Angiotensin–Neprilysin Inhibition in Acute Decompensated Heart Failure

Velázquez, Eric J.; Morrow, David A.; DeVore, Adam D.; Duffy, Charles J.; Ambrosy, Andrew P.; McCague, Kevin; Rocha, Ricardo; Braunwald, Eugene; Investigators, Pioneer-Hf

doi:10.1056/nejmoa1812851

Cited by 894 publications

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References 9 publications

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“…2,3 However, patients included in clinical trials frequently do not represent the real-life population. 2,3 However, patients included in clinical trials frequently do not represent the real-life population.…”

Section: Discussionmentioning

confidence: 99%

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Safety of sacubitril/valsartan initiated during hospitalization: data from a non‐selected cohort

et al. 2019

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Aims Sacubitril/valsartan is safe when initiated during hospitalization in a clinical trial setting. Its safety in real-life population is not stablished. We compared the initiation of sacubitril/valsartan during hospitalization in a non-selected population, in the PIONEER-HF trial, and in non-selected outpatients. Methods and results Multicentre registry included 527 patients: 100 were started on sacubitril/valsartan during hospitalization (19.0%) and 427 as outpatients (81.0%). Compared with those in the pivotal trial, inpatients in our cohort were older (71 ± 12 vs. 61 ± 14 years; P < 0.001); had more frequently Functional Class II (41 [41.0%] vs. 100 [22.7%]; P < 0.001), higher levels of N-terminal pro-B type natriuretic peptide (4044 [1630-8680] vs. 2013 [1002-4132] pg/mL; P < 0.001), better glomerular filtration rate (63.5 [51.0-80.0] vs. 58.4 [47.5-71.5] mL/min; P = 0.01), and higher systolic blood pressure (121 [110-136] vs. 118 [110-133] mmHg; P = 0.03); and received angiotensin-converting enzyme inhibitors/angiotensin receptor blockers more frequently (92 [92.0%] vs. 208 [52.7%]; P < 0.001). Compared with non-selected outpatients, inpatients were older (71 ± 12 vs. 68 ± 12 years, P = 0.02), had more frequent Functional Class III-IV (58 [58.0%] vs. 129 [30.3%], P < 0.001), had higher levels of N-terminal pro-B type natriuretic peptide (4044 [1630-8680] vs. 2182 [1134-4172]; P < 0.001), and were receiving angiotensin-converting enzyme inhibitors/angiotensin receptor blockers target dose less frequently (55 [55.0%] vs. 335 [78.5%]; P < 0.001). They also started sacubitril/valsartan with a low dose (50 mg/12 h) more frequently (80 [80.0%] vs. 209 [48.8%], P < 0.001). The initiation of sacubitril/valsartan in outpatients was an independent predictor of high-dose use (OR 3.1; 95% confidence interval 1.7-5.6, P < 0.001). The follow-up time in both cohorts, including all patients enrolled, was similar (7.0 ± 0.1 vs. 7.2 ± 2.6 months, P = 0.72). All-cause admissions during follow-up were more frequent in inpatients (30 [30.0%] vs. 68 outpatients [15.9%], P = 0.001), with no relevant differences in all-cause mortality. There was no significant difference in sacubitril/valsartan withdrawal rate (17 inpatients [17.0%] vs. 49 outpatients [11.5%], P = 0.13). The incidence of adverse effects was also similar: hypotension (16 inpatients [16.0%] vs. 71 outpatients [16.7%], P = 0.88), worsening renal function (7 inpatients [7.0%] vs. 29 outpatients [6.8%], P = 0.94), and hyperkalaemia (1 inpatient [1.0%] vs. 21 outpatients [4.9%], P = 0.09). We did not register any case of angioedema. Conclusions It is safe to initiate sacubitril/valsartan during hospitalization in daily clinical practice. Inpatients have a higher risk profile and receive low starting doses more frequently than outpatients.

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Section: Discussionmentioning

confidence: 99%

“…2 The second objective of our work is to compare the safety and tolerance of sacubitril/valsartan in two real-life cohorts. 2 The second objective of our work is to compare the safety and tolerance of sacubitril/valsartan in two real-life cohorts.…”

Section: Introductionmentioning

confidence: 99%

Safety of sacubitril/valsartan initiated during hospitalization: data from a non‐selected cohort

et al. 2019

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“…4 Ivabradine is indicated in patients in sinus rhythm whose heart rate remains >70 bpm. 4,45 Based on more recent trials, 44,46 it may be considered also in patients hospitalized for acute HF, including also those with new onset HF. 40 Further, 34% of the patients who had a primary event experienced at least one other HF hospitalization and sacubitril/valsartan had a similar efficacy to reduce recurrent events ( Figure 1).…”

