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 guan...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.展开更多
BACKGROUND Heart failure(HF),an end-stage manifestation of various cardiac diseases,poses an enormous economic and health burden on society.Vericiguat may be an effective drug in the treatment of HF.AIM To explore by ...BACKGROUND Heart failure(HF),an end-stage manifestation of various cardiac diseases,poses an enormous economic and health burden on society.Vericiguat may be an effective drug in the treatment of HF.AIM To explore by meta-analysis the efficacy and safety of Vericiguat in treating chronic heart failure.METHODS Databases,including PubMed,EMBASE,Web of Science,and Cochrane Library,were searched to collect all published randomized controlled trials(RCTs)on Vericiguat treatment of chronic heart failure from the earliest electronic records to those published in March 2023.Two investigators independently screened the literature according to inclusion and exclusion criteria,evaluated the quality of the studies,and extracted valid data before conducting a meta-analysis using RevMan5.4.RESULTS Four RCTs with 5919 patients were included,and the meta-analysis showed that treatment with 10 mg Vericiguat reduced the incidence of the primary endpoint(a composite of cardiovascular mortality and first heart-failure-related hospital-ization)in patients with chronic heart failure compared to placebo[relative risk(RR)=0.91,95%confidence interval(CI):0.85–0.98,P=0.01],and reduced the incidence of heart-failure-related hospitalization(RR=0.92,95%CI:0.84–1.00,P=0.05).However,for the incidence of cardiovascular and all-cause death,there were no significant differences between the Vericiguat and placebo groups.In addition,the two groups did not show significant differences in blood pressure,heart rate,and Kansas Cardiomyopathy Questionnaire physical limitation score.In terms of safety,10 mg Vericiguat did not increase the risk of adverse effects in patients with chronic heart failure.Vericiguat may increase the risk of symp-tomatic hypotension(RR=1.17,95%CI:0.98–1.39,P=0.08)and syncope(RR=1.18,95%CI:0.90–1.55,P=0.24),but not significantly.CONCLUSION Vericiguat(10 mg)was more effective than placebo in treating patients with chronic heart failure and had a better safety profile.展开更多
目的 探讨维立西呱对脂多糖(LPS)诱导的大鼠心肌细胞炎症反应和细胞凋亡的影响以及其对环状RNA PRKCI(circ PRKCI)表达的调控机制。方法 取大鼠心肌细胞H9C2,采用LPS诱导方式构建心肌细胞损伤模型;按随机数字表法分为对照组、LPS组、LPS...目的 探讨维立西呱对脂多糖(LPS)诱导的大鼠心肌细胞炎症反应和细胞凋亡的影响以及其对环状RNA PRKCI(circ PRKCI)表达的调控机制。方法 取大鼠心肌细胞H9C2,采用LPS诱导方式构建心肌细胞损伤模型;按随机数字表法分为对照组、LPS组、LPS+维立西呱-L组(1μmol/L)、LPS+维立西呱-M组(3μmol/L)、LPS+维立西呱-H组(10μmol/L)、LPS+空载体质粒(p c DNA)组、LPS+c irc PRKCI过表达载体(p c DNA-c irc PRKCI)组、LPS+维立西呱-H+阴性对照(s h-NC)组、LPS+维立西呱-H+circ PRKCI慢病毒短发夹RNA(sh-circ PRKCI)组。检测并比较各组H9C2细胞肿瘤坏死因子-α(TNF-α)、白细胞介素6(IL-6)等炎症因子水平,细胞凋亡率和裂解的胱天蛋白酶(Cleaved Caspase)-3、Cleaved Ca s p a s e-9等凋亡相关蛋白表达水平,以及c irc PRKCI mRNA表达水平。结果 与对照组比较,LPS组TNF-α水平、IL-6水平、细胞凋亡率及凋亡相关蛋白Cle a ve d Ca s p a s e-3、Cle a ve d Ca s p a s e-9蛋白表达水平均明显升高(均P<0.05);与LPS组比较,LPS+维立西呱-L组、LPS+维立西呱-M组、LPS+维立西呱-H组上述指标均明显降低(均P<0.05),且LPS+维立西呱-L组>LPS+维立西呱-M组>LPS+维立西呱-H组(均P<0.05)。与对照组比较,LPS组c irc PRKCI mRNA表达水平明显降低(P<0.05);与LPS组比较,LPS+维立西呱-L组、LPS+维立西呱-M组、LPS+维立西呱-H组c irc PRKCI mRNA表达水平均明显升高(均P<0.05),且LPS+维立西呱-L组<LPS+维立西呱-M组<LPS+维立西呱-H组(均P<0.05)。与LPS+pc DNA组比较,LPS+pc DNA-circ PRKCI组circ PRKCI mRNA表达水平明显升高(P<0.05),而TNF-α水平、IL-6水平、细胞凋亡率以及凋亡相关蛋白Cle a ve d Ca s p a s e-3、Cle a ve d Ca s p a s e-9蛋白表达水平均明显降低(均P<0.05)。与LPS+维立西呱-H+sh-NC组比较,LPS+维立西呱-H+sh-circ PRKCI组circ PRKCI mRNA表达水平明显降低(P<0.05),而TNF-α水平、IL-6水平、细胞凋亡率以及凋亡相关蛋白Cleaved Caspase-3、Cleaved Caspase-9蛋白表达水平均明显升高(均P<0.05)。结论 维立西呱可抑制LPS诱导的大鼠心肌细胞炎症反应和细胞凋亡,其作用机制是上调circ PRKCI mRNA表达。展开更多
文摘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.
