Related Experiment Video
Updated: Feb 8, 2026
In Silico Clinical Trials for Cardiovascular Disease
Published on: May 27, 2022
Sacubitril/valsartan: from a large clinical trial to clinical practice
Edoardo Sciatti1, Michele Senni2, Carlo M Lombardi1
1Cardiology, Department of medical and surgical specialties, radiological sciences and public health, University and ASST Spedali Civili, Brescia.
Insights
Sacubitril/valsartan significantly reduces mortality and hospitalizations in heart failure with reduced ejection fraction (HFrEF). Implementation guidance is crucial for this new treatment in clinical practice.
Area of Science:
- Cardiology
- Pharmacology
- Clinical Practice Guidelines
Background:
- The PARADIGM-HF trial demonstrated sacubitril/valsartan's superiority over enalapril in reducing mortality and heart failure hospitalizations for patients with HFrEF.
- Current guidelines recommend replacing ACE inhibitors or AT1 blockers with sacubitril/valsartan for HFrEF patients.
Purpose of the Study:
- To review factors influencing the clinical implementation of sacubitril/valsartan based on PARADIGM-HF findings.
- To identify challenges and considerations for adopting sacubitril/valsartan in heart failure management.
Main Methods:
- Review of the PARADIGM-HF trial data and subsequent clinical practice guidelines.
- Analysis of patient populations, drug tolerability, and economic factors impacting implementation.
Main Results:
- Sacubitril/valsartan offers significant benefits for HFrEF patients, leading to guideline recommendations for its use.
- Key limitations include its current non-indication for heart failure with preserved ejection fraction (HFpEF) and hospitalized patients.
- Tolerability is generally good, with lower renal dysfunction risk than enalapril, though hypotension can occur; cost is a consideration.
Conclusions:
- Successful implementation requires addressing guideline limitations, particularly for HFpEF and acutely ill patients.
- Improving awareness of heart failure outcomes and enhancing patient management programs are vital for widespread adoption of sacubitril/valsartan.
Abstract:
: The Prospective Comparison of Angiotensin Receptor Antagonist and Neprilysin Inhibitor with Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial (PARADIGM-HF) has shown a reduction in the risk of death and heart failure hospitalizations with sacubitril/valsartan, compared with enalapril, in patients with heart failure and reduced ejection fraction. Guidelines now recommend the substitution of angiotensin-converting enzyme inhibitors or AT1 blockers with sacubitril/valsartan in patients with heart failure and reduced ejection fraction. The aim of this review is to discuss factors that may have an impact on the implementation of these guidelines into clinical practice. The main limitation is that, based on the inclusion criteria of PARADIGM-HF, sacubitril/valsartan is not indicated in patients with heart failure and preserved ejection fraction, although they may be the majority of the patients with heart failure. The trial enrolled ambulatory patients and thus start of sacubitril/valsartan is not indicated in those hospitalized for heart failure. A drug's tolerability may be limited by hypotension with, however, a lower rate of renal dysfunction, compared with enalapril. The cost of the new treatment is also an issue. Similarly to what occurred when other neurohormonal antagonists have been introduced in clinical practice, increased awareness of poor heart failure outcomes and better patients' management programs may be of utmost importance for the implementation of this new agent.
More Related Videos
05:16Characterizing Exon Skipping Efficiency in DMD Patient Samples in Clinical Trials of Antisense Oligonucleotides
Published on: May 7, 2020
14:45Enumeration of Major Peripheral Blood Leukocyte Populations for Multicenter Clinical Trials Using a Whole Blood Phenotyping Assay
Published on: September 16, 2012
Related Concept Videos
01:16Clinical Trials
There are four phases in a clinical trial. A phase one...
01:11Clinical Trials: Overview
01:12Statistical Software for Data Analysis and Clinical Trials
01:27Nursing Clinical Information System
A Nursing Clinical Information System (NCIS) is a specialized type of healthcare information system tailored to meet the unique needs of nursing practice. It incorporates the principles of nursing informatics to streamline information management and improve the quality of care delivery.
Critical attributes of NCIS include:
01:14Changes in Skin Color: Clinical Perspectives
Albinism
Albinism is a genetic disorder that affects (completely or partially) the coloring of skin, hair, and eyes. The defect is primarily...
01:20COPD: Pathogenesis and Clinical Features
The primary cause for the onset of COPD is cigarette smoking and exposure to air pollution. These hazardous factors initiate a chain reaction within the lungs, resulting in chronic inflammation, damage to the airways, and a...