Integrating Current Knowledge into Consensus Guidelines for Acute Decompensated Heart Failure

Integrating Current Knowledge into Consensus Guidelines for Acute Decompensated Heart Failure J. Herbert Patterson, Pharm.D., FCCP One of Four Continuing Education Programs in the Series, Acute Decompensated Heart Failure: Integrating Consensus Guidelines and Individual Patient Characteristics into Optimal Treatment Regimens Recorded August 1, 2006 Chicago, Illinois

Integrating Current Knowledge into Consensus Guidelines for Acute Decompensated Heart Failure Target Audience This continuing education program is beneficial for pharmacists and pharmacy managers in all practice settings who are involved in improving care for patients with ADHF. Program Description Until recently, there were no guidelines available for the treatment of acute decompensated heart failure (ADHF). Within the last year, both the Heart Failure Society of America (HFSA) and the European Society of Cardiology (ESC) have published consensus guidelines related to the treatment of ADHF. This presentation reviews key points from the HFSA guidelines related to acute heart failure, including a description of the guideline development process and the evidence behind selected recommendations. Learning Outcomes After listening to this program, the participant should be able to: Characterize the strength of evidence supporting recommendations in the consensus guidelines. Apply an effective strategy for hospitalizing patients with ADHF based on guideline criteria. Apply an effective strategy for treating ADHF based on guideline criteria. Apply an effective strategy for discharging patients with ADHF. Compare and contrast the HFSA and ESC guidelines for ADHF treatment. Continuing Education Accreditation The American Society of Health-System Pharmacists is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education. This continuing education program provides 1.0 hours (0.1 CEUs) of continuing education credit (program number 204-000-06-425-H01). This program is provided free of charge. After participating in the program, pharmacists may complete the CE test online at the ASHP Advantage CE Testing Center (www.ashp.org/advantage/ce). A passing grade of 70% is required to receive continuing education credit for this program, and pharmacists can print their CE statement immediately. Continuing education credit for this program is available from September 15, 2006, through September 14, 2007.

Integrating Current Knowledge into Consensus Guidelines for Acute Decompensated Heart Failure Program Faculty J. Herbert Patterson, Pharm.D., FCCP Associate Professor of Pharmacy Research Associate Professor of Medicine University of North Carolina at Chapel Hill School of Pharmacy Chapel Hill, North Carolina J. Herbert Patterson, Pharm.D., FCCP, BCPS, is Associate Professor of Pharmacy and Research Associate Professor of Medicine at the University of North Carolina (UNC) at Chapel Hill. He received his Bachelor of Science and Doctor of Pharmacy degrees from the University of Tennessee. After completing a residency, he joined the faculty at the UNC School of Pharmacy in 1981. Since then, his research, teaching, and clinical activities have focused on cardiovascular pharmacotherapy with a special emphasis on heart failure. He has been active in the UNC Heart Failure Program since its inception in 1984, serving as an investigator on numerous clinical trials involving heart failure. Dr. Patterson is a fellow in the American College of Clinical Pharmacy and is a member of the American Heart Association, the American College of Cardiology, and the Heart Failure Society of America (HFSA). From 1998 to 2006, he served on the HFSA Clinical Practice Guidelines committee. Faculty Disclosure Statement In accordance with the Accreditation Council for Continuing Medical Education s Standards for Commercial Support, ASHP Advantage requires that all faculty members involved in the development of program content to disclose their relevant financial relationships. A faculty member has a relevant financial relationship if the individual or his or her spouse/partner has a financial relationship (e.g., employee, consultant, research grant recipient, speakers bureau, or stockholder) in any amount occurring in the last 12 months with a commercial interest whose products or services may be discussed in the CME activity content over which the faculty member has control. The existence of these relationships is provided for the information of attendees and should not be assumed to have an adverse impact on faculty presentations. The faculty reports the following relationships: Dr. Patterson declares that he has served on the speakers bureau and/or the advisory boards for AstraZeneca, GlaxoSmithKline, Novartis, and Scios Inc.

