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Clinical Practice Guidelines
for Acute Coronary Syndrome General System of Social Security in Health -‐ Colombia
For health professionals GPC-‐2013-‐17
National Research Center on Evidence and Health Technology CINETS
© Ministry of Health and Social Protection -‐ Colciencias
Quick Reference Guide. Guidelines for Acute Coronary Syndrome GSSS – CPG-‐2013-‐17
ISBN: 978-‐958-‐8838-‐16-‐8 Bogotá, Colombia
Legal Note: In all cases in which this ACS-‐CPG is to be used for the management of health sector organizations in Colombia, both copyright ownership belonging to the Ministry and the University of Antioquia co-‐authorship, represented by the ACS-‐CPG Development Group, should be disclosed. No partial or complete reproduction of the ACS-‐CPG is allowed without the authorization of the Ministry of Health and Social Protection.
This document should be cited as follows: Colombia. Ministry of Health and Social Protection, Colciencias, University of Antioquia. Quick Reference Guide. Guidelines for Acute Coronary Syndrome. ACS-‐CPG. Bogotá, 2013. CPG-‐2013-‐17
MINISTRY OF HEALTH AND SOCIAL PROTECTION Alejandro Gaviria Uribe Minister of Health and Social Protection
Fernando Ruiz Gómez Deputy Minister of Health and Services
Norman Julio Muñoz Muñoz Deputy Minister of Social Protection
Burgos Gerardo Bernal Secretary General
José Luis Ortiz Hoyos Head of the Office of Quality
COLCIENCIAS
Carlos Fonseca Zárate General Director
Paula Marcela Arias Pulgarín Deputy General Director
Arleys Cuesta Simanca Secretary General
Alicia Rios Hurtado Director of Knowledge Networks
Carlos Caicedo Escobar Director of Research Development
Vianney Motavita García Health Program Manager in Science, Technology and Innovation
INSTITUTE OF TECHNOLOGY ASSESSMENT IN HEALTHCARE Héctor Eduardo Castro Jaramillo Executive Director
Aurelio Mejía Mejía Deputy Director of Health Technology Assessment
Iván Darío Flórez Gómez Assistant Production Director of Clinical Practice Guidelines
Diana Esperanza Rivera Rodríguez Assistant Director of Participation and Deliberation
Raquel Sofía Amaya Arias Dissemination and Communication Branch
Guide Development Group
Coronary Syndrome CCG Leader JUAN MANUEL SÉNIOR SÁNCHEZ Medical Doctor, specialist in Internal Medicine, specialist in Clinical Cardiology University of Antioquia
CCG Coordinator U of A LUZ HELENA LUGO AGUDELO Medical, physiatrist, Master in Clinical Epidemiology University of Antioquia
Development Team NATALIA ACOSTA BAENA Medical Doctor, Master in Clinical Sciences University of Antioquia JORGE LUIS ACOSTA REYES Medical Doctor, Master in Clinical Sciences University of Antioquia JAMES DÍAZ BETANCUR Medical Doctor, specialist in Internal Medicine, Master in Clinical Sciences University of Antioquia OSCAR HORACIO OSÍO URIBE Medical Doctor, specialist in Internal Medicine, Master in Clinical Epidemiology University of Antioquia JESÚS ALBERTO PLATA CONTRERAS Medical Doctor, specialist in Physical Medicine and Rehabilitation, Master in Clinical Sciences University of Antioquia CLARA INÉS SALDARRIAGA GIRALDO Medical Doctor, specialist in Internal Medicine, specialist in Cardiology University of Antioquia ERIK JAVIER TRESPALACIOS ALIES Medical doctor specialist in Internal Medicine, specialist in Cardiology Universidad de Antioquia JUAN MANUEL TORO ESCOBAR Medical Doctor, specialist in Internal Medicine, specialist in Cardiology
University of Antioquia
CCG Implementation MARÍA DEL PILAR PASTOR Nurse, MA in Public Health, Ph.D. in Public Health Sciences
International Reviewer AGUSTIN CIAPPONI Cochrane Center Coordinator Argentina Scientific Secretary of the Association of Family Medicine in Argentina
Economic Group AURELIO ENRIQUE MEJÍA MEJÍA SARA ATEHORTÚA BECERRA MATEO CEBALLOS GONZÁLEZ MARÍA ELENA MEJÍA PASCUALES CAROLINA RAMÍREZ ZULUAGA
Patient guide MARÍA STELLA MORENO VÉLEZ Bachelor Degree in Nutrition and Dietetics Antioquia University CLAUDIA MARCELA VÉLEZ Medical Doctor, specialist in Public Health and Social Security management, MA in Clinical Sciences University of Antioquia
Support Group PAULA ANDREA CASTRO GARCÍA GILMA HERNÁNDEZ HERRERA ÁNGELA MARÍA OROZCO GIRALDO JESENIA AVENDAÑO RAMÍREZ PAOLA ANDREA RAMÍREZ PÉREZ
Editorial Board JUAN MANUEL SENIOR SÁNCHEZ LUZ HELENA LUGO AGUDELO NATALIA ACOSTA BAENA PAOLA ANDREA RAMÍREZ PÉREZ
Design and Illustrations MAURICIO RODRIGUEZ SOTO
External subject experts and representatives of scientific societies
WILSON RICARDO BOHÓRQUEZ RODRÍGUEZ Medical Doctor, specialist in Internal Medicine, specialist in Cardiology Pontificia Javierana University
FERNÁN DEL CRISTO MENDOZA Medical Doctor, specialist in Internal Medicine, specialist in Cardiology, and specialist in Critical and Intensive Care Medicine, specialist in Bioethics, specialist in Clinical Epidemiology Colombian Society of Cardiology and Cardiovascular Surgery
EDUARDO RAMÍREZ VALLEJO Medical Doctor, specialist in Internal Medicine, specialist in Cardiology Colombian Association of Internal Medicine
MANUEL URINA TRIANA Medical Doctor, specialist in Internal Medicine, specialist in Cardiology, specialist in Hemodynamics and Interventional Cardiology, MA in Clinical Epidemiology Pontificia Javierana University
JUAN JOSÉ VÉLEZ CADAVID Medical Doctor, specialist in Emergency Medicine, specialist in Critical and Intensive Care Medicine
SEBASTIÁN VÉLEZ PELÁEZ Medical Doctor, specialist in Internal Medicine, specialist in Cardiology, specialist in Echocardiography Colombian Association of Internal Medicine
Participating Entities Colombian Association of Internal Medicine (ACMI, for its initials in Spanish) Colombian Society of Cardiology and Cardiovascular Surgery Colombian Association of Physical Medicine and Rehabilitation Academic Clinical Epidemiology Group of the University of Antioquia (GRAEPIC, for its initials in Spanish) Health Rehabilitation Research Group (GRS, for its initials in Spanish) Sustainability Strategy U of A 2013-‐2014 Cardiovascular Disease Study Group Health Economics Research Group at the University of Antioquia (GES, for its initials in Spanish) CINETS Alliance
39
Content
7 Introduction
11 Initial care and pre-‐hospital treatment 1. Pre-‐hospital drug therapy 12 2. Pre-‐hospital fibrinolysis 12
13 Emergency care and hospitalization 3. Risk classification 13 4. Diagnostic methods with non-‐diagnostic electrocardiogram 14
and negative biomarkers of myocardial necrosis 5. Drug therapy in Acute Coronary Syndrome 14
with and without ST-‐segment elevation 6. ACS revascularization therapy without ST elevation 30 7. ACS revascularization therapy with ST elevation 33 8. Three vessel or left main coronary artery disease 38
Secondary prevention 9. Drug therapy in secondary prevention 39 10. Controlling cardiovascular risk factors 41 11. Nutritional program 42 12. Cardiopulmonary exercise testing 42 13. Cardiac rehabilitation 42
6 I University of Antioquia
Ministry of Health and SociaL Protection -‐ Colciencias 7
omeario
uía para el Síndr
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Guía de
Introduction
In Colombia, ischemic heart disease in the last decade has been the leading cause of death in people over 55 years of age, surpassing cancer and violence. Understanding this priority in our country, as part of the call 500 of 2009, there was a need to develop the first Clinical Practice Guideline (CPG) for patients with acute coronary syndrome (ACS) in Colombia.
