Numerator Patients with acute STEMI (or its equivalent*) defined by characteristic symptoms of myocardial ischemia with diagnostic ST elevation on ECG, who are comatose after resuscitated out-of-hospital cardiac arrest (VF or pulseless VT), who receive therapeutic hypothermia *Patients with STEMI equivalent on ECG may have: hyperacute T-wave changes, true posterior MI, multilead ST depression with coexistent ST elevation in lead aVR, characteristic diagnostic criteria in the setting of LBBB. Denominator All patients with STEMI who are comatose after resuscitated out-of-hospital cardiac arrest (VF or pulseless VT) Denominator Exclusions Patients age <18 y Patients who die shortly after arrival (<12 h) Patients who become comfort care measures only or hospice shortly after arrival (<12 h) Patients who are transferred to another hospital for inpatient care shortly after arrival (<12 h) Patients received in transfer from the inpatient setting from another facility Denominator Exceptions Documentation of a medical reason for not receiving therapeutic hypothermia for comatose STEMI patients with out-of-hospital cardiac arrest (eg, intracranial hemorrhage, severe/active bleeding, significant hypotension refractory to multiple vasopressors, severe sepsis, pregnancy, other evidence of medical futility) Measurement Period Encounter Sources of Data Medical record or other database (eg administrative, clinical, registry) Attribution Measure reportable at the facility or provider level Care Setting Inpatient Rationale Therapeutic hypothermia in comatose patients with acute MI after certain types of cardiac arrest (predominantly related to VF or pulseless VT) has been shown to improve outcomes (eg, increased survival to hospital discharge with good neurologic function, higher rate of a favorable neurologic outcome, and possibly reduced intermediate-term mortality).12,192 194 Clinical Recommendation(s) 2013 ACCF/AHA Guideline for the Management of Patients With ST-Elevation Myocardial Infarction12 1.


Denominator All patients with STEMI who are comatose after resuscitated out-of-hospital cardiac arrest (VF or pulseless VT) Denominator Exclusions Patients age <18 y Patients who die shortly after arrival (<12 h) Patients who become comfort care measures only or hospice shortly after arrival (<12 h) Patients who are transferred to another hospital for inpatient care shortly after arrival (<12 h) Patients received in transfer from the inpatient setting from another facility Denominator Exceptions Documentation of a medical reason for not receiving therapeutic hypothermia for comatose STEMI patients with out-of-hospital cardiac arrest (eg, intracranial hemorrhage, severe/active bleeding, significant hypotension refractory to multiple vasopressors, severe sepsis, pregnancy, other evidence of medical futility) Measurement Period Encounter Sources of Data Medical record or other database (eg administrative, clinical, registry) Attribution Measure reportable at the facility or provider level Care Setting Inpatient Rationale Therapeutic hypothermia in comatose patients with acute MI after certain types of cardiac arrest (predominantly related to VF or pulseless VT) has been shown to improve outcomes (eg, increased survival to hospital discharge with good neurologic function, higher rate of a favorable neurologic outcome, and possibly reduced intermediate-term mortality).12,192 194 Clinical Recommendation(s) 2013 ACCF/AHA Guideline for the Management of Patients With ST-Elevation Myocardial Infarction12 1. Therapeutic hypothermia should be started as soon as possible in comatose patients with STEMI and out-of-hospital cardiac arrest caused by ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT), including patients who undergo primary PCI.192 194 (Class I, Level of Evidence: B) ACCF indicates American College of Cardiology Foundation; AHA, American Heart Association; LBBB, left bundle branch block; MI, myocardial infarction; PCI, percutaneous coronary intervention; STEMI, ST-elevation myocardial infarction; VF, ventricular fibrillation; and VT, ventricular tachycardia. Appendix A.


Therapeutic hypothermia should be started as soon as possible in comatose patients with STEMI and out-of-hospital cardiac arrest caused by ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT), including patients who undergo primary PCI.192 194 (Class I, Level of Evidence: B) ACCF indicates American College of Cardiology Foundation; AHA, American Heart Association; LBBB, left bundle branch block; MI, myocardial infarction; PCI, percutaneous coronary intervention; STEMI, ST-elevation myocardial infarction; VF, ventricular fibrillation; and VT, ventricular tachycardia. Appendix A. Continued 37 Short Title: QM-4: Aldosterone Antagonist at Discharge QM-4: AMI: Aldosterone Antagonist Prescribed at Discharge Measure description: Percentage of eligible patients, age 18 y, hospitalized with AMI, who are prescribed an aldosterone antagonist at hospital discharge. Numerator Eligible* patients with AMI who are prescribed an aldosterone antagonist at hospital discharge *Eligible AMI patients for an aldosterone antagonist are patients with no contraindications who are already receiving an ACE inhibitor and beta blocker, and who have an EF 40%, and either HF or diabetes mellitus (aldosterone antagonists are appropriately used when the ACE inhibitor and/or beta blocker cannot be used or tolerated).


Numerator Eligible* patients with AMI who are prescribed an aldosterone antagonist at hospital discharge *Eligible AMI patients for an aldosterone antagonist are patients with no contraindications who are already receiving an ACE inhibitor and beta blocker, and who have an EF 40%, and either HF or diabetes mellitus (aldosterone antagonists are appropriately used when the ACE inhibitor and/or beta blocker cannot be used or tolerated). Denominator All post-AMI patients who: [a] are receiving an ACE inhibitor and a beta blocker; AND [b] have a LVEF 40%; AND [c] have either diabetes mellitus or HF Denominator Exclusions Patients age <18 y Patients who leave against medical advice Patients who die during hospitalization Patients who are on comfort care measures only or hospice Patients who are transferred to another hospital for inpatient acute care Denominator Exceptions Documentation of a medical reason for not prescribing an aldosterone antagonist at hospital discharge (eg, allergy or intolerance to aldosterone antagonist, significant renal dysfunction [Cr >2.5 mg/dL in men; >2.0 mg/dL in women], hyperkalemia [K >5.0 mEq/L]) Patient currently enrolled in a clinical trial related to AMI (eg, trials involving renin-angiotensin-aldosterone system inhibitors) Measurement Period Encounter Sources of Data Medical record or other database (eg, administrative, clinical, registry) Attribution Measure reportable at the facility or provider level Care Setting Inpatient Rationale The EPHESUS (Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival) study demonstrated benefits from adding eplerenone, a selective aldosterone antagonist, to ACE inhibitors or ARBs (in 87% of patients) and beta blockers (75%), including a 15% and 17% reduction in overall and cardiovascular mortality, respectively. Therefore, in the absence of contraindications, post-MI patients with HF may benefit from adding an aldosterone antagonist to an ACE inhibitor or ARB, and a beta blocker.


Therefore, in the absence of contraindications, post-MI patients with HF may benefit from adding an aldosterone antagonist to an ACE inhibitor or ARB, and a beta blocker. Monitoring of patients renal function, electrolytes (screening for hyperkalemia, in particular), and blood pressure should be undertaken.11,12,29 Clinical Recommendation(s) 2013 ACCF/AHA Guideline for the Management of Patients With ST-Elevation Myocardial Infarction12 1. An aldosterone antagonist should be given to patients with STEMI and no contraindications who are already receiving an ACE inhibitor and beta blocker and who have an EF less than or equal to 0.40 and either symptomatic HF or diabetes mellitus.29 (Class I, Level of Evidence: B) 2014 AHA/ACC Guideline for the Management of Patients with Non ST-Elevation Acute Coronary Syndromes11 1. Aldosterone blockade is recommended in post MI patients without significant renal dysfunction (creatinine >2.5 mg/dL in men or >2.0 mg/dL in women) or hyperkalemia (K +>5.0 mEq/L) who are receiving therapeutic doses of ACE inhibitor and beta blocker and have a LVEF 0.40 or less, diabetes mellitus, (Class I, Level of Evidence: A) ACC indicates American College of Cardiology; ACCF, American College of Cardiology Founcation; ACE, angiotensin-converting enzyme; AHA, American Heart Association; AMI, acute myocardial infarction; ARB, angiotensin receptor blockers; Cr, creatinine; EF, ejection fraction; K, potassium; HF, heart failure; LVEF, left ventricular ejection fraction; MI, myocardial infarction; and STEMI, ST-elevation myocardial infarction. Appendix A. Continued 38 Short Title: QM-5: Inappropriate In-Hospital Use of NSAIDs QM-5: AMI: Inappropriate In-Hospital Use of NSAIDs Measure Description: Percentage of patients, age 18 y, hospitalized with AMI who are inappropriately prescribed NSAIDs during hospitalization.


Continued 38 Short Title: QM-5: Inappropriate In-Hospital Use of NSAIDs QM-5: AMI: Inappropriate In-Hospital Use of NSAIDs Measure Description: Percentage of patients, age 18 y, hospitalized with AMI who are inappropriately prescribed NSAIDs during hospitalization. Numerator Patients with AMI who were prescribed NSAIDs (with the exception of aspirin) in the hospital For purposes of this measure, a noninclusive list of NSAIDs include these medications: Ibuprofen Ketoprofen Sulindac Naproxen Etodolac Fenoprofen Diclofenac Flurbiprofen Ketorolac Piroxicam Indomethacin Mefenamic Acid Meloxicam Celecoxib Nabumetone Oxaprozin Ketoprofen Meclofenamate Tolmeti Salsalate Denominator All patients with AMI Denominator Exclusions Patients age <18 y Denominator Exceptions Documentation of a medical reason for prescribing NSAIDs during the AMI hospitalization (eg, patient with refractory arthritis pain that is unresponsive to other analgesics) Measurement Period Encounter Sources of Data Medical record or other database (eg, administrative, clinical, registry). Attribution Measure reportable at the facility or provider level Care Setting Inpatient Rationale NSAIDs likely increase the risk of major adverse events in patients with myocardial infarction (eg, impaired infarct healing, possibly increased risk of rupture following transmural infarction, higher risk of accompanying acute kidney injury, and increased risk of gastrointestinal bleeding in at-risk AMI patients who are already receiving antithrombotic therapies).195,196 Clinical Recommendation(s) 2013 ACCF/AHA Guideline for the Management of Patients With ST-Elevation Myocardial Infarction12 1. Glucocorticoids and nonsteroidal anti-inflammatory drugs are potentially harmful for treatment of pericarditis after STEMI.197,198 (Class III, Level of Evidence: B) 2014 AHA/ACC Guideline for the Management of Patients With Non ST-Elevation Acute Coronary Syndromes11 1.


