Despite recent advances, the management of heart failure (HF), which usually presents as a complex disease, remains a challenge. This is reflected in the relatively high rate of readmissions along with the increased mortality and morbidity associated with HF. Medical care for HF includes a number of non-pharmacological, pharmacological and invasive strategies to limit and reverse its manifestationsCitation1. Depending on the severity of the illness, non-pharmacological therapies include dietary sodium and fluid restriction, physical activity as appropriate and attention to weight gain. Pharmacological therapies include the use of diuretics, vasodilators, inotropic agents, anticoagulants, beta-blockers and digoxin. Invasive therapies for HF include electrophysiological intervention such as cardiac resynchronization therapy (CRT), pacemakers, implantable cardioverter–defibrillators (ICDs), revascularization procedures such as coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI), valve replacement or repair and ventricular restorationCitation2.
The ideal treatment of HF aims to improve clinical status, functional capacity and quality of life, reduce disease-related mortality and prevent hospitalizations. In HF patients with reduced ejection fraction (HFrEF), the use of neuro-hormonal antagonists disease modifiers drugs (DMDs) such as angiotensin-converting enzyme (ACE) inhibitors, mineralocorticoid receptor antagonists and beta-blockers is recommended to control disease progression. Nevertheless, morbidity and mortality still remain high.
The sacubitril/valsartan combination was introduced into the pharmacological scenario of managing HFrEF supporting the opportunity to introduce the beneficial effects of the natriuretic peptides while maintaining RAAS system modulation. Specifically, sacubitril/valsartan belongs to the newly established class of dual-acting angiotensin receptor/neprilysin inhibitors (ARNIs)Citation3. ARNIs represent significant progress over angiotensin-converting enzyme (ACE) inhibition or angiotensin receptor blockade alone, because neprilysin inhibition acts synergistically with RAAS blockadeCitation4. Evidence from clinical trials for sacubitril/valsartan supports its use in out-patients as well as in hospitalized ones.
In PARADIGM-HF (Prospective Comparison of ARNI with angiotensin converting enzyme inhibitor (ACEI) to Determine Impact on Global Mortality and Morbidity in Heart Failure), one of the largest clinical trials involving HF (8442 participants), the synergistic effects of RAAS and neprilysin inhibition (sacubitril/valsartan) versus RAAS inhibition (enalapril) showed that sacubitril/valsartan reduced the risk of cardiovascular death and hospitalization in optimally treated HFrEF patients, first-time evidence versus an active comparatorCitation5. PARADIGM-HF subgroup analyses support the efficacy of sacubitril/valsartan regardless of background therapy, clinical stability, dose reductions, comorbidities or previous hospitalizationCitation6. The recently published TRANSITION and PIONEER study resultsCitation7,Citation8 provide evidence to guide the start with sacubitril/valsartan in patients stabilized after acute decompensated HF, in D (refractory HF requiring specialized interventions, as for ACCF/AHA definition) stage, with a good safety profile versus enalapril and positive clinical outcomes on recurrent hospitalizations and on NT-pro BNP (brain natriuretic peptide) reduction. Moreover, the European Society of Cardiology (ESC) guidelines recommend replacing ACEIs with sacubitril/valsartan in patients with HFrEF who remain symptomatic (New York Heart Association [NYHA] classes II–IV) despite optimal therapyCitation9.
While the efficacy of sacubitril/valsartan was established in the clinical trial setting, real-life experience could help add the effectiveness of the drug in daily clinical management and patient follow up. The potential of ARNI therapy for improving outcomes supports the recommendations for its broad adoption into clinical practice; at the same time, the benefits of sacubitril/valsartan are substantiated by real-world studiesCitation6. To this end, Italian HF specialists collected, as clinical cases or case series, the most relevant experiences of sacubitril/valsartan in clinical practice. Case reports of sacubitril/valsartan have observed reversal of left ventricular (LV) remodelling and improvements in NYHA classCitation10–12. By sharing their clinical experiences with sacubitril/valsartan, clinicians can support colleagues, make informed treatment decisions and ensure that patients obtain optimal care.
In this supplement, we present new clinical experience from Italian centres, in a real-life setting, regarding sacubitril/valsartan. This case series describes the effectiveness of sacubitril/valsartan and investigates the different clinical outcomes and their impact on patient quality of life.
Monzo et al.Citation13 show that after 3 months of treatment with sacubitril/valsartan patients were completely asymptomatic and N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration was normalized; transthoracic echocardiography (TTE) showed a remarkable recovery in LV function and magnetic resonance imaging (MRI) showed a dramatically improvement in left ventricular ejection fraction (LVEF) and a decrease in LV volume.
Severini and MboumiCitation14 describe the behaviour of elderly patients with HFrEF.
Pugliese et al.Citation15 state that their case series suggest that BNP may still have a role in guiding chronic HF management of patients treated with this drug, in cases where NT-proBNP testing is not available.
Gubelli and CaivanoCitation16 report a case of a young male with HF and atrial fibrillation with reduced LVEF treated with sacubitril/valsartan that showed a progressive recovery of LVEF, functionality and reduction of cardiac volumes, in two years.
Complementing the ones already published, this supplement adds new “practical information”, useful for the international community, in order to better characterize sacubitril/valsartan effectiveness and safety in the therapy of HF, establishing this combination as a new disease modifying drug, to slow the progression of HFrEF with positive impact on clinical and effectiveness endpoints.
Since HF remains a condition with high morbidity and mortality rates and recurrent hospitalizations, every strategy should be used to reverse disease at each stage, the earlier the better to optimize treatment. The adoption of ARNIs should be considered at any phase of disease progression and patient journey.
Transparency
Declaration of funding
This manuscript forms part of a supplement that was funded by Novartis Farma (Origgio, Italy).
Declaration of financial/other relationships
No potential conflict of interest was reported by the author. CMRO peer reviewers on this editorial have no relevant financial or other relationships to disclose.
Acknowledgements
The author thanks Novartis Farma for editorial assistance.
References
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