Integrating Current Knowledge into Consensus Guidelines for Acute Decompensated Heart Failure ASHP Advantage Instructions for Receiving Your CE Credit and Statements Online for Podcast Activities The online ASHP Advantage CE Testing Center allows participants to obtain their CE statements conveniently and immediately using any computer with an Internet connection.* To take the CE test and obtain your CE statement for this ASHP Advantage Podcast activity, please follow these steps: 1. Type www.ashp.org/advantage/ce/ in your internet browser. 2. If you have previously logged in to the ASHP Advantage site, then you need only enter your e-mail address and password. If you have not logged in to the ASHP Advantage site before, click on Create Account and follow the brief instructions to set up a user account and password. You will only need to create your account once to have access to register, take CE tests, and process CE online from ASHP Advantage in the future. 3. After logging in, you will see the list of activities for which CE is available. To process CE for one of the activities in the list, click on the Start button next to the name of the activity. This activity is listed under ADHF Series. 4. Click on the radio button next to the correct answer for each question. Once you are satisfied with your selections, click Finish CE to process your test and complete the remaining steps to print your CE statement. 5. Repeat the above steps for each Podcast activity in which you participate. If you have any problems processing your CE, contact ASHP Advantage at support@ashpadvantage.com. *Except that this site does not support the AOL Web browser.

Integrating Current Knowledge into Consensus Guidelines for Acute Decompensated Heart Failure J. Herbert Patterson, Pharm.D., FCCP Associate Professor of Pharmacy Research Associate Professor of Medicine University of North Carolina School of Pharmacy Chapel Hill, North Carolina Learning Objectives Characterize the strength of evidence supporting recommendations in the consensus guidelines Apply an effective strategy for hospitalizing patients with acute decompensated heart failure (ADHF) based on guideline criteria Apply an effective strategy for treating ADHF based on guideline criteria Apply an effective strategy for discharging patients with ADHF Compare and contrast the Heart Failure Society of America (HFSA) and European Society of Cardiology (ESC) guidelines for ADHF treatment Steps in Development of the HFSA Practice Guideline Determine the scope of the practice guideline Identify the medical evidence relevant to the guideline Specify the type of evidence and relative weight of evidence Formulate the strength of evidence used Establish therapeutic justification for recommended therapies Steps in Development of the HFSA Practice Guideline (cont) Formulate recommendations of specific strength Create the initial document Develop a review process for the document Disseminate the practice guideline Determine the life cycle of the document Executive Summary: HFSA 2006 Comprehensive Heart Failure Practice Guideline Heart Failure Society of America Adams KF et al. J Card Fail. 1006; 12:10-38. HFSA: Table of Contents Section 1. Development and Implementation of a Comprehensive Heart Failure Practice Guideline Section 2. Conceptualization and Working Definition of Heart Failure (HF) Section 3. Prevention of Ventricular Remodeling, Cardiac Dysfunction and HF Section 4. Evaluation of Patients for Ventricular Dysfunction and HF

HFSA: Table of Contents (cont) Section 5. Management of Asymptomatic Patients with Reduced Left Ventricular Ejection Fraction (LVEF) Section 6. Non-pharmacologic Management and Health Care Maintenance in Patients with Chronic HF Section 7. HF in Patients with Left Ventricular Systolic Dysfunction Section 8. Disease Management in HF HFSA: Table of Contents (cont) Section 9. Electrophysiologic Testing and the Use of Devices in HF Section 10. Surgical Approaches to the Treatment of HF Section 11. Evaluation and Management of Patients with HF and Preserved LVEF Section 12. Evaluation and Management of Patients with ADHF HFSA: Table of Contents (cont) Section 13. Evaluation and Therapy for HF in the Setting of Ischemic Heart Disease Section 14. Managing Patients with Hypertension and HF Section 15. Management of HF in Special Populations Section 16. Myocarditis: Current Treatment Relative Weight of Evidence Used to Develop HFSA Practice Guideline Level A: Randomized, controlled, clinical trials May be assigned based on results of a single-trial Level B: Cohort and case-control studies Post hoc, subgroup analysis, and meta-analysis Prospective observational studies or registries Level C: Expert opinion Observational studies epidemiologic findings Safety reporting from large-scale use in practice HFSA System of Classifying the Strength of Recommendations Is recommended Part of routine care Exceptions to therapy should be minimized Should be considered Majority of patients should receive the intervention Some discretion in application to individual patients should be allowed HFSA System of Classifying the Strength of Recommendations (cont) May be considered Individualization of therapy is indicated Is not recommended Therapeutic intervention should not be used