Glucocorticoids and nonsteroidal anti-inflammatory drugs are potentially harmful for treatment of pericarditis after STEMI.197,198 (Class III, Level of Evidence: B) 2014 AHA/ACC Guideline for the Management of Patients With Non ST-Elevation Acute Coronary Syndromes11 1. Nonsteroidal anti-inflammatory drugs (NSAIDs) (except aspirin) should not be initiated and should be discontinued during hospitalization for NSTE-ACS because of the increased risk of MACE associated with their use.195,196 (Class III, Level of Evidence: B) ACC indicates American College of Cardiology; ACCF, American College of Cardiology Foundation; AHA, American Heart Association; AMI, acute myocardial infarction; MACE, major adverse cardiac events; NSAIDs, nonsteroidal anti-inflammatory drugs; NSTE-ACS, non ST-elevation acute coronary syndrome; STEMI, ST-elevation myocardial infarction. Appendix A. Continued 39 Short Title: QM-6: Inappropriate Prasugrel at Discharge in TIA/Stroke Patients QM-6: AMI: Inappropriate Prescription of Prasugrel at Discharge in Patients With a History of Prior Stroke or TIA Measure Description: Percentage of patients, age 18 y, hospitalized with AMI, who had a history of prior stroke or TIA and who are inappropriately prescribed prasugrel at discharge.


Continued 39 Short Title: QM-6: Inappropriate Prasugrel at Discharge in TIA/Stroke Patients QM-6: AMI: Inappropriate Prescription of Prasugrel at Discharge in Patients With a History of Prior Stroke or TIA Measure Description: Percentage of patients, age 18 y, hospitalized with AMI, who had a history of prior stroke or TIA and who are inappropriately prescribed prasugrel at discharge. Numerator Patients with AMI who are prescribed prasugeral at discharge Denominator All patients with AMI and a history of prior stroke (ischemic or hemorrhagic) or TIA Denominator Exclusions Patients age <18 y Patients who leave against medical advice Patients who die during hospitalization Patients who are on comfort care measures only or hospice Patients who are transferred to another hospital for inpatient acute care Denominator Exceptions None Measurement Period Encounter Sources of Data Medical record or other database (eg, administrative, clinical, registry) Attribution Measure reportable at the facility or provider level Care Setting Inpatient Rationale The TRITON-TIMI 38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel Thrombolysis in Myocardial Infarction) randomized clinical trial demonstrated the superiority of prasugrel over clopidogrel in reducing the composite of cardiovascular death, nonfatal MI, or nonfatal stroke among AMI patients (albeit with an increased risk of major bleeding). Although the elderly and underweight patients did not experience net clinical benefit from the use of prasugrel, the subgroup of patients with TIA or stroke had an increased net clinical harm with prasugrel compared with clopidogrel.12,116 Notably, a history of ischemic or hemorrhagic stroke or TIA symptoms were considered exclusion criteria in the TRITON-TIMI 38 trial, although a small group ended up being randomized in error and exhibited increased harm with prasugrel. Subsequently, the FDA issued a boxed warning cautioning against the use of prasugrel in patients with TIA or stroke.


Subsequently, the FDA issued a boxed warning cautioning against the use of prasugrel in patients with TIA or stroke. Overall, patients with prior history of ischemic or hemorrhagic stroke or TIA symptoms should not receive prasugrel. Although ischemic stroke is defined as a permanent infarction (symptomatic or asymptomatic) of the central nervous system, TIA is defined as a transient neurologic dysfunction caused by focal ischemia without ensuing infarction. Hemorrhagic strokes result from either subarachnoid or intracerebral bleeding, and usually represent 20% of all stroke events. Clinical Recommendation(s) 2013 ACCF/AHA Guideline for the Management of Patients With ST-Elevation Myocardial Infarction12 1. Prasugrel should not be administered to patients with a history of prior stroke or transient ischemic attack.116 (Class III, Level of Evidence: B) 2014 AHA/ACC Guideline for the Management of Patients With Non ST-Elevation Acute Coronary Syndromes11 1. Prasugrel should not be administered to patients with a prior history of stroke or transient ischemic attack.116 (Class III, Level of Evidence: B) ACC indicates American College of Cardiology; ACCF, American College of Cardiology Foundation; AHA, American Heart Association; AMI acute myocardial infarction; and TIA, transient ischemic attack. Appendix A. Continued 40 Short Title: QM-7: Inappropriate High-Dose Aspirin With Ticagrelor at Discharge QM-7: AMI: Inappropriate Prescription of High-Dose Aspirin With Ticagrelor at Discharge Measure Description: Percentage of patients, age 18 y, hospitalized with AMI who are prescribed ticagrelor and high-dose aspirin at discharge. Numerator Patients with AMI who are prescribed ticagrelor and high-dose aspirin at discharge Note: The recommended maintenance dose of aspirin is 81 mg daily in patients treated with ticagrelor. A high-dose aspirin is defined as a daily maintenance dose >100 mg. In the United States, a high-dose aspirin for thromboprophylaxis is usually a 162 mg or a 325-mg regimen.


In the United States, a high-dose aspirin for thromboprophylaxis is usually a 162 mg or a 325-mg regimen. Denominator All patients with AMI who are prescribed ticagrelor at discharge Denominator Exclusions Patients age <18 y Patients who leave against medical advice Patients who die during hospitalization Patients who are on comfort care measures only or hospice Patients who are transferred to another hospital for inpatient acute care Denominator Exceptions None Measurement Period Encounter Sources of Data Medical record or other database (eg, administrative, clinical, registry) Attribution Measure reportable at the facility or provider level Care Setting Inpatient Rationale In the PLATO (Platelet Inhibition and Patient Outcomes) trial, a prespecified subgroup analysis showed a significant regional variation in the comparative efficacy of ticagrelor with diminished benefits in North America compared with the rest of the world. Subsequent analyses demonstrated that the lowest risk of the composite ischemic outcome with ticagrelor compared with clopidogrel is associated with a low-maintenance dose of concomitant aspirin.7,12,40 Overall, a high- dose aspirin (>100 mg) is associated with increased bleeding hazard without an improved antiplatelet efficacy. The FDA also issued a boxed warning indicating that aspirin daily maintenance doses of >100 mg decrease the effectiveness of ticagrelor. Clinical Recommendation(s) 2013 ACCF/AHA Guideline for the Management of Patients With ST-Elevation Myocardial Infarction12 inhibitor therapy should be given for 1 year to patients with STEMI who receive a stent (bare-metal or drug-eluting) during primary PCI using the following maintenance doses: a. Clopidogrel 75 mg daily115,116 (Class I, Level of Evidence: B); or b. Prasugrel 10 mg daily115 (Class I, Level of Evidence: B); or c. Ticagrelor 90 mg twice a day*117 (Class I, Level of Evidence: B) *The recommended maintenance dose of aspirin to be used with ticagrelor is 81 mg daily.


Clinical Recommendation(s) 2013 ACCF/AHA Guideline for the Management of Patients With ST-Elevation Myocardial Infarction12 inhibitor therapy should be given for 1 year to patients with STEMI who receive a stent (bare-metal or drug-eluting) during primary PCI using the following maintenance doses: a. Clopidogrel 75 mg daily115,116 (Class I, Level of Evidence: B); or b. Prasugrel 10 mg daily115 (Class I, Level of Evidence: B); or c. Ticagrelor 90 mg twice a day*117 (Class I, Level of Evidence: B) *The recommended maintenance dose of aspirin to be used with ticagrelor is 81 mg daily. 2014 AHA/ACC Guideline for the Management of Patients With Non ST-Elevation Acute Coronary Syndromes11 1. Aspirin should be continued indefinitely. The maintenance dose should be 81 mg daily in patients treated with ticagrelor and 81 mg to 325 mg daily in all (Class I, Level of Evidence: A) ACC indicates American College of Cardiology; ACCF, American College of Cardiology Foundation; AHA, American Heart Association; AMI, acute myocardial infarction; FDA, US Food and Drug Administration; PCI, percutaneous coronary intervention; and STEMI, ST-elevation myocardial infarction. Appendix A. Continued 41 Appendix B.


The maintenance dose should be 81 mg daily in patients treated with ticagrelor and 81 mg to 325 mg daily in all (Class I, Level of Evidence: A) ACC indicates American College of Cardiology; ACCF, American College of Cardiology Foundation; AHA, American Heart Association; AMI, acute myocardial infarction; FDA, US Food and Drug Administration; PCI, percutaneous coronary intervention; and STEMI, ST-elevation myocardial infarction. Appendix A. Continued 41 Appendix B. Author Listing of Relationships With Industry and Other Entities (Relevant) 2017 AHA/ACC Clinical Performance and Quality Measures for Adults With ST-Elevation and Non ST-Elevation Myocardial Infarction Committee Member Employment Consultant Speaker Ownership/ Partnership/ Principal Research Institutional, Organizational, or Other Financial Benefit Expert Witness Hani Jneid, Chair Baylor College of Medicine Associate Professor of Medicine; Director of Interventional Cardiology Research The Michael DeBakey VA Medical Center Director of Interventional Cardiology None None None None None None Daniel Addison Fellow at Massachusetts General Hospital None None None None None None Deepak L. Bhatt Executive Director of Interventional Cardiovascular Programs, Brigham and Women s Hospital Heart & Vascular Center; Harvard Medical School Professor of Medicine Duke Clinical Research Institute: Ferring Pharmaceuticals Duke Clinical Research Institute: Novartis Duke Clinical Research Institute: Bristol-Myers Squibb/Pfizer Duke Clinical Research Institute: Eli Lilly None None Amarin Amgen Inc. AstraZeneca BIOFLOW-V (Biotronik)-clinical trial Bristol Myers Squibb Eisai Ethicon EVOLVE Short DAPT Study (Boston Scientific) Flowco* Forest Laboratories Ischemix Medtronic Merck and Co, Inc* Pfizer PLxPharma* Roche Sanofi Aventis Takeda* The Medicines Company Cardax* Duke Clinical Research Institute Data Safety Monitoring Board Harvard Clinical Research Institute: Boehringer Ingelheim Harvard Clinical Research Institute: St. Jude Data Safety Monitoring Board Harvard Clinical Research Institute (St. Jude) Data Safety Monitoring Board Merck & Co., Inc. Planning Committee for Clinical Study* Novartis None Gregg C. Fonarow Ahmanson-UCLA Cardiomyopathy Center Division of Cardiology Director of UCLA's Cardiology Fellowship Program Amgen Boston Scientific Janssen Johnson & Johnson Medtronic Novartis St. Jude Medical Takeda The Medicines Company ZS Pharma None None Medtronic Novartis None None Sana Gokak ACC/AHA None None None None None None (Continued) 42 Kathleen L. Grady Northwestern University Feinberg School of Medicine Professor of Surgery and Medicine; and Administrative Director for Heart Failure None None None None None None Lee A.


