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Foundational 4 therapies are started before personalized therapies.
2.
Each visit, NPs initiate or titrate 1 medication from each cluster to a maximum of 3.
3.
Patient and laboratory characteristics guide selection of medication class within each cluster.
4.
Titration occurs every 1-2 weeks with a goal of full titration of foundational 4 within 12 weeks.
Abstract
This review presents an evidence-based approach to heart failure with reduced ejection fraction (HFrEF), focusing on the foundational 4 drugs: renin-angiotensin-aldosterone system inhibitors/angiotensin receptor-neprilysin inhibitor, β-blockers, mineralocorticoid receptor antagonist, and sodium–glucose cotransporter-2 inhibitor. Given the benefits of the foundational 4 drugs, combined initiation of these therapies is preferable to the conventional paradigm of targeting maximally tolerated β-blockers and renin-angiotensin-aldosterone system inhibitors before adding other therapies. The conventional approach is linked to treatment gaps and delayed introduction of life-saving therapies in patients with HFrEF. The conventional approach was replaced with the cluster approach, based on large-scale randomized control trials. The cluster approach demonstrated a reduction in morbidity and mortality in patients with HFrEF.
American Association of Nurse Practitioners (AANP) members may receive 1.0 continuing education contact hour, approved by AANP, by reading this article and completing the online posttest and evaluation at aanp.inreachce.com.
Introduction
Heart failure (HF) is inadequate cardiac output caused by structural or functional cardiac deformity,
2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure of the European Society of Cardiology (ESC) developed with the special contribution of the Heart Failure Association (HFA) of the ESC.
Given the low ejection fraction, the sympathetic nervous system (SNS) and the renin-angiotensin-aldosterone system (RAAS) mediate a compensatory neurohormonal reaction to boost cardiac output.
Initially, these systems act by increasing the myocardial contractility and heart rate; however, prolonged activation of the compensatory mechanisms becomes maladaptive, leading to myocardial hypertrophy and downregulation of the β-1 adrenergic receptor.
The compensatory activation of SNS and stimulation of the RAAS result in the release of angiotensin II and aldosterone, which trigger vasoconstriction and sodium and water reabsorption, respectively.
In turn, the blood volume increases, resulting in distention of the cardiac chamber and subsequent release of atrial natriuretic peptides (ANP) and B-type natriuretic peptides (BNP) from the atria and ventricles.
Current pharmacologic treatments for HFrEF aim to block these maladaptive neurohormonal compensatory mechanisms to attenuate or reverse their adverse remodeling effect on the myocardial muscle.
The latest Canadian Cardiovascular Society (CCS) guideline (2021) emphasizes the importance of using the pharmacologic titration steps based on the New York Heart Association (NYHA) functional classes (Table 1)
2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure of the European Society of Cardiology (ESC) developed with the special contribution of the Heart Failure Association (HFA) of the ESC.
The aim of this review is to provide an updated and comprehensive overview of the current titration approach of pharmacotherapy in patients with HFrEF.
Table 1Definition of New York Heart Association Classification
Class
Definition
Descriptor
I
No symptoms. No limitation of physical activity
Asymptomatic
II
Symptoms with ordinary activity. Comfortable at rest
Estimating lifetime benefits of comprehensive disease-modifying pharmacological therapies in patients with heart failure with reduced ejection fraction: a comparative analysis of three randomised controlled trials.
In following the conventional approach, it may take 6 months to prescribe all of the recommended therapies to achieve the target doses of each drug class.
Estimating lifetime benefits of comprehensive disease-modifying pharmacological therapies in patients with heart failure with reduced ejection fraction: a comparative analysis of three randomised controlled trials.
Estimating lifetime benefits of comprehensive disease-modifying pharmacological therapies in patients with heart failure with reduced ejection fraction: a comparative analysis of three randomised controlled trials.
The cluster approach emphasizes in-hospital initiation and titration because it allows close monitoring of the patients and early recognition of adverse effects.
After discharge from the hospital, the nurse practitioner (NP) or general practitioner in the clinic can use the cluster approach algorithms to expedite the process of further titration and initiation of drug therapy.