Despite the effects caused by atherosclerotic disease and, particularly, its manifestation in ACS, there is sufficient evidence to demonstrate that an appropriate intervention, backed by a specific CPG, can modify disease progression and minimize damage with a subsequent decrease in mortality and an improvement in the quality of life.
The preparation of this CPG was conducted by the University of Antioquia in conjunction with CINETS Alliance, formed by two other universities: Pontificia Javeriana University and the National University of Colombia. Other participating organizations were the Colombian Association of Internal Medicine and the Colombian Society of Cardiology and Cardiovascular Surgery, the Colombian Association of Physical Medicine and Rehabilitation, the Health Rehabilitation Research Group, the Academic Group of Clinical Epidemiology of the University of Antioquia (GRAEPIC, for its initials in Spanish), the Health Rehabilitation Research Group, the Cardiovascular Disease Study Group, and the Research Group on Health Economics at the University of Antioquia.
8 University of Antioquia
Introduction
The Comprehensive Care Guide (CCG) of patients with ACS aims to standardize comprehensive treatment with the highest possible clinical consensus from the current available scientific evidence, considering the knowledge and experience of the development group and taking into account patient preferences.
The development of the CPG for ACS was an integrative research project to prepare recommendations based on evidence or proof of published scientific studies with explicit evaluation of the effectiveness, harm, and cost-‐benefit ratio. Each recommendation answers a scientific question aimed at improving the management of an acute coronary event. These questions were posed in each area of the health care process, where users of the guide and patients must make decisions regarding specific interventions. To answer each question, it was necessary to conduct a systematic review of the literature of previous clinical practice guidelines, systematic reviews, and primary studies published worldwide. The process included the search, selection and extraction of information, the critical appraisal of the quality, evidence charting, and consensus in the formulation of recommendations. According to the specificities of certain questions, it was necessary to also conduct a systematic literature review (SLR) for economic studies and evaluations.
The recommendations were classified according to the methodology described by the GRADE Working Group. This system includes two concepts: evidence quality and the strength of the given recommendations. See Table 1. GRADE Classification System.
The quality can be "high," "intermediate," "low," or "very low” based on the methodological characteristics and the risk of bias of the available evidence defining each outcome. While the evidence quality in some outcomes may be low or intermediate, the quality of the overall evidence is based on the summary of all important outcomes for the clinical setting.
The recommendations are graded as "strong" or "weak," and each can be positive or negative regarding an intervention. The implications of a strong or weak recommendation are described in Table 1.
The population considered for this guide: Adult men and women over 18 years of age with an ACS diagnosis with or without ST-‐segment elevation.
Ministry of Health and SociaL Protection -‐ Colciencias 9
Quick Reference Guide. Guidelines for Acute Coronary Syndrome Groups that were not considered: • Chronic, stable angina • Variant or Prinzmetal's angina • Chest pain of non-‐cardiac origin
Users: The recommendations of this CCG are aimed at pre-‐hospital care staff, general practitioners, nurses, and specialists in the following areas: Emergency Medicine, Internal Medicine, Cardiology, Hemodynamics, Cardiovascular Surgery, Critical Care, Physical Medicine and Rehabilitation, Sports Medicine, Cardiac Rehabilitation and caregivers.
Objectives
General Objectives • To systematically develop a Clinical Practice Guide based
on evidence to reduce mortality and morbidity and to improve the functionality and quality of life of people with ACS through an interdisciplinary team with the participation of patients and stakeholders involved in the care of this condition.
Specific Objectives • To make recommendations based on the evidence for pre-‐hospital, hospital,
and outpatient care of people with ACS with ST and ACS without ST to improve the effectiveness and safety of the interventions.
• To develop safe and effective recommendations based on the evidence for secondary prevention for people who have had ACS.
• To provide evidence-‐based recommendations for the diagnosis, pharmacological, interventional, and rehabilitation interventions to improve mortality, morbidity, functionality, and quality of life of people with ACS.
• To perform economic evaluations of treatment alternatives based on certain Guideline recommendations, when appropriate and in accordance with strict prioritization criteria.
• To propose strategies and performance indicators to monitor implementation and compliance by different users.
• To engage patients and users in the development of the Guide through dissemination and socialization strategies in each of the Guide’s development phases.
Clinical aspects covered by the Guide: 1. Pre-‐hospital Care 2. Emergency Care Management 3. Hospital and Interventional Care 4. Secondary Prevention
Introduction
10 University of Antioquia
⊕ ��� D
Clinical aspects not covered by the Guide: 1. Primary prevention 2. Nonspecific chest pain 3. Percutaneous revascularization technique 4. Surgical revascularization techniques 5. Mechanical complications of acute coronary syndromes 6. Rhythm complications during an acute coronary syndrome
Table 1. GRADE classification system
Quality of Evidence
High High confidence: It is highly unlikely that new studies would change confidence in the estimated effect. ���� A
Moderate
Moderate confidence: It is likely that further research would have a significant impact on the confidence of the
estimated effect, and the results may change.
��� B
Low
Limited confidence in the estimated effect: It is very likely that new studies would have an important impact on the
confidence in the estimated effect and likely change the results.
��
C
Very Low Confidence is very low in the estimated effect: Any estimated effect is uncertain.
Strength of Recommendations
Strong positive
Most well-‐informed people would agree with the
recommended action; only a small proportion would not.
The recommendations may be accepted as a health care policy in most cases.
!!
1
Strong negative
"" 1
Weak positive
Most well-‐informed people would agree with the recommended action, but a significant number would
not.
The values and preferences may vary widely.
The decision as a health policy deserves important debate and discussion with all stakeholders.
!?
2
Weak negative
"?