Author Listing of Relationships With Industry and Other Entities (Relevant) 2017 AHA/ACC Clinical Performance and Quality Measures for Adults With ST-Elevation and Non ST-Elevation Myocardial Infarction Committee Member Employment Consultant Speaker Ownership/ Partnership/ Principal Research Institutional, Organizational, or Other Financial Benefit Expert Witness Hani Jneid, Chair Baylor College of Medicine Associate Professor of Medicine; Director of Interventional Cardiology Research The Michael DeBakey VA Medical Center Director of Interventional Cardiology None None None None None None Daniel Addison Fellow at Massachusetts General Hospital None None None None None None Deepak L. Bhatt Executive Director of Interventional Cardiovascular Programs, Brigham and Women s Hospital Heart & Vascular Center; Harvard Medical School Professor of Medicine Duke Clinical Research Institute: Ferring Pharmaceuticals Duke Clinical Research Institute: Novartis Duke Clinical Research Institute: Bristol-Myers Squibb/Pfizer Duke Clinical Research Institute: Eli Lilly None None Amarin Amgen Inc. AstraZeneca BIOFLOW-V (Biotronik)-clinical trial Bristol Myers Squibb Eisai Ethicon EVOLVE Short DAPT Study (Boston Scientific) Flowco* Forest Laboratories Ischemix Medtronic Merck and Co, Inc* Pfizer PLxPharma* Roche Sanofi Aventis Takeda* The Medicines Company Cardax* Duke Clinical Research Institute Data Safety Monitoring Board Harvard Clinical Research Institute: Boehringer Ingelheim Harvard Clinical Research Institute: St. Jude Data Safety Monitoring Board Harvard Clinical Research Institute (St. Jude) Data Safety Monitoring Board Merck & Co., Inc. Planning Committee for Clinical Study* Novartis None Gregg C. Fonarow Ahmanson-UCLA Cardiomyopathy Center Division of Cardiology Director of UCLA's Cardiology Fellowship Program Amgen Boston Scientific Janssen Johnson & Johnson Medtronic Novartis St. Jude Medical Takeda The Medicines Company ZS Pharma None None Medtronic Novartis None None Sana Gokak ACC/AHA None None None None None None (Continued) 42 Kathleen L. Grady Northwestern University Feinberg School of Medicine Professor of Surgery and Medicine; and Administrative Director for Heart Failure None None None None None None Lee A. Green University of Michigan Professor Emeritus None None None None None None Paul A. Heidenreich Stanford VA Palo Alto Health Care System Professor of Medicine None None None None None None P. Michael Ho VA Eastern Colorado Health Care System University of Colorado School of Medicine Associate Professor of Medicine Anthem, Inc. Janssen Pharmaceuticals, Inc Premier, Inc. Telligen* None None None None None Corrine Y. Jurgens Stony Brook University Associate Professor None None None None None None Marjorie L. King Helen Hayes Hospital None None None None None None Dharam J. Kumbhani UT Southwestern Medical Center Assistant Professor of Medicine None None None None None None Samir Pancholy The Wright Center for Graduate Medical Education None Medtronic Pfizer Terumo Medical Duke Clinical Research Institute Odyssey Outcomes Trial None None This table represents the relationships of committee members with industry and other entities that were reported by authors to be relevant to this document.


Green University of Michigan Professor Emeritus None None None None None None Paul A. Heidenreich Stanford VA Palo Alto Health Care System Professor of Medicine None None None None None None P. Michael Ho VA Eastern Colorado Health Care System University of Colorado School of Medicine Associate Professor of Medicine Anthem, Inc. Janssen Pharmaceuticals, Inc Premier, Inc. Telligen* None None None None None Corrine Y. Jurgens Stony Brook University Associate Professor None None None None None None Marjorie L. King Helen Hayes Hospital None None None None None None Dharam J. Kumbhani UT Southwestern Medical Center Assistant Professor of Medicine None None None None None None Samir Pancholy The Wright Center for Graduate Medical Education None Medtronic Pfizer Terumo Medical Duke Clinical Research Institute Odyssey Outcomes Trial None None This table represents the relationships of committee members with industry and other entities that were reported by authors to be relevant to this document. These relationships were reviewed and updated in conjunction with all meetings and/or conference calls of the writing committee during the document development process. The table does not necessarily reflect relationships with industry at the time of publication. A person is deemed to have a significant interest in a business if the interest represents ownership of 5% or more of the voting stock or share of the business entity, or ownership of $5000 or more of the fair market value of the business entity; or if funds received by the person from the business entity exceed 5% of the person s gross income for the previous year. A relationship is considered to be modest if it is less than significant under the preceding definition.


A relationship is considered to be modest if it is less than significant under the preceding definition. Relationships in this table are modest unless otherwise noted.According to the ACC/AHA, a person has a relevant relationship IF: a) the relationship or interest relates to the same or similar subject matter, intellectual property or asset, topic, or issue addressed in the document; or b) the company/entity (with whom the relationship exists) makes a drug, drug class, or device addressed in the document, or makes a competing drug or device addressed in the document; or c) the person or a member of the person s household has a reasonable potential for financial, professional, or other personal gain or loss as a result of the issues/content addressed in the document. *No financial relationship. Significant (greater than $5000) relationship. ACC indicates American College of Cardiology; AHA, American Heart Association; BIOFLOW-V, A Prospective Randomized Multicenter Study to Assess the SaFety and Effectiveness of the Orsiro SiroLimus Eluting Coronary Stent System in the Treatment Of Subjects With up to Three De Novo or Restenotic Coronary Artery Lesions - V; EVOLVE DAPT, A Prospective, Multicenter, Single-arm Study Designed to Assess the Safety of 3-month Dual Antiplatelet Therapy in Subjects at High Risk for Bleeding Undergoing Percutaneous Coronary Intervention With the SYNERGY Everolimus-Eluting Platinum Chromium Coronary Stent System; and UT, University of Texas. Appendix B.


ACC indicates American College of Cardiology; AHA, American Heart Association; BIOFLOW-V, A Prospective Randomized Multicenter Study to Assess the SaFety and Effectiveness of the Orsiro SiroLimus Eluting Coronary Stent System in the Treatment Of Subjects With up to Three De Novo or Restenotic Coronary Artery Lesions - V; EVOLVE DAPT, A Prospective, Multicenter, Single-arm Study Designed to Assess the Safety of 3-month Dual Antiplatelet Therapy in Subjects at High Risk for Bleeding Undergoing Percutaneous Coronary Intervention With the SYNERGY Everolimus-Eluting Platinum Chromium Coronary Stent System; and UT, University of Texas. Appendix B. Continued Committee Member Employment Consultant Speaker Ownership/ Partnership/ Principal Research Institutional, Organizational, or Other Financial Benefit Expert Witness 43 Appendix C. Peer Reviewer Relationships With Industry and Other Entities 2017 AHA/ACC Clinical Performance and Quality Measures for Adults With ST-Elevation and Non ST-Elevation Myocardial Infarction Peer Reviewer Representation Consultant Speakers Bureau Ownership/ Partnership/ Principal Personal Research Institutional, Organizational, or Other Financial Benefit Expert Witness Randal Thomas Official TFPM Lead None None None None None None Timothy A. Dewhurst Official ACC BOG None None None Biotronik- Protoge Phase IV registry clinical trial enroller None None Fredrick A. Masoudi Official AHA None None None None None None Hitinder Gurm Official SCAI Osprey Medical None None None None None Michael Kontos Content: ACTION Steering Committee Astra Zeneca Medicure Roche Diagnostics None None None Astellas Novartis* None Matthew Roe Content: NCDR SQOC AstraZeneca Boehringer Ingelheim Pharmaceuticals, Inc Quest Diagnostics None None Daiichi-Sankyo Ely Lilly Janssen Pharmaceuticals Merck Sanofi-Aventis Bristol-Myers Squibb Company Eli Lilly and Company None Claire Duvernoy Content: AUCTF None None None None None None H. Vernon Anderson Content: ACC/ AHA TFDS None None None Capricor: ALLSTAR (Clinical Trial Enroller) DSMB: MedPace Medical Devices None Fredrick G. Kushner Content: ACC/ AHA TFPG None None None None None None Ezra Amsterdam Content: ACC/ AHA TFPG None None None None None None This table represents the relationships of reviewers with industry and other entities that were disclosed at the time of peer review and determined to be relevant.


Continued Committee Member Employment Consultant Speaker Ownership/ Partnership/ Principal Research Institutional, Organizational, or Other Financial Benefit Expert Witness 43 Appendix C. Peer Reviewer Relationships With Industry and Other Entities 2017 AHA/ACC Clinical Performance and Quality Measures for Adults With ST-Elevation and Non ST-Elevation Myocardial Infarction Peer Reviewer Representation Consultant Speakers Bureau Ownership/ Partnership/ Principal Personal Research Institutional, Organizational, or Other Financial Benefit Expert Witness Randal Thomas Official TFPM Lead None None None None None None Timothy A. Dewhurst Official ACC BOG None None None Biotronik- Protoge Phase IV registry clinical trial enroller None None Fredrick A. Masoudi Official AHA None None None None None None Hitinder Gurm Official SCAI Osprey Medical None None None None None Michael Kontos Content: ACTION Steering Committee Astra Zeneca Medicure Roche Diagnostics None None None Astellas Novartis* None Matthew Roe Content: NCDR SQOC AstraZeneca Boehringer Ingelheim Pharmaceuticals, Inc Quest Diagnostics None None Daiichi-Sankyo Ely Lilly Janssen Pharmaceuticals Merck Sanofi-Aventis Bristol-Myers Squibb Company Eli Lilly and Company None Claire Duvernoy Content: AUCTF None None None None None None H. Vernon Anderson Content: ACC/ AHA TFDS None None None Capricor: ALLSTAR (Clinical Trial Enroller) DSMB: MedPace Medical Devices None Fredrick G. Kushner Content: ACC/ AHA TFPG None None None None None None Ezra Amsterdam Content: ACC/ AHA TFPG None None None None None None This table represents the relationships of reviewers with industry and other entities that were disclosed at the time of peer review and determined to be relevant. It does not necessarily reflect relationships with industry at the time of publication.


It does not necessarily reflect relationships with industry at the time of publication. A person is deemed to have a significant interest in a business if the interest represents ownership of 5% of the voting stock or share of the business entity, or ownership of $5000 of the fair market value of the business entity; or if funds received by the person from the business entity exceed 5% of the person s gross income for the previous year. A relationship is considered to be modest if it is less than significant under the preceding definition. Relationships that exist with no financial benefit are also included for the purpose of transparency. Relationships in this table are modest unless otherwise noted. According to the ACC/AHA, a person has a relevant relationship IF: a) the relationship or interest relates to the same or similar subject matter, intellectual property or asset, topic, or issue addressed in the document; or b) the company/entity (with whom the relationship exists) makes a drug, drug class, or device addressed in the document, or makes a competing drug or device addressed in the document; or c) the person or a member of the person s household has a reasonable potential for financial, professional, or other personal gain or loss as a result of the issues/content addressed in the document. *No financial relationship. Significant (greater than $5000) relationship.