HFSA: Angiotensin-Converting Enzyme (ACE) Inhibitors HFSA Section 7: Heart Failure in Patients with Left Ventricular Systolic Dysfunction Recommendations 7.1 7.2 Recommended in all patients with a LVEF < 40% Substitute angiotensin receptor blocker (ARB) if intolerant to ACE inhibitors (cough) Substitute the combination of hydralazine and an oral nitrate if intolerant to ACE inhibitors due to hyperkalemia HFSA: Beta-Adrenergic Receptor Blockers Recommendations 7.3 7.9 Recommended in all patients with a LVEF < 40%, even those who have traditionally not received β-blockers (diabetes mellitus, chronic obstructive pulmonary disease, peripheral vascular disease) Start in hospital if patient is stable Continue during exacerbation of HF HFSA: Angiotensin Receptor Blockers Recommendations 7.10 7.13 Recommended in patients intolerant to ACE inhibitors May be considered as initial therapy in some conditions (HF post-myocardial infarction [MI], chronic HF with LV systolic dysfunction) Should be considered in patients with a history of ACE-inhibitor induced angioedema Not recommended in addition to ACE inhibitor and beta-blocker in patients with recent MI and LV dysfunction HFSA: Aldosterone Antagonists Recommendations 7.14 7.18 Recommended in severe HF in addition to standard therapy Should be considered in patients post-mi with LV dysfunction in addition to standard therapy Monitoring of potassium status and renal function is critical HFSA: Hydralazine and Oral Nitrates Recommendations 7.19 7.20 Recommended in African Americans with LV dysfunction in addition to standard therapy of ACE inhibitor and beta-blocker May be considered in non-african American patients with LV dysfunction and symptoms on standard therapy

HFSA: Polypharmacy Recommendations 7.21 7.22 Additional pharmacologic therapy (ARB, aldosterone antagonist, or combination of hydralazine/isosorbide dinitrate) should be considered in patients with persistent symptoms despite optimized therapy with an ACE inhibitor and β-blocker, depending on the clinical scenario Triple combination of an ACE inhibitor, ARB, and aldosterone antagonist is not recommended HFSA: Diuretic Therapy Recommendations 7.23 7.28 Loop diuretics preferred Identify effective dose then give multiple times a day for additional diuresis Combine diuretics if needed Monitor for electrolyte disturbances Executive Summary of the Guidelines on the Diagnosis and Treatment of Acute Heart Failure The Task Force on Acute Heart Failure of the European Society of Cardiology Nieminen MS et al. Eur Heart J. 2005; 26:384-416. Levels of Evidence Used to Develop ESC Guidelines Level A: Data derived from multiple randomized clinical trials or meta-analyses Level B: Data derived from a single randomized clinical trial or large nonrandomized studies Level C: Consensus of opinion of the experts or small studies; retrospective studies and registries ESC System of Classifying the Usefulness or Efficacy of Recommendations: Class I Evidence or general agreement that a given diagnostic procedure or treatment is beneficial, useful, and effective ESC System of Classifying Recommendations: Class II Conflicting evidence or divergence of opinion about the usefulness or efficacy of the treatment Class IIa: Weight of evidence and opinion is in favor Class IIb: Usefulness or efficacy is less well established