2
Ministry of Health and Social Protection-‐ Colciencias 11
Coronario Agudo
Guía para el Síndrome
eferencia rápida.
Guía de r
Typical angina
EKG diagnostic Elevation ST
Initial care and pre-‐hospital treatment
Figure 1. Initial diagnosis of probable ACS
Probable ACS
• Angina at rest over 20-‐30 min
• New grade III angina; according to CCS
• Angina In Crescendo
Non-‐diagnostic ECG
No ST elevation
Enzymes -‐
Monitor 12 hours
Positive enzymes
ACS
with ST
Negative troponin
Unstable Angina
Positive troponin
ACS no ST
Non-‐diagnostic ECG Negative enzymatic control
• Positive stress SPECT • Another non-‐invasive positive test
CCS = Canadian Cardiovascular Society classification of angina class III with
symptoms in activities of daily living.
In the first medical contact with a patient consulting for chest pain and typical angina, it becomes necessary to determine the ACS diagnosis and classify it as ACS with or without ST by performing an electrocardiogram and measuring cardiac
enzymes.
Patients with atypical symptoms and suspected ACS who present to the emergency department and whose initial studies are negative could benefit from further testing: tomographic angiography; myocardial perfusion imaging; or stress echocardiography. Similarly, clinical, ECG, and enzymatic monitoring for short periods (6-‐8 hours) in chest pain units provide important data for diagnosis.
Initial care and prehospital treatment
12 University of Antioquia
1. Pre-‐hospital drug treatment In patients older than 18 years with ACS, does the administration of acetylsalicylic acid (ASA), clopidogrel, morphine, nitrates, or glycoprotein IIb/IIIa inhibitors by the pre-‐hospital care (PHC) staff decrease myocardial revascularization, heart failure, cardiogenic shock, overall death, cardiovascular death, reinfarction, and major bleeding at 30 days compared with not using them?
Recommendations
!!
���## We recommend the use of ASA by pre-‐hospital care staff in patients with ACS without ST. Strong positive recommendation, moderate quality evidence in patients with ACS without ST. We recommend the use of ASA by pre-‐hospital care staff
!! in patients with ACS with ST. Strong positive recommendation, high quality evidence in patients with ���� ACS with ST. We suggest the use of nitrates by pre-‐hospital care staff in patients with ACS. Weak positive recommendation, low quality evidence.
!? ��#
We do not recommend the use of clopidogrel by pre-‐hospital care staff in patients with ACS. Strong negative recommendation, low quality evidence.
""
��## We do not recommend the use of glycoprotein IIb/IIIa inhibitors by pre-‐hospital care staff in patients with ACS. Strong negative recommendation, low quality evidence.
""
��## We do not recommend the use of morphine by pre-‐hospital care staff in patients with ACS. Strong negative recommendation, low quality evidence.
""
��##
2. Pre-‐hospital fibrinolysis In patients older than 18 years with ACS with ST of less than 12 hours of evolution, does the use of pre-‐hospital fibrinolysis reduce the risk of urgent myocardial revascularization, heart failure, cardiogenic shock, overall death, and major bleeding at 30 days compared with not using it?
Recommendations
We recommend using pre-‐hospital fibrinolysis in patients older than 18 years with ACS and ST of less than 12 hours of evolution, when the patient cannot be transferred to a center providing percutaneous intervention within 90 minutes of first presentation. Strong positive recommendation, low quality evidence. We recommend using pre-‐hospital fibrinolysis, provided pre-‐hospital care staff are trained and skilled in the application of fibrinolytic agents and are coordinated by a specialized center. Strong positive recommendation, very low quality evidence. .
!!
�##
Coronario Agudo
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Guía de r
We recommend utilizing the GRACE risk score to stratify risk of hospital death and nonfatal reinfarction. If the GRACE score is not available, we suggest using the TIMI risk score. Strong positive recommendation, moderate quality evidence.
Emergency care and hospitalization
3. Risk Classification
In patients older than 18 years with ACS, does the Global Registry of Acute Coronary Events (GRACE) scale, compared with the Thrombolysis In Myocardial Infarction (TIMI) scale, better classify mortality risk and nonfatal reinfarction in the first 30 days?
Recommendation
Figure 2. GRACE risk score
ACS with ST/no ST
GRACE score
!!
���#
In-‐hospital death or myocardial reinfarction
High Moderate Low
It is important to determine the risk to choose the best treatment. This score can be downloaded directly from the
following link: http://www.outcomes-‐umassmed.org/grace/acs_risk/acs_risk_content.html
Ministry of Health and Social Protection -‐ Colciencias 13
Emergency care and hospitalization
14 University of Antioquia
4. Diagnostic methods with non-‐diagnostic electrocardiogram and negative biomarkers of myocardial necrosis
4.1. Baseline echocardiography compared with coronary
angiography In patients older than 18 years with suspected ACS with a non-‐diagnostic electrocardiogram and negative biomarkers of myocardial necrosis, what is the diagnostic accuracy of baseline echocardiography compared with coronary angiography in terms of positive and negative likelihood ratio (LR), sensitivity, and specificity?
Recommendation
We do not recommend the use of echocardiography for the diagnosis of ACS in patients older than 18 years with suspected ACS with a non-‐diagnostic electrocardiogram, and negative biomarkers of myocardial necrosis Strong negative recommendation, low quality evidence.
"" ��#
4.2. SPECT compared with coronary
angiography In patients older than 18 years with suspected ACS, a non-‐diagnostic electrocardiogram, and negative biomarkers of myocardial necrosis, what is the diagnostic accuracy of stress SPECT myocardial perfusion compared with coronary angiography?
Recommendation We recommend the use of stress SPECT myocardial perfusion in patients with suspected ACS with a non-‐diagnostic ECG and negative biomarkers of myocardial necrosis. Strong positive recommendation, low quality evidence.
!! ⊕⊕##
5. Drug therapy in ACS with and without ST-‐segment elevation 5.1. Antiplatelet therapy
a. Acetyl salicylic acid
In patients older than 18 years who present to the emergency department with ACS, does ASA administration at high maintenance doses (> 150 mg/day) compared with low doses (< 150 mg/day) reduce the incidence of death, cerebrovascular event, nonfatal reinfarction, and major bleeding at 30 days?
Quick Reference Guide. Guidelines for Acute Coronary Syndrome
Ministry of Health and Social Protection -‐ Colciencias 15
Recommendation We recommend a maintenance dose of ASA between 75 and 100 mg daily after the loading dose of 300 mg for ACS patients. Strong positive recommendation, high quality evidence.
!!
����
a. Clopidogrel
Clopidogrel loading dose
In patients older than 18 years who present to the emergency department with ACS, does the administration of a loading dose of 300 mg compared with 600 mg of clopidogrel reduce the incidence of death, nonfatal reinfarction, cerebrovascular event, and major bleeding at 30 days?