According to the ACC/AHA, a person has a relevant relationship IF: a) the relationship or interest relates to the same or similar subject matter, intellectual property or asset, topic, or issue addressed in the document; or b) the company/entity (with whom the relationship exists) makes a drug, drug class, or device addressed in the document, or makes a competing drug or device addressed in the document; or c) the person or a member of the person s household has a reasonable potential for financial, professional, or other personal gain or loss as a result of the issues/content addressed in the document. *No financial relationship. Significant (greater than $5000) relationship. ACC indicates American College of Cardiology; AHA, American Heart Association; ALLSTAR, The Allogeneic Heart Stem Cells to Achieve Myocardial Regeneration clinical trial; AUCTF, Appropriate Use Criteria Task Force; BOG, Board of Governors; DSMB, Data and Safety Monitoring Board; MER, Medical Education Resources; NCDR, National Cardiovascular Data Registry; NIH, National Institutes of Health; SCAI, Society for Cardiovascular Angiography and Interventions; SQOC, Science and Quality Oversight Committee; TFDS, Task Force on Data Standards; TFPG, Task Force on Practice Guidelines; TFPM, Task Force on Performance Measures; VA, US Department of Veterans Affairs; and VHAC, Virginia Heart Attack Coalition.


Chronic heart failure in adults: diagnosis and management NICE guideline NICE 2023. All rights reserved. Subject to Notice of rights (https://www.nice.org.uk/terms-and- conditions#notice-of-rights). Your responsibility The recommendations in this guideline represent the view of NICE, arrived at after careful consideration of the evidence available. When exercising their judgement, professionals and practitioners are expected to take this guideline fully into account, alongside the individual needs, preferences and values of their patients or the people using their service. It is not mandatory to apply the recommendations, and the guideline does not override the responsibility to make decisions appropriate to the circumstances of the individual, in consultation with them and their families and carers or guardian. All problems (adverse events) related to a medicine or medical device used for treatment or in a procedure should be reported to the Medicines and Healthcare products Regulatory Agency using the Yellow Card Scheme. Local commissioners and providers of healthcare have a responsibility to enable the guideline to be applied when individual professionals and people using services wish to use it. They should do so in the context of local and national priorities for funding and developing services, and in light of their duties to have due regard to the need to eliminate unlawful discrimination, to advance equality of opportunity and to reduce health inequalities. Nothing in this guideline should be interpreted in a way that would be inconsistent with complying with those duties. Commissioners and providers have a responsibility to promote an environmentally sustainable health and care system and should assess and reduce the environmental impact of implementing NICE recommendations wherever possible. 2 of Contents Overview 5 Who is it for?


Commissioners and providers have a responsibility to promote an environmentally sustainable health and care system and should assess and reduce the environmental impact of implementing NICE recommendations wherever possible. 2 of Contents Overview 5 Who is it for? 5 1.1 Team working in the management of heart failure 6 1.2 Diagnosing heart failure 9 1.3 Giving information to people with heart failure 12 1.4 Treating heart failure with reduced ejection fraction 12 1.5 Treating heart failure with reduced ejection fraction in people with chronic kidney disease . 18 1.6 Managing all types of heart failure 18 1.7 Monitoring treatment for all types of heart failure 21 1.9 Cardiac rehabilitation 23 1.10 Palliative care 24 Terms used in this guideline 24 Putting this guideline into practice 26 Key facts and figures 28 Current practice 28 Recommendations for research 29 1 Diuretic therapy for managing fluid overload in people with advanced heart failure in the community 29 2 Cardiac MRI versus other imaging techniques for diagnosing heart failure 29 3 The impact of atrial fibrillation on the natriuretic peptide threshold for diagnosing heart 4 The impact of advanced kidney disease on the natriuretic peptide threshold for diagnosing heart failure 31 5 Risk tools for predicting non-sudden death in heart failure 31 Finding more information and committee details 32 3 of Update information 33 4 of This guideline replaces CG108. This guideline is the basis of QS167, QS9 and QS181. Overview This guideline covers diagnosing and managing chronic heart failure in people aged 18 and over. It aims to improve diagnosis and treatment to increase the length and quality of life for people with heart failure. NICE has also produced a guideline on acute heart failure. Who is it for?


NICE has also produced a guideline on acute heart failure. Who is it for? Healthcare professionals People with heart failure and their families and carers 5 of Recommendations People have the right to be involved in discussions and make informed decisions about their care, as described in NICE's information on making decisions about your care. Making decisions using NICE guidelines explains how we use words to show the strength (or certainty) of our recommendations, and has information about prescribing medicines (including off-label use), professional guidelines, standards and laws (including on consent and mental capacity), and safeguarding. 1.1 Team working in the management of heart failure 1.1.1 The core specialist heart failure multidisciplinary team (MDT) should work in collaboration with the primary care team, and should include: a lead physician with subspecialty training in heart failure (usually a consultant cardiologist) who is responsible for making the clinical diagnosis a specialist heart failure nurse a healthcare professional with expertise in specialist prescribing for heart 1.1.2 The specialist heart failure MDT should: diagnose heart failure give information to people newly diagnosed with heart failure (see the section on giving information to people with heart failure) manage newly diagnosed, recently decompensated or advanced heart failure (NYHA [New York Heart Association] class III to IV) optimise treatment 6 of start new medicines that need specialist supervision continue to manage heart failure after an interventional procedure such as implantation of a cardioverter defibrillator or cardiac resynchronisation device manage heart failure that is not responding to treatment. [2018] 1.1.3 The specialist heart failure MDT should directly involve, or refer people to, other services, including rehabilitation, services for older people and palliative care services, as needed.


[2018] 1.1.3 The specialist heart failure MDT should directly involve, or refer people to, other services, including rehabilitation, services for older people and palliative care services, as needed. [2018] 1.1.4 The primary care team should carry out the following for people with heart failure at all times, including periods when the person is also receiving specialist heart failure care from the MDT: ensure effective communication links between different care settings and clinical services involved in the person's care lead a full review of the person's heart failure care, which may form part of a long-term conditions review recall the person at least every 6 months and update the clinical record ensure that changes to the clinical record are understood and agreed by the person with heart failure and shared with the specialist heart failure MDT arrange access to specialist heart failure services if needed. [2018] Care after an acute event For recommendations on the diagnosis and management of acute heart failure, see the NICE guideline on acute heart failure. 1.1.5 People with heart failure should generally be discharged from hospital only when their clinical condition is stable and the management plan is optimised. Timing of discharge should take into account the wishes of the person and their family or carer, and the level of care and support that can be provided in the community. [2003] 1.1.6 The primary care team should take over routine management of heart 7 of failure as soon as it has been stabilised and its management optimised.


[2003] 1.1.6 The primary care team should take over routine management of heart 7 of failure as soon as it has been stabilised and its management optimised. Writing a care plan 1.1.7 The specialist heart failure MDT should write a summary for each person with heart failure that includes: diagnosis and aetiology medicines prescribed, monitoring of medicines, when medicines should be reviewed and any support the person needs to take the medicines functional abilities and any social care needs social circumstances, including carers' needs. [2018] 1.1.8 The summary should form the basis of a care plan for each person, which should include: plans for managing the person's heart failure, including follow-up care, rehabilitation and access to social care symptoms to look out for in case of deterioration a process for any subsequent access to the specialist heart failure MDT if needed contact details for a named healthcare coordinator (usually a specialist heart failure nurse) alternative local heart failure specialist care providers, for urgent care or review. additional sources of information for people with heart failure. [2018] 1.1.9 Give a copy of the care plan to the person with heart failure, their family or carer if appropriate, and all health and social care professionals involved in their care. [2018] 8 of 1.2 Diagnosing heart failure Symptoms, signs and investigations 1.2.1 Take a careful and detailed history, and perform a clinical examination and tests to confirm the presence of heart failure. [2010] 1.2.2 Measure N-terminal pro-B-type natriuretic peptide (NT-proBNP) in people with suspected heart failure. [2018] 1.2.3 Because very high levels of NT-proBNP carry a poor prognosis, refer people with suspected heart failure and an NT-proBNP level above 2,000 ng/litre (236 pmol/litre) urgently, to have specialist assessment and transthoracic echocardiography within 2 weeks.


[2018] 1.2.3 Because very high levels of NT-proBNP carry a poor prognosis, refer people with suspected heart failure and an NT-proBNP level above 2,000 ng/litre (236 pmol/litre) urgently, to have specialist assessment and transthoracic echocardiography within 2 weeks. [2018] 1.2.4 Refer people with suspected heart failure and an NT-proBNP level between 400 and 2,000 ng/litre (47 to 236 pmol/litre) to have specialist assessment and transthoracic echocardiography within 6 weeks. [2018] 1.2.5 Be aware that: an NT-proBNP level less than 400 ng/litre (47 pmol/litre) in an untreated person makes a diagnosis of heart failure less likely the level of serum natriuretic peptide does not differentiate between heart failure with reduced ejection fraction and heart failure with preserved ejection 1.2.6 Review alternative causes for symptoms of heart failure in people with NT-proBNP levels below 400 ng/litre. If there is still concern that the symptoms might be related to heart failure, discuss with a physician with subspeciality training in heart failure. [2018] 1.2.7 Be aware that: 9 of obesity, African or African Caribbean family background, or treatment with diuretics, angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, angiotensin II receptor blockers (ARBs) or mineralocorticoid receptor antagonists (MRAs) can reduce levels of serum natriuretic peptides high levels of serum natriuretic peptides can have causes other than heart failure (for example, age over 70 years, left ventricular hypertrophy, ischaemia, tachycardia, right ventricular overload, hypoxaemia [including pulmonary embolism], renal dysfunction [eGFR less than 60 ml/minute/1.73 m2 ], sepsis, chronic obstructive pulmonary disease, diabetes, or cirrhosis of the liver). 1.2.8 Perform transthoracic echocardiography to exclude important valve disease, assess the systolic (and diastolic) function of the (left) ventricle, and detect intracardiac shunts. See the section on referral for echocardiography and specialist assessment in the NICE guideline on heart valve disease.


