Shift of conventional paradigm of heart failure treatment: from angiotensin receptor neprilysin inhibitor to sodium–glucose co-transporter 2 inhibitors?

2021 ◽  
Vol 17 (3) ◽  
pp. 497-506
Author(s):  
Alexander E Berezin ◽  
Alexander A Berezin
Keyword(s):  
Heart Failure ◽  
Wide Spectrum ◽  
Large Body ◽  
Renin Angiotensin System ◽  
Angiotensin Receptor ◽  
Heart Failure Treatment ◽  
Angiotensin System ◽  
Reduced Ejection Fraction ◽  
Neprilysin Inhibitor ◽  
Angiotensin Receptor Neprilysin Inhibitor

Current clinical guidelines for heart failure (HF) contain a brand new therapeutic strategy for HF with reduced ejection fraction (HFrEF), which is based on neurohumoral modulation through the use of angiotensin receptor neprilysin inhibitors. There is a large body of evidence for the fact that sodium-glucose co-transporter 2 inhibitors may significantly improve all-cause mortality, cardiovascular mortality and hospitalization for HF in patients with HFrEF who received renin–angiotensin system blockers including angiotensin receptor neprilysin inhibitors, β-blockers and mineralocorticoid receptor antagonists. The review discusses that sodium-glucose co-transporter 2 inhibitors have a wide spectrum of favorable molecular effects and contribute to tissue protection, improving survival in HFrEF patients.

Effectiveness of angiotensin-neprilysin inhibitor treatment versus renin-angiotensin system blockade in older adults with heart failure in clinical care

Heart ◽  
2021 ◽  
pp. heartjnl-2021-319405
Author(s):  
Rishi J Desai ◽  
Elisabetta Patorno ◽  
Muthiah Vaduganathan ◽  
Mufaddal Mahesri ◽  
Kristyn Chin ◽  
...  
Keyword(s):  
Heart Failure ◽  
Older Adults ◽  
Fixed Effects ◽  
Clinical Care ◽  
Renin Angiotensin System ◽  
Fee For Service ◽  
Angiotensin Receptor ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Neprilysin Inhibitor

ObjectiveTo evaluate the effectiveness of angiotensin receptor-neprilysin inhibitor (ARNI) versus renin-angiotensin system (RAS) blockade alone in older adults with heart failure with reduced ejection fraction (HFrEF).MethodsWe conducted a cohort study using US Medicare fee-for-service claims data (2014–2017). Patients with HFrEF ≥65 years were identified in two cohorts: (1) initiators of ARNI or RAS blockade alone (ACE inhibitor, ACEI; or angiotensin receptor blocker, ARB) and (2) switchers from an ACEI to either ARNI or ARB. HR with 95% CI from Cox proportional hazard regression and 1-year restricted mean survival time (RMST) difference with 95% CI were calculated for a composite outcome of time to first worsening heart failure event or all-cause mortality after adjustment for 71 pre-exposure characteristics through propensity score fine-stratification weighting. All analyses of initiator and switcher cohorts were conducted separately and then combined using fixed effects.Results51 208 patients with a mean age of 76 years were included, with 16 193 in the ARNI group. Adjusted HRs comparing ARNI with RAS blockade alone were 0.92 (95% CI 0.84 to 1.00) among initiators and 0.79 (95% CI 0.74 to 0.85) among switchers, with a combined estimate of 0.84 (95% CI 0.80 to 0.89). Adjusted 1-year RMST difference (95% CI) was 4 days in the initiator cohort (−1 to 9) and 12 days (8 to 17) in the switcher cohort, resulting in a pooled estimate of 9 days (6 to 12) favouring ARNI.ConclusionARNI treatment was associated with lower risk of a composite effectiveness endpoint compared with RAS blockade alone in older adults with HFrEF.

scholarly journals The Efficacy and Safety of Sacubitril/Valsartan in Heart Failure Patients: A Review

2022 ◽  
Vol 27 ◽  
pp. 107424842110586
Author(s):  
Rui Zhang ◽  
Xiaotong Sun ◽  
Ya Li ◽  
Wenzheng He ◽  
Hongguang Zhu ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Renin Angiotensin System ◽  
Efficacy And Safety ◽  
Reduced Ejection Fraction ◽  
Neprilysin Inhibitor ◽  
Regulation Of Metabolism ◽  
Angiotensin Receptor Neprilysin Inhibitor ◽  
Peptide System ◽  
Near Future

Heart failure (HF) is one of the leading causes of morbidity and mortality worldwide. Sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor, has been approved for the treatment of HF. At present, there have been few systematic and detailed reviews discussing the efficacy and safety of sacubitril/valsartan in HF. In this review, we first introduced the pharmacological mechanisms of sacubitril/valsartan, including the reduction in the degradation of natriuretic peptides in the natriuretic peptide system and inhibition of the renin-angiotensin system. Then, we summarized the efficacy of sacubitril/valsartan in HF patients with reduced ejection fraction (HFrEF) or preserved ejection fraction (HFpEF) including the reduction in risks of mortality and hospitalization, reversal of cardiac remodeling, regulation of biomarkers of HF, improvement of the quality of life, antiarrhythmia, improving renal dysfunction and regulation of metabolism. Finally, we discussed the safety and tolerability of sacubitril/valsartan in the treatment of HFrEF or HFpEF. Compared with ACEIs/ARBs or placebo, sacubitril/valsartan showed good safety and tolerability, although the risk of hypotension might be high. In conclusion, the overwhelming majority of studies show that sacubitril/valsartan is effective and safe in the treatment of HFrEF patients but that it has little benefit in HFpEF patients. Sacubitril/valsartan will probably be a promising anti-HF drug in the near future.

scholarly journals Key Considerations For Integrating Sacubitril/Valsartan Into Chronic Heart Failure Management

2018 ◽  
Vol 2 (2) ◽  
pp. 34-43
Author(s):  
Matthew P. Lillyblad
Keyword(s):  
Heart Failure ◽  
Clinical Practice ◽  
Chronic Heart Failure ◽  
Ejection Fraction ◽  
Drug Administration ◽  
Angiotensin Receptor ◽  
Heart Failure Management ◽  
Reduced Ejection Fraction ◽  
Neprilysin Inhibitor ◽  
Angiotensin Receptor Neprilysin Inhibitor

Heart failure with reduced ejection fraction remains a prevalent clinical syndrome associated with significant morbidity and mortality. Despite significant advances in heart failure with reduced ejection fraction pharmacotherapy, 5-year mortality remains 50%. Sacubitril/valsartan is a first-in-class angiotensin-receptor-neprilysin inhibitor, Food and Drug Administration–approved to reduce the risk of cardiovascular death and hospitalization for heart failure in patients with chronic heart failure with reduced ejection fraction. Sacubitril/valsartan is recognized as a significant therapeutic advancement and endorsed by national guidelines, yet adoption into clinical practice has lagged across the United States. Recommendations for use differ greatly between the Prospective Comparison of Angiotensin-Receptor-Neprilysin Inhibitor with Angiotensin-Converting-Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure clinical trial, international guidelines, and the Food and Drug Administration-approved labeling, which can lead to uncertainty with prescribing. It is essential to establish an evidence-based, pragmatic approach to patient selection and management of sacubitril-valsartan facilitate integration into clinical practice. This review summarizes the pharmacology of sacubitril/valsartan, its known benefits and risks, and important considerations for incorporating sacubitril/valsartan into chronic heart failure management.

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