Enalapril In Patients Research Articles

Cost-Effectiveness Analysis of Sacubitril-Valsartan Compared with Enalapril in Patients with Heart Failure with Reduced Ejection Fraction in Thailand.

Sacubitril-valsartan is a new medication that has recently been recommended as a replacement for enalapril in the treatment of patients with heart failure with reduced ejection fraction (HFrEF). This study aimed to determine the cost effectiveness of sacubitril-valsartan compared with enalapril. An analytical decision model was developed to estimate the long-term costs and outcomes from a healthcare perspective. Clinical inputs were mostly derived from the PARADIGM-HF study. Enalapril-related costs, risk of non-cardiovascular death, and all-cause readmission rate were based on data from Thailand. The costs and outcomes were discounted at 3% annually. The incremental cost-effectiveness ratio (ICER) was calculated and presented for the year 2017. A series of sensitivity analyses were also performed. For the base-case, the increased cost (144,146 vs. 16,048 Thai baht [THB]) of sacubitril-valsartan was associated with gains in both life-years (9.214 vs. 8.367years) and quality-adjusted life-years (QALYs) (7.698 vs. 6.909) compared with enalapril, yielding an ICER of 162,276 THB/QALY ($US4857.11/QALY). This ICER is not considered to be cost effective at the willingness-to-pay (WTP) level of 160,000 THB/QALY. The risk of cardiovascular death and costs of both sacubitril-valsartan and hospitalization influenced the ICER. At a WTP of 160,000 THB/QALY, sacubitril-valsartan had a 48% probability of being a cost-effective treatment. At its current price in Thailand, sacubitril-valsartan may not represent good value for the nations's limited healthcare resources. The cost of sacubitril-valsartan needs to reduce by approximately 2% to yield an ICER below the threshold.

Angioedema in heart failure patients treated with sacubitril/valsartan (LCZ696) or enalapril in the PARADIGM-HF study

BackgroundPARADIGM-HF demonstrated significant clinical benefits for sacubitril/valsartan (LCZ696, an angiotensin receptor neprilysin inhibitor) versus the angiotensin-converting enzyme inhibitor (ACEI) enalapril in patients with heart failure with reduced ejection fraction. As inhibition of ACE, and co-inhibition of ACE and neprilysin, may increase the risk of angioedema, this was an adverse event of special interest. MethodsFollowing sequential enalapril and sacubitril/valsartan run-ins, patients were randomized to twice-daily sacubitril/valsartan 200 mg or enalapril 10 mg. The study design incorporated two wash-out periods (~36 h each) to minimize any potential risk of angioedema due to overlapping ACE and neprilysin inhibition. Suspected cases of angioedema were reported to, and blindly adjudicated by, an independent angioedema adjudication committee (AAC). ResultsOf the 10,513 patients entering the enalapril run-in, 9419 entered the sacubitril/valsartan run-in and 8432 received double-blind treatment. Overall, 148 suspected angioedema events occurring in 144 patients were reported to AAC, with one event reported during screening period. Of the remaining 147 events, 54 were confirmed as angioedema by AAC. A confirmed event was experienced by 15 (0.14%) and 10 (0.11%) patients, during the enalapril and sacubitril/valsartan run-ins, respectively, and by 10 (0.24%) and 19 (0.45%) patients in the corresponding randomized arms during the double-blind phase. The frequency of confirmed angioedema was higher in black patients. Most events were mild. Only five patients required hospitalization and none required mechanical airway support. ConclusionThe number of confirmed angioedema events in PARADIGM-HF was low and there was no-marked excess risk of angioedema with sacubitril/valsartan versus enalapril.