See the section on referral for echocardiography and specialist assessment in the NICE guideline on heart valve disease. [2003, amended 2018] 1.2.9 Transthoracic echocardiography should be performed on high-resolution equipment by experienced operators trained to the relevant professional standards. Need and demand for these studies should not compromise 1.2.10 Ensure that those reporting echocardiography are experienced in doing 1.2.11 Consider alternative methods of imaging the heart (for example, radionuclide angiography [multigated acquisition scanning], cardiac MRI or transoesophageal echocardiography) if a poor image is produced by transthoracic echocardiography. [2003, amended 2018] 1.2.12 Perform an ECG and consider the following tests to evaluate possible aggravating factors and/or alternative diagnoses: chest X-ray 10 of blood tests: renal function profile thyroid function profile liver function profile lipid profile glycosylated haemoglobin (HbA1c) full blood count urinalysis peak flow or spirometry. [2010, amended 2018] 1.2.13 Try to exclude other disorders that may present in a similar manner. 1.2.14 When a diagnosis of heart failure has been made, assess severity, aetiology, precipitating factors, type of cardiac dysfunction and correctable causes. [2010] Heart failure caused by valve disease 1.2.15 Refer people with heart failure caused by valve disease for specialist assessment and advice regarding follow-up. See the section on referral for echocardiography and specialist assessment in the NICE guideline on heart valve disease. [2003] Reviewing existing diagnoses 1.2.16 Review the basis for a historical diagnosis of heart failure, and manage care in accordance with this guideline only if the diagnosis is confirmed. 1.2.17 If the diagnosis of heart failure is still suspected, but confirmation of the underlying cardiac abnormality has not occurred, then the person should have appropriate further investigation.


1.2.17 If the diagnosis of heart failure is still suspected, but confirmation of the underlying cardiac abnormality has not occurred, then the person should have appropriate further investigation. [2003] 11 of 1.3 Giving information to people with heart failure 1.3.1 When giving information to people with heart failure, follow the recommendations in the NICE guideline on patient experience in adult NHS services. [2018] 1.3.2 Discuss the person's prognosis in a sensitive, open and honest manner. Be frank about the uncertainty in predicting the course of their heart failure. Revisit this discussion as the person's condition evolves. [2018] 1.3.3 Provide information whenever needed throughout the person's care. 1.3.4 Consider training in advanced communication skills for all healthcare professionals working with people who have heart failure. [2018] First consultations for people newly diagnosed with heart failure 1.3.5 The specialist heart failure MDT should offer people newly diagnosed with heart failure an extended first consultation, followed by a second consultation to take place within 2 weeks if possible. At each consultation: discuss the person's diagnosis and prognosis explain heart failure terminology discuss treatments address the risk of sudden death, including any misconceptions about that risk encourage the person and their family or carers to ask any questions they 1.4 Treating heart failure with reduced ejection fraction See the section on managing all types of heart failure for general recommendations on 12 of managing all types of heart failure. See NICE's technology appraisal guidance on dapagliflozin and empagliflozin for treating chronic heart failure with reduced ejection fraction. When managing pharmacological treatment, follow the recommendations in the NICE guidelines on medicines adherence and medicines optimisation. First-line treatment 1.4.1 Offer an angiotensin-converting enzyme (ACE) inhibitor and a beta-blocker licensed for heart failure to people who have heart failure with reduced ejection fraction.


First-line treatment 1.4.1 Offer an angiotensin-converting enzyme (ACE) inhibitor and a beta-blocker licensed for heart failure to people who have heart failure with reduced ejection fraction. Use clinical judgement when deciding which drug to start first. [2010] ACE inhibitors 1.4.2 Do not offer ACE inhibitor therapy if there is a clinical suspicion of haemodynamically significant valve disease until the valve disease has been assessed by a specialist. See the section on referral for echocardiography and specialist assessment in the NICE guideline on heart valve disease. [2003] 1.4.3 Start ACE inhibitor therapy at a low dose and titrate upwards at short intervals (for example, every 2 weeks) until the target or maximum tolerated dose is reached. [2010] 1.4.4 Measure serum sodium and potassium, and assess renal function, before and 1 to 2 weeks after starting an ACE inhibitor, and after each dose 1.4.5 Measure blood pressure before and after each dose increment of an ACE inhibitor. Follow the recommendations on measuring blood pressure, including measurement in people with symptoms of postural hypotension, in the NICE guideline on hypertension in adults. [2018] 1.4.6 Once the target or maximum tolerated dose of an ACE inhibitor is reached, monitor treatment monthly for 3 months and then at least every 13 of 6 months, and at any time the person becomes acutely unwell. [2010, Alternative treatments if ACE inhibitors are not tolerated 1.4.7 Consider an ARB licensed for heart failure as an alternative to an ACE inhibitor for people who have heart failure with reduced ejection fraction and intolerable side effects with ACE inhibitors. [2010] 1.4.8 Measure serum sodium and potassium, and assess renal function, before and after starting an ARB and after each dose increment. [2010, 1.4.9 Measure blood pressure after each dose increment of an ARB.


[2010, 1.4.9 Measure blood pressure after each dose increment of an ARB. Follow the recommendations on measuring blood pressure, including measurement in people with symptoms of postural hypotension, in the NICE guideline on hypertension in adults. [2018] 1.4.10 Once the target or maximum tolerated dose of an ARB is reached, monitor treatment monthly for 3 months and then at least every 6 months, and at any time the person becomes acutely unwell. [2010, 1.4.11 If neither ACE inhibitors nor ARBs are tolerated, seek specialist advice and consider hydralazine in combination with nitrate for people who have heart failure with reduced ejection fraction. [2010] Beta-blockers 1.4.12 Do not withhold treatment with a beta-blocker solely because of age or the presence of peripheral vascular disease, erectile dysfunction, diabetes, interstitial pulmonary disease or chronic obstructive pulmonary 1.4.13 Introduce beta-blockers in a 'start low, go slow' manner. Assess heart rate and clinical status after each titration. Measure blood pressure before and after each dose increment of a beta-blocker. [2010,amended 14 of 1.4.14 Switch people whose condition is stable and who are already taking a beta-blocker for a comorbidity (for example, angina or hypertension), and who develop heart failure with reduced ejection fraction, to a beta- blocker licensed for heart failure. [2010] Mineralocorticoid receptor antagonists 1.4.15 Offer an mineralocorticoid receptor antagonists (MRA), in addition to an ACE inhibitor (or ARB) and beta-blocker, to people who have heart failure with reduced ejection fraction if they continue to have symptoms of heart failure. [2018] 1.4.16 Measure serum sodium and potassium, and assess renal function, before and after starting an MRA and after each dose increment. [2018] 1.4.17 Measure blood pressure before and after after each dose increment of an MRA.


[2018] 1.4.17 Measure blood pressure before and after after each dose increment of an MRA. Follow the recommendations on measuring blood pressure, including measurement in people with symptoms of postural hypotension, in the NICE guideline on hypertension in adults. [2018] 1.4.18 Once the target, or maximum tolerated, dose of an MRA is reached, monitor treatment monthly for 3 months and then at least every 6 months, and at any time the person becomes acutely unwell. [2018] Specialist treatment Ivabradine These recommendations are from the NICE technology appraisal guidance on ivabradine for treating chronic heart failure. 1.4.19 Ivabradine is recommended as an option for treating chronic heart failure for people: with New York Heart Association (NYHA) class II to IV stable chronic heart failure with systolic dysfunction and 15 of who are in sinus rhythm with a heart rate of 75 beats per minute (bpm) or more and who are given ivabradine in combination with standard therapy including beta- blocker therapy, angiotensin-converting enzyme (ACE) inhibitors and aldosterone antagonists, or when beta-blocker therapy is contraindicated or not tolerated and with a left ventricular ejection fraction of 35% or less. [2012] 1.4.20 Ivabradine should only be initiated after a stabilisation period of 4 weeks on optimised standard therapy with ACE inhibitors, beta-blockers and aldosterone antagonists. [2012] 1.4.21 Ivabradine should be initiated by a heart failure specialist with access to a multidisciplinary heart failure team. Dose titration and monitoring should be carried out by a heart failure specialist, or in primary care by either a GP with a special interest in heart failure or a heart failure specialist nurse. [2012] Sacubitril valsartan These recommendations are from the NICE technology appraisal guidance on sacubitril valsartan for treating symptomatic chronic heart failure with reduced ejection fraction.


[2012] Sacubitril valsartan These recommendations are from the NICE technology appraisal guidance on sacubitril valsartan for treating symptomatic chronic heart failure with reduced ejection fraction. 1.4.22 Sacubitril valsartan is recommended as an option for treating symptomatic chronic heart failure with reduced ejection fraction, only in people: with New York Heart Association (NYHA) class II to IV symptoms and with a left ventricular ejection fraction of 35% or less and who are already taking a stable dose of angiotensin-converting enzyme (ACE) inhibitors or ARBs. [2016] 1.4.23 Treatment with sacubitril valsartan should be started by a heart failure specialist with access to a multidisciplinary heart failure team. Dose titration and monitoring should be performed by the most appropriate team member (see the section on team working in the management of 16 of heart failure). [2016] 1.4.24 This guidance is not intended to affect the position of patients whose treatment with sacubitril valsartan was started within the NHS before this guidance was published. Treatment of those patients may continue without change to whatever funding arrangements were in place for them before this guidance was published until they and their NHS clinician consider it appropriate to stop. [2016] Hydralazine in combination with nitrate 1.4.25 Seek specialist advice and consider offering hydralazine in combination with nitrate (especially if the person is of African or Caribbean family origin and has moderate to severe heart failure [NYHA class III/IV] with reduced ejection fraction). [2010] Digoxin For recommendations on digoxin for people with atrial fibrillation see the section on rate and rhythm control in the NICE guideline on atrial fibrillation. 1.4.26 Digoxin is recommended for worsening or severe heart failure with reduced ejection fraction despite first-line treatment for heart failure. Seek specialist advice before initiating. [2010, amended 2018] 1.4.27 Routine monitoring of serum digoxin concentrations is not recommended.


[2010, amended 2018] 1.4.27 Routine monitoring of serum digoxin concentrations is not recommended. A digoxin concentration measured within 8 to 12 hours of the last dose may be useful to confirm a clinical impression of toxicity or 1.4.28 The serum digoxin concentration should be interpreted in the clinical context as toxicity may occur even when the concentration is within the 'therapeutic range'. [2003] 17 of 1.5 Treating heart failure with reduced ejection fraction in people with chronic kidney disease 1.5.1 For people who have heart failure with reduced ejection fraction and chronic kidney disease with an eGFR of 30 ml/min/1.73 m2 or above: offer the treatment outlined in the section on treating heart failure with reduced ejection fraction and if the person's eGFR is 45 ml/min/1.73 m2 or below, consider lower doses and/ or slower titration of dose of ACE inhibitors or ARBs, MRAs and digoxin. [2018] 1.5.2 For people who have heart failure with reduced ejection fraction and chronic kidney disease with an eGFR below 30 ml/min/1.73 m2 , the specialist heart failure MDT should consider liaising with a renal 1.5.3 Monitor the response to titration of medicines closely in people who have heart failure with reduced ejection fraction and chronic kidney disease, taking into account the increased risk of hyperkalaemia. [2018] 1.6 Managing all types of heart failure When managing pharmacological treatment, follow the recommendations in the NICE guidelines on medicines adherence and medicines optimisation.