The cluster-based strategy consists of 3 clusters, where each cluster represents a category of drugs with similar hemodynamic or neurohormonal effects.
Cluster A includes sodium–glucose cotransporter-2 inhibitor (SGLT2I) and loop diuretics. Cluster B includes angiotensin receptor-neprilysin inhibitor (ARNI) as the preferred medication instead of angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) and mineralocorticoid receptor antagonists (MRAs). Cluster C includes β-blockers and ivabradine.
To implement the cluster approach, NPs should be cognizant of the risks of starting additional HFrEF therapies before all of the foundational 4 drug classes are initiated.
indicated that patients with systolic blood pressure >110 mm Hg, heart rate >70 beats/min, estimated glomerular filtration rate (eGFR) >40 mL/min/1.73 m2, and potassium ˂5.0 mmol/L can typically withstand 3 drug class changes per visit with a low risk of adverse effects. Whereas for weaker patients possibly intolerant to medication, changing a single drug class every 2 weeks is recommended.
recommend a faster titration interval of 1 to 2 weeks within 3 months, suggesting rapid changes can optimize HFrEF treatment outcomes.
The Foundational Four
The developers of guideline-directed medical therapy for HFrEF evidence-based recommendations include the simultaneous use of 4 foundational medications to improve clinical outcomes and achieve maximal benefits in terms of mortality, morbidity, and quality of life.
While the guidelines encourage clinicians to gradually uptitrate the doses of these classes to reach the maximally tolerated dose within 3 to 6 months, reaching medication optimization can take an average of 12 months.
while a large percentage of these patients do not receive the foundational 4 or receive suboptimal dosing, resulting in frequent hospitalization, poor quality of life, and sometimes death.
It includes the simultaneous and rapid sequence initiation and titration of the foundational 4 therapy and is linked to improved survival by achieving timely targeted or maximally tolerated doses.
ACEIs were the gold standard medication for HFrEF patients for the past 3 decades because of their ability to inhibit ACEs that convert angiotensin I to angiotensin II.
2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure of the European Society of Cardiology (ESC) developed with the special contribution of the Heart Failure Association (HFA) of the ESC.
Effect of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers on cardiovascular events in patients with heart failure: a meta-analysis of randomized controlled trials.
conducted a meta-analysis of 38 randomized controlled trials. They established that the use of ACEI is associated with a reduction in all-cause mortality and cardiovascular mortality compared with ARBs, where ACEI administration reduced all-cause mortality by 11% (P < .001) and cardiovascular mortality by 14% (P < .001).
Effect of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers on cardiovascular events in patients with heart failure: a meta-analysis of randomized controlled trials.
Effect of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers on cardiovascular events in patients with heart failure: a meta-analysis of randomized controlled trials.
ARNI works by blocking the action of neprilysin, thus preventing the breakdown of the natriuretic peptides (atrial natriuretic peptide, brain natriuretic peptide [BNP]) and bradykinin.
recommend that it is best practice for NPs to prescribe and/or titrate ARNI during HFrEF patient hospitalizations. The Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial (n = 8,399) investigated patients with NYHA functional class II to IV classification and with LVEF of ≤40% already taking HF medications to determine the efficacy of ARNI over ACEI.
Effects of sacubitril/valsartan in the PARADIGM-HF Trial (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) according to background therapy.
The PARADIGM-HF trial has proven that using ARNI vs ACEI reduced recurring hospitalization and, most significantly, the risk of cardiovascular deaths in patients with chronic HF (P < .001).
Effects of sacubitril/valsartan in the PARADIGM-HF Trial (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) according to background therapy.
Initiation of sacubitril/valsartan in haemodynamically stabilised heart failure patients in hospital or early after discharge: primary results of the randomised TRANSITION study.
Initiation of angiotensin-neprilysin inhibition after acute decompensated heart failure: secondary analysis of the open-label extension of the PIONEER-HF Trial.
Writing Committee 2021 Update to the 2017 ACC expert consensus decision pathway for optimization of heart failure treatment: answers to 10 pivotal issues about heart failure with reduced ejection fraction: a report of the American College of Cardiology Solution Set Oversight Committee.