Treatment optimization of angiotensin converting enzyme inhibitors and associated factors in Ayder Comprehensive Specialized Hospital: a cross-sectional study

BackgroundAngiotensin-converting enzyme inhibitors have morbidity and mortality benefits in heart failure. Failure to optimize treatment using these medications increases hospitalizations, worsens signs and symptoms of heart failure, and reduces the overall treatment outcome. Therefore, the main purpose of this study was to assess the practice of treatment optimization of these medications and associated factors.ResultsA hospital-based cross-sectional study was conducted on 61 ambulatory heart failure patients, recruited using a convenience sampling technique, from February 25 to May 24, 2016 at the cardiology clinic of Ayder Comprehensive Specialized Hospital. Descriptive, inferential and Kaplan–Meier ‘tolerability’ analyses were employed. All patients were taking only enalapril as part of their angiotensin converting enzyme inhibitor treatment. According to the 2013 American College of Cardiology/American Heart Association guideline, about fourth-fifth (80.3%) of the patients were tolerating to the hypotensive effect of enalapril. The dose of enalapril was timely titrated (every 2–4 weeks) and was optimized for only 11.5 and 27.8% of the patients, respectively. Considering the tolerance, timely titration, and dose optimization, only 3.3% of the overall enalapril treatment was optimized. Multivariate regression results showed that the odds of having timely titration of enalapril for patients who were taking enalapril and calcium channel blockers were almost 20 times [adjusted odds ratio (AOR) = 21.68, 95% confidence interval (CI) 1.23–383.16, p < 0.036] more compared to patients who were taking enalapril and β-blockers. A Log Rank Chi Square result showed a 19.42 magnitude of better toleration of enalapril (p < 0.001) for patients who were taking enalapril for more than 1 year compared to less than a year.ConclusionThis study provides a platform for assessment of the treatment optimization practice of enalapril, which remains the pressing priority and found to be poor in the ambulatory setting, despite a better tolerability to the hypotensive effect of enalapril. We call for greater momentum of efforts by health care providers in optimizing the treatment practice to benchmark with other optimization practices.

Rationale and design of the comParIson Of sacubitril/valsartaN versus Enalapril on Effect on nt-pRo-bnp in patients stabilized from an acute Heart Failure episode (PIONEER-HF) trial

ObjectiveThe objective is to assess the safety, tolerability, and efficacy of sacubitril/valsartan compared with enalapril in patients with heart failure (HF) with a reduced ejection fraction (EF) stabilized during hospitalization for acute decompensated HF. BackgroundSacubitril/valsartan, a first-in-class angiotensin receptor-neprilysin inhibitor, improves survival among ambulatory HF patients with a reduced EF. However, there is very limited experience with the in-hospital initiation of sacubitril/valsartan in patients who have been stabilized following hospitalization for acute decompensated HF. MethodsPIONEER-HF is a 12-week, prospective, multicenter, double-blind, randomized controlled trial enrolling a planned 882 patients at more than 100 participating sites in the United States. Medically stable patients >18 years of age with an EF <40% and an amino terminal-pro b-type natriuretic peptide >1600 pg/mL or b-type natriuretic peptide >400 pg/mL are eligible for participation no earlier than 24 hours and up to 10 days from initial presentation while still hospitalized. Patients are randomly assigned 1:1 to in-hospital initiation of sacubitril/valsartan titrated to 97/103 mg by mouth twice daily versus enalapril titrated to 10 mg by mouth twice daily for 8 weeks. All patients receive open-label treatment with sacubitril/valsartan for the remaining 4 weeks of the study. The primary efficacy end point is the time-averaged proportional change in amino terminal-pro b-type natriuretic peptide from baseline through weeks 4 and 8. Secondary and exploratory end points include serum and urinary biomarkers as well as clinical outcomes. Safety end points include the incidence of angioedema, hypotension, renal insufficiency, and hyperkalemia. ConclusionThe PIONEER-HF trial will inform clinical practice by providing evidence on the safety, tolerability, and efficacy of in-hospital initiation of sacubitril/valsartan among patients who have been stabilized following an admission for acute decompensated HF with a reduced EF.