[2018] 1.6 Managing all types of heart failure When managing pharmacological treatment, follow the recommendations in the NICE guidelines on medicines adherence and medicines optimisation. Pharmacological treatment Diuretics 1.6.1 Diuretics should be routinely used for the relief of congestive symptoms and fluid retention in people with heart failure, and titrated (up and down) according to need following the initiation of subsequent heart failure 1.6.2 People who have heart failure with preserved ejection fraction should usually be offered a low to medium dose of loop diuretics (for example, 18 of less than 80 mg furosemide per day). People whose heart failure does not respond to this treatment will need further specialist advice. [2003, Calcium-channel blockers 1.6.3 Avoid verapamil, diltiazem and short-acting dihydropyridine agents in people who have heart failure with reduced ejection fraction. [2003, Amiodarone 1.6.4 Make the decision to prescribe amiodarone in consultation with a 1.6.5 Review the need to continue the amiodarone prescription at the 1.6.6 Offer people taking amiodarone liver and thyroid function tests, and a review of side effects, as part of their routine 6-monthly clinical review. Anticoagulants 1.6.7 For people who have heart failure and atrial fibrillation, follow the recommendations on anticoagulation in the NICE guideline on atrial fibrillation. Be aware of the effects of impaired renal and liver function on anticoagulant therapies. [2018] 1.6.8 In people with heart failure in sinus rhythm, anticoagulation should be considered for those with a history of thromboembolism, left ventricular aneurysm or intracardiac thrombus. [2003] Vaccinations 1.6.9 Offer people with heart failure an annual vaccination against influenza. 19 of 1.6.10 Offer people with heart failure vaccination against pneumococcal disease (only required once). [2003] Contraception and pregnancy 1.6.11 In women of childbearing potential who have heart failure, contraception and pregnancy should be discussed.


[2003] Contraception and pregnancy 1.6.11 In women of childbearing potential who have heart failure, contraception and pregnancy should be discussed. If pregnancy is being considered or occurs, specialist advice should be sought. Subsequently, specialist care should be shared between the cardiologist and obstetrician. [2003] Depression See NICE's guideline on depression in adults with a chronic physical health problem. Lifestyle advice Salt and fluid restriction 1.6.12 Do not routinely advise people with heart failure to restrict their sodium or fluid consumption. Ask about salt and fluid consumption and, if needed, advise as follows: restricting fluids for people with dilutional hyponatraemia reducing intake for people with high levels of salt and/or fluid consumption. Continue to review the need to restrict salt or fluid. [2018] 1.6.13 Advise people with heart failure to avoid salt substitutes that contain Smoking and alcohol See NICE's guidance on smoking and tobacco and alcohol. Air travel 1.6.14 Air travel will be possible for the majority of people with heart failure, 20 of depending on their clinical condition at the time of travel. [2003] Driving 1.6.15 Large Goods Vehicle and Passenger Carrying Vehicle licence: physicians should be up to date with the latest Driver and Vehicle Licensing Agency (DVLA) guidelines. Check the DVLA website for regular updates. [2003] 1.7 Monitoring treatment for all types of heart failure See the section on treating heart failure with reduced ejection fraction for specific recommendations on monitoring treatment for heart failure with reduced ejection fraction. Clinical review 1.7.1 All people with chronic heart failure need monitoring. This monitoring should include: a clinical assessment of functional capacity, fluid status, cardiac rhythm (minimum of examining the pulse), cognitive status and nutritional status a review of medication, including need for changes and possible side effects an assessment of renal function. Note: This is a minimum.


This monitoring should include: a clinical assessment of functional capacity, fluid status, cardiac rhythm (minimum of examining the pulse), cognitive status and nutritional status a review of medication, including need for changes and possible side effects an assessment of renal function. Note: This is a minimum. People with comorbidities or co-prescribed medications will need further monitoring. Monitoring serum potassium is particularly important if a person is taking digoxin or an MRA. [2010, amended 1.7.2 More detailed monitoring will be needed if the person has significant comorbidity or if their condition has deteriorated since the previous 1.7.3 The frequency of monitoring should depend on the clinical status and stability of the person. The monitoring interval should be short (days to 2 weeks) if the clinical condition or medication has changed, but is 21 of needed at least 6-monthly for stable people with proven heart failure. 1.7.4 People with heart failure who wish to be involved in monitoring of their condition should be provided with sufficient education and support from their healthcare professional to do this, with clear guidelines as to what to do in the event of deterioration. [2003] Measuring NT-proBNP 1.7.5 Consider measuring NT-proBNP (N-terminal pro-B-type natriuretic peptide) as part of a treatment optimisation protocol only in a specialist care setting for people aged under 75 who have heart failure with reduced ejection fraction and an eGFR above 60 ml/min/1.73 m2 1.8 Interventional procedures Coronary revascularisation 1.8.1 Do not routinely offer coronary revascularisation to people who have heart failure with reduced ejection fraction and coronary artery disease. Cardiac transplantation 1.8.2 Specialist referral for transplantation should be considered for people with severe refractory symptoms or refractory cardiogenic shock.


Cardiac transplantation 1.8.2 Specialist referral for transplantation should be considered for people with severe refractory symptoms or refractory cardiogenic shock. [2003] Implantable cardioverter defibrillators and cardiac resynchronisation therapy See NICE's technology appraisal guidance on implantable cardioverter defibrillators and cardiac resynchronisation therapy for arrhythmias and heart failure. 1.8.3 When discussing implantation of a cardioverter defibrillator: 22 of explain the risks, benefits and consequences of cardioverter defibrillator implantation, following the principles on shared decision making in the NICE guideline on patient experience in adult NHS services ensure the person knows that the defibrillator function can be deactivated without affecting any cardiac resynchronisation or pacing, and reactivated later explain the circumstances in which deactivation might be offered discuss and dispel common misconceptions about the function of the device and the consequences of deactivation provide the person and, if they wish, their family or carers with written information covering the information discussed. [2018] 1.8.4 Review the benefits and potential harms of a cardioverter defibrillator remaining active in a person with heart failure: at each 6-monthly review of their heart failure care whenever their care goals change as part of advance care planning if it is thought they are nearing the end of life. 1.9 Cardiac rehabilitation 1.9.1 Offer people with heart failure a personalised, exercise-based cardiac rehabilitation programme, unless their condition is unstable. The programme: should be preceded by an assessment to ensure that it is suitable for the person should be provided in a format and setting (at home, in the community or in the hospital) that is easily accessible for the person should include a psychological and educational component may be incorporated within an existing cardiac rehabilitation programme 23 of should be accompanied by information about support available from healthcare professionals when the person is doing the programme.


The programme: should be preceded by an assessment to ensure that it is suitable for the person should be provided in a format and setting (at home, in the community or in the hospital) that is easily accessible for the person should include a psychological and educational component may be incorporated within an existing cardiac rehabilitation programme 23 of should be accompanied by information about support available from healthcare professionals when the person is doing the programme. [2018] 1.10 Palliative care 1.10.1 Do not offer long-term home oxygen therapy for advanced heart failure. Be aware that long-term home oxygen therapy may be offered for comorbidities, such as for some people with chronic obstructive pulmonary disease (see the section on oxygen in the NICE guideline on chronic obstructive pulmonary disease in over 16s). [2018] 1.10.2 Do not use prognostic risk tools to determine whether to refer a person with heart failure to palliative care services. [2018] 1.10.3 If the symptoms of a person with heart failure are worsening despite optimal specialist treatment, discuss their palliative care needs with the specialist heart failure multidisciplinary team and consider a needs assessment for palliative care. [2018] 1.10.4 People with heart failure and their families or carers should have access to professionals with palliative care skills within the heart failure team. 1.10.5 If it is thought that a person may be entering the last 2 to 3 days of life, follow the NICE guideline on care of dying adults in the last days of life. Terms used in this guideline Heart failure with preserved ejection fraction This is usually associated with impaired left ventricular relaxation, rather than left ventricular contraction, and is characterised by normal or preserved left ventricular ejection fraction with evidence of diastolic dysfunction .


Terms used in this guideline Heart failure with preserved ejection fraction This is usually associated with impaired left ventricular relaxation, rather than left ventricular contraction, and is characterised by normal or preserved left ventricular ejection fraction with evidence of diastolic dysfunction . 24 of Heart failure with reduced ejection fraction Heart failure with an ejection fraction below 40%. Mineralocorticoid receptor antagonist A drug that antagonises the action of aldosterone at mineralocorticoid receptors. 25 of Putting this guideline into practice NICE has produced tools and resources to help you put this guideline into practice. Putting recommendations into practice can take time. How long may vary from guideline to guideline, and depends on how much change in practice or services is needed. Implementing change is most effective when aligned with local priorities. Changes recommended for clinical practice that can be done quickly like changes in prescribing practice should be shared quickly. This is because healthcare professionals should use guidelines to guide their work as is required by professional regulating bodies such as the General Medical and Nursing and Midwifery Councils. Changes should be implemented as soon as possible, unless there is a good reason for not doing so (for example, if it would be better value for money if a package of recommendations were all implemented at once). Different organisations may need different approaches to implementation, depending on their size and function. Sometimes individual practitioners may be able to respond to recommendations to improve their practice more quickly than large organisations. Here are some pointers to help organisations put NICE guidelines into practice: 1. Raise awareness through routine communication channels, such as email or newsletters, regular meetings, internal staff briefings and other communications with all relevant partner organisations. Identify things staff can include in their own practice straight away. 2.


Identify things staff can include in their own practice straight away. 2. Identify a lead with an interest in the topic to champion the guideline and motivate others to support its use and make service changes, and to find out any significant issues locally. 3. Carry out a baseline assessment against the recommendations to find out whether there are gaps in current service provision. 4. Think about what data you need to measure improvement and plan how you will collect it. You may want to work with other health and social care organisations and specialist 26 of groups to compare current practice with the recommendations. This may also help identify local issues that will slow or prevent implementation. 5. Develop an action plan, with the steps needed to put the guideline into practice, and make sure it is ready as soon as possible. Big, complex changes may take longer to implement, but some may be quick and easy to do. An action plan will help in both cases. 6. For very big changes include milestones and a business case, which will set out additional costs, savings and possible areas for disinvestment. A small project group could develop the action plan. The group might include the guideline champion, a senior organisational sponsor, staff involved in the associated services, finance and information professionals. 7. Implement the action plan with oversight from the lead and the project group. Big projects may also need project management support. 8. Review and monitor how well the guideline is being implemented through the project group. Share progress with those involved in making improvements, as well as relevant boards and local partners. NICE provides a comprehensive programme of support and resources to maximise uptake and use of evidence and guidance. See NICE's into practice pages for more information.