Recommendation We recommend, preferably administered in the emergency department, a 300-‐mg loading dose of clopidogrel to all ACS patients. Add 300 mg if the patient is to undergo percutaneous coronary intervention (PCI) Strong positive recommendation, high quality evidence.
!! ⊕⊕⊕⊕
Maintenance dose of clopidogrel
In adult patients presenting to the emergency department with ACS, does the administration of a maintenance dose of 75 mg/day compared with 150 mg/day of clopidogrel reduce the incidence of death, nonfatal reinfarction, cerebrovascular event, and major bleeding at 30 days?
Recommendation
The administration of a 150-‐mg/day maintenance dose of clopidogrel in ACS patients is not recommended Strong negative recommendation, low quality evidence.
""
��##
The administration of a 75-‐mg/day maintenance dose of clopidogrel in patients with ACS is recommended. Strong positive recommendation, low quality evidence.
!!
��###
Emergency care and hospitalization
16 University of Antioquia
c. Dual antiplatelet therapy
Figure 3. Dual therapy
ACS with and without ST
ASA Loading dose 300 mg
Maintenance 100 mg/day
Add P2Y12 receptor inhibitor
for 12 months
Ticagrelor Prasugrel Clopidogrel
Figure 4. Indications for antiplatelet agents
Ticagrelor Prasugrel
High or Intermediate Risk
Clopidogrel
1. Low-‐risk patients 2. Contraindication for another P2Y12 inhibitor 3. Oral anticoagulation requirement 4. Fibrinolysis 5. Unavailability of other P2Y12 inhibitor
ACS
High or Intermediate Risk
Clopidogrel
Prior Revascularization Unplanned
intervention
Ticagrelor PCI Fibrinolysis Ticagrelor
Known
anatomy Clopidogrel
Yes No
PCI: Percutaneous coronary intervention * Prasugrel: Diabetes, no history of stroke/TIA, > 60 Kg, < 75 years
*Prasugrel Ticagrelor
Quick Reference Guide. Guidelines for Acute Coronary Syndrome
Ministry of Health and Social Protection -‐ Colciencias 17
ASA + clopidogrel compared with ASA alone
In patients older than 18 years who present to the emergency department with ACS, does the early administration of ASA + clopidogrel reduce the incidence of nonfatal myocardial infarction, death, cerebrovascular event, and major bleeding at one year compared with ASA alone?
Recommendations
We recommend the early administration of dual antiplatelet therapy with ASA plus clopidogrel in patients with ACS without ST. Strong positive recommendation, moderate quality evidence.
!!
���#
We recommend the early administration of dual antiplatelet therapy with ASA plus clopidogrel in patients with ACS with ST, regardless of the reperfusion strategy (fibrinolysis or primary angioplasty). Strong positive recommendation, high quality evidence.
!!
����
Dual antiplatelet therapy in the emergency room
In patients older than 18 years who present with ACS, does the early administration of dual antiplatelet therapy in the emergency room compared with the cardiac catheterization laboratory reduce the incidence of nonfatal myocardial infarction, death, and bleeding at 30 days?
Recommendation We recommend administering the loading dose of clopidogrel at the emergency room to all patients with ACS with ST and to patients with ACS without ST of moderate and high risk. Strong positive recommendation, low quality evidence.
!! ��
ASA + clopidogrel compared with ASA + ticagrelor
In patients older than 18 years who present to the emergency department with ACS, does the early administration of ASA + clopidogrel compared with ASA + ticagrelor reduce the incidence of nonfatal myocardial infarction, death, cerebrovascular events, and major bleeding after one year?
Recommendation
We recommend the use of ticagrelor + ASA in patients with ACS without ST of moderate or high risk, regardless of the initial treatment strategy, including those who previously received clopidogrel, which should be stopped once ticagrelor is initiated. Strong positive recommendation, high quality evidence. .
!! ����
Emergency care and hospitalization
18 University of Antioquia
We recommend the use of ticagrelor + ASA in patients with ACS with ST who have not received fibrinolytic therapy within the previous 24 hours and with a planned primary percutaneous coronary intervention.
Strong positive recommendation, high quality evidence.
!!
����
ASA + clopidogrel compared with ASA + prasugrel
In patients older than 18 years who present to the emergency department with ACS, does the early administration of ASA + clopidogrel compared with ASA + prasugrel reduce the incidence of nonfatal myocardial infarction, death, cerebrovascular events, and major bleeding after one year?
Recommendation
We recommend the use of prasugrel + aspirin in patients with known coronary anatomy, with an indication for percutaneous revascularization who have not received clopidogrel, in the absence of predictors for high risk of bleeding: a previous cerebrovascular event or transient ischemic attack, weighing less than 60 kg, or older than 75 years. Strong positive recommendation, high quality evidence.
!! ����
Proton pump inhibitors
In patients older than 18 years who present to the emergency department with ACS receiving double antiplatelet therapy (ASA + clopidogrel), does the administration of proton pump inhibitors reduce the incidence of gastrointestinal bleeding, cerebrovascular events, nonfatal reinfarction, or death compared with no administration?
Recommendation We recommend administering proton pump inhibitors to all patients at high risk of bleeding who are being treated with dual antiplatelet therapy with ASA and clopidogrel. Strong positive recommendation, low quality evidence.
!! ��
Quick Reference Guide. Guidelines for Acute Coronary Syndrome
Ministry of Health and Social Protection -‐ Colciencias 19
FONDAPARINUX
Riesgo sangrado
5.2. Anticoagulant therapy
Figure 5. Indications for anticoagulants in patients with ACS without ST
ACS no ST
Anticoagulation
ENOXAPARIN UFH *BIVALIRUDIN
Choice If
fondaparinux
is unavailable
If fondaparinux or enoxaparin
are unavailable
In percutaneous intervention
and High bleeding risk
ACS no ST
Anticoagulation
Fondaparinux
Yes No PCI
HIGH LOW In-‐hospital fondaparinux
*Bivalirudin UFH or Bivalirudin alone with
or without GP IIb/IIIA Inh.
*Bivalirudin: not marketed in Colombia
PCI: Percutaneous Coronary Intervention UFH: Unfractionated Heparin GP IIb/IIIa Inh. : Glycoprotein IIb/IIIa Inhibitor
a. Unfractionated heparin compared with low-‐molecular-‐
weight heparins In adult patients presenting with ACS, does the initiation of anticoagulation with unfractionated heparin compared with low-‐molecular-‐weight heparins (enoxaparin, dalteparin, fraxiparine, reviparin) reduce the incidence of nonfatal myocardial infarction, death, and major bleeding at 30 days?
Emergency care and hospitalization
20 University of Antioquia
Recommendations The use of anticoagulation with enoxaparin instead of unfractionated heparin in patients with ACS without ST is recommended. If enoxaparin is unavailable, unfractionated heparin can be administered. Strong positive recommendation, high quality evidence.
!! ����
The use of enoxaparin in patients with ACS with ST instead of unfractionated heparin is recommended, regardless of the reperfusion strategy (primary angioplasty or fibrinolysis). In case of unavailability of enoxaparin, unfractionated heparin can be administered. Strong positive recommendation, moderate quality evidence.
