Anatomical versus Physiological Lesion Characteristics in Prediction of Acute Coronary Syndrome (JACC Cardiovascular Interventions December 2025)-Article: Anatomical versus Physiological Lesion Characteristics in Prediction of Acute Coronary Syndrome

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This updated systematic review and network meta-analysis evaluated pharmacologic treatments for heart failure with reduced ejection fraction (HFrEF), incorporating data from 89 randomized controlled trials (RCTs) involving 103,754 patients and including recent large trials such as the VICTOR trial. The study aimed to compare effectiveness among various drug regimens on all-cause mortality, cardiovascular (CV) death, and a composite of CV death or heart failure hospitalization.<br /><br />Findings reaffirm that the contemporary quadruple therapy—consisting of angiotensin receptor–neprilysin inhibitors (ARNi), β-blockers, mineralocorticoid receptor antagonists (MRAs), and sodium-glucose cotransporter 2 inhibitors (SGLT2i)—is most effective in reducing mortality and morbidity in HFrEF patients. The quadruple regimen reduced all-cause mortality with a hazard ratio (HR) of 0.39 compared to placebo. Adding vericiguat, a soluble guanylyl cyclase stimulator, to form quintuple therapy further lowered mortality risk (HR 0.35), providing an exploratory incremental survival benefit of approximately 0.7 years beyond quadruple therapy. However, this additional benefit stems from a secondary endpoint of a single trial and should be interpreted cautiously.<br /><br />Survival modeling using real-world cohort data estimated that, for a 70-year-old patient, quadruple therapy adds about 5.3 life-years compared to no treatment, while quintuple therapy adds about 6.0 life-years. The analysis indicated consistent benefits across outcomes, with hydralazine–isosorbide dinitrate, MRAs, and ARNi also showing strong individual mortality reductions.<br /><br />The study acknowledges limitations including potential undetected inconsistencies within the network, exclusion of limited data on GLP-1 receptor agonists, generalizability concerns given trial populations, and assumptions about long-term adherence in survival projections.<br /><br />In summary, this comprehensive network meta-analysis confirms the substantial mortality and morbidity benefits of the guideline-recommended quadruple therapy for HFrEF. The addition of vericiguat may confer modest extra survival benefit, but further research is needed to validate this finding and assess its clinical feasibility.

Meta Tag

Concept Heart Failure with Reduced Ejection Fraction

Concept Quadruple Therapy

Concept All-Cause Mortality

Concept Pharmacologic Treatment

Concept Network Meta-Analysis

Keywords

heart failure with reduced ejection fraction

HFrEF

quadruple therapy

angiotensin receptor–neprilysin inhibitors

beta-blockers

mineralocorticoid receptor antagonists

sodium-glucose cotransporter 2 inhibitors

vericiguat

network meta-analysis

mortality reduction

Heart Failure with Reduced Ejection Fraction

Quadruple Therapy

All-Cause Mortality

Pharmacologic Treatment

Network Meta-Analysis