Valsartan/Sacubitril for Treatment of Hfref: A Single Center&amp;apos;s Paradigm

PARADIGM-HF compared valsartan/sacubitril (ARNI) with enalapril in symptomatic patients with heart failure with reduced ejection fraction (HFrEF) (1). It was stopped early after the boundary for overwhelming benefit in favor of ARNI had been reached. Patients taking ARNI had decreased symptoms, risk of HF hospitalization and all-cause and cardiovascular mortality. We sought to describe our center’s initial year of experience with this novel agent. A retrospective chart review was completed of all patients in our advanced HF clinic who were prescribed ARNI between August 2015 and October 2016. Outcomes data were collected through August 2017. Consistent with the Food and Drug Administration (FDA) indication, patients treated had NYHA class II, III or IV HF symptoms with LVEF of 35% or less. The majority of those prescribed ARNI were able to initiate the medication. However, a significant proportion of patients (26.4%) had to discontinue ARNI due to a variety of reasons, most commonly symptomatic hypotension (31.0%) and insufficient insurance coverage (31.0%). Only 30.5% of patients successfully treated reached the maximum dose; in 85% of these patients, hypotension limited up titration of therapy. PARADIGM-HF demonstrated benefit of ARNI therapy over enalapril in patients with HFrEF and therapy was well tolerated. In our real world experience, hypotension and lack of insurance coverage limited utilization. Further experience with this therapy in a non-trial setting will inform optimal patient selection and titration strategies. Expanded insurance coverage will be crucial to allow for patient access.

Cost-effectiveness of sacubitril/valsartan versus enalapril in patients with heart failure and reduced ejection fraction

Background: Sacubitril/valsartan reduces cardiovascular death and hospitalizations for heart failure (HF). However, decision-makers need to determine whether its benefits are worth the additional costs, given the low-cost generic status of traditional standard of care.Aims: To evaluate the cost-effectiveness of sacubitril/valsartan compared to enalapril in patients with HF and reduced ejection fraction, from the Singapore healthcare payer perspective.Methods: A Markov model was developed to project clinical and economic outcomes of sacubitril/valsartan vs enalapril for 66-year-old patients with HF over 10 years. Key health states included New York Heart Association classes I–IV and deaths; patients in each state incurred a monthly risk of hospitalization for HF and cardiovascular death. Sacubitril/valsartan benefits were modeled by applying the hazard ratios (HRs) in PARADIGM-HF trial to baseline probabilities. Primary model outcomes were total and incremental costs and quality-adjusted life years (QALYs) and the incremental cost-effectiveness ratio (ICER) for sacubitril/valsartan relative to enalaprilResults: Compared to enalapril, sacubitril/valsartan was associated with an ICER of SGD 74,592 (USD 55,198) per QALY gained. A major driver of cost-effectiveness was the cardiovascular mortality benefit of sacubitril/valsartan. The uncertainty of this treatment benefit in the Asian sub-group was tested in sensitivity analyses using a HR of 1 as an upper limit, where the ICERs ranged from SGD 41,019 (USD 30,354) to SGD 1,447,103 (USD 1,070,856) per QALY gained. Probabilistic sensitivity analyses showed the probability of sacubitril/valsartan being cost-effective was below 1%, 12%, and 71% at SGD 20,000, SGD 50,000, and SGD 100,000 per QALY gained, respectively.Conclusions: At the current daily price sacubitril/valsartan may not represent good value for limited healthcare dollars compared to enalapril in reducing cardiovascular morbidity and mortality in HF in the Singapore healthcare setting. This study highlights the cost-benefit trade-off that healthcare professionals and patients face when considering therapy.

Similar clinical benefits from below-target and target dose enalapril in patients with heart failure in the SOLVD Treatment trial.

To examine associations of below-target and target dose of enalapril, an angiotensin-converting enzyme (ACE) inhibitor, with outcomes in patients with heart failure and reduced ejection fraction (HFrEF) in the Studies of Left Ventricular Dysfunction (SOLVD) Treatment trial. Two thousand five hundred and sixty-nine patients with HFrEF (ejection fraction ≤35%) were randomized to below-target (5-10 mg/day) dose placebo (n = 1284) or enalapril (n = 1285). One month post-randomization, blind up-titration to target (20 mg/day) dose was attempted for both study drugs in 2458 patients. Among the 1444 patients who achieved dose up-titration (placebo, n = 748; enalapril, n = 696; mean dose for both groups, 20.0 mg/day), target dose enalapril (vs. target dose placebo) was associated with a 9% absolute lower risk of the combined endpoint of heart failure hospitalization or all-cause mortality [adjusted hazard ratio (HR) 0.70; 95% confidence interval (CI) 0.60-0.81; P < 0.001] during 4 years of follow-up. Among the 1014 patients who could not achieve target dose (placebo, n = 486; enalapril, n = 528; mean dose for both groups, 8.8 mg/day), below-target dose enalapril (vs. below-target dose placebo) was associated with a 12% absolute lower risk of the combined endpoint of heart failure hospitalization or all-cause mortality (adjusted HR 0.68; 95% CI 0.57-0.81; P < 0.001). Among the 1224 patients receiving enalapril, target (vs. below-target) dose had no association with the combined endpoint of heart failure hospitalization or all-cause mortality (adjusted HR 1.04; 95% CI 0.87-1.23; P = 0.695). In patients with HFrEF, the clinical benefits of ACE inhibitors appear to be similar at both below-target and target doses.