!! ���
b. Fondaparinux vs. enoxaparin compared with unfractionated heparin
In patients older than 18 years who present with ACS, does the administration of fondaparinux compared with enoxaparin or unfractionated heparin reduce the incidence of nonfatal myocardial infarction, refractory ischemia, death, and major bleeding at 30 days?
Recommendations
The use of fondaparinux in patients with ACS without ST instead of enoxaparin is recommended. An additional dose of unfractionated heparin should be administered during percutaneous intervention to prevent catheter thrombosis. Strong positive recommendation, high quality evidence.
!! ����
The use of fondaparinux in patients with ACS without ST in medical treatment or reperfusion non-‐fibrin specific drugs as an alternative to unfractionated heparin. Strong positive recommendation moderate quality evidence.
!!
���## c. Bivalirudin
In patients older than 18 years who present to the emergency department with ACS, does the administration of bivalirudin compared with enoxaparin reduce the incidence of nonfatal myocardial infarction, major bleeding, cerebrovascular event, and death at 30 days?
Recommendation The use of bivalirudin in patients with ACS who will undergo percutaneous intervention and have a high risk of bleeding is recommended. Strong positive recommendation, moderate quality evidence.
!! ���#
Quick Reference Guide. Guidelines for Acute Coronary Syndrome
Ministry of Health and Social Protection -‐ Colciencias 21
5.3. Beta blockers
In patients older than 18 years who present with ACS, does the use of oral and intravenous betablockers in the emergency room reduce the incidence of death, nonfatal reinfarction, cardiac arrest, heart failure, re-‐hospitalization, and cardiogenic shock at 30 days and one year compared with not using them?
Recommendation
We recommend the administration of oral betablockers in patients with ACS with no contraindications for use. Strong positive recommendation, moderate quality evidence.
!!
���#
We do not recommend the administration of betablockers in patients with ACS at risk for cardiogenic shock until their clinical condition is stable. Strong negative recommendation, moderate quality evidence.
""
���# 5.4. Inhibitors of the renin-‐angiotensin-‐aldosterone system and angiotensin II receptor antagonists
In patients older than 18 years who present with ACS, does the administration of ACE/ARA II inhibitors in the emergency room reduce the incidence of death, nonfatal reinfarction, and heart failure at 30 days compared with not doing so?
Recommendations
!! ����
We recommend the administration of angiotensin-‐converting enzyme inhibitors Inhibitors in the first 36 hours of hospitalization in patients with ACS and ejection fraction less than 40% in the absence of hypotension (systolic blood pressure less than 100 mm Hg). Strong recommendation for, with high quality of evidence. We recommend the administration of angiotensin-‐converting enzyme inhibitors
!? enzyme inhibitors in the first 36 hours of hospitalization in patients
with ACS and ejection fraction greater than 40% in the absence of hypotension (systolic blood pressure less than 100 mm Hg). ��# Weak positive recommendation, low quality evidence. We recommend the use of angiotensin II receptor antagonists
!! in patients who would not tolerate angiotensin-‐converting enzyme inhibitors. ��## Strong positive recommendation, low quality evidence.
Emergency care and hospitalization
22 University of Antioquia
4.1. Glycoprotein IIb/IIIa inhibitors
In patients older than 18 years who present with ACS, does the administration of glycoprotein IIb/IIIa inhibitors reduce the incidence of nonfatal myocardial infarction, death, major bleeding, refractory ischemia, and rehospitalization at 30 days compared with not doing so?
Recommendations
!!
We recommend the use of glycoprotein IIb/IIIa inhibitors in the catheterization laboratory in patients with ACS without ST with high Ischemic risk and low bleeding risk when a high risk ⊕⊕⊕⊕ percutaneous coronary intervention is to be performed Strong positive recommendation, high quality evidence. We recommend the use of glycoprotein IIb/IIIa inhibitors only in the
!?
catheterization laboratory , in patients with ACS with ST and low bleeding risk, who are to undergo primary coronary percutaneous intervention and in whom there is a high thrombotic load. ⊕⊕⊕# Weak positive recommendation, moderate quality evidence. We do not recommend the routine use of glycoprotein IIb/IIIa inhibitors in the emergency department in ACS patients. Strong negative recommendation, high quality evidence.
""
⊕⊕⊕⊕
4.2. Eplerenone In patients older than 18 years who present with ACS with ST, does the administration of eplerenone in the emergency room reduce the incidence of death and hospitalization at 30 days compared with not doing so?
Recommendation
We recommend the administration of eplerenone in patients with ACS with ST with an ejection fraction less than 40% and at least one of the following conditions: symptoms of heart failure or diabetes mellitus. Strong positive recommendation, high quality evidence.
!! ⊕⊕⊕⊕
5.5. Statins in the emergency room In patients older than 18 years who present to the emergency department with ACS, does the administration of statins plus standard therapy reduce the incidence of nonfatal reinfarction and death at 30 days compared with standard treatment only?
Recommendation
We recommend administering statins after an ACS in the emergency room. Strong positive recommendation, moderate quality evidence.
!!
⊕⊕⊕#
Quick Reference Guide. Guidelines for Acute Coronary Syndrome
Ministry of Health and Social Protection -‐ Colciencias 23
5.6. Calcium channel blockers
In patients older than 18 years who present with ACS, does the administration of calcium channel blockers in the emergency room reduce the incidence of nonfatal reinfarction and death at 30 days compared with not doing so?
Recommendation
We recommend the use of non-‐dihydropyridine-‐type calcium channel blockers for controlling the symptoms of continuous or recurrent ischemia in patients with ACS with contraindication to the use of betablockers and having no systolic dysfunction. Weak positive recommendation, low quality evidence.
We suggest the use of long-‐acting, non-‐dihydropyridine-‐type calcium-‐channel blockers with the same purpose in patients with ACS who are receiving betablockers and nitrates in full doses. Weak positive recommendation, low quality evidence.
!? ⊕⊕##
Table 2. ACS drug therapy with and without ST elevation.
ACS drug therapy summary Drug
Indication Initial medical treatment
During PCI
After PCI
At discharge
Antiplatelet Aspirin
All ACS patients
Loading dose,
300 mg; maintenance, 75-‐100 mg/day
Continue maintenance dose
Continue maintenance dose
75-‐100 mg/day
indefinitely
Nitrates Isosorbide dinitrate
Management of
pain and ischemia
5 mg sublingual every 5
minutes until 3 doses
No indication
No indication
No indication
Emergency care and hospitalization
24 University of Antioquia
Nitrogly cerin
10 mcg/min infusion
Titrated to 200
mcg/min
Decrease dose until discontinu
ation
No indication
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Ministry of Health and Social Protection -‐ Colciencias 25
Antiplatelet agents (P2Y12 Inhibitors) Clopido-‐ grel
In low-‐risk patients;
when there is contraindication to
another P2Y12 inhibitor; when there is unavailability of another P2Y12
inhibitor; when oral anticoagulation is required in patients
with ACS with ST who will receive fibrinolysis.
