Practical recommendations for the use of ACE inhibitors, beta-blockers and spironolactone in heart failure: putting guidelines into practice

Surveys of prescribing in both hospitals and primary care have shown delays in translating improved survival data from clinical trials into clinical practice thereby denying patients the benefits of proven treatments, such as the angiotensin converting enzyme inhibitors. This may be due to unfamiliarity with clinical guidelines and concerns about adverse events. Recent trials have shown that substantial improvements in survival are associated with spironolactone and beta-blocker therapy. In order to accelerate the uptake of these treatments, and to ensure that all eligible patients should receive the most appropriate medications, a clear and concise set of clinical recommendations has been prepared by a group of clinicians with practical expertise in the management of heart failure. The objective of these recommendations is to provide practical guidance for non-specialists in order to support the implementation of evidenced-based therapy for heart failure. These practical recommendations are meant to supplement rather than replace existing guidelines.     

NT-proBNP and BNP: biomarkers for heart failure management

Guidelines for the pharmacological treatment of heart failure (HF) are based on results from large clinical trials demonstrating benefit. State of the art pharmacological management of HF assumes that target doses should be the same as those used in trials. Thus equal doses are recommended for all in practical guidelines, but this strategy might not fit individual needs. NT-proBNP and BNP emerged as potential biomarkers of clinical interest in HF management. NT-proBNP and BNP are related to HF severity and to clinical status. NT-proBNP and BNP are strongly associated with prognosis across the whole spectrum of HF patients. A pilot study has shown that NT-proBNP-guided therapy is associated with improved outcome in HF. Although at present there are still few data to make firm recommendations on the use of NT-proBNP or BNP levels as biomarkers for HF management, future studies will provide further insight on this issue.     

Should a statin be prescribed to every patient with heart failure?

Chronic heart failure (HF) represents an emerging epidemic since its prevalence is continuously increasing despite advances in treatment. Many recent clinical studies have clearly demonstrated that statin therapy is associated with improved outcomes in HF irrespective of aetiology (ischaemic or not) or baseline cholesterol levels. Indeed, most of the conducted large statin trials and trials in HF have demonstrated a positive effect of statins in HF patients. Furthermore, the use of statins in HF seems to be safe as none of the recent trials has resulted in worse outcomes for HF patients treated with statins. Potential mechanisms through which statins could benefit the failing myocardium include non-sterol effects of statins, as well as effects on nitric oxide and endothelial function, inflammation and adhesion molecules, apoptosis and myocardial remodelling and neurohormonal activation. This review discusses the pathophysiological basis of statin effects on HF and focuses on clinical data for the benefit from statin use in this setting. Until today there are no official recommendations in both the American and the European guidelines regarding the use of statins in HF patients, as the available data come from small observational or larger but retrospective, non-randomised studies. Therefore, HF patients should be treated according to current lipid guidelines. Large randomised clinical trials are underway and will further delineate the role of statin therapy in HF patients. Until more data are available, we could not recommend statin use to every patient with HF irrespective of HF aetiology and baseline cholesterol levels.     

Heart failure and diabetes: Clinical significance and epidemiology of this two-way association

People with type 2 diabetes (T2DM) and those with prediabetes have an increased risk of heart failure (HF). Longer duration of T2DM correlates with a greater risk of HF, but HF is also seen in patients with recent-onset diabetes. Insulin resistance is more likely to be present in patients with HF. The risk of HF persists even in the face of standard-of-care preventive treatments for atherosclerotic cardiovascular (CV) disease. HF is commonly the presenting symptom of CV disease in people with diabetes and is the most expensive complication of diabetes because of the high cost of hospitalizations. Recently hospitalization for HF has been included in CV outcome trials (CVOTs), including for medications that are used to treat T2DM, which has led to new therapies for all HF patients. In addition, these CVOTs have shown that many drugs used in the therapy of diabetes are either neutral or detrimental in the HF patient and should be used with caution in patients with existing HF or those at high risk of HF. Most recently, sodium-glucose cotransporter-2 receptor blockers have shown efficacy in both HF with reduced ejection fraction (EF) and HF with preserved EF. The only other oral or injectable diabetes agent shown to improve outcomes in both is metformin.     

