Enalapril In Patients Research Articles

Real-world effectiveness and safety of sacubitril/valsartan in heart failure: A systematic review

Background:PARADIGM-HF demonstrated superiority of sacubitril/valsartan (sac/val) over enalapril in patients with heart failure with reduced ejection fraction (HFrEF). However, patients in clinical practice may differ in their characteristics and overall risk compared with patients in clinical trials, and additional outcomes can be observed in real world (RW). Hence, a systematic review was conducted to identify and describe RW data on sac/val.Methods:RW studies evaluating the effects of sac/val in adult patients with HFrEF with a sample size ≥100 were identified via MEDLINE® and Embase® from 2015 to January 2020. Citations were screened, critically appraised and relevant data were extracted.Results:A total of 68 unique studies were identified. Nearly half of the studies were conducted in Europe (n = 34), followed by the US (n = 15) and Asia (n = 11). Median follow-up period varied from 1 to 19 months. Mean age ranged between 48.7 and 79.0 years; patients were mostly male and in New York Heart Association (NYHA) functional class II/III, and mean left ventricular ejection fraction varied between 23%and 38%. Of studies performing comparisons, most reported superior efficacy of sac/val in reducing the risk of HF hospitalisations, all-cause hospitalisations, and all-cause mortality as compared to standard-of-care. Many studies reported significant improvements in NYHA functional class and reduction in biomarker levels post sac/val. Hypotension and hyperkalaemia were the most frequently reported adverse events.Conclusions:This comprehensive overview of currently available RW evidence on sac/val complements the evidence from randomised controlled trials, substantiating its effectiveness in heterogeneous real-world HF populations.

Hospitalization and Mortality in Patients With Heart Failure Treated With Sacubitril/Valsartan vs. Enalapril: A Real-World, Population-Based Study.

Background: The effect of sacubitril/valsartan on survival and hospitalization risk in older patients with heart failure has not been explored. We aimed to investigate the risk of hospitalization and mortality with the use of sacubitril/valsartan vs. enalapril in patients with heart failure.Methods: This was a population-based cohort study using the Hong Kong-wide electronic healthcare database. Patients diagnosed with heart failure and newly prescribed sacubitril/valsartan or enalapril between July 2016 and June 2019 were included. The risk of primary composite outcome of cardiovascular mortality or heart failure-related hospitalization, all-cause hospitalization, heart failure-related hospitalization, cardiovascular mortality and all-cause mortality were compared using Cox regression with inverse probability treatment weighting. Additional analysis was conducted by age stratification.Results: Of the 44,503 patients who received sacubitril/valsartan or enalapril, 3,237 new users (sacubitril/valsartan, n = 1,056; enalapril, n = 2,181) with a diagnosis of heart failure were identified. Compared with enalapril, sacubitril/valsartan users were associated with a lower risk of primary composite outcome [hazard ratio (HR) 0.58; 95% confidence interval (CI), 0.45–0.75], heart failure-related hospitalization (HR 0.59; 95% CI, 0.45–0.77), all-cause mortality (HR 0.51; 95% CI, 0.36–0.74) and borderline non-significant reductions in all-cause hospitalization (HR 0.85; 95% CI, 0.70–1.04) and cardiovascular mortality (HR 0.63; 95% CI, 0.39–1.02). The treatment effect of sacubitril/valsartan remains unaltered in the patient subgroup age ≥ 65 years (73%).Conclusions: In real-world settings, sacubitril/valsartan was associated with improved survival and reduced heart failure-related hospitalization compared to enalapril in Asian patients with heart failure. The effectiveness remains consistent in the older population.