NICE provides a comprehensive programme of support and resources to maximise uptake and use of evidence and guidance. See NICE's into practice pages for more information. Also see Leng G, Moore V, Abraham S, editors (2014) Achieving high quality care practical experience from NICE. Chichester: Wiley. 27 of Context Key facts and figures Heart failure is a complex clinical syndrome of symptoms and signs that suggest the efficiency of the heart as a pump is impaired. It is caused by structural or functional abnormalities of the heart. Around 920,000 people in the UK today have been diagnosed with heart failure. Both the incidence and prevalence of heart failure increase steeply with age, and the average age at diagnosis is 77. Improvements in care have increased survival for people with ischaemic heart disease, and treatments for heart failure have become more effective. But the overall prevalence of heart failure is rising because of population ageing and increasing rates of obesity. Current practice Uptake of NICE's 2010 guidance on chronic heart failure appears to be good. However, the Department of Health and Social Care's policy paper on improving cardiovascular disease outcomes: strategy noted that prescribing of ACE inhibitors, beta-blockers and aldosterone antagonists remains suboptimal, and that improved use of these drugs has the potential to reduce hospitalisations and deaths caused by heart failure. This update reviewed evidence on the clinical and cost effectiveness of these therapies. Interdisciplinary working has contributed to better outcomes in heart failure but there is further room to improve the provision of multidisciplinary teams (MDTs) and integrate them more fully into healthcare processes. This update highlights and further expands on the roles of the MDT and collaboration between the MDT and the primary care team.


This update highlights and further expands on the roles of the MDT and collaboration between the MDT and the primary care team. The Department of Health and Social Care's policy paper on improving cardiovascular disease outcomes: strategy also noted that the proportion of people with heart failure who have cardiac rehabilitation was around 4%, and that increasing this proportion would reduce mortality and hospitalisation. This update recommends that all people with heart failure are offered an easily accessible, exercise-based cardiac rehabilitation programme, if this is suitable for them. 28 of Recommendations for research The guideline committee has made the following key recommendations for research. The committee's full set of research recommendations is detailed in the full guideline. 1 Diuretic therapy for managing fluid overload in people with advanced heart failure in the community In people with advanced heart failure and significant peripheral fluid overload, what is the clinical and cost effectiveness of oral, subcutaneous and intravenous diuretic therapy in the community? Why this is important This research is critical to inform practice of how best to manage people with advanced heart failure in the community if they develop significant peripheral fluid overload. These people are more likely to have multiple admissions that, together with fluid overload, have a negative impact on their quality of life. Management in the community can minimise disruption for the person and reduce costs from hospital admissions. Knowledge of the most clinically and cost-effective routes of administration for diuretic therapy will dictate the level of resource needed to provide the service. Intravenous and subcutaneous diuretics usually need to be administered by nursing or healthcare staff. although a pump for self-administration of subcutaneous diuretics has recently been developed. Oral formulations can be self-administered.


although a pump for self-administration of subcutaneous diuretics has recently been developed. Oral formulations can be self-administered. 2 Cardiac MRI versus other imaging techniques for diagnosing heart failure What is the optimal imaging technique for the diagnosis of heart failure? Why this is important The role of cardiac MRI in the detection and characterisation of several structural and 29 of functional cardiac abnormalities has become well established over the past 25 years. In people with heart failure, cardiac MRI provides reliable and reproducible assessments of the left ventricular (and to a degree the right ventricular) shapes, volumes and ejection fractions. It also provides spatial assessments of the congenital and acquired structural abnormalities of the heart and their interrelationships with the remainder of the heart, as well as functional and haemodynamic assessments of these abnormalities on the heart's performance. Finally, cardiac MRI provides valuable information about the myocardial structure and metabolism, including the presence of inflammation, scarring, fibrosis and infiltration. Cardiac MRI is an expensive form of imaging, and much of this diagnostic information could be provided by less costly non-invasive imaging techniques, chiefly echocardiography. This question aims to find the most clinically and cost-effective imaging technique for the clinical diagnosis of heart failure. 3 The impact of atrial fibrillation on the natriuretic peptide threshold for diagnosing heart failure What is the optimal NT-proBNP threshold for the diagnosis of heart failure in people with atrial fibrillation? Why this is important Atrial fibrillation is a common arrhythmia in the general population, and occurs in 30 to 40% of people with heart failure. Atrial fibrillation can raise the level of serum natriuretic peptides, including NT-proBNP, even in the absence of heart failure.


Atrial fibrillation can raise the level of serum natriuretic peptides, including NT-proBNP, even in the absence of heart failure. This is complicated further in heart failure with preserved ejection fraction, in which 2 echocardiographic diagnostic criteria become unreliable (the left atrial volume and the tissue doppler imaging assessment of diastolic function). These factors contribute to the complexity of the diagnosis and have a potential impact on the usual thresholds for NT-proBNP in people who have atrial fibrillation. This has been recognised in several ongoing randomised controlled trials of heart failure, which are using higher NT-proBNP thresholds for the diagnosis of heart failure in people with atrial fibrillation. 30 of 4 The impact of advanced kidney disease on the natriuretic peptide threshold for diagnosing heart failure What are the optimal NT-proBNP thresholds for diagnosing heart failure in people with stage IIIb, IV or V chronic kidney disease? Why this is important Heart failure incidence and prevalence increase with age, with the rise starting at age 65 and peaking between 75 and 85. Both advancing age and heart failure are associated with a gradual and progressive decline in renal function. In addition, the progression of heart failure and some treatments for heart failure lead to progressive deterioration of renal function. A decline in renal function is associated with increased fluid retention and a rise in the level of the serum natriuretic peptides, including NT-proBNP, even in the absence of heart failure. There is some evidence that the use of higher NT-proBNP thresholds would improve diagnostic accuracy for heart failure in people with significant deterioration of creatinine clearance.


There is some evidence that the use of higher NT-proBNP thresholds would improve diagnostic accuracy for heart failure in people with significant deterioration of creatinine clearance. 5 Risk tools for predicting non-sudden death in heart failure What is the most accurate prognostic risk tool in predicting 1-year mortality from heart failure at specific clinically relevant thresholds (for example, sensitivity, specificity, negative predictive value and positive predictive value at a threshold of 50% risk of mortality at 1 year)? Why this is important There are a number of validated prognostic risk tools for heart failure but most do not report sensitivity and specificity at clinically relevant thresholds. This information is crucial to enable accurate prediction of a person's risk of mortality. The ability to accurately predict a person's prognosis would allow clearer communication and timely referral to other services such as palliative care. Inaccurate prediction has the potential to lead to significant psychological harm and increased morbidity. 31 of Finding more information and committee details You can see everything NICE says on this topic in the NICE Pathway on chronic heart failure. To find out what NICE has said on related topics, including guidance in development, see the NICE webpage on cardiovascular conditions. For full details of the evidence and the guideline committee's discussions, see the full guideline. You can also find information about how the guideline was developed, including details of the committee. NICE has produced tools and resources to help you put this guideline into practice. For general help and advice on putting our guidelines into practice, see resources to help you put NICE guidance into practice. 32 of Update information September 2018: This guideline updates and replaces NICE clinical guideline 108 (published August 2010). NICE clinical guideline 108 updated and replaced NICE clinical guideline 5 (published July 2003).


NICE clinical guideline 108 updated and replaced NICE clinical guideline 5 (published July 2003). [2018] indicates that the evidence was reviewed and the recommendation added, updated or unchanged in 2018. [2016] refers to NICE technology appraisal guidance published in 2016. [2012] refers to NICE technology appraisal guidance published in 2012. [2010] indicates that the evidence was reviewed in 2010. [2010, amended 2018] indicates that the evidence was reviewed in 2010 but changes were made to the recommendation wording in 2018 that changed the meaning. [2003] indicates that the evidence was reviewed in 2003. [2003, amended 2018] indicates that the evidence was reviewed in 2003 but changes were made to the recommendation wording in 2018 that changed the meaning. [2003, amended 2010] indicates that the evidence was reviewed in 2003 but changes were made to the recommendation wording in 2010 that changed the meaning. 'Heart failure due to left ventricular systolic dysfunction (LVSD)' has been replaced in all recommendations by 'heart failure with reduced ejection fraction' in line with current terminology and the 2018 guideline scope. 'Aldosterone antagonists' has been replaced in all recommendations by 'mineralocorticoid receptor antagonists (MRAs') to clarify the function of the receptor, and in line with the 2018 guideline scope. 33 of 'African or African-Caribbean family origin' has been added to recommendation 1.2.7 because of the high incidence of heart failure with preserved ejection fraction in these populations. Recent evidence shows that NT-proBNP levels are lower in people of west African family background and are a confounder in the diagnosis of heart failure. Doppler 2D has been deleted from recommendations 1.2.8, 1.2.9 and 1.2.11 because all transthoracic echocardiography would have doppler 2D as a minimum and it is no longer necessary to specify this.


Doppler 2D has been deleted from recommendations 1.2.8, 1.2.9 and 1.2.11 because all transthoracic echocardiography would have doppler 2D as a minimum and it is no longer necessary to specify this. 'Multigated acquisition scanning' has been added to recommendation 1.2.11 to reflect current imaging technology. Measurement of urea has been deleted from recommendations 1.2.12, 1.4.8 and 1.7.1 because the guideline committee agreed that it is not needed and is not part of renal function profiles in most centres in the UK. Blood tests for electrolytes, creatinine and eGFR have been grouped together under the term 'renal function profile' because they are provided as a unified set of analyses in the NHS. The term 'profile' is applied to a group of tests (assays). Thus these tests are more accurately described as 'profiles' as they contain multiple individual assays and have replaced thyroid function test, liver function test and lipid measurement. 'Fasting glucose' has been replaced by 'glycosylated haemoglobin (HbA1c)' in line with the NICE guidelines on diabetes. Measurement of serum urea has been deleted from recommendation 1.4.4 because the guideline committee agreed that it is not needed and is not part of renal function profiles in most centres in the UK. Measurement of potassium has been added to ensure that monitoring is consistent across treatments. Recommendations 1.4.6 and 1.4.10 have been added to clarify the timing of monitoring after treatment starts. In recommendation 1.4.8, monitoring for hyperkalaemia has been replaced by potassium measurement for clarity. Blood pressure measurement has been clarified in recommendation 1.4.13 and made consistent with other treatments. 34 of As a result of new evidence the treatment pathway for heart failure with reduced ejection fraction in recommendation 1.4.26 has been amended. Second line treatment has been replaced by specialist treatment.