ACC/AHA Versus ESC Guidelines on Heart Failure: JACC Guideline Comparison

The 2013 (with updates in 2016 and 2017) American College of Cardiology/American Heart Association and 2016 European Society of Cardiology guidelines provide practical evidence-based clinical guidelines for the diagnosis and treatment of both acute and chronic heart failure (HF). Both guidelines address noninvasive and invasive testing to establish the diagnosis of HF with reduced ejection fraction and HF with preserved ejection fraction. Extensive trial evidence supports the use of guideline-directed medical therapy and device-based therapies for the optimal management of patients with HF with reduced ejection fraction. Specific recommendations are also provided for HF with preserved ejection fraction although the evidence is substantially weaker. Management of medical comorbidities is now addressed in both guidelines. Acute HF and end-stage disease requiring advanced therapies are also discussed. This review compares specific recommendations across the spectrum of HF phenotypes and disease severity, highlights areas where differences exist, and lists consequential studies published since the latest guidelines.     

The 2013 ACC/AHA Cholesterol Treatment Guidelines: Applicability to Patients with Diabetes

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death worldwide and the management of blood cholesterol is a cornerstone of medical therapy for the primary and secondary prevention of cardiovascular disease. Patients with diabetes represent an important high-risk group in whom clinicians should advocate the use of statins and lifestyle modification for the reduction of ASCVD. The recent 2013 ACC/AHA guidelines on managing blood cholesterol provide an important framework for the effective implementation of this important risk reduction strategy. The guidelines identify four groups of individuals who have been shown to benefit from statin therapy and update the dosing and monitoring recommendations based on evidence from published, large-scale randomized controlled trials (RCTs) with clinical hard endpoints. Primary care physicians and specialists play key roles in identifying populations at elevated ASCVD risk and providing effective care for patients, especially those with diabetes. This article will summarize the 2013 ACC/AHA guidelines on managing blood cholesterol and provide a practical management overview in order to facilitate implementation of these guidelines for patients with diabetes.     

Current status of implantable cardioverter-defibrillator therapy in heart failure

Sudden cardiac arrest is one of the leading causes of death in patients with heart failure (HF). The implantable cardioverter-defibrillator (ICD) is the only evidence-based treatment strategy for patients who have survived a life-threatening ventricular arrhythmic event. Randomized clinical trials have shown that specific subsets of HF patients with ischemic and nonischemic dilated cardiomyopathy benefit from ICD therapy for primary prevention of sudden cardiac arrest. Cardiac resynchronization therapy has become the device-based therapy of choice for improving symptoms and survival in severe HF patients with evidence of ventricular dyssynchrony. This review summarizes the current status of ICD therapy in treating HF patients based on randomized clinical trials and current practice guidelines.     

Primer: practical approach to the selection of patients for and application of EECP

Over the past decade, the frequency of use of enhanced external counterpulsation (EECP) has increased in patients with angina, irrespective of medical therapy and coronary revascularization status. Many patients referred for EECP have one or more comorbidities that could affect this treatment's efficacy, safety, or both. By use of data from more than 8,000 patients enrolled in the International EECP Patient Registry, we provide practical guidelines for the selection and treatment of patients. We have focused on considerations for patients who have one or more of the following characteristics: age older than 75 years, diabetes, obesity, heart failure, and peripheral vascular disease. We have also reviewed outcomes and treatment recommendations for individuals with poor diastolic augmentation during treatment, for those with atrial fibrillation or pacemakers, and for those receiving anticoagulation therapy. Lastly, we examined relevant data regarding extended courses of EECP, repeat therapy, or both. While clinical studies have demonstrated the usefulness of EECP in selected patients, these guidelines permit recommendations for the extended application of this important treatment to subsets of patients excluded from clinical trials.     