Efficacy and safety of sacubitril/valsartan compared with enalapril in patients with chronic heart failure and reduced ejection fraction: Results from PARADIGM-HF India sub-study

ObjectivesTo determine efficacy and safety of sacubitril/valsartan compared with enalapril in Indian patients of PARADIGM-HF trial. MethodsA randomized, double-blind, active-controlled, phase III sub-study (NCT01035255) was conducted between April 2010 and May 2014. Patients with chronic heart failure (HF), aged >18 years with left ventricular ejection fraction ≤40% were randomized (1:1) to receive either sacubitril/valsartan 200 mg twice-daily or enalapril 10 mg twice-daily. The primary endpoint was to compare efficacy of sacubitril/valsartan to enalapril in delaying time-to-first occurrence of the composite endpoint (cardiovascular [CV] death or HF hospitalization). ResultsThe trial was stopped after a median follow-up of 27 months, because the boundary for benefit with sacubitril/valsartan had crossed. Among 637 Indian patients in PARADIGM-HF (sacubitril/valsartan, n = 322 and enalapril, n = 315), the primary outcome, CV death, and the first hospitalization for HF occurred in 21.81% and 24.76% (HR 0.89; 95% CI, 0.646–1.231), 17.45% and 20.63% (HR 0.87; 95% CI, 0.605–1.236), and 7.48% and 9.52% (HR 0.78; 95% CI, 0.461–1.350) patients in the sacubitril/valsartan and enalapril group, respectively. The all-cause mortality (19.0% vs. 21.9%) and adverse events (78.4% vs. 82.2%) were comparatively lower in the sacubitril/valsartan than enalapril group. No significant difference was seen between the benefits of treatment in Indian and the total PARADIGM-HF cohort (p value for interaction >0.05). ConclusionResults support the use of sacubitril/valsartan in Indian patients with chronic HF with reduced ejection fraction with treatment benefits similar to global PARADIGM-HF cohort.

The AWAKE-HF Study: Sacubitril/Valsartan Impact on Daily Physical Activity and Sleep in Heart Failure.

AWAKE-HF evaluated the effect of the initiation of sacubitril/valsartan versus enalapril on activity and sleep using actigraphy in patients who have heart failure with reduced ejection fraction (HFrEF). In this randomized, double-blind study, patients with HFrEF (n = 140) were randomly assigned to sacubitril/valsartan or enalapril for 8weeks, followed by an 8-week open-label phase with sacubitril/valsartan. Primary endpoint was change from baseline in mean activity counts during the most active 30min/day at week 8. The key secondary endpoint was change in mean nightly activity counts/minute from baseline to week 8. Kansas City Cardiomyopathy Questionnaire-23 (KCCQ-23) was an exploratory endpoint. There were no detectable differences between groups in geometric mean ratio of activity counts during the most active 30min/day at week 8 compared with baseline (0.9456 [sacubitril/valsartan:enalapril]; 95% confidence interval [CI] 0.8863-1.0088; P = 0.0895) or in mean change from baseline in activity during sleep (difference: 2.038counts/min; 95% CI - 0.062 to 4.138; P = 0.0570). Change from baseline to week 8 in KCCQ-23 was 2.89 for sacubitril/valsartan and 4.19 for enalapril, both nonsignificant. In AWAKE-HF, no detectable differences in activity and sleep were observed when comparing sacubitril/valsartan with enalapril in patients with HFrEF using a wearable biosensor. ClinicalTrials.gov, NCT02970669.

Efficacy and safety of sacubitril-valsartan in heart failure: a meta-analysis of randomized controlled trials.

