Guanylate cyclase modulators Novel agents were developed to target soluble guanylate cyclase modulators ( sGC ) and allow for vasodilation without the presence of nitric oxide (NO), thereby avoiding the tolerance that...Guanylate cyclase modulators Novel agents were developed to target soluble guanylate cyclase modulators ( sGC ) and allow for vasodilation without the presence of nitric oxide (NO), thereby avoiding the tolerance that occurs with traditional nitrate therapy [1] .Two classes of sGC modulators exist, sGC stimulators and sGC activators [2] . Stimulators, such as vericiguat , enhance sGC to increase activity, even in the condition of low levels of NO .Activators, such as cinaciguat , can stimulate sGC independently of NO [3] . Cinaciguat:Cinaciguat was found to moderately reduce preload and afterload and increase cardiac output in a non-randomized , proof-of-concept study [4] .This study also found cinaciguat to be well tolerated with mild to moderate hypotension as the main adverse effect . The COMPOSE program , a set of three randomized phase Ⅱ studies, COMPOSE 1, 2 and COMPOSE early, sought to analyze the safety and efficacy of this drug in acute heart failure (AHF) patients[5] .However, the study was stopped early due to safety concerns after 71 (71.5%) patients who received cinaciguat experienced hypotension compared to 13 ( 25.5%) patients who received placebo [6] . In addition, cinaciguat was not found to improve dyspnea or cardiac index . Vericiguat:Vericiguat was investigated by the soluble guanylate cyclase stimulator in heart failure study (SOCRATES), a set of two studies examining AHF patients with either reduced ejection fraction < 45% ( SOCRATES-REDUCED ) or preserved ejection fraction (SOCRATES-PRESERVED)[7].AHF patients in both studies were randomized to varying doses of vericiguat from 1.25 mg daily to 10 mg daily versus placebo for 12 weeks. In SOCRATES-REDUCED, vericiguat, although well tolerated , did not produce a statistically significant change in N-terminal B-type natriuretic peptide ( NT-proBNP ) [8] .展开更多
With an estimated prevalence of over 523 million people worldwide,heart failure (HF) remains a growing public health problem[1-2].The prevalence of HF is estimated to increase 46% by 2030[1,3].The growth in HF prevale...With an estimated prevalence of over 523 million people worldwide,heart failure (HF) remains a growing public health problem[1-2].The prevalence of HF is estimated to increase 46% by 2030[1,3].The growth in HF prevalence can be attributed to the improved survival of an increasingly elderly population[4].This growth in prevalence is accompanied by substantial financial burden,with total cost of HF around ($) 30 billion in the United States,a value that is predicted to increase to ($) 70 billion by 2030[2-3].Hospital care for acute HF (AHF) accounts for a significant amount of this total expenditure[5].展开更多
This document is about heart failure(HF),including acute and chronic heart failure,heart failure with reduced ejection fraction and heart failure with preserved ejection fraction as well as cardiomyopathies.Context-sp...This document is about heart failure(HF),including acute and chronic heart failure,heart failure with reduced ejection fraction and heart failure with preserved ejection fraction as well as cardiomyopathies.Context-specific recommendations tailored to individual patient needs are highlighted providing a thorough evaluation of the risks,benefits,and overall value of each therapy,aiming to establish a standard of care that improves patient outcomes and reduces the burden of hospitalization in this susceptible population.These guidelines provide evidence-based recommendations that represent a group consensus considering many other published guidelines that have reviewed many of the issues discussed here,but they also make new recommendations where new evidence has recently emerged.Most importantly these guidelines also provide recommendations on a number of issues where resource limitations may put constraints on the care provided to HF patients.Such"economic adjustment"recommendations aim to provide guidance for situations when"Resources are somewhat limited"or when"Resources are severely limited".Hence,this document presents not only a comprehensive but also concise update to HF management guidelines thereby aiming to provide a unified strategy for the pharmacological,non-pharmacological,invasive and interventional management of this significant global health challenge that is applicable to the needs of healthcare around the globe.展开更多
文摘Guanylate cyclase modulators Novel agents were developed to target soluble guanylate cyclase modulators ( sGC ) and allow for vasodilation without the presence of nitric oxide (NO), thereby avoiding the tolerance that occurs with traditional nitrate therapy [1] .Two classes of sGC modulators exist, sGC stimulators and sGC activators [2] . Stimulators, such as vericiguat , enhance sGC to increase activity, even in the condition of low levels of NO .Activators, such as cinaciguat , can stimulate sGC independently of NO [3] . Cinaciguat:Cinaciguat was found to moderately reduce preload and afterload and increase cardiac output in a non-randomized , proof-of-concept study [4] .This study also found cinaciguat to be well tolerated with mild to moderate hypotension as the main adverse effect . The COMPOSE program , a set of three randomized phase Ⅱ studies, COMPOSE 1, 2 and COMPOSE early, sought to analyze the safety and efficacy of this drug in acute heart failure (AHF) patients[5] .However, the study was stopped early due to safety concerns after 71 (71.5%) patients who received cinaciguat experienced hypotension compared to 13 ( 25.5%) patients who received placebo [6] . In addition, cinaciguat was not found to improve dyspnea or cardiac index . Vericiguat:Vericiguat was investigated by the soluble guanylate cyclase stimulator in heart failure study (SOCRATES), a set of two studies examining AHF patients with either reduced ejection fraction < 45% ( SOCRATES-REDUCED ) or preserved ejection fraction (SOCRATES-PRESERVED)[7].AHF patients in both studies were randomized to varying doses of vericiguat from 1.25 mg daily to 10 mg daily versus placebo for 12 weeks. In SOCRATES-REDUCED, vericiguat, although well tolerated , did not produce a statistically significant change in N-terminal B-type natriuretic peptide ( NT-proBNP ) [8] .
文摘With an estimated prevalence of over 523 million people worldwide,heart failure (HF) remains a growing public health problem[1-2].The prevalence of HF is estimated to increase 46% by 2030[1,3].The growth in HF prevalence can be attributed to the improved survival of an increasingly elderly population[4].This growth in prevalence is accompanied by substantial financial burden,with total cost of HF around ($) 30 billion in the United States,a value that is predicted to increase to ($) 70 billion by 2030[2-3].Hospital care for acute HF (AHF) accounts for a significant amount of this total expenditure[5].
文摘This document is about heart failure(HF),including acute and chronic heart failure,heart failure with reduced ejection fraction and heart failure with preserved ejection fraction as well as cardiomyopathies.Context-specific recommendations tailored to individual patient needs are highlighted providing a thorough evaluation of the risks,benefits,and overall value of each therapy,aiming to establish a standard of care that improves patient outcomes and reduces the burden of hospitalization in this susceptible population.These guidelines provide evidence-based recommendations that represent a group consensus considering many other published guidelines that have reviewed many of the issues discussed here,but they also make new recommendations where new evidence has recently emerged.Most importantly these guidelines also provide recommendations on a number of issues where resource limitations may put constraints on the care provided to HF patients.Such"economic adjustment"recommendations aim to provide guidance for situations when"Resources are somewhat limited"or when"Resources are severely limited".Hence,this document presents not only a comprehensive but also concise update to HF management guidelines thereby aiming to provide a unified strategy for the pharmacological,non-pharmacological,invasive and interventional management of this significant global health challenge that is applicable to the needs of healthcare around the globe.