300 mg loading dose
300 mg additional if PCI
75 mg every day 75 mg every 12 hours at high risk of stent throm bosis
75 mg/day
for 12 months
Ticagre-‐
At high or
180 mg Continue Continue 90 mg every loading dose with dose with dose 12 hours
lor Intermediate risk 90 mg every 12 of main-‐ of main-‐ for 12 hours tenance tenance months
Prasu-‐ grel
At high or moderate risk; in patients with diabetes and no
history of ECV/ICT, > 60 kg, <
75 years, with known
coronary anatomy.
No indication
60 mg loading dose in the catheterization lab
10 mg daily
10 mg/ day for 12 months
Anticoagulants Fondapa-‐ rinux
Of choice in ACS without ST,
in patients with ACS with ST with no reperfusion or reperfusion with streptokinase.
2.5 mg SC /day
Add UFH
Until discharge
Not for
outpatients
Enoxapa-‐ rin
Of choice in ACS with ST,
if there is no availability of
fondaparinux in ACS without ST.
1 mg/Kg/ SC/12 h
En >75 years: 0.75 mg/Kg/
SC/12 h
Depuration < 30 mL/min:
1 mg/Kg/SC/day
Adjust dose proc.: last dose > 16 h or did not receive it: 0.75 mg/kg; last dose between 8-‐16 hours: 0.3 mg/kg. No additional UFH.
Until discharge
Not for
outpatients
Emergency care and hospitalization
26 University of Antioquia
Unfractionated heparin (UFH)
If there is no availability of
fondaparinux or enoxaparin
Without GP IIb/IIIa
inhibitor: 85 IU/Kg/IV bolus,
12 IU/kg/h infusion
With GP IIb/IIIa inhibitor: 60 IU/Kg/IV
bolus
Continue initial dose
Until discharge
Not for
outpatients
Bivaliru-‐ din
Of choice in patients
at high risk of bleeding.
Initial
0.1 mg/kg/IV bolus, 0.25 mg/kg/h infusion
Pre-‐PCI: 0.75 mg/ Kg/IV bolus, 1.75 mg/ Kg/hour infusion
Continue until 4 hours after PCI, at the discretion of the treating physician. After 4 hours, an IV infusion of additional bivalirudin may be initiated at a rate of 0.2 or 0.25 mg/kg/h for up to 20 hours, if necessary
Not for
outpatients
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Beta blockers: No intrinsic sympathomimetic activity Metoprolol succinate
In all patients without contraindications and no risk factors for cardiogenic shock
12.5-‐25 mg oral daily; titration to maximum dose.
-‐
-‐
Continue to maximum tolerated dose or up to 200 mg daily
Carve-‐ dilol
Nebivo-‐ lol
3.125 mg every 12 hours orally; titration to maximum dose.
-‐
-‐
Continue to maximum tolerated dose or up to 25 mg given every 12 hours
1.25 mg every day orally; titration to maximum dose.
-‐
-‐
Continue to maximum tolerated dose or up to 10 mg daily
Bisopro-‐ lol
1.25 mg every day orally; titration to maximum dose.
-‐
-‐
Continue to maximum tolerated dose or up to 10 mg daily
Emergency care and hospitalization
28 University of Antioquia
ACEIs Captopril
In all ACS patients
6.25 mg each 8 hours; titration to maximum dose.
-‐
-‐
Continue to maximum tolerated dose or up to 50 mg every 8 hours
Enalapril
2.5 mg every 12 hours; titration to maximum dose.
-‐
-‐
Continue to maximum tolerated dose or up to 10-‐20 mg every 12 hours
Lisinopril
2.5-‐5 mg daily; titration to maximum dose.
-‐
-‐
Continue to maximum tolerated dose or up to 20-‐35 mg daily
Ramipril
2.5 mg daily; titration to maximum dose.
-‐
-‐
Continue to maximum tolerated dose or up to 5 mg daily
Trando-‐ lapril
0.5 mg daily; titration to maximum dose.
-‐
-‐
Continue to maximum tolerated dose or up to 4 mg daily
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ARBs Can-‐ desartan
Patient intolerance to ACE
4-‐8 mg daily; titration to maximum dose.
-‐
-‐
Continue to maximum tolerated dose or up to 32 mg daily
Valsartan
40 mg every 12 hours; titration to maximum dose.
-‐
-‐
Continue to maximum tolerated dose or up to 160 mg every 12 hours
Losartan
50 mg daily; titration to maximum dose.
-‐
-‐
Continue to maximum tolerated dose or up to 150 mg daily
Glycoprotein IIb/IIIa inhibitors Tirofiban
Patients with high thrombus burden or
reflux in the catheterization
laboratory
No indication
25 mcg/kg IV bolus or IC infusion 0.15 mcg/kg/minute for 18-‐24 hours
50% bolus and infusion if clearance < 30 mL/minute
No indication
Eptifiba-‐ tide
No indication
180 mcg/ Kg/minute bolo Infusion 2 mcg/kg/ minute for 18-‐24 hours
Contraindicated when clearance is < 30 mL/min; infusion 1 mcg/Kg/min when clearance is < 50 mL/minute
No indication
Emergency care and hospitalization
30 University of Antioquia
Abcixi-‐ mab
No indication
0.25 mg/kg bolus IV infusion, 0.125 mcg/Kg/min for 12 hours
No change in renal failure.
No indication
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Anti-‐aldosterone agents Eplere-‐ none
In patients with EF < 40% and symptoms of heart failure. In patients with diabetes mellitus, no renal failure
25 mg daily; titration to maximum dose.
Titration dose
No changes
Continue to maximum tolerated dose or up to 50 mg daily
Espiro-‐ nolacto-‐ ne
25 mg daily; titration to maximum dose.
Titration dose
No changes
Continue to maximum tolerated dose or up to 25-‐50 mg daily
Statins Atorvas-‐ tatin
In all patients to achieve
LDL <100 mg/dL
40-‐80 mg daily
No changes
No changes
40 mg daily
Simvas-‐ tatin
40 mg daily 40 mg daily
Rosuvas-‐ tatin
20 mg daily 20 mg daily
Lovasta-‐ tin
40 mg daily
40 mg daily
Calcium antagonists Long-‐acting diltiazem
Non-‐dihydropyridine agent for ischemia control in patients
with contraindications to beta-‐ blockers with
EF > 40%
30-‐60 mg daily
-‐
-‐
Continue to maximum tolerated dose or up to 240 mg daily
Long-‐acting nifedipine
Dihydropyridine agent for ischemia control in patients treated with beta-‐blockers with EF >
40%
20-‐30 mg daily
-‐
-‐
Continue to maximum tolerated dose or up to 60 mg daily
Emergency care and hospitalization
32 University of Antioquia
6. Revascularization therapy in ACS without ST elevation
Figure 6. Types of revascularization therapy in ACS without ST
ACS no ST
Invasive strategy
Early Selective
1. Routine cardiac catheterization for all patients
2. Revascularization according to findings 3. Within the first 72 hours of admission
1. If no response to standard medical treatment
2. Recurrent ischemia 3. Positive for inducible ischemia
Urgent Immediate Deferred
<2 hours after
admission
<24 hours after
admission
24 -‐ 72 hours after
admission
6.1. Early invasive strategy compared with selective invasive strategy
In patients older than 18 years who present with ACS without ST, does an early invasive strategy reduce the incidence of refractory angina, re-‐hospitalization, nonfatal reinfarction, cerebrovascular event, and death at 30 days compared with a selective invasive strategy?