AimsSacubitril‐valsartan has been shown to have superior effects over angiotensin‐converting enzyme inhibitors and angiotensin receptor blockers in patients with heart failure (HF) and hypertension. The efficacy and safety of sacubitril‐valsartan in patients with HF are controversial. We performed a meta‐analysis of randomized controlled trials to assess and compare the effect and adverse events of sacubitril‐valsartan, valsartan, and enalapril in patients with HF.Methods and resultsWe conducted a systematic search using PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov. Randomized controlled trials involving the use of sacubitril‐valsartan in patients with HF were included. We assessed the pooled odds ratio (OR) of all‐cause mortality, cardiovascular mortality, and hospitalization for HF in fixed‐effects models and the pooled risk ratio (RR) of symptomatic hypotension, worsening renal function, and hyperkalaemia in fixed‐effects models. Of the 315 identified records, six studies involving 14 959 patients were eligible for inclusion. Sacubitril‐valsartan reduced the endpoints of all‐cause mortality and cardiovascular mortality in patients with HF with reduced ejection fraction (HFrEF) in three trials with pooled ORs of 0.83 (P = 0.0006) and 0.78 (P < 0.0001), respectively. Regarding the composite outcome of hospitalization for HF in five trials, the pooled OR was 0.79 (P < 0.00001). Compared with enalapril or valsartan, sacubitril‐valsartan was associated with a high risk of symptomatic hypotension (RR 1.47, P < 0.00001), low risk of worsening renal function (RR 0.81, P = 0.005), and low rate of serious hyperkalaemia (≥6.0 mmol/L) (RR 0.76, P = 0.0007) in all six trials.ConclusionsCompared with angiotensin‐converting enzyme inhibitors or angiotensin receptor blockers, sacubitril‐valsartan significantly decreased the risk of death from all causes or cardiovascular causes in HFrEF and hospitalization for HF in both patients with HFrEF and HF with preserved ejection fraction. Sacubitril‐valsartan reduced the risk of renal dysfunction and serious hyperkalaemia but was associated with more symptomatic hypotension.

Cardiovascular Outcomes with Sacubitril-Valsartan in Heart Failure: Emerging Clinical Data.

One of the defining features of heart failure (HF) is neurohormonal activation. The renin-angiotensin-aldosterone-system (RAAS) and sympathetic nervous system (SNS) cause vasoconstriction and fluid retention and, in response, the secretion of natriuretic peptides (NPs) from volume and pressure-overloaded myocardium promotes vasodilation and diuresis. Inhibition of the RAAS with either angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) has been the cornerstone of medical treatment for HF with a reduced ejection fraction (HFrEF) but, until recently, it was unclear how the beneficial effects of NPs may be augmented in patients with HF. Neprilysin, a metalloproteinase widely distributed throughout the body, plays a role in degrading the gross excess of circulating NPs in patients with HF. Early studies of neprilysin inhibition suggested possible physiological benefits. In 2014, the PARADIGM-HF trial found that sacubitril-valsartan, a combination of the ARB valsartan, and the neprilysin inhibitor sacubitril, was superior to enalapril in patients with HFrEF, reducing the relative risk of cardiovascular (CV) death or first hospitalisation with HF by 20%. Almost half of the patients with HF symptoms have a “preserved” ejection fraction (HFpEF); however, the PARAGON-HF study found that sacubitril-valsartan in patients with LVEF ≥45% had no effect on CV death or first and recurrent hospitalisations with HF compared to valsartan. Guidelines across the world have changed to include sacubitril-valsartan for patients with HFrEF yet, nearly 6 years after PARADIGM-HF, there is still uncertainty as to when and in whom sacubitril-valsartan should be started. Furthermore, there may yet be subsets of patients with HFpEF who might benefit from treatment with sacubitril-valsartan. This review will describe the mechanisms behind the outcome benefit of sacubitril-valsartan in patients with HFrEF and to consider its future role in the management of patients with HF.

WORSENING RENAL FUNCTION, HYPERKALEMIA AND HYPOTENSION IN SACUBITRIL-VALSARTAN VS. ENALAPRIL IN HFREF: A META-ANALYSIS

Sacubitril-valsartan has shown significant promise in patients with Heart Failure with reduced Ejection Fraction (HFrEF). We compared the safety of the sacubitril-valsartan with enalapril in patients with HFrEF. A comprehensive search was performed on PubMed, Embase, and Cochrane for randomized

Understanding the early mortality benefit observed in the PARADIGM-HF trial: considerations for the management of heart failure with sacubitril/valsartan.