Writing Committee 2021 Update to the 2017 ACC expert consensus decision pathway for optimization of heart failure treatment: answers to 10 pivotal issues about heart failure with reduced ejection fraction: a report of the American College of Cardiology Solution Set Oversight Committee.
Writing Committee 2021 Update to the 2017 ACC expert consensus decision pathway for optimization of heart failure treatment: answers to 10 pivotal issues about heart failure with reduced ejection fraction: a report of the American College of Cardiology Solution Set Oversight Committee.
Selective β-1, such as bisoprolol and metoprolol succinate, can reverse remodeling in the left ventricle, decrease heart rate (independent of SNS inhibition), and promote nitric oxide production.
They reduce myocardial workload due to their effective rate-lowering action and their interference with catecholamine-related ventricular tachyarrhythmias.
from the European Society of Cardiology (ESC) showed that β-blockers reduced all-cause mortality among patients with severe HF or recent decompensation by 34% to 35% demonstrated in 3 large-scale trials. On the other hand, the American College of Cardiology 2021 recommended avoiding β-blockers in patients with decompensated HF and monitoring heart rate, blood pressure, and signs of congestion during and after their administration.
Writing Committee 2021 Update to the 2017 ACC expert consensus decision pathway for optimization of heart failure treatment: answers to 10 pivotal issues about heart failure with reduced ejection fraction: a report of the American College of Cardiology Solution Set Oversight Committee.
Writing Committee 2021 Update to the 2017 ACC expert consensus decision pathway for optimization of heart failure treatment: answers to 10 pivotal issues about heart failure with reduced ejection fraction: a report of the American College of Cardiology Solution Set Oversight Committee.
(the incremental initiation and target dose are detailed in Table 2). To ensure that β-blockers are initiated safely, practitioners should ensure that patients are clinically euvolemic before starting therapy.
CCS guidelines recommend initiating β-blockers as a first-line treatment in the foundational 4 therapies immediately after a HF diagnosis using NYHA class I to III without disruption unless contraindicated. For NYHA class IV, initiate a β-blocker once patients’ symptoms have stabilized.
β-Blockers should be initiated to an optimal or maximal tolerated dose (Table 2) as long as excessive bradycardia and hypotension are not a deterring factor.
Moreover, MRAs exert antifibrotic properties by decreasing the synthesis of matrix metalloproteinases and other enzymes involved in interstitial myocardium remodeling.
conducted a systematic review and meta-analysis to examine the effectiveness of MRAs in HFrEF, focusing on cardiovascular death, all-cause mortality, and cardiac hospitalization as the main composite end points. They established that MRAs are linked to a reduction in cardiovascular death (relative risk, 0.81; 95% CI, 0.75-0.87), all-cause mortality (relative risk, 0.83; 95% CI, 0.77-0.88), and cardiac hospitalization (relative risk, 0.80; 95% CI, 0.70-0.92) in patients with HFrEF.
Although SGLT2Is were initially studied and indicated for treating diabetes mellitus (DM) by increasing the urinary excretion rate of glucose, they have shown favorable outcomes in HFrEF patients.
The Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) trial results showed that individuals with HFrEF who received SGLT2I had a reduced risk of worsening HF or CV death (P = .00001) compared with placebo.
Additionally, SGLT2Is reduced the risk of having the first incidence of worsening HF, hospitalization for HF/urgent HF visits, and the risk of CV mortality.
Similarly, the Empagliflozin Outcome Trial in Patients with Chronic Heart Failure and Reduced Ejection Fraction (EMPEROR-Reduced) established low CV mortality and HF hospitalization rates, regardless of DM status, in patients who were given SGLT2I (P ˂ .0001).
Effect of empagliflozin on the clinical stability of patients with heart failure and a reduced ejection fraction: The EMPEROR-Reduced Trial [published correction appears in Circulation. 2021;143(4):e30].
Effect of empagliflozin on the clinical stability of patients with heart failure and a reduced ejection fraction: The EMPEROR-Reduced Trial [published correction appears in Circulation. 2021;143(4):e30].
Effect of empagliflozin on the clinical stability of patients with heart failure and a reduced ejection fraction: The EMPEROR-Reduced Trial [published correction appears in Circulation. 2021;143(4):e30].
Effect of empagliflozin on the clinical stability of patients with heart failure and a reduced ejection fraction: The EMPEROR-Reduced Trial [published correction appears in Circulation. 2021;143(4):e30].
Owing to the progression of HF and renal events, particularly patients presenting with albuminuria, NPs should use SGLT2Is, such as canagliflozin or dapagliflozin, regardless of DM status.
In additional to the foundational 4, the NP should consider adding additional therapies to better control HFrEF symptoms and improve clinical outcomes.
Ivabradine
Ivabradine should be added to patients with HF in sinus rhythm with heart rate ≥70 beats/min in combination with foundational therapies to prevent CV death and reduce the incidence of HF hospitalization.
Writing Committee 2021 Update to the 2017 ACC expert consensus decision pathway for optimization of heart failure treatment: answers to 10 pivotal issues about heart failure with reduced ejection fraction: a report of the American College of Cardiology Solution Set Oversight Committee.
A systematic review and meta-analysis of 6 studies that included patients with HFrEF (LVEF ˂40%) and mean heart rate ≥70 beats/min, who were on ivabradine and β-blockers or β-blocker alone, showed a significant reduction in heart rates in the combination group compared with the β-blocker group (P ˂ .001).
Writing Committee 2021 Update to the 2017 ACC expert consensus decision pathway for optimization of heart failure treatment: answers to 10 pivotal issues about heart failure with reduced ejection fraction: a report of the American College of Cardiology Solution Set Oversight Committee.
The 2017 CCS and the 2021 American College of Cardiology guidelines recommend that NPs should make every attempt to reach the target or maximum tolerable β-blocker dosages before initiating ivabradine.
Writing Committee 2021 Update to the 2017 ACC expert consensus decision pathway for optimization of heart failure treatment: answers to 10 pivotal issues about heart failure with reduced ejection fraction: a report of the American College of Cardiology Solution Set Oversight Committee.
The addition of oral soluble guanylate cyclase (sGC) stimulator, such as vericiguat, increases cyclic guanylate monophosphate, thus increasing the sensitivity of endogenous sGC to nitric oxide.
In the Vericiguat Global Study in Subjects With Heart Failure With Reduced Ejection Fraction (VICTORIA) trial, the researchers enrolled 5,050 patients with chronic HF NYHA class II, III, or IV, LVEF ˂45%, and high levels of BNP or pro-BNP to determine the impact of vericiguat in reducing CV death or first HF hospitalization.
The new current Canadian guidelines recommend against using vericiguat in patients with systolic blood pressure ˂100 mm Hg or patients on nitrate therapy.
Patients with natriuretic peptide levels >8,000 pg/mL did not benefit from the therapy compared with patients in the lower quartile range of natriuretic peptide.
Regarding safety and tolerability, vericguat appeared to be safe without severe adverse effects on renal function or electrolytes compared with the placebo.
Based on the VICTORIA outcomes and when vericiguat is approved by Health Canada, NPs can prescribe sGC stimulator for HFrEF patients with worsening symptoms that leads to hospitalization.
Several studies reported outcomes of patients with class III or IV HF who were randomly assigned to isosorbide dinitrate plus hydralazine or placebo in addition to foundational 4 therapy for HF.
Hydralazine and isosorbide dinitrate (H-ISDN) compared with placebo reduced all-cause mortality, initial hospitalization for HF, and optimized the quality of life in Black patients.
In self-identified Black patients with HFrEF and NYHA class III to IV, the 2016 ESC, CCS 2017, and 2021 American College of Cardiology guidelines recommend H-ISDN be initiated in Black patients to reduce hospitalization for HF and CV death.
2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure of the European Society of Cardiology (ESC) developed with the special contribution of the Heart Failure Association (HFA) of the ESC.
H-ISDN can be used in patients with a serum creatinine >220 mmol/L (2.49 mg/dL) due to renal insufficiency or experienced hyperkalemia from RAASI therapies.
found that most patients on H-ISDN had a history of renal insufficiency, hyperkalemia, or ACEI/ARB intolerance. Although H-ISDN therapy is the preferred treatment in the Black patients’ subgroup, ARNI (or alternatively ACEI/ARB) must be considered and carefully introduced before adding H-ISDN.
Based on previous research and the current findings, NPs should consider the H-ISDN combination (not separately) for Black patients with HFrEF after thorough clinical assessment and consideration of foundational therapies.
OM has an inotropic effect, which improves the heart’s systolic function without raising its energy demand or the risks associated with increased calcium in cardiac myocytes or increasing the risk of ventricular arrhythmias.
No recommendations have been given at this time due to the drug’s relatively small impact compared with placebo in a high-risk HF patient and the uncertainty surrounding whether OM will obtain regulatory approval in Canada.
The 2016 ESC and the 2017 and 2021 CCS guidelines recommend using digoxin for patients in sinus rhythm with persistent symptoms of HF despite optimal therapy.
2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure of the European Society of Cardiology (ESC) developed with the special contribution of the Heart Failure Association (HFA) of the ESC.
2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure of the European Society of Cardiology (ESC) developed with the special contribution of the Heart Failure Association (HFA) of the ESC.
Ideally, NPs should aim to optimize each cluster during a clinic visit and initiate 1 drug class within each cluster to a maximum of 3 changes per visit.
Frail patients specifically may not tolerate starting all 4 classes at once, and features such as advanced age, lower systolic blood pressure, and lower eGFR should guide which medication class within each cluster is chosen to avoid medication intolerance.
During the first face-to-face encounter, NPs should prescribe the preferred medications in each cluster; as such, SGLT2I, ARNI, and β-blocker should be initiated simultaneously.
On the second encounter within 1 to 2 weeks, NPs can see the patients face-to-face or virtually to continue SGLT2I in cluster A, start MRA in cluster B, and adjust cluster C.
The third visit can be a virtual visit, and NPs can add a loop diuretic as needed to achieve euvolemia and treat volume overload, titrate cluster B medication (ARNI, MRAs), and titrate cluster C (β-blockers) medication.
For cluster C, β-blocker can be titrated weekly for up to 2 to 3 months, and if the sinus rate remains >70 beats/min, ivabradine, a selective sinus node inhibitor, is recommended.
ESC noted that MRA could be initiated before ARNI if the patient cannot tolerate the hypotensive episodes of angiotensin receptor–neprilysin inhibition (eg, patients with a systolic blood pressure <100 mm Hg).
noted that patients’ adherence to drug therapy, clinical improvements between clinic visits, and low hospital readmissions could be maintained by involving clinical pharmacists. Similarly, providing safe and rapid titration for HFrEF patients can be maintained while transitioning from the inpatient to outpatient environment.
indicated that strategies such as telephone follow-up, education, self-management, weight monitoring, sodium restriction or dietary advice, exercise recommendations, medication review, and social and psychological support can be used to help with the implementation of the cluster approach.
Further, within 1 to 2 weeks after discharge, laboratory results, such as renal function indicators, potassium, and glucose, should be examined to assess for adverse responses to foundational therapies.
Remote optimization of guideline-directed medical therapy in patients with heart failure with reduced ejection fraction [published correction appears in JAMA Cardiol. 2021;6(4):485].
stated that using a remote medication optimization approach enhanced initiation and titration of foundational 4 therapy to target dosage and bridged the gap between guideline-directed medical therapy guidelines and clinical application. At 3 months, 197 of 1,131 patients who were enrolled in the remote medication approach demonstrated favorable increase in baseline use of renin-angiotensin system antagonists (138 [70.1%] to 170 [86.3%]; P < .001) and β-blockers (152 [77.2%] to 181 [91.9%]; P < .001) but not MRA (51 [25.9%] to 60 [30.5%]; P = .14) due to its assessment difficulties.
Remote optimization of guideline-directed medical therapy in patients with heart failure with reduced ejection fraction [published correction appears in JAMA Cardiol. 2021;6(4):485].
indicated that measuring renal function and electrolytes is based on the patient’s characteristics and the clinical incidence of complications. In stable patients, serum electrolytes, creatinine, and serum urea nitrogen are regularly tested every 1 to 3 months.
Further adherence strategies for medical optimization include pillboxes, smartphone apps, medications logs, and referral to HF-specific medication titration clinics.
FigureSimplified medication sequencing algorithm for heart failure with reduced ejection fraction. aVericiguat is not yet approved by Health Canada. Adapted from Miller et al
Furthermore, the mentioned cluster scheme was designed with the understanding that patients require personalized therapies based on parameters such as tolerability, medical history, vital signs, and so on.
The purpose of each clinical visit is to start or titrate 1 drug class within each cluster. For instance, practitioners cannot titrate ARNI and MRA simultaneously because they are in a similar cluster.
The NP should attempt to schedule a meeting with the patient every 1 to 2 weeks, if possible, with a goal of full foundational therapy titration within 12 weeks.
Intolerance of a medication initiation/titration not related to volume depletion should stop further changes in that class until other foundational therapy titration is achieved.
Although there is some preferability in sequencing order of HFrEF drugs; for example, starting only with ARNI or combined with SGLT2I as a first step, followed by simultaneous treatment of β-blocker and MRA as a second step, ESC noted it is unwise to debate the subtle differences.
The NP should focus on initiating the foundational 4 drug classes as soon as HFrEF is diagnosed. Mortality and morbidity are reduced when 4 foundational drug classes therapy are initiated within 4 weeks; thus, the rate of medication titration should not exceed 3 months (12 weeks) when possible. It is critical to initiate 1 medication from each cluster at each visit and uptitrate simultaneously. Initiating medications from the same cluster is not recommended within the same visit. In the absence of a preferred choice within a cluster, uptitrate each at alternating visits. The NP can make up to 3 changes per visit based on their assessment of the patient’s symptoms, vital signs, and renal function. The cluster approach to HFrEF therapy titration can guide NPs to improve morbidity and mortality in this high-risk patient population.
References
Ponikowski P.
Voors A.A.
Anker S.D.
et al.
2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure of the European Society of Cardiology (ESC) developed with the special contribution of the Heart Failure Association (HFA) of the ESC.
Estimating lifetime benefits of comprehensive disease-modifying pharmacological therapies in patients with heart failure with reduced ejection fraction: a comparative analysis of three randomised controlled trials.
Effect of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers on cardiovascular events in patients with heart failure: a meta-analysis of randomized controlled trials.
Effects of sacubitril/valsartan in the PARADIGM-HF Trial (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) according to background therapy.
Initiation of sacubitril/valsartan in haemodynamically stabilised heart failure patients in hospital or early after discharge: primary results of the randomised TRANSITION study.
Initiation of angiotensin-neprilysin inhibition after acute decompensated heart failure: secondary analysis of the open-label extension of the PIONEER-HF Trial.
2021 Update to the 2017 ACC expert consensus decision pathway for optimization of heart failure treatment: answers to 10 pivotal issues about heart failure with reduced ejection fraction: a report of the American College of Cardiology Solution Set Oversight Committee.
Effect of empagliflozin on the clinical stability of patients with heart failure and a reduced ejection fraction: The EMPEROR-Reduced Trial [published correction appears in Circulation. 2021;143(4):e30].
Remote optimization of guideline-directed medical therapy in patients with heart failure with reduced ejection fraction [published correction appears in JAMA Cardiol. 2021;6(4):485].
Mohamed Toufic El Hussein, PhD, NP, is professor at the school of Nursing and Midwifery, Faculty of Health, Community & Education, Mount Royal University and adjunct associate professor, Faculty of Nursing, University of Calgary, and Acute Care Nurse Practitioner Medical Cardiology, Coronary Care Unit, Rockyview General Hospital, Calgary, Alberta, Canada, and can be contacted at [email protected] and on twitter @drmohamednp.
Samir Negash is a BN student at Mount Royal University, Calgary, Alberta, Canada.
Article info
Publication history
Published online: March 02, 2022
Footnotes
In compliance with standard ethical guidelines, the author reports no relationships with business or industry that would pose a conflict of interest.
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