Recommendation We recommend starting an early invasive strategy (< 72 hours) after admission rather than selective for patients with ACS without ST of
intermediate and high risk Strong positive recommendation, moderate quality evidence.
!! ⊕⊕⊕#
6.2 Early invasive strategy for patients with intermediate-‐
and high-‐risk scores In patients older than 18 years with ACS without ST and with a TIMI or GRACE score of intermediate and high risk, does conducting early invasive strategy (< 72 hours) reduce the incidence of death, re-‐infarction, cerebrovascular events, and bleeding compared with standard medical therapy?
Recommendation
We recommend starting an early invasive strategy (< 72 hours) after admission instead of standard medical treatment in patients with ACS without ST of intermediate and high risk. Strong positive recommendation, low quality evidence.
!! ⊕⊕##
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6.3. Early percutaneous coronary intervention with high-‐risk markers compared with standard medical treatment In patients older than 18 years with ACS without ST with high-‐risk AHCPR markers or high-‐risk biomarkers (troponin, brain natriuretic peptide, and high-‐sensitivity C-‐reactive protein), does performing early PCI reduce the incidence of death, reinfarction, cerebrovascular event and bleeding compared with standard medical therapy?
Recommendations
!! ⊕⊕
We recommend using an early invasive strategy (< 72 hours) in patients with ACS without ST at high risk according to the Agency for Health Care Policy and Research (AHCPR) classification (> 75 years, presence of mitral insufficiency murmur, ejection fraction less than 40%, pulmonary edema, prolonged angina > 20 minutes at rest, dynamic changes of the ST segment > 0.05 mV, or presumed new bundle branch block left bundle branch block). Strong positive recommendation, low quality evidence. We recommend using an early invasive strategy (within 72
!! hours) in patients with ACS without ST, with positive biomarkers (Troponin-‐CPK MB elevation). ⊕⊕⊕# Strong positive recommendation, moderate quality evidence. We suggest using an early invasive strategy in patients with ACS
!? without ST with elevated brain natriuretic peptide or high-‐sensitivity C-‐reactive protein reactive protein. ⊕⊕## Weak positive recommendation, low quality evidence.
6.4. Immediate-‐early invasive strategy vs. deferred In patients older than 18 years with ACS without ST, does the immediate early invasive strategy (< 24 hours) compared with deferred (24-‐72 hours) reduce the incidence of refractory ischemia, nonfatal reinfarction, cerebrovascular event, and death at 30 days?
Recommendation
The immediate-‐early invasive strategy (< 24 hours) in patients with ACS without ST is suggested in high-‐risk patients by the GRACE (> 140) or TIMI (> 4) score. Weak positive recommendation, low quality evidence.
!? ⊕⊕#
Emergency care and hospitalization
34 University of Antioquia
Figure 7. Selection of revascularization therapy in ACS patients without ST
ACS no ST
6.2.1 Hemodynamic
or electrical instability 6.2.2 Recurrent
ischemia 6.2.3 Heart failure
Risk Stratification
Very High High Intermediate Low
Urgent
EIS
Immediate EIS
Deferred EIS
Selective Invasive Strategy
EIS: Early Invasive Strategy.
6.5 Urgent-‐invasive strategy compared with standard medical
therapy In patients older than 18 years with ACS without ST with hemodynamic or electrical instability, recurrent ischemia, or heart failure, does an urgent-‐invasive strategy (first 2 hours) reduce the incidence of death, reinfarction, cerebrovascular event, cardiogenic shock, and bleeding compared with standard medical therapy?
Recommendation
We recommend an urgent-‐invasive strategy (first 2 hours of admission) in patients with ACS without ST, with hemodynamic or electrical instability, recurrent ischemia, or heart failure. Strong positive recommendation, low quality evidence.
!! ⊕⊕#
6.6 Coronary intervention with positive stress test before discharge In patients older than 18 years with ACS without ST with initial medical treatment (no invasive strategy) and a positive stress test prior to discharge, does performing a coronary intervention (catheterization and revascularization according to findings) reduce the incidence of death, reinfarction, cerebrovascular events, and bleeding compared with standard medical therapy?
Recommendation We recommend performing a coronary intervention in patients with ACS without ST who received initial medical treatment (no invasive strategy) and had a positive stress test, prior to discharge. Strong positive recommendation, very low quality evidence.
!! ⊕###
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6.7 Statins prior to early invasive strategy
In patients older than 18 years who present with ACS without ST with an indication for early invasive strategy, does the administration of high doses of statins before the procedure reduce the incidence of death, myocardial infarction, or target vessel revascularization at 30 days?
Recommendation
We recommend administering a high loading dose of atorvastatin, simvastatin, or rosuvastatin before percutaneous coronary intervention (PCI) to patients with ACS without ST with no contraindications for use. Strong positive recommendation, low quality evidence.
!! ⊕⊕##
7. Revascularization therapy for ACS with ST elevation
Figure 8. Reperfusion Strategies for ACS with ST
ACS no ST
Symptoms < 12 hours 12-‐72 hours > 72 hours
PCI availability < 90
MIN
Medical treatment. *PCI
Medical treatment *PCI
YES NO
+ Primary PCI ** Fibrinolysis
Failed Successful
Rescue PCI ++PCI < 24 hours
* PCI: useful in special situations ** Door-‐to-‐needle time < 30
minutes + Choice treatment. Door-‐to-‐
balloon time < 90 minutes ++If available
PCI scenarios
Primary PCI (PPCI): PCI performed within 12 hours of symptom onset as a reperfusion strategy of the target vessel without having received prior fibrinolytic therapy
Rescue PCI: After failed thrombolysis.
Failed thrombolysis:: Electrocardiographic findings at 90 minutes after completion of thrombolytic therapy with less than 50% resolution of ST segment elevation.
PCI after successful thrombolysis: PCI routinely to all patients after successful thrombolysis (first 24 hours).
Facilitated PCI: PCI immediately after administration of any of the following drugs: heparin at high doses; glycoprotein IIb/IIIa inhibitors; thrombolytic agents (low dose); or the combination of inhibitors of platelet glycoprotein IIb/IIIa and a reduced dose of a thrombolytic.
Farmacoinvasive strategy: PCI performed within the first hours (6-‐12 hours) after receiving full dose fibrinolysis as a combined strategy established from the start of reperfusion.