基金Key Research and Development projects in Jiangxi Province,No.20223BBG71010National Natural Science Foundation of China,No.81960058.
文摘BACKGROUND Heart failure(HF),an end-stage manifestation of various cardiac diseases,poses an enormous economic and health burden on society.Vericiguat may be an effective drug in the treatment of HF.AIM To explore by meta-analysis the efficacy and safety of Vericiguat in treating chronic heart failure.METHODS Databases,including PubMed,EMBASE,Web of Science,and Cochrane Library,were searched to collect all published randomized controlled trials(RCTs)on Vericiguat treatment of chronic heart failure from the earliest electronic records to those published in March 2023.Two investigators independently screened the literature according to inclusion and exclusion criteria,evaluated the quality of the studies,and extracted valid data before conducting a meta-analysis using RevMan5.4.RESULTS Four RCTs with 5919 patients were included,and the meta-analysis showed that treatment with 10 mg Vericiguat reduced the incidence of the primary endpoint(a composite of cardiovascular mortality and first heart-failure-related hospital-ization)in patients with chronic heart failure compared to placebo[relative risk(RR)=0.91,95%confidence interval(CI):0.85–0.98,P=0.01],and reduced the incidence of heart-failure-related hospitalization(RR=0.92,95%CI:0.84–1.00,P=0.05).However,for the incidence of cardiovascular and all-cause death,there were no significant differences between the Vericiguat and placebo groups.In addition,the two groups did not show significant differences in blood pressure,heart rate,and Kansas Cardiomyopathy Questionnaire physical limitation score.In terms of safety,10 mg Vericiguat did not increase the risk of adverse effects in patients with chronic heart failure.Vericiguat may increase the risk of symp-tomatic hypotension(RR=1.17,95%CI:0.98–1.39,P=0.08)and syncope(RR=1.18,95%CI:0.90–1.55,P=0.24),but not significantly.CONCLUSION Vericiguat(10 mg)was more effective than placebo in treating patients with chronic heart failure and had a better safety profile.
文摘目的 探讨维立西呱对脂多糖(LPS)诱导的大鼠心肌细胞炎症反应和细胞凋亡的影响以及其对环状RNA PRKCI(circ PRKCI)表达的调控机制。方法 取大鼠心肌细胞H9C2,采用LPS诱导方式构建心肌细胞损伤模型;按随机数字表法分为对照组、LPS组、LPS+维立西呱-L组(1μmol/L)、LPS+维立西呱-M组(3μmol/L)、LPS+维立西呱-H组(10μmol/L)、LPS+空载体质粒(p c DNA)组、LPS+c irc PRKCI过表达载体(p c DNA-c irc PRKCI)组、LPS+维立西呱-H+阴性对照(s h-NC)组、LPS+维立西呱-H+circ PRKCI慢病毒短发夹RNA(sh-circ PRKCI)组。检测并比较各组H9C2细胞肿瘤坏死因子-α(TNF-α)、白细胞介素6(IL-6)等炎症因子水平,细胞凋亡率和裂解的胱天蛋白酶(Cleaved Caspase)-3、Cleaved Ca s p a s e-9等凋亡相关蛋白表达水平,以及c irc PRKCI mRNA表达水平。结果 与对照组比较,LPS组TNF-α水平、IL-6水平、细胞凋亡率及凋亡相关蛋白Cle a ve d Ca s p a s e-3、Cle a ve d Ca s p a s e-9蛋白表达水平均明显升高(均P<0.05);与LPS组比较,LPS+维立西呱-L组、LPS+维立西呱-M组、LPS+维立西呱-H组上述指标均明显降低(均P<0.05),且LPS+维立西呱-L组>LPS+维立西呱-M组>LPS+维立西呱-H组(均P<0.05)。与对照组比较,LPS组c irc PRKCI mRNA表达水平明显降低(P<0.05);与LPS组比较,LPS+维立西呱-L组、LPS+维立西呱-M组、LPS+维立西呱-H组c irc PRKCI mRNA表达水平均明显升高(均P<0.05),且LPS+维立西呱-L组<LPS+维立西呱-M组<LPS+维立西呱-H组(均P<0.05)。与LPS+pc DNA组比较,LPS+pc DNA-circ PRKCI组circ PRKCI mRNA表达水平明显升高(P<0.05),而TNF-α水平、IL-6水平、细胞凋亡率以及凋亡相关蛋白Cle a ve d Ca s p a s e-3、Cle a ve d Ca s p a s e-9蛋白表达水平均明显降低(均P<0.05)。与LPS+维立西呱-H+sh-NC组比较,LPS+维立西呱-H+sh-circ PRKCI组circ PRKCI mRNA表达水平明显降低(P<0.05),而TNF-α水平、IL-6水平、细胞凋亡率以及凋亡相关蛋白Cleaved Caspase-3、Cleaved Caspase-9蛋白表达水平均明显升高(均P<0.05)。结论 维立西呱可抑制LPS诱导的大鼠心肌细胞炎症反应和细胞凋亡,其作用机制是上调circ PRKCI mRNA表达。