Profile of sacubitril/valsartan in the treatment of heart failure: patient selection and perspectives.

With an estimated prevalence of 5.8 million in the USA and over 23 million people worldwide, heart failure (HF) is growing in epidemic proportions. Despite the use of guideline-directed medical therapies such as angiotensin-converting enzyme inhibitors, beta-adrenergic blockers, angiotensin receptor blockers, and mineralocorticoid receptor antagonists for chronic systolic HF for almost two decades, HF remains a leading cause of morbidity, mortality, and health care expenditures. The Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor with Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial provided compelling evidence for the cardiovascular and mortality benefit of sacubitril/valsartan when compared to enalapril in patients with heart failure and reduced ejection fraction (HFrEF). Sacubitril/valsartan performed better than enalapril across various HFrEF patient characteristics and showed substantial benefit in patients with other common comorbidities. Following the trial, the US Food and Drug Administration approved this drug for the treatment of HF. Various international HF consensus guidelines endorse sacubitril/valsartan as a class I recommendation for the management of symptomatic HFrEF. Although this high-quality clinical study is the largest and the most globally represented trial in HFrEF patients, concerns have been raised regarding the generalizability of the trial results in real-world HF population. The gaps in US Food and Drug Administration labeling and guideline recommendations might lead to this medication being used in a larger population than it was studied in. In this review, we will discuss the current role of sacubitril/valsartan in the management of HF, concerns related to PARADIGM-HF and answers, shortcomings of this novel drug, effects on patient characteristics, real-world eligibility, and the role of ongoing and further investigations to clarify the profile of sacubitril/valsartan in the management of HF.

POTENTIAL CLINICAL APPLICATION OF LCZ696 IN REAL LIFE CLINICAL PRACTICE BASED ON 2016 ACC/AHA/HFSA AND ESC HEART FAILURE GUIDELINES CRITERIA: RESULTS FROM TREAT HF STUDY

Background: LCZ696 has been proven to reduce adverse clinical outcomes when compared to enalapril in patients with heart failure (HF). Potential clinical use of LCZ696 in real life clinical practice is uncertain. TREAT HF data were analyzed for potential use of LCZ696 in HF patients in real life

Dose–response effect of the lercanidipine/enalapril combination: a pooled analysis

Objective: The dose–effect relationship of fixed-dose combinations of anti-hypertensive drugs has been only poorly explored. This pooled analysis investigates the dose–response relationship of fixed-dose lercanidipine + enalapril in patients with mild-to-moderate hypertension.Research design and methods: This was an individual patient data analysis of four randomized studies (n = 2340).Main outcome measures: The primary efficacy variable was the change from baseline in sitting diastolic blood pressure (SDBP). Secondary variables were change from baseline in sitting systolic BP (SSBP), proportion of responder patients, and safety.Results: All fixed-dose combinations were superior to placebo in the reduction of SDBP. The greatest effect was observed with the market-available combination lercanidipine 20 mg/enalapril 20 mg (−15.3 mmHg vs. baseline; p < 0.05). The reduction in SDBP associated with the other two marketed fixed combinations of lercanidipine/enalapril were −10.7 mmHg for the 10 mg/20 mg combination and −9.8 mmHg for the 10 mg/10 mg combination (p < .05 for both comparisons). Similar findings were reported for SSBP reduction: the greatest effect was observed with lercanidipine 20 mg/enalapril 20 mg (−19.2 mmHg). The reduction in SSBP was −12.5 mmHg for the 10 mg/20 mg combination and −11.1 mmHg for the 10 mg/10 mg combination (p < .05 for all comparisons). The highest responder rate was reported with lercanidipine 20 mg/enalapril 20 mg (75.0%); this figure was 56.1% with the 10 mg/20 mg and 53.0% with the 10/10 mg combination. No safety concerns were reported.Conclusion: This pooled analysis of four randomized studies shows evidence of a dose–response effect in BP reduction with different fixed combinations of lercanidipine + enalapril. To our knowledge, this is the first analysis investigating the dose–response effect of a specific fixed-dose combination of anti-hypertensive agents. Further studies on this intriguing topic are however necessary.