ESC System of Classifying Recommendations: Class III Class III Evidence or general agreement that the treatment is not useful/effective and in some cases may be harmful ESC: General Therapeutic Approach in Acute HF by Findings on Invasive Hemodynamic Monitoring Hemodynamic Characteristic Cardiac index (CI) Pulmonary capillary wedge pressure (PCWP) Systolic blood pressure (SBP) (mmhg) Outline of therapy Findings and Suggested Therapeutic Approach Decreased Low Fluid loading In patients with acute HF: CI: decreased if < 2.2 L/min/m 2 PCWP: low if < 14 mmhg, high if > 18-20 mmhg ESC: General Therapeutic Approach in Acute HF by Findings on Invasive Hemodynamic Monitoring (cont) ESC: General Therapeutic Approach in Acute HF by Findings on Invasive Hemodynamic Monitoring (cont) Hemodynamic Characteristic CI PCWP SBP mmhg Outline of therapy Findings and Suggested Therapeutic Approach Decreased High or normal > 85 Vasodilator (nitroprusside, nitroglycerin) fluid loading may become necessary Hemodynamic Characteristic CI PCWP SBP mmhg Outline of therapy Findings and Suggested Therapeutic Approach Decreased High < 85 Consider inotropic agents (dobutamine, dopamine) and i.v. diuretics ESC: General Therapeutic Approach in Acute HF by Findings on Invasive Hemodynamic Monitoring (cont) ESC: General Therapeutic Approach in Acute HF by Findings on Invasive Hemodynamic Monitoring (cont) Hemodynamic Characteristic CI Findings and Suggested Therapeutic Approach Decreased Hemodynamic Characteristic CI Findings and Suggested Therapeutic Approach Maintained PCWP SBP mmhg Outline of therapy High > 85 Vasodilators (nitroprusside, nitroglycerin) and i.v. diuretics and consider inotrope (dobutamine, levosimendan, phosphodiesterase inhibitor) PCWP SBP mmhg Outline of therapy High I.V. diuretics; if SBP is low, vasoconstrictive inotropes

Patient Selection and Treatment No Low Perfusion at Rest Yes SVR = systemic vascular resistance Congestion at Rest No Warm and dry PCWP normal CI normal (compensated) Cold and dry PCWP low/normal CI decreased Inotropic drugs Dobutamine Milrinone Calcium sensitizers Yes Warm and wet PCWP elevated CI normal Cold and wet PCWP elevated CI decreased Normal SVR High SVR Vasodilators Nitroprusside Nitroglycerin or Natriuretic peptide Nesiritide Stevenson LW. Eur J Heart Fail. 1999; 1:251-7. ESC: 10.3 Vasodilators in the treatment of acute HF Vasodilators are indicated in most patients with acute heart failure as first line therapy, if hypoperfusion is associated with an adequate blood pressure and signs of congestion with low diuresis, to open the peripheral circulation and to lower pre-load. ESC: 10.5.1 Diuretics Administration of diuretics is indicated in patients with acute and acutely decompensated heart failure in the presence of symptoms secondary to fluid retention. Class I recommendation, level of evidence B ESC: 10.7.1 Inotropic Agents Inotropic agents are indicated in the presence of peripheral hypoperfusion (hypotension, decreased renal function) with or without congestion or pulmonary edema refractory to diuretics and vasodilators at optimal doses. Class IIa recommendation, level of evidence C Executive Summary: HFSA 2006 Comprehensive Heart Failure Practice Guideline Heart Failure Society of America HFSA Section 12: Evaluation and Management of Patients with Acute Decompensated Heart Failure Adams KF et al. J Card Fail. 1006; 12:10-38.

HFSA: Hospitalization Recommended for Patients Presenting with ADHF Evidence of severely decompensated HF, including: Hypotension Worsening renal function Altered mentation Dyspnea at rest Typically reflected by resting tachypnea Less commonly reflected by oxygen saturation <90% Hemodynamically significant arrhythmia Including new onset of rapid atrial fibrillation Acute coronary syndrome HFSA: Hospitalization Should be Considered Worsened congestion Even without dyspnea Typically reflected by a weight gain of 5 kg Signs and symptoms of pulmonary or systemic congestion Even in the absence of weight gain Major electrolyte disturbance HFSA: Hospitalization Should be Considered (cont) Associated comorbid conditions Pneumonia, pulmonary embolus, diabetic ketoacidosis, and symptoms suggestive of transient ischemic accident or stroke Repeated implantable cardioverterdefibrillator firings Previously undiagnosed HF with signs and symptoms of systemic or pulmonary congestion HFSA: Treatment Goals for Patients Admitted for ADHF Improve symptoms, especially congestion and low-output symptoms Optimize volume status Identify etiology Identify precipitating factors Optimize chronic oral therapy Minimize side effects HFSA: Treatment Goals for Patients Admitted for ADHF (cont) Identify patients who might benefit from revascularization Educate patients concerning medications and self assessment of HF Consider and, where possible, initiate a disease management program. HFSA: Diuretics Recommendation 12.5 It is recommended that patients admitted with ADHF and evidence of fluid overload be treated initially with loop diuretics usually given intravenously rather then orally. (Strength of Evidence = B)