Review of the 2005 American College of Cardiology, American Heart Association, and Society for Cardiovascular Interventions guidelines for adjunctive pharmacologic therapy during percutaneous coronary interventions: practical implications, new clinical data, and recommended guideline revisions

In 2006, the American College of Cardiology, American Heart Association, and Society for Cardiovascular Interventions published the 2005 update of the evidence-based guidelines for the treatment of patients undergoing percutaneous coronary intervention (PCI). Together with procedural recommendations, these guidelines for percutaneous coronary intervention provide clinicians with guidance in the appropriate use of adjunctive pharmacologic therapy in patients undergoing PCI. However, there remain substantial variations in practice among clinicians and within and across institutions. Furthermore, the guidelines (being a static document) cannot incorporate additional evidence that has accumulated since their publication. Several landmark trials, notably Intracoronary Stenting and Antithrombotic Regimen-Rapid Early Action for Coronary Treatment (ISAR-REACT 2) and Acute Catheterization and Urgent Intervention Triage strategY (ACUITY), have added substantially to the knowledge base about pharmacologic therapy since publication of the guidelines. This article is therefore intended to discuss implementation into clinical practice of the revised guidelines for antiplatelet and antithrombotic pharmacologic therapy during PCI and to evaluate recent clinical evidence and make recommendations for revision of the guidelines incorporating the outcomes of recently completed trials.     

CCS/CHFS Heart Failure Guidelines Update: Defining a New Pharmacologic Standard of Care for Heart Failure With Reduced Ejection Fraction

In this update of the Canadian Cardiovascular Society heart failure (HF) guidelines, we provide comprehensive recommendations and practical tips for the pharmacologic management of patients with HF with reduced ejection fraction (HFrEF). Since the 2017 comprehensive update of the Canadian Cardiovascular Society guidelines for the management of HF, substantial new evidence has emerged that has informed the care of these patients. In particular, we focus on the role of novel pharmacologic therapies for HFrEF including angiotensin receptor-neprilysin inhibitors, sinus node inhibitors, sodium glucose transport 2 inhibitors, and soluble guanylate cyclase stimulators in conjunction with other long established HFrEF therapies. Updated recommendations are also provided in the context of the clinical setting for which each of these agents might be prescribed; the potential value of each therapy is reviewed, where relevant, for chronic HF, new onset HF, and for HF hospitalization. We define a new standard of pharmacologic care for HFrEF that incorporates 4 key therapeutic drug classes as standard therapy for most patients: an angiotensin receptor-neprilysin inhibitor (as first-line therapy or after angiotensin converting enzyme inhibitor/angiotensin receptor blocker titration); a β-blocker; a mineralocorticoid receptor antagonist; and a sodium glucose transport 2 inhibitor. Additionally, many patients with HFrEF will have clinical characteristics for which we recommended other key therapies to improve HF outcomes, including sinus node inhibitors, soluble guanylate cyclase stimulators, hydralazine/nitrates in combination, and/or digoxin. Finally, an approach to management that integrates prioritized pharmacologic with nonpharmacologic and invasive therapies after a diagnosis of HFrEF is highlighted.     

Statins, ACE inhibitors and ARBs in cardiovascular disease

Several trials have indicated that classical cardiovascular risk factors, including hyperlipidemia and hypertension, are not associated with a great number of acute cardiovascular events. Given the crucial role of inflammation in atherogenesis, inflammatory factors have been proposed to better define and predict acute cardiovascular events. In this promising context, treatments with lipid-lowering drugs (statins) and anti-hypertensive drugs (ACE inhibitors and ARBs) have been also investigated from an ‘anti-inflammatory’ point of view, with some encouraging results. At present, statins are recommended by the National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III guidelines as the first-line choice for drug therapy lowering LDL cholesterol in high-risk patients (LDL goal <70 mg/dL, <1.8 mmol/L). In moderate-risk patients (LDL goal <100 mg/dL, <2.6 mmol/L), statin therapy is indicated mainly in metabolic syndrome and in diabetic patients. Treatment with ACE inhibitors or ARBs is recommended in both hypertension and cardiovascular diseases, particularly in diabetic patients. The use of ACE inhibitors is recommended in all patients with ST-elevation myocardial infarction with LVEF ≤40%, with normal LVEF in the presence of well-controlled cardiovascular risk factors and revascularization, hypertension, diabetes or chronic kidney disease. On the other hand, the use of ARBs is recommended in patients intolerant of ACE inhibitors or who have heart failure or hypertension. In the future, these recommendations will probably be frequently updated as the pleiotropic activities of statins, ACE inhibitors and ARB are also taken into account.     