Emergency care and hospitalization
36 University of Antioquia
7.1. Primary percutaneous coronary intervention compared with
fibrinolysis In patients older than 18 years who present with ACS with ST with less than 12 hours of evolution, does primary mechanical reperfusion with angioplasty and stenting reduce the incidence of death, nonfatal reinfarction, cerebrovascular event, and heart failure compared with the administration of fibrinolysis?
Recommendation We recommend primary percutaneous coronary intervention with angioplasty and stenting in patients with ACS with ST with less than 12 hours of progression. For the implementation of this recommendation, the patient should be taken to the catheterization laboratory within 90 minutes of the first medical contact. Strong positive recommendation, high quality evidence.
!! ⊕⊕⊕⊕
7.2. Fibrinolytic reperfusion therapy in the first 12 hours
In patients older than 18 years who present with ACS with ST, does the administration of fibrinolytic reperfusion therapy within 12 hours of the onset of symptoms reduce the incidence of nonfatal reinfarction, death, cerebrovascular event, ventricular dysfunction, and bleeding at 30 days compared with the administration after the first 12 hours?
Recommendation
We recommend the administration of fibrinolytic therapy in patients with ACS with ST during the first 12 hours of the onset of symptoms, ideally in the first 30 minutes of first medical contact. Strong positive recommendation, high quality evidence.
!! ⊕⊕⊕⊕
Table 3. Contraindications to fibrinolytic therapy
Contraindications to fibrinolytic therapy (Adapted from Braunwald’s Heart Disease)
Absolute
Intracranial hemorrhage history Known structural cerebral vascular lesion (e.g., arteriovenous malformation) Known malignant intracranial neoplasm (primary or metastatic) Ischemic stroke in last 3 months, except when occurring in last 3 hours Suspected aortic dissection Active bleeding or bleeding diathesis (excluding menses) Severe head or facial trauma in the last 3 months
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Drug Indication
Initial medical
treatment
During PCI
After PCI
At discharge
Streptokinase
Primary reperfusion in case of no
1.500,000 U in 30 minutes No
indication
No indicatio
n No
Indication
disponer de
minutos
angioplastia en < 90 mi-‐ nutos
Un solo bolo IV 30 mg si peso < 60 Kg
Relative
Poorly controlled chronic hypertension Uncontrolled systemic hypertension at the time of presentation (SBP ≥ 180 mmHg, DBP ≥ 110 mmHg. History of ischemic stroke of more than 3 months duration, dementia, or other intracranial pathology not covered in the absolute contraindications Traumatic or prolonged CPR (10 min) and/or major surgery in the past 3 weeks
Recent internal bleeding (2-‐4 weeks) Non-‐compressible vascular puncture Prior exposure to streptokinase or ASPAC (> 5 days) or allergic reactions to these.
7.3. Non-‐fibrin specific vs. fibrin specific
In patients older than 18 years who present with ACS with ST and with an indication for pharmacological reperfusion, does the use of non-‐fibrin-‐specific thrombolytic agents (streptokinase) compared with the use of fibrin-‐specific drugs (tecnecteplase, alteplase and reteplase) improve the efficiency and safety of pharmacological reperfusion?
Recommendation
We recommend the use of fibrin-‐specific thrombolytic agents in patients with ACS with ST with an indication for fibrinolysis. Strong positive recommendation, moderate quality evidence.
!! ⊕⊕⊕
Table 4. Fibrinolytic drug doses
Tissue plasminogen activator
15 mg IV bolus, 0.75 mg/Kg (50 mg) in 30 minutes; 0.5 mg/Kg (35 mg) in 60 minutes
No indicatio
n
No indicatio
n
No indication
Emergency care and hospitalization
38 University of Antioquia
7.4. Percutaneous coronary intervention after successful fibrinolysis
In patients older than 18 years who present with ACS with ST who underwent successful fibrinolysis, does the routine performance of percutaneous coronary intervention with angioplasty and stenting reduce the incidence of death, nonfatal reinfarction, recurrent ischemia, and bleeding compared with guidance by ischemia induction?
Recommendation
We recommend routine early percutaneous coronary intervention rather than percutaneous coronary intervention guided by induction of ischemia in patients with ACS with ST who received successful fibrinolysis. Strong positive recommendation, low quality evidence.
!! ⊕###
7.5. Rescue percutaneous coronary intervention
In patients older than 18 years who present with ACS with ST with failed fibrinolysis, does conducting rescue percutaneous coronary intervention reduce the incidence of death, nonfatal reinfarction, cerebrovascular events, and heart failure compared with continued medical treatment or a new dose of fibrinolysis?
Recommendation
We recommend using rescue percutaneous coronary intervention instead of repeated thrombolysis or continuation of medical treatment in patients with ACS with ST after failed fibrinolysis. Strong positive recommendation, moderate quality evidence.
!! ⊕⊕⊕#
7.6. Facilitated percutaneous coronary intervention
In patients older than 18 years who present with ACS with ST, does conducting facilitated PCI reduce the incidence of death, nonfatal reinfarction, cerebrovascular events, and heart failure compared with primary percutaneous coronary intervention?
Recommendation
We do not recommend facilitated percutaneous coronary intervention in patients with ACS with ST requiring percutaneous coronary intervention. Strong negative recommendation, high quality evidence.
"" ⊕⊕⊕⊕
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7.7. Percutaneous coronary intervention after 12 hours of evolution
In patients older than 18 years who present with ACS with ST with 12-‐72 hours of evolution, does performing percutaneous coronary intervention with angioplasty and stenting reduce the incidence of death, nonfatal reinfarction, cerebrovascular events, and heart failure compared with continued medical therapy?
Recommendation
We suggest not performing routine PCI to the culprit vessel in patients with ACS with ST with 12 to 72 hours of evolution. Weak negative recommendation, low quality evidence.
"? ⊕⊕
In patients older than 18 years who present with ACS with ST with more than 72 hours of evolution, does performing percutaneous coronary intervention with angioplasty and stenting reduce the incidence of death, non-‐fatal reinfarction, cerebrovascular events, and heart failure compared with continued medical treatment?
Recommendation We do not recommend routine percutaneous coronary intervention for the culprit vessel in patients with ACS with ST with more than 72 hours of evolution. Strong negative recommendation, moderate quality evidence.
"" ⊕⊕⊕#
# 7.8. Farmacoinvasive strategy
In patients older than 18 years who present with ACS with ST, in whom it is not possible to perform primary percutaneous coronary intervention, does farmacoinvasive strategy (angiography and routine percutaneous coronary intervention after fibrinolysis) compared with standard treatment (angiography and need-‐based percutaneous coronary intervention after fibrinolysis) reduce the incidence of nonfatal reinfarction, cerebrovascular events, death, and bleeding at 30 days?
Recommendation We recommend farmacoinvasive strategy instead of the standard medical treatment in patients with ACS with ST undergoing fibrinolysis with reteplase, tenecteplase, or tissue plasