Safety and efficacy of soluble guanylate cyclase stimulators in patients with heart failure: A systematic review and meta-analysis

BACKGROUND The utility of novel oral soluble guanylate cyclase(sGC)stimulators(vericiguat and riociguat),in patients with reduced or preserved ejection fraction heart failure(HFrEF/HFpEF)is currently unclear.AIM To determine the efficacy and safety of sGC stimulators in HF patients.METHODS Multiple databases were searched to identify relevant randomized controlled trials(RCTs).Data on the safety and efficacy of sGC stimulators were compared using relative risk ratio(RR)on a random effect model.RESULTS Six RCTs,comprising 5604 patients(2801 in sGC stimulator group and 2803 placebo group)were included.The primary endpoint(a composite of cardiovascular mortality and first HF-related hospitalization)was significantly reduced in patients receiving sGC stimulators compared to placebo[RR 0.92,95%confidence interval(CI):0.85-0.99,P=0.02].The incidence of total HF-related hospitalizations were also lower in sGC group(RR 0.91,95%CI:0.86-0.96,P=0.0009),however,sGC stimulators had no impact on all-cause mortality(RR 0.96,95%CI:0.86-1.07,P=0.45)or cardiovascular mortality(RR 0.94,95%CI:0.83-1.06,P=0.29).The overall safety endpoint(a composite of hypotension and syncope)was also similar between the two groups(RR 1.50,95%CI:0.93-2.42,P=0.10).By contrast,a stratified subgroup analysis adjusted by type of sGC stimulator and HF(vericiguat vs riociguat and HFrEF vs HFpEF)showed near identical rates for all safety and efficacy endpoints between the two groups at a mean follow-up of 19 wk.For the primary composite endpoint,the number needed to treat was 35,the number needed to harm was 44.CONCLUSION The use of vericiguat and riociguat in conjunction with standard HF therapy,shows no benefit in terms of decreasing HF-related hospitalizations or mortality.

Impact of vericiguat on heart failure with reduced ejection fraction:a review

Introduction:Heart failure is a major public health issue with a prevalence of about 26 million people worldwide.Reduced nitric oxide availability,lower soluble guanylate cyclase(sGC)activity,and decreased cyclic guanosine monophosphate(cGMP)production are the causes of HF's development.Vericiguat prescribed under the brand name Verquvo was approved by U.S.Food and Drug Administration(FDA)in January 2021.It is a novel agent and the first sGC stimulator which helps to treat patients suffering from heart failure with reduced ejection fraction(HFrEF).Objective:The mechanism of action(cGMP pathway)of vericiguat,its clinical trials,its use in the treatment of heart failure,and its possible future aspects in therapeutic recommendations are all covered in this review.It will also raise awareness amongst healthcare professionals about the pharmacokinetic and pharmacodynamic parameters,dosing,administration,and drug-related problems of this new drug.Methods:Various databases for drug review were used in this review like PubMed,Medline,Google scholar,Drug bank,U.s.FDA,Medscape,and European society of cardiology guidelines.A total of 58 articles were screened out of which 39 articles were included in this review.Results:This review discusses vericiguat's mechanism of action(cGMP pathway),clinical studies,application in the treatment of heart failure,and potential future considerations in therapeutic recommendations.It will also educate healthcare professionals about the new drug's pharmacokinetics and pharmacodynamics,dose,administration,and drug-related problems.Conclusion:After hospitalization for HFrEF,the 5-year survival rate is just 25%,and disease morbidity and death are stil significant.As adjunctive therapy for individuals with heart failure and a low ejection fraction,vericiguat has a moderate level of effectiveness.Vericiguat's efficacy as an adjunct therapy to different drugs used to cure HF has to be further investigated.Vericiguat's safety and dosage in patients who have severe renal or hepatic illness need to be studied further.