Device therapy in heart failure patients with chronic kidney disease

Heart failure (HF) and chronic kidney disease (CKD) both carry significant risk for sudden cardiac death, hospitalization, and mortality; when combined, however, they markedly increase the risk of morbidity and mortality. Device therapies such as implantable cardioverter-defibrillators (ICDs) and cardiac resynchronization therapy (CRT) are treatments proven to have significant benefit on clinical outcomes in select patients with HF. However, the majority of studies supporting the use of these devices have limited data on patients with CKD or end-stage renal disease. In this review, we discuss the intersection of HF and CKD as it relates to progressive HF and the risk of sudden death. Although these disorders are common and have a poor prognosis, the evidence available for guiding treatment decisions for the use of ICD and CRT devices in these patients is lacking. Given this lack of clear evidence, pragmatic clinical trials and comparative effectiveness studies are needed to help identify the appropriate use of ICD and CRT devices in this high-risk population of patients with HF and CKD.     

Clinical practice update on heart failure 2019: pharmacotherapy,procedures, devices and patient management. An expert consensus meeting report of the Heart Failure Association of the European Society of Cardiology

The European Society of Cardiology (ESC) has published a series of guidelines on heart failure (HF) over the last 25 years, most recently in 2016. Given the amount of new information that has become available since then, the Heart Failure Association (HFA) of the ESC recognized the need to review and summarise recent developments in a consensus document. Here we report from the HFA workshop that was held in January 2019 in Frankfurt, Germany. This expert consensus report is neither a guideline update nor a position statement, but rather a summary and consensus view in the form of consensus recommendations. The report describes how these guidance statements are supported by evidence, it makes some practical comments, and it highlights new research areas and how progress might change the clinical management of HF. We have avoided re‐interpretation of information already considered in the 2016 ESC/HFA guidelines. Specific new recommendations have been made based on the evidence from major trials published since 2016, including sodium–glucose co‐transporter 2 inhibitors in type 2 diabetes mellitus, MitraClip for functional mitral regurgitation, atrial fibrillation ablation in HF, tafamidis in cardiac transthyretin amyloidosis, rivaroxaban in HF, implantable cardioverter‐defibrillators in non‐ischaemic HF, and telemedicine for HF. In addition, new trial evidence from smaller trials and updated meta‐analyses have given us the chance to provide refined recommendations in selected other areas. Further, new trial evidence is due in many of these areas and others over the next 2 years, in time for the planned 2021 ESC guidelines on the diagnosis and treatment of acute and chronic heart failure.     

CCS/CHFS Heart Failure Guidelines: Clinical Trial Update on Functional Mitral Regurgitation,SGLT2 Inhibitors,ARNI in HFpEF,and Tafamidis in Amyloidosis

In this update, we focus on selected topics of high clinical relevance for health care providers who treat patients with heart failure (HF), on the basis of clinical trials published after 2017. Our objective was to review the evidence, and provide recommendations and practical tips regarding the management of candidates for the following HF therapies: (1) transcatheter mitral valve repair in HF with reduced ejection fraction; (2) a novel treatment for transthyretin amyloidosis or transthyretin cardiac amyloidosis; (3) angiotensin receptor-neprilysin inhibition in patients with HF and preserved ejection fraction (HFpEF); and (4) sodium glucose cotransport inhibitors for the prevention and treatment of HF in patients with and without type 2 diabetes. We emphasize the roles of optimal guideline-directed medical therapy and of multidisciplinary teams when considering transcatheter mitral valve repair, to ensure excellent evaluation and care of those patients. In the presence of suggestive clinical indices, health care providers should consider the possibility of cardiac amyloidosis and proceed with proper investigation. Tafamidis is the first agent shown in a prospective study to alter outcomes in patients with transthyretin cardiac amyloidosis. Patient subgroups with HFpEF might benefit from use of sacubitril/valsartan, however, further data are needed to clarify the effect of this therapy in patients with HFpEF. Sodium glucose cotransport inhibitors reduce the risk of incident HF, HF-related hospitalizations, and cardiovascular death in patients with type 2 diabetes and cardiovascular disease. A large clinical trial recently showed that dapagliflozin provides significant outcome benefits in well treated patients with HF with reduced ejection fraction (left ventricular ejection fraction ≤ 40%), with or without type 2 diabetes.     

