untreated group it was already below 10%. However, after some time the beneficial activity of BAY41 started to decline. Additionally, BAY41 administered together with ACEi decreased the beneficial activity of the ACEi. The telemetry data revealed a transient decrease in blood pressure (-10 mmHg) two days after BAY41 administration, but early on SBP started to rise and by the end of the 2-week observation it was on the same level as in untreated rats (124±2 vs 134±3 mmHg, respectively; NS).

It seems that the sGC stimulation is a promising strategy to treat HFrEF based on improved survival. However, the results in the combination group call for special attention. One hypothesis is that the dose regimen of BAY41 could be improved, e.g. higher dosage of sGC stimulator combined with titration protocol should be tested, i.e. to avoid the initial hypotension, but to prevent the “escape” from the treatment after long-term administration.