34 of As a result of new evidence the treatment pathway for heart failure with reduced ejection fraction in recommendation 1.4.26 has been amended. Second line treatment has been replaced by specialist treatment. A sentence has been added to clarify that specialist advice should be sought before starting treatment with digoxin. The first part of recommendation 1.6.2 has been removed because it is now covered in section 1.1 on team working in the management of heart failure. Amlodipine to treat hypertension has been deleted from recommendation 1.6.3 because it has been superseded by the NICE guideline on hypertension in adults. 'Regularly' has been replaced by 'at the 6-monthly clinical review' in recommendation 1.6.5 for clarification. The wording in recommendation 1.6.6 has been amended in line with recommendation 1.6.5. Minor changes since publication April 2022: In section 1.4 we added links to NICE's technology appraisal guidance on dapagliflozin and empagliflozin for treating chronic heart failure with reduced ejection fraction. November 2021: We added a link to the NICE guideline on heart valve disease in recommendations 1.2.8, 1.2.15 and 1.4.2. 35 of Accreditation 36 of


CHEST Supplement Parenteral Anticoagulants ANTITHROMBOTICTHERAPY AND PREVENTION OFTHROMBOSIS, 9TH ED: ACCP GUIDELINES This article focuses on parenteral anticoagulants in current use. These agents can be divided into indirect anticoagulants whose activity is mediated by plasma cofactors and direct anticoagulants that do not require plasma cofactors to express their activity. The indirect parenteral anticoagulants in current use include heparin, low-molecular-weight-heparins (LMWHs), fondaparinux, and danaparoid. These drugs have little or no intrinsic anticoagulant activity, and exert their anticoagulant activity by potentiating antithrombin (AT), an endogenous inhibitor of var- ious activated clotting factors. The parenteral direct anticoagulants in current use all target thrombin. These agents include recombinant hirudins, bivaliru- din, and argatroban. 1.0 Indirect Parenteral Anticoagulants More than 90 years ago, McLean1 discovered that heparin has anticoagulant properties. Brinkhous and associates2 then demonstrated that heparin requires a plasma cofactor to express its anticoagulant activity. This article describes the pharmacology of approved parenteral anticoagulants. These include the indirect anticoagulants, unfractionated heparin (UFH), low-molecular-weight heparins (LMWHs), fondaparinux, and danaparoid, as well as the direct thrombin inhibitors hirudin, biva- lirudin, and argatroban. UFH is a heterogeneous mixture of glycosaminoglycans that bind to antithrombin via a unique pentasaccharide sequence and catalyze the inactivation of thrombin, factor Xa, and other clotting enzymes. Heparin also binds to cells and plasma proteins other than antithrombin causing unpredictable pharmacokinetic and pharmacodynamic properties and trig- gering nonhemorrhagic side effects, such as heparin-induced thrombocytopenia (HIT) and osteo- porosis. LMWHs have greater inhibitory activity against factor Xa than thrombin and exhibit less binding to cells and plasma proteins than heparin. Consequently, LMWH preparations have more predictable pharmacokinetic and pharmacodynamic properties, have a longer half-life than heparin, and are associated with a lower risk of nonhemorrhagic side effects. LMWHs can be administered once daily or bid by subcutaneous injection, without coagulation monitoring.


LMWHs can be administered once daily or bid by subcutaneous injection, without coagulation monitoring. Based on their greater convenience, LMWHs have replaced UFH for many clinical indications. Fonda- parinux, a synthetic pentasaccharide, catalyzes the inhibition of factor Xa, but not thrombin, in an antithrombin-dependent fashion. Fondaparinux binds only to antithrombin. Therefore, fonda- parinux-associated HIT or osteoporosis is unlikely to occur. Fondaparinux exhibits complete bio- availability when administered subcutaneously, has a longer half-life than LMWHs, and is given once daily by subcutaneous injection in xed doses, without coagulation monitoring. Three addi- tional parenteral direct thrombin inhibitors and danaparoid are approved as alternatives to hep- arin in patients with HIT. CHEST 2012; 141(2)(Suppl):e24S e43S Abbreviations: aPTT 5 activated partial thromboplastin time; AT 5 antithrombin; CrCl 5 creatinine clearance; HCII 5 heparin cofactor II; HIT 5 heparin-induced thrombocytopenia; INR 5 international normalized ratio; Parenteral Anticoagulants Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines David A. Garcia, MD; Trevor P. Baglin, MBChB, PhD; Jeffrey I. Weitz, MD, FCCP; and Meyer Michel Samama, MD 2012 American College of Chest Physicians by Kimberly Henricks on February 10, 2012 chestjournal.chestpubs.org Downloaded from www.chestpubs.org CHEST / 141 / 2 / FEBRUARY, 2012 SUPPLEMENT e25S At even higher concentrations, low-af nity heparin impairs factor Xa generation through AT- and HCII- independent mechanisms13 (Table 2). The heparin/AT complex inactivates thrombin (factor IIa) and factors Xa, IXa, XIa, and XIIa.5 Hep- arin catalyzes AT-mediated thrombin inhibition in a nonspeci c charge-dependent fashion to form a ter- nary heparin/AT/thrombin complex. In contrast, to catalyze factor Xa inhibition by AT, heparin needs only to bind to AT.14 In both cases binding occurs at the unique pentasaccharide sequence found within some heparin molecules.


In contrast, to catalyze factor Xa inhibition by AT, heparin needs only to bind to AT.14 In both cases binding occurs at the unique pentasaccharide sequence found within some heparin molecules. Heparin chains consisting of ,18 saccharide units are too short to bridge AT to thrombin. Consequently, these chains are unable to catalyze thrombin inhibition. However, short heparin chains can catalyze inhibition of factor Xa by AT.15-18 By inactivating thrombin or attenuating its genera- tion, heparin not only prevents brin formation but also inhibits thrombin-induced activation of platelets and factors V, VIII, and XI.19-21 The interaction of heparin with HCII is charge dependent, but pentasaccharide independent. Catalysis In 1968, Abildgaard identi ed this cofactor as anti- thrombin III,3 which is now referred to as anti- thrombin. The major anticoagulant action of heparin is mediated by the heparin/AT interaction. The mech- anism of this interaction was demonstrated in the 1970s.4-6 Heparin binds to positively charged residues on AT, producing a conformational change at the AT arginine reactive center that converts AT from a slow to a rapid inhibitor of serine proteases. The arginine reactive center on AT binds covalently to the active center serine of thrombin and other coagulation enzymes, thereby irreversibly inhibiting their proco- agulant activity.5 Heparin then dissociates from AT and is reused (Fig 1).7 1.1.1 Structure and Mechanism of Action: Heparin is a highly sulfated mucopolysaccharide. It is hetero- geneous with respect to molecular size, anticoagulant activity, and pharmacokinetic properties (Table 1).


It is hetero- geneous with respect to molecular size, anticoagulant activity, and pharmacokinetic properties (Table 1). Heparin molecules range in molecular weight from 3,000 to 30,000 kDa with a mean of 15,000, which corresponds to approximately 45 saccharide units (Fig 2).8-10 Only about one-third of the heparin mole- cules possess the unique pentasaccharide sequence and it is this fraction that is responsible for most of the anticoagulant effect of heparin.8,11 Heparin chains that lack the pentasaccharide sequence have minimal anticoagulant activity when heparin is given in thera- peutic concentrations. However, at concentrations higher than those usually administered clinically, heparin chains with or without the pentasaccharide sequence can catalyze thrombin inhibition by hep- arin cofactor II (HCII), a second plasma cofactor.12 Figure 1. Inactivation of clotting enzymes by heparin. Top, ATIII is a slow inhibitor without heparin. Middle, Heparin binds to ATIII through a high-af nity pentasaccharide and induces a con- formational change in ATIII, thereby converting ATIII from a slow inhibitor to a very rapid inhibitor. Bottom, ATIII binds cova- lently to the clotting enzyme, and the heparin dissociates from the complex and can be reused. AT5antithrombin. (Reprinted with permission from Hirsh et al.7) Table 1 Molecular Size, Anticoagulant Activity, and Pharmacokinetic Properties of Heparin Attribute Characteristics Molecular size Mean molecular weight, 15,000 kDa Anticoagulant activity Only one-third of heparin molecules contain the high-af nity pentasaccharide required for anticoagulant activity Clearance High-molecular-weight moieties are cleared more rapidly than lower-molecular-weight moieties Revision accepted August 31, 2011. Af liations: From the University of New Mexico (Dr Garcia), Albuquerque, NM; the Cambridge University Hospitals NHS Trust (Dr Baglin), Addenbrooke s Hospital, Cambridge, England; the Thrombosis and Atherosclerosis Research Institute and McMaster University (Dr Weitz), Hamilton, ON, Canada; and the Hotel Dieu University Hospital (Dr Samama), Place du Parvis Notre Dame, Paris, France.


Af liations: From the University of New Mexico (Dr Garcia), Albuquerque, NM; the Cambridge University Hospitals NHS Trust (Dr Baglin), Addenbrooke s Hospital, Cambridge, England; the Thrombosis and Atherosclerosis Research Institute and McMaster University (Dr Weitz), Hamilton, ON, Canada; and the Hotel Dieu University Hospital (Dr Samama), Place du Parvis Notre Dame, Paris, France. Funding/Support: The Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines received support from the National Heart, Lung, and Blood Institute [R13 HL104758] and Bayer Schering Pharma AG. Support in the form of educational grants was also provided by Bristol-Myers Squibb; P zer, Inc; Canyon Pharmaceuticals; and sano -aventis US. Disclaimer: American College of Chest Physician guidelines are intended for general information only, are not medical advice, and do not replace professional medical care and physician advice, which always should be sought for any medical condi- tion. The complete disclaimer for this guideline can be accessed at http://chestjournal.chestpubs.org/content/141/2_suppl/1S. Correspondence to: David A. Garcia, MD, 1 University of New Mexico, MSC07-4025, Albuquerque, NM 87131; e-mail: davgarcia@ salud.unm.edu 2012 American College of Chest Physicians. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/ site/misc/reprints.xhtml). 2012 American College of Chest Physicians by Kimberly Henricks on February 10, 2012 chestjournal.chestpubs.org Downloaded from e26S Parenteral Anticoagulants 1.1.2 Pharmacokinetics: Heparin is not absorbed orally and therefore must be administered parenter- ally. The two preferred routes of administration are by continuous IV infusion or subcutaneous injection.