DCRM Multispecialty Practice Recommendations for the management of diabetes,cardiorenal, and metabolic diseases

Type 2 diabetes (T2D), chronic kidney disease (CKD), atherosclerotic cardiovascular disease (ASCVD), and heart failure (HF)—along with their associated risk factors—have overlapping etiologies, and two or more of these conditions frequently occur in the same patient. Many recent cardiovascular outcome trials (CVOTs) have demonstrated the benefits of agents originally developed to control T2D, ASCVD, or CKD risk factors, and these agents have transcended their primary indications to confer benefits across a range of conditions. This evolution in CVOT evidence calls for practice recommendations that are not constrained by a single discipline to help clinicians manage patients with complex conditions involving diabetes, cardiorenal, and/or metabolic (DCRM) diseases. The ultimate goal for these recommendations is to be comprehensive yet succinct and easy to follow by the nonexpert—whether a specialist or a primary care clinician. To meet this need, we formed a volunteer task force comprising leading cardiologists, nephrologists, endocrinologists, and primary care physicians to develop the DCRM Practice Recommendations, a multispecialty consensus on the comprehensive management of the patient with complicated metabolic disease. The task force recommendations are based on strong evidence and incorporate practical guidance that is clinically relevant and simple to implement, with the aim of improving outcomes in patients with DCRM. The recommendations are presented as 18 separate graphics covering lifestyle therapy, patient self-management education, technology for DCRM management, prediabetes, cognitive dysfunction, vaccinations, clinical tests, lipids, hypertension, anticoagulation and antiplatelet therapy, antihyperglycemic therapy, hypoglycemia, nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH), ASCVD, HF, CKD, and comorbid HF and CKD, as well as a graphical summary of medications used for DCRM.     

The role of prophylactic implantable cardioverter defibrillators in heart failure: Recent trials usher in a new era of device therapy

Sudden cardiac death (SCD) manifested as ventricular fibrillation or sustained ventricular tachycardia has been a major focus of cardiovascular research for more than three decades. Although mortality in patients with heart failure (HF) caused by left ventricular systolic dysfunction has declined in recent years through effective pharmacotherapeutic strategies, SCD remains the major cause of death in symptomatic HF, with little improvement by drug therapy. Although it is clear that the implantable cardioverter defibrillator (ICD) is efficacious and should be used to prevent a recurrence of sustained ventricular arrhythmia (secondary prevention) in most patients, the guidelines for prophylactic use of ICDs (primary prevention) are less well defined. The results of recent clinical trials examining the efficacy of prophylactic ICD therapy in HF patients have clarified the role of ICD treatment in this population. This article reviews these trials and summarizes our current approach to the prevention of SCD in HF.     

Contemporary approach to treating heart failure

Over the past several decades, important advances have been made in the treatment of patients with heart failure (HF). Whereas in the past, the main goal of drug therapy was to relieve congestion, there is now compelling evidence from randomized clinical trials (RCTs) showing that several classes of drugs, most of which work predominantly by blocking or modulating neurohormonal activity, can substantially reduce morbidity and mortality as well as improve quality of life in patients with HF. Most of these trials, however, separated patients according to whether their ejection fraction (EF) was reduced (HFrEF) or preserved (HFpEF) and for the most part, favorable effects on clinical outcomes were demonstrated only in patients with HFrEF. In addition to the paucity of effective agents for managing patients with HFpEF, it has become apparent that underutilization of available therapies has greatly limited the overall impact of medical therapy on outcomes. This review provides an overview of current medical management of HF across the spectrum of EF, including the underutilization of treatment modalities. The focus is to provide clinicians the rationale for the use of specific agents and to present a practical approach for patient management. The strategies discussed are based on results of RCTs, guideline recommendations and the authors’ own experience in managing patients with HF over the years.     