Cost-effectiveness Analysis of Sacubitril/Valsartan vs Enalapril in Patients With Heart Failure and Reduced Ejection Fraction.

The angiotensin receptor neprilysin inhibitor sacubitril/valsartan was associated with a reduction in cardiovascular mortality, all-cause mortality, and hospitalizations compared with enalapril. Sacubitril/valsartan has been approved for use in heart failure (HF) with reduced ejection fraction in the United States and cost has been suggested as 1 factor that will influence the use of this agent. To estimate the cost-effectiveness of sacubitril/valsartan vs enalapril in the United States. Data from US adults (mean [SD] age, 63.8 [11.5] years) with HF with reduced ejection fraction and characteristics similar to those in the PARADIGM-HF trial were used as inputs for a 2-state Markov model simulated HF. Risks of all-cause mortality and hospitalization from HF or other reasons were estimated with a 30-year time horizon. Quality of life was based on trial EQ-5D scores. Hospital costs combined Medicare and private insurance reimbursement rates; medication costs included the wholesale acquisition cost for sacubitril/valsartan and enalapril. A discount rate of 3% was used. Sensitivity analyses were performed on key inputs including: hospital costs, mortality benefit, hazard ratio for hospitalization reduction, drug costs, and quality-of-life estimates. Hospitalizations, quality-adjusted life-years (QALYs), costs, and incremental costs per QALY gained. The 2-state Markov model of US adult patients (mean age, 63.8 years) calculated that there would be 220 fewer hospital admissions per 1000 patients with HF treated with sacubitril/valsartan vs enalapril over 30 years. The incremental costs and QALYs gained with sacubitril/valsartan treatment were estimated at $35 512 and 0.78, respectively, compared with enalapril, equating to an incremental cost-effectiveness ratio (ICER) of $45 017 per QALY for the base-case. Sensitivity analyses demonstrated ICERs ranging from $35 357 to $75 301 per QALY. For eligible patients with HF with reduced ejection fraction, the Markov model calculated that sacubitril/valsartan would increase life expectancy at an ICER consistent with other high-value accepted cardiovascular interventions. Sensitivity analyses demonstrated sacubitril/valsartan would remain cost-effective vs enalapril.

064 - Sacubitril/Valsartan Associated with Lower Declines in Health-Related Quality of Life Compared with Enalapril in Patients with Heart Failure Hospitalization

064 - Sacubitril/Valsartan Associated with Lower Declines in Health-Related Quality of Life Compared with Enalapril in Patients with Heart Failure Hospitalization

Critical Questions about PARADIGM-HF and the Future.

Cardiovascular (CV) diseases in general and heart failure (HF) in particular are major contributors to death and morbidity and are also recognized as important drivers of health care expenditure. The PARADIGM-HF trial was a pivotal trial designed to compare the long-term effects of LCZ696 with enalapril in patients with symptomatic HF with reduced ejection fraction (HFrEF). This review article presents an in-depth view of the PARADIGM-HF trial and the implications of the results in the management of patients with HF and is based on peer reviewed manuscripts, editorials, perspectives and opinions written about the PARADIGM-HF trial. The article presents the key safety and efficacy results of the trial with specific emphasis on the clinical implications of these findings. The review highlights the highly statistically significant, 20% reduction in the primary composite endpoint of cardiovascular death or HF hospitalization, and a 16% reduction in the risk of death from any cause. It also provides an overview of the design, clinical findings, limitations and special areas of clinical interest. The review discusses the future of LCZ696 and additional trials that seek to answer questions in other sub-populations of patients with HF. The article reiterates what has been concluded by many experts in the field of HF- the introduction of LCZ696 into routine clinical care, while dependent on the regulatory approvals in various countries as well as acceptance by physicians, payers and patients, will change the treatment landscape for patients with HFrEF.

Features of zofenopril and enalapril in patients with stable ischemic heart disease in combination with arterial hypertension

Objective. Optimization of drug therapy in patients with stable coronary heart disease and arterial hypertension (AH) in the application of ACE inhibitors: zofenopril compared with enalapril. Material and methods. We studied 80 patients with stable angina II-III functional class (FC) and AG 1-2 degree (Mean age 58.8±8.8 years) who were randomly divided into 2 groups of observation for 40 people in each: 1 - receiving zofenopril, 2 - enalapril - composed of basic therapy consisting of nitrates, .-blocker, statin, aspirin. The duration of follow-up was 6 months. At baseline and in the dynamics of all patients underwent clinical, laboratory and instrumental studies. It evaluated the quality of life through «Seattle questionnaire» for patients with angina. The daily monitoring of blood pressure at the same time with an electrocardiogram, treadmill test according to the modified protocol R.Bruce, echocardiography was conducted. Conclusion. The use of zofenopril, more than enalapril leads to significantly improved quality of life, exercise tolerance, normalizes the diurnal profile of blood pressure, reduces episodes of ischemia.

PS076 The Increased States of Cardiac Autonomic Nervous Activity at Late Night and the Effect of Enalapril in Patients With Essential Hypertension

PS076 The Increased States of Cardiac Autonomic Nervous Activity at Late Night and the Effect of Enalapril in Patients With Essential Hypertension

Combined Angiotensin Receptor Antagonism and Neprilysin Inhibition.

Heart failure affects ≈5.7 million people in the United States alone. Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, β-blockers, and aldosterone antagonists have improved mortality in patients with heart failure and reduced ejection fraction, but mortality remains high. In July 2015, the US Food and Drug Administration approved the first of a new class of drugs for the treatment of heart failure: Valsartan/sacubitril (formerly known as LCZ696 and currently marketed by Novartis as Entresto) combines the angiotensin receptor blocker valsartan and the neprilysin inhibitor prodrug sacubitril in a 1:1 ratio in a sodium supramolecular complex. Sacubitril is converted by esterases to LBQ657, which inhibits neprilysin, the enzyme responsible for the degradation of the natriuretic peptides and many other vasoactive peptides. Thus, this combined angiotensin receptor antagonist and neprilysin inhibitor addresses 2 of the pathophysiological mechanisms of heart failure: activation of the renin-angiotensin-aldosterone system and decreased sensitivity to natriuretic peptides. In the Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial, valsartan/sacubitril significantly reduced mortality and hospitalization for heart failure, as well as blood pressure, compared with enalapril in patients with heart failure, reduced ejection fraction, and an elevated circulating level of brain natriuretic peptide or N-terminal pro-brain natriuretic peptide. Ongoing clinical trials are evaluating the role of valsartan/sacubitril in the treatment of heart failure with preserved ejection fraction and hypertension. We review here the mechanisms of action of valsartan/sacubitril, the pharmacological properties of the drug, and its efficacy and safety in the treatment of heart failure and hypertension.

Should Angiotensin Receptor Neprilysin Inhibitors Replace Angiotensin-converting Enzyme Inhibitors in Heart Failure With a Reduced Ejection Fraction?

Angiotensin-converting enzyme inhibitors (ACEIs) have been the cornerstone of treatment of heart failure with reduced ejection fraction (HFrEF) for over two decades. Inhibition of neprilyisin augments vasoactive substances including natriuretic peptides, which may have multiple advantageous effects in chronic HF. Early studies of neprilyisin inhibition led to drug discontinuation due to lack of efficacy or safety concerns. Sacubitril/valsartan is a first-in-class combined angiotensin receptor/neprilysin inhibitor (ARNI). The PARADIGM-HF study demonstrated robust superiority of ARNI compared with enalapril in patients with chronic symptomatic HFrEF, raising the question of whether ACEI should still have a role in the management of HFrEF.

The Mechanism of Action of LCZ696.

Heart failure (HF) represents a growing financial burden on healthcare systems and despite therapeutic advances, mortality remains high. Current treatments focus on blocking neurohormonal pathways, such as the renin-angiotensin aldosterone system (RAAS). Recent research has focused on the natriuretic peptide system, which confers beneficial effects in HF, whereas activation of the RAAS and of the sympathetic nervous system has detrimental effects. LCZ696 (sacubutril/valsartan), a first-in-class angiotensin II AT[1] receptor neprilysin inhibitor, has a unique mode of action that targets both pathways. Clinical studies to date indicate that LCZ696 is effective and safe in mild to moderate arterial hypertension and in HF patients with preserved ejection fraction, and has been shown to be superior to enalapril in patients with moderate to severe HF due to reduced left ventricular ejection fraction.

The Role of Neprilysin Inhibitors in Cardiovascular Disease.

Heart failure affects over five million Americans each year and contributes to morbidity, mortality, and high health care costs. Despite the benefits of RAAS and SNS blockers, 5-year survival rates in patients with heart failure remain low, necessitating continued research and new drug targets. LCZ696 (sacubitril/valsartan) is an angiotensin-receptor neprilysin inhibitor recently approved for HFrEF, with dual actions that result in enhancement of natriuretic peptide levels and blockade of angiotensin II activities. This drug shows promise in further improving clinical outcomes in HFrEF and is being studied in patients with HFpEF. In the PARADIGM-HF study, LCZ696 (sacubitril/valsartan) was shown to reduce the composite of cardiovascular mortality and heart failure hospitalizations compared with enalapril in patients with HFrEF taking guideline-directed medical therapies and resulted in prolonged survival. In trials, hypotension occurred more frequently with LCZ696 (sacubitril/valsartan) compared to an ACE inhibitor, warranting careful dose titration. Further clinical experience with LCZ696 (sacubitril/valsartan) will provide additional information on tolerability in a broad range of patients of various demographics.

Study of the Effect of Amlodipine, Atenolol, Enalapril and Losartan in Patients with Mild to Moderate Hypertension

Objectives: To evaluate and compare the efficacy and tolerability of amlodipine, atenolol, enalapril and losartan in patients with mild to moderate hypertension. Research design and method: This study was conducted in medicine department of tertiary care teaching hospital. This was prospective, open labelled, observational, randomized controlled clinical trial. Patients aged 30-60 years, newly diagnosed as mild to moderate hypertension were enrolled in the study. Pretreatmentevaluation of all the patients was done. Detailed clinical history, physical examination and routine laboratory investigations were done. Eligible patients were randomized to receive Amlodipine 2.5/5 mg, Atenolol 25/ 50 mg, Enalapril5/ 10 mg, Losartan 25/50 mg and followed them for 12 weeks, patient’svisits scheduled at 2 weeks interval. Primary efficacy end point was reduction in mean systolic blood pressure (SBP) and mean diastolic blood pressure (DBP). Safety was assessed in terms of systemic adverse events both subjective and objective (clinical and biochemical examinations). Results: Total 154 patients were enrolled, patients’ demographic and baseline clinical characteristics were comparable in all treatment groups. After 12 weeks of treatment the reduction in mean systolic blood pressure were 22.55±7.74, 21±7.94, 20.35±5.48, 22.61±8.41. Reduction in mean diastolic blood pressure were 13.11±4.31, 10.11±3.24, 11.5±3.39, 12.72±3.38. The change in heart rate was 84.22 ± 5.71 to 85.56 ± 5.81, 83.27 ± 5.72 to 69.05 ± 7.68, 84 ± 6.17 to 85.72±5.47, 82.33 ± 7.15 to 83.5±7.54. The change in average serum potassium levels 3.81 ± 0.39 to 3.79 ± 0.36, 3.79 ± 0.33 to 3.69 ± 0.22, 3.72 ± 0.35 to 4.08 ± 0.38, 3.74 ± 0.40 to 3.81 ± 0.27. Adverse events percentage was 38.88 percent, 36.11 percent, 36.11 percent and 13.88 percent in all 4 study group respectively. Conclusion: Amlodipine, Atenolol, Enalapril, and Losartan are equal efficacious to reduce SBP and DBP, whereas losartan is better tolerated and comparatively safer than amlodipine, atenolol and enalapril in patients with mild to moderate hypertension.