This review aims to elucidate the optimal dosing of angiotensin receptor-neprilysin inhibitor (ARNI) therapy in the heart failure (HF) treatment paradigm through examination of the trial population characteristics and the mortality benefit observed in the Prospective Comparison of ARNI with angiotensin-converting enzyme inhibitor (ACEI) to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF; NCT01035255) trial. Considerations regarding the initiation and titration of sacubitril/valsartan, a first-in-class ARNI, will also be addressed. The approval of sacubitril/valsartan heralded the first novel pharmacological class in over a decade for the treatment of heart failure with reduced ejection fraction (HFrEF). The PARADIGM-HF trial showed that treatment with valsartan/valsartan reduced the risk of first occurrence of either cardiovascular death or HF-related hospitalization (composite primary endpoint) by 20% compared with enalapril in patients with HFrEF. The incremental benefits of treatment with valsartan/valsartan over enalapril demonstrated in the PARADIGM-HF trial led to strong recommendations for its use over ACEIs or angiotensin receptor blockers to further reduce morbidity and mortality in the 2016 and 2017 American College of Cardiology/American Heart Association/Heart Failure Society of America updates to the guidelines for the management of HF. Although the optimal timing for the initiation of valsartan/valsartan has yet to be determined, its early use is likely to have a positive impact on patient outcomes.

Pharmacokinetics of enalapril in patients with arterial hypertension depending on the glomerular filtration rate

Aim. To study the pharmacokinetics of enalapril in patients with arterial hypertension, depending on the value of the prescribed dose of enalapril and the state of renal function to improve the efficiency and safety of treatment. Materials and methods. The study was performed in a group of 328 patients (107 men and 221 women aged 43 to 88 years) who received treatment for hypertension of 1-2 degrees. As the main antihypertensive drug was prescribed enalapril in doses of 2.5 to 20 mg twice a day. Patients underwent therapeutic drug monitoring to determine the concentration of enalapril and its metabolite - enalaprilat. Results. Among the examined patients in 31% of cases there was a decrease in GFR less than 60 ml/min, and in 9 (3%) patients GFR was less than 30 ml/min. This indicates a high prevalence of chronic kidney disease among patients with hypertension. During therapeutic drug monitoring enalapril in patients with hypertension and reduced GFR (less than 60 ml/min) serum concentration of the main metabolite was 1.5-2 times higher than in patients with GFR more than 60 ml/min. Conclusion. It is advisable to carry out therapeutic drug monitoring to determine the concentrations of enalapril and enalaprilat in the serum of patients receiving the drug in high doses and having impaired renal function. In the appointment of enalapril in high doses to patients with reduced GFR, the concentration of enalaprilat significantly exceeds similar indicators in patients with normal GFR and in some cases goes beyond the therapeutic range, indicating the need to consider the correction of the treatment regimen.

Early Effects of Starting Doses of Enalapril in Patients with Chronic Heart Failure in the SOLVD Treatment Trial

BackgroundIn the Studies of Left Ventricular Dysfunction (SOLVD) treatment trial, similar clinical benefits were observed between starting doses of enalapril and the target dose achieved by postrandomization up-titration. In our current analysis, protecting the randomization, we examined the early effects of starting doses of enalapril. MethodsThere were 2569 patients with mild-to-moderate chronic heart failure with reduced ejection fraction (ejection fraction ≤35%) randomized to receive starting doses (5-10 mg/day) of placebo (n = 1284) or enalapril (n = 1285). At day 14, both study drugs were blindly up-titrated to the target dose (20 mg/day). Overall, 96% (2458/2569) of the patients returned for dose up-titration, which was achieved in 59% (1444/2458), 48% (696/1444) of whom were in the enalapril group. Hazard ratios (HRs) and 95% confidence intervals (CIs) for outcomes in the enalapril group were estimated. ResultsHRs (95% CIs) for all-cause mortality, heart failure hospitalization, and the combined endpoint of heart failure hospitalization or all-cause mortality at 14 days after randomization were 0.80 (0.32-2.03), 0.63 (0.35-1.12), and 0.65 (0.39-1.06), respectively. Corresponding HRs (95% CIs) at 30 days were 0.82 (0.41-1.67), 0.43 (0.27-0.68), and 0.43 (0.27-0.68), respectively. The magnitude of these early effects of starting doses of enalapril is similar to its previously reported long-term effects at the target dose. ConclusionThese data suggest that in stable ambulatory patients with heart failure with reduced ejection fraction, the magnitude of the early effect of starting doses of enalapril is similar to that observed during longer-term therapy with the target doses of the drug.

Cost-effectiveness of sacubitril/valsartan for the treatment of patients with heart failure with reduced ejection fraction in Portugal

ABSTRACTObjectives: This study assesses the cost-effectiveness of sacubitril/valsartan versus enalapril in patients with symptomatic heart failure with reduced ejection fraction (HFrEF).Methods: We used a previously developed Markov model calibrated with patient-level data from the PARADIGM-HF trial, adapted to the Portuguese setting. The model considers two health states (alive or dead) and uses regression analyzes to estimate hospitalizations and deaths over time. A panel of experts estimated resource consumption in the outpatient setting. To estimate resource consumption with hospitalizations, the National Health Service Diagnosis Related Groups database was used. Unit costs were based on national legislation, and on the Infomed database. The model considers a societal perspective, a time horizon of 30-years, and a 5% annual discount rate. Sensitivity analyses assessed the robustness of results.Results: Sacubitril/valsartan increases life expectancy by 0.5 life-years, corresponding to 0.4 incremental quality adjusted life-years (QALY) versus enalapril. The estimated incremental cost-effectiveness ratio (ICER) is 22,702€/QALY. Sensitivity analysis shows that results are robust, but sensitive to the parameter estimates of the cardiovascular survival curve.Conclusion: Sacubitril/valsartan is a cost-effective therapeutic option in the treatment of Portuguese patients with HFrEF and translate into significant health gains and increased life expectancy versus the current standard of care.

Efficacy of telmisartan and enalapril in patients with diabetic nephropathy

Efficacy of telmisartan and enalapril in patients with diabetic nephropathy

Cost-Effectiveness of Switching Patients With Heart Failure and Reduced Ejection Fraction to Sacubitril/Valsartan: The Australian Perspective

The cost-effectiveness, from the Australian health care perspective, of switching patients with heart failure and reduced ejection fraction (HFREF) stable on angiotensin converting enzyme (ACE) inhibitors/angiotensin II receptor blockers (ARBs) to the angiotensin receptor neprilysin inhibitor (ARNi) sacubitril/valsartan is unclear. We sought to assess the cost-effectiveness of sacubitril/valsartan versus enalapril in patients with HFREF in the contemporary Australian setting. We developed a Markov model with two health states ('Alive' and 'Dead') to assess the cost-effectiveness of sacubitril/valsartan versus enalapril in patients with HFREF. Model subjects were 63 years of age at entry and had simulated follow-up over 20 years. Transition probabilities were derived from the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure (PARADIGM-HF) study. Costs and utility data were derived from published sources. All costs and effects were discounted at an annual rate of 5% and are presented in Australian dollars. Sensitivity analyses were undertaken to test variability in key data inputs. In the base-case analysis, sacubitril/valsartan was found to reduce non-fatal heart failure hospitalisations and cardiovascular deaths, with numbers-needed-to-treat over a 20-year period of 40 and 27, respectively. The use of sacubitril/valsartan led to an additional 6 months of life gained per patient, translating to A$27,954 per years of life saved (YoLS) and A$40,513 per quality-adjusted-life-years (QALY) gained. The results of the sensitivity analyses indicated that the results were robust. Our analysis supports switching HFREF patients on ACE inhibitor or ARB to sacubitril/valsartan.

\u201cReal World\u201d Eligibility for Sacubitril/Valsartan in Unselected Heart Failure Patients: Data from the Swedish Heart Failure Registry

PurposePARADIGM-HF demonstrated the superiority of sacubitril/valsartan over enalapril in patients with heart failure and reduced ejection fraction (HF-REF). How widely applicable sacubitril/valsartan treatment is in unselected patients with HF-REF is not known. We examined eligibility of patients with HF-REF for treatment with sacubitril/valsartan, according to the criteria used in PARADIGM-HF, in the Swedish Heart Failure Registry (SwedeHF).MethodsPatients were considered potentially eligible if they were not hospitalized, had symptoms (NYHA class II–IV) and a reduced LVEF (≤ 40%), and were prescribed an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) at a dose equivalent to enalapril ≥ 10 mg daily. In these patients, we evaluated further eligibility according to the main additional PARADIGM-HF inclusion criteria.ResultsOf 12,866 outpatients in NYHA functional class II–IV with an LVEF ≤ 40%, 9577 were prescribed at least 10 mg of enalapril (or equivalent) daily. Complete additional data were available for 3099 of these patients (32.4%) and of them 75.5% were potentially eligible for treatment with sacubitril/valsartan. The most common reason for ineligibility was a low natriuretic peptide level (n = 462, 14.9%). Only a small proportion of patients were ineligible due to low eGFR or serum potassium level. Because only 78% of patients were taking ≥ 10 mg enalapril or equivalent daily, only 58.9% of all patients (75.5% of 78%) were eligible for sacubitril/valsartan.ConclusionsBetween 34 and 76% of symptomatic patients with HF-REF in a ‘real world’ population are eligible for treatment with sacubitril/valsartan, depending on background ACEI/ARB dose. The most common reason for ineligibility is a low natriuretic peptide level.

SACUBITRIL-VALSARTAN VERSUS ANGIOTENSIN CONVERTING ENZYME INHIBITORS OR ANGIOTENSIN RECEPTOR BLOCKERS IN SYSTOLIC HEART FAILURE: COMPARATIVE OUTCOMES IN CLINICAL PRACTICE

In a single randomized trial, sacubitril-valsartan reduced risks of death and hospitalization for heart failure (HF) versus enalapril in patients with HF and reduced ejection fraction. However, studies comparing the effectiveness of sacubitril-valsartan with ACE inhibitors / angiotensin receptor

Reduced loop diuretic use in patients taking sacubitril/valsartan compared with enalapril: the PARADIGM-HF trial.

AimsTo assess differences in diuretic dose requirements in patients treated with sacubitril/valsartan compared with enalapril in the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure (PARADIGM‐HF) trial.Methods and resultsOverall, 8399 patients with New York Heart Association class II–IV heart failure and reduced LVEF were randomized to sacubitril/valsartan 200 mg bid or enalapril 10 mg twice daily. Loop diuretic doses were assessed at baseline, 6, 12, and 24 months, and furosemide dose equivalents were calculated via multiplication factors (2x for torsemide and 40x for bumetanide). Percentages of participants with reductions or increases in loop diuretic dose were determined. At baseline, 80.8% of participants were taking any diuretics (n = 6290 for loop diuretics, n = 496 for other diuretics); of those, recorded dosage data for loop diuretics were available on 5487 participants. Mean baseline furosemide equivalent doses were 48.2 mg for sacubitril/valsartan and 49.6 mg for enalapril (P = 0.25). Patients treated with sacubitril/valsartan were more likely to reduce diuretic dose and less likely to increase diuretic dose relative to those randomized to enalapril at 6, 12, 24 months post‐randomization, with an overall decreased diuretic use of 2.0% (P = 0.02), 4.1% (P < 0.001), and 6.1% (P < 0.001) at 6, 12, and 24 months, respectively, with similar findings in an on‐treatment analysis.ConclusionTreatment with sacubitril/valsartan was associated with more loop diuretic dose reductions and fewer dose increases compared with enalapril, suggesting that treatment with sacubitril/valsartan may reduce the requirement for loop diuretics relative to enalapril in patients with heart failure with reduced ejection fraction.

In-Hospital Initiation of Sacubitril/Valsartan in Stabilised Patients with Heart Failure and Reduced Ejection Fraction Naïve to Renin-Angiotensin System Blocker: An Analysis of the Transition Study

Background: In the PIONEER-HF study, in-hospital initiation of sacubitril/valsartan (S/V) versus enalapril in patients with heart failure (HF) and reduced ejection fraction (HFrEF), stabilised after acute decompensation, was associated with superior reduction of NT-proBNP, irrespective of prior use of angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB). Methods: In TRANSITION (NCT02661217), 1002 patients with HFrEF, hospitalised for acute decompensated HF after haemodynamic stabilisation, were randomised 1:1 and initiated open-label S/V either pre- or post-discharge (1–14 days). Primary endpoint was the proportion of patients achieving the target dose (97/103 mg, bid) at 10 weeks post-randomisation. Endpoints, adverse events (AEs) and serious AEs (SAEs) were compared by ACEi/ARB status in the combined pre- and post-discharge arms. Results: ACEi/ARB-naïve group [326 (32.9%)] had lower systolic blood pressure, serum creatinine, higher heart rate, and more often had non-ischaemic HF aetiology. Similar proportions of ACEi/ARB-naïve and non-naïve patients achieved the target dose of S/V (48.3% vs 47.9%, RRR 1.01 [0.88–1.16]) (Figure) and 88% patients from both groups were maintained on any S/V dose at Week 10. The rate of permanent discontinuation of S/V due to AEs was low and comparable. Overall incidence of AEs was 65.3% in ACEi/ARB-naïve and 68.3% in non-naïve patients (RRR 0.96 [0.87–1.05]) and incidence of SAEs was 16.3% and 19.4% respectively (RRR 0.83 [0.63–1.12]) (Table). Conclusion: In hospitalised patients with HFrEF naïve to ACEi/ARB, S/V can be safely initiated pre-discharge or shortly after discharge, and up-titration is well tolerated.

A comparative study of sacubitril/valsartan with enalapril in patients with borderline reduced ejection fraction - A single tertiary centre experience in eastern India

A comparative study of sacubitril/valsartan with enalapril in patients with borderline reduced ejection fraction - A single tertiary centre experience in eastern India

Sacubitril/Valsartan versus enalapril in nonischemic heart failure in Paradigm-Hf trial

<strong>Background :</strong>We compared the angiotensin receptor–neprilysin inhibitor LCZ696 (sacubitril/valsartan) with enalapril in patients who had nonischemic heart failure with a reduced ejection fraction.

Angiotensin Receptor Neprilysin Inhibitor Therapy Improves Ejection Fraction in Patients with Systolic Heart Failure

Introduction The PARADIGM-HF study showed that angiotensin receptor-neprilysin inhibitor (ARNI) therapy with sacubitril/valsartan significantly reduced cardiovascular mortality, heart failure hospitalization, and all-cause mortality compared to ace inhibitor therapy with enalapril in patients with heart failure with reduced ejection fraction (HFrEF). Since being fast tracked for HFrEF treatment in 2015, ARNI has been studied in various aspects related to efficacy and long-term effects. However, the effect of ARNI specifically on ejection fraction (EF) in patients with HFrEF on guideline directed medical therapy (GDMT) remains unknown. Hypothesis Given preliminary data, our hypothesis is that patients with heart failure on GDMT will show significant recovery and improvement in EF after initiating ARNI therapy. Methods A retrospective chart review was conducted to identify all patients treated with ARNI at a dedicated heart failure clinic in the past 12 months meeting the following criteria: (i) age ≥ 18 years, (ii) NYHA class II-III symptoms, (iii) on GDMT (beta blocker, ace inhibitor/angiotensin receptor blocker, and aldosterone antagonist) prior to ARNI initiation, (iv) EF ≤35% at time of ARNI initiation, (v) HFrEF on echo for ≥6 months prior to ARNI initiation, and (vi) follow up echo >3-6 months after ARNI initiation. Interval changes in EF since starting ARNI were compared changes in EF prior to starting ARNI. Results Patients started on ARNI showed significant recovery and improvement in EF at an average follow up of 6 months compared to EF at time of ARNI initiation (32.7% vs 22.6%, respectively, p = 0.0013). Conclusions ARNI therapy shows significant improvement and recovery of EF in patients with HFrEF on GDMT. These findings suggest that ARNI therapy could potentially reduce or delay the necessity for defibrillators and other costly procedures, while also contributing to decreased rates of hospitalizations and overall morbidity and mortality of patients with systolic heart failure.