Section: Neurohormonal Antagonistsmentioning

confidence: 99%

Highlights in heart failure

et al. 2019

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Heart failure (HF) remains a major cause of mortality, morbidity, and poor quality of life. It is an area of active research. This article is aimed to give an update on recent advances in all aspects of this syndrome. Major changes occurred in drug treatment of HF with reduced ejection fraction (HFrEF). Sacubitril/valsartan is indicated as a substitute to ACEi/ARBs after PARADIGM-HF (hazard ratio [HR], 0.80; 95% confidence interval [CI], 0.73 to 0.87 for sacubitril/valsartan vs. enalapril for the primary endpoint and Wei, Lin and Weissfeld HR 0.79, 95% CI 0.71-0.89 for recurrent events). Its initiation was then shown as safe and potentially useful in studies in patients hospitalized for acute HF. More recently, DAPA-HF trial showed the beneficial effects of the sodium-glucose transporter type 2 (SGLT2) inhibitor dapaglifozin vs. placebo, added to optimal standard therapy [HR, 0.74; 95% CI, 0.65 to 0.85;0.74; 95% CI, 0.65 to 0.85 for the primary endpoint]. Trials with other SGLT 2 inhibitors and in other patients, such as those with HF with preserved ejection fraction (HFpEF) or with recent decompensation, are ongoing. Multiple studies showed the unfavourable prognostic significance of abnormalities in serum potassium levels. Potassium lowering agents may allow initiation and titration of mineralocorticoid antagonists in a larger proportion of patients. Meta-analyses suggest better outcomes with ferric carboxymaltose in patients with iron deficiency. Drugs effective in HFrEF may be useful also in HF with mid-range ejection fraction. Better diagnosis and phenotype characterization seem warranted in HF with preserved ejection fraction. These and other burning aspects of HFpEF research are summarized and reviewed in this article.A multiparametric approach is often proposed for risk stratification of HF patients. The prognostic accuracy of the metabolic exercise test data combined with cardiac and kidney indexes risk score was found as superior to the HF Survival Score and Seattle HF model risk scores in a cohort of 6112 1106 D. Tomasoni et al.

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“…[3][4][5] Actigraphy may also be able to provide information, such as patterns of activity, that could identify responders and nonresponders to therapy and the time course of patient improvement. 10 In theory, the decreased pulmonary congestion that results from the natriuretic effects of sacubitril/valsartan may improve sleep and reduce fatigue by improving wakeful activity. 6 Sacubitril/valsartan is a first-in-class angiotensin receptor/neprilysin inhibitor (ARNI) therapy approved for the treatment of symptomatic HF with reduced ejection fraction (HFrEF).…”

Section: Introductionmentioning

confidence: 99%

Activity Sensors to Evaluate the Effect of Sacubitril/Valsartan on Quality‐of‐Life in Heart Failure: rational and design of the AWAKE‐HF study

et al. 2019

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Aims Limited data are available regarding the ability of sacubitril/valsartan to provide clinically meaningful health-related quality of life (HRQoL) improvements among individuals with heart failure (HF). Objective measurement of physical activity and sleep using actigraphy can provide insight into daily functioning and HRQoL. Methods and resultsWe designed an 18 week, multicenter, randomized, double-blind, double-dummy, parallel-group study to objectively assess changes in function and HRQoL directly after initiating sacubitril/valsartan vs. enalapril in participants with HF in their home environments. A total of 136 outpatient, ambulatory participants with New York Heart Association Class II or III HF with reduced ejection fraction (HFrEF) will be included in the study. Patients will undergo a 2 week baseline observational phase (continuing current HF treatment); data from the second week of this phase will be the baseline value for comparison with those of subsequent periods. Patients will then enter an 8 week blinded-treatment phase (randomly assigned 1:1 to sacubitril/valsartan or enalapril), followed by an 8 week open-label extension phase (treatment with only sacubitril/valsartan). The primary efficacy endpoint is the change in mean activity counts during the most active 30 min of the participant's day between baseline and the final randomized treatment phase measurement. Secondary endpoints include the change in mean sleep activity during the randomized and open-label phases; questionnaires will also assess HRQoL measures. Rather than analysing pooled actigraphy data, the researchers are considering each participant to be acting as his or her own control. Conclusions This will be the first study to assess the effects of sacubitril/valsartan on objective measures of sleep and activity in individuals with HFrEF within the context of their daily lives. Wearable accelerometer devices will be used to gain insight into how the medication affects physical activity and sleep.

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Angiotensin–Neprilysin Inhibition in Acute Decompensated Heart Failure

Cited by 894 publications

References 9 publications

Safety of sacubitril/valsartan initiated during hospitalization: data from a non‐selected cohort

Safety of sacubitril/valsartan initiated during hospitalization: data from a non‐selected cohort

Highlights in heart failure

Activity Sensors to Evaluate the Effect of Sacubitril/Valsartan on Quality‐of‐Life in Heart Failure: rational and design of the AWAKE‐HF study

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