HFSA: Diuretics (cont) Recommendation 12.11 When congestion fails to improve in response to diuretic therapy, the following options should be considered: Sodium and fluid restriction Increased doses of loop diuretic Continuous infusion of a loop diuretic, or Addition of a second type of diuretic orally (metolazone or spironolactone) or intravenously (chlorothiazide) A fifth option, ultrafiltration, may be considered. (Strength of Evidence = C) HFSA: Vasodilators Recommendation 12.15 In the absence of symptomatic hypotension, intravenous nitroglycerin, nitroprusside, or nesiritide may be considered as an addition to diuretic therapy for rapid improvement of congestive symptoms in patients admitted with ADHF. Frequent blood pressure monitoring is recommended with these agents. (Strength of Evidence = B) These agents should be decreased in dosage or discontinued if symptomatic hypotension develops. (Strength of Evidence = B) Reintroduction in increasing doses may be considered once symptomatic hypotension is resolved. (Strength of Evidence = C) HFSA: Vasodilators (cont) Recommendation 12.16 Intravenous vasodilators (intravenous nitroglycerin or nitroprusside) and diuretics are recommended for rapid symptom relief in patients with acute pulmonary edema or severe hypertension. (Strength of Evidence = C) HFSA: Vasodilators (cont) Recommendation 12.17 Intravenous vasodilators (nitroprusside, nitroglycerin, or nesiritide) may be considered in patients with ADHF and advanced HF who have persistent severe HF despite aggressive treatment with diuretics and standard oral therapies. (Strength of Evidence = C) HFSA: Inotropes Recommendation 12.18 Intravenous inotropes (milrinone or dobutamine) may be considered to relieve symptoms and improve end-organ function in patients with advanced HF characterized by LV dilation, reduced LVEF, and diminished peripheral perfusion or end-organ dysfunction (low output syndrome), particularly if these patients have marginal SBP (<90 mm HG), have symptomatic hypotension despite adequate filling pressure, or are unresponsive to, or intolerant of, intravenous vasodilator. (Strength of Evidence = C) HFSA: Inotropes (cont) Recommendation 12.18 These agents may be considered in similar patients with evidence of fluid overload if they respond poorly to intravenous diuretics or manifest diminished or worsening renal function. (Strength of Evidence = C)

HFSA: Inotropes (cont) Recommendation 12.18 When adjunctive therapy is needed in other patients with ADHF, administration of vasodilators should be considered instead of intravenous inotropes (milrinone or dobutamine). (Strength of Evidence = B) Intravenous inotropes (milrinone or dobutamine) are not recommended unless left heart failure filling pressures are known to be elevated based on direct measurement or clear clinical signs. (Strength of Evidence = B) HFSA: Recommended Discharge Criteria for All Patients with HF Exacerbating factors addressed At least near optimal volume status achieved Transition from i.v. to oral diuretic successfully completed Patient and family education completed At least near optimal pharmacologic therapy achieved Follow-up clinic visit scheduled, usually for 7-10 days HFSA: Discharge Criteria to Consider for Patients with Advanced HF or Recurrent Admissions Oral medication regimen stable for 24 hrs No i.v. vasodilator or inotropic agent for 24 hrs Ambulation before discharge to assess functional capacity after therapy Plans for post-discharge management (scale present in home, visiting nurse or telephone follow-up generally no longer than 3 days after discharge) Referral for disease management Guidelines Available Online HFSA 2006 HF Practice Guideline www.heartfailureguideline.com ESC 2005 Acute HF Guidelines www.eurheartj.oxfordjournals.org Both are available under the Handouts and Resources tab on the left. Conclusions Guidelines provide guidance for the clinician to apply the information to an individual patient Pharmacists can play a critical role in the management of patients with heart failure, both acutely and chronically, and are in a key position to help disseminate and apply the information from the guidelines

Integrating Current Knowledge into Consensus Guidelines for Acute Decompensated Heart Failure References 1. Adams KF, Lindenfeld J, Arnold JMO et al. Executive summary: HFSA 2006 Comprehensive Heart Failure Practice Guideline. J Card Fail. 2006; 12:10-38. 2. Nieminen MS, Böhm M, Cowie MR et al. Executive summary of the guidelines on the diagnosis and treatment of acute heart failure: The Task Force on Acute Heart Failure of the European Society of Cardiology. Eur Heart J. 2005; 26:384-416. 3. Stevenson LW. Tailored therapy to hemodynamic goals for advanced heart failure. Eur J Heart Fail. 1999; 1:251-7.

Integrating Current Knowledge into Consensus Guidelines for Acute Decompensated Heart Failure Self-Assessment Questions 1. According to the Heart Failure Society of America (HFSA) 2006 Comprehensive Heart Failure Practice Guideline, level B strength of evidence for making recommendations is based on a. Randomized, controlled clinical trials. b. Cohort and case-control studies. c. Expert opinion. d. Conflicting evidence or divergence of opinion. 2. In the HFSA guideline, the recommendation that an intervention should be considered means that a. It should be part of routine care and exceptions should be minimized. b. It should be used for the majority of patients and some discretion in application to individual patients should be allowed. c. Individualization of therapy is indicated. d. It should not be used. 3. Both the 2005 European Society of Cardiology (ESC) Guidelines on the Diagnosis and Treatment of Acute Heart Failure and the HFSA guidelines use which one of the following to support their highest level of evidence (level A)? a. Expert opinion. b. Registries. c. Observational studies. d. Randomized clinical trials. 4. In the HFSA guideline, the is not recommended classification is most closely aligned with which of the following recommendation classes in the ESC guidelines? a. Class I. b. Class IIa. c. Class IIb. d. Class III. 5. According to the ESC guidelines, which of the following therapies should be considered in a patient with ADHF undergoing invasive hemodynamic monitoring who has a decreased cardiac index, high pulmonary capillary wedge pressure, and systolic blood pressure less than 85 mm Hg? a. I.V. diuretics. b. Vasodilators. c. Inotropic agents and i.v. diuretics. d. Vasodilators and i.v. diuretics.

Integrating Current Knowledge into Consensus Guidelines for Acute Decompensated Heart Failure 6. According to the HFSA guideline, hospitalization is recommended if a patient with ADHF presents with which of the following clinical circumstances? a. Dyspnea at rest. b. Major electrolyte disturbance. c. Worsened congestion. d. Any associated comorbid conditions. 7. According to the HFSA guideline, all of the following are treatment goals for patients admitted with ADHF except a. Improving symptoms. b. Optimizing volume status. c. Administering intermittent inotropic therapy. d. Optimizing chronic oral therapy. 8. According to the HFSA guideline, it is recommended that patients admitted with ADHF and evidence of fluid overload be treated initially with intravenous a. Nitroglycerin. b. Nesiritide. c. Loop diuretics. d. Dobutamine. 9. According to the HFSA guideline, three of the following four options should be considered if a patient s congestion fails to improve in response to diuretic therapy. Which of the following options may be considered in that situation? a. Sodium and fluid restriction. b. Increased doses of a loop diuretic. c. Addition of a second type of diuretic, such as metolazone. d. Ultrafiltration. 10. In general, both the ESC and the HFSA guidelines for ADHF recommend the use of intravenous vasodilators instead of inotropes in patients with an elevated pulmonary capillary wedge pressure (congestion) and adequate blood pressure. a. True. b. False. 11. A patient with heart failure is ready to be discharged from the hospital. The HFSA guideline recommends that all of the following criteria are met before discharge except a. Exacerbating factors addressed. b. At least near optimal volume status achieved. c. Transition process from i.v. to oral diuretic begun. d. Patient and family education completed.

Integrating Current Knowledge into Consensus Guidelines for Acute Decompensated Heart Failure 12. According to the HFSA guideline, a criterion that should be considered before discharge for patients with advanced heart failure or recurrent admissions for heart failure is a. Oral medication regimen stable for 48 hours. b. No i.v. vasodilator or inotropic agent for 48 hours. c. Ambulation before discharge to assess functional capacity after therapy. d. Plans for post-discharge management, including follow-up nursing visit or phone call within 5 days of discharge.