A review of current key guidelines for managing high-risk patients with diabetes and heart failure and future prospects

We reviewed recent guidelines on the management of heart failure (HF) in patients with diabetes. Major recommendations in European and US society guidelines were scrutinized. First, sodium-glucose co-transporter 2 inhibitors are now recommended treatments for all patients with symptomatic HF (stage C and D; New York Heart Association class II-IV), irrespective of the presence of type 2 diabetes and left ventricular ejection fraction (LVEF). Second, patients with HF and reduced EF (LVEF ≤40%) should have foundational therapies from four drug classes (sodium-glucose co-transporter 2 inhibitor, angiotensin-receptor neprilysin inhibitor, beta-blocker and mineralocorticoid receptor antagonist). Third, patients with HF with mildly reduced (41%-49%) and preserved (≥50%) LVEF may also benefit from angiotensin-receptor neprilysin inhibitor, beta-blocker and mineralocorticoid receptor antagonist therapy, although evidence for these is less robust. Fourth, selected patients should be considered for other therapies such as diuretics (if congestion), anticoagulation (if atrial fibrillation) and cardiac device therapy. Fifth, glucose-lowering therapies such as thiazolidinediones and certain dipeptidyl peptidase-4 inhibitors (such as saxagliptin and alogliptin) should be avoided in patients with HF. Sixth, guidelines recommend enrolment of patients with HF into exercise rehabilitation and multidisciplinary HF management programmes. Particular attention should be paid to important comorbidities such as obesity, alongside pharmacological therapies. As diabetes and obesity are major risk factors for HF, earlier consideration of, and diagnosis of HF, followed by guideline-directed medical therapy can meaningfully improve patients' lives. Diabetes doctors would do well to understand the basics of such guidelines to help improve all aspects of HF diagnosis and care.     

Use of sodium–glucose co‐transporter‐2 inhibitors in patients with and without type 2 diabetes: implications for incident and prevalent heart failure

Type 2 diabetes (T2D) is associated with an increased risk of heart failure (HF), with recent reports indicating that HF with preserved ejection fraction (HFpEF) may be more common than HF with reduced ejection fraction (HFrEF) in patients with T2D. T2D and HF result in worse outcomes than either disease alone. Sodium–glucose co‐transporter‐2 inhibitors (SGLT‐2is) have significantly improved HF outcomes in patients with T2D and may represent a new therapeutic alternative for patients with T2D at risk for or with HF. Current guidelines recommend prevention of HF through risk factor management. Once developed, treatment of HFrEF should include neurohormonal and haemodynamic modulations; however, there are no specific treatments available for HFpEF. SGLT‐2is are the first class of glucose‐lowering therapy to prevent HF in clinical trials and real‐world studies in patients with T2D (with or without established cardiovascular disease and with or without baseline HF). Mechanistic studies suggest that SGLT‐2is have beneficial effects on both systolic and diastolic function and additional systemic effects that could benefit HF outcomes. In patients with HFrEF, SGLT‐2i treatment as add‐on to standard HF therapy has had beneficial effects on HF outcomes, irrespective of T2D status. These results and those of ongoing outcomes trials with SGLT‐2is may help establish this drug class as a treatment for HF in patients with HFrEF and HFpEF, as well as HF in patients without T2D.     

Heart Failure and Its Management With β-Blockade: Potential Applications of Once-Daily Therapy

Heart failure (HF) due to left ventricular (LV) systolic dysfunction is a progressive disease beginning with a primary injury that activates compensatory cardiovascular mechanisms including varying degrees of neurohormonal activation. Within the neurohormonal cascade, activation of the sympathetic nervous system is in part responsible for ongoing myocardial injury, progressive LV remodeling, and functional deterioration eventually leading to symptomatic HF. Large randomized clinical trials of certain β-blockers added to standard therapies have shown unequivocal benefits in patients with chronic systolic HF resulting in reduced remodeling, fewer total and cardiovascular deaths, and less risk of hospitalization for worsening HF. Evidence-based clinical guidelines recommend β-blockers as part of the regimen for patients with systolic HF as well as LV dysfunction following myocardial infarction. Based on published clinical trial results, bisoprolol, carvedilol, and sustained-release metoprolol succinate are recommended for systolic HF. Carvedilol, propranolol, and timolol are recommended for post-myocardial infarction LV dysfunction. Unfortunately, these evidence-based therapies are often underused in actual practice. Various strategies to increase β-blocker use in HF have been attempted, including in-hospital initiation of β-blocker therapy. Simplifying dosing regimens may also improve adherence to prescribed medications. Use of controlled-release carvedilol may encourage better adherence in patients with LV dysfunction and help overcome at least one barrier to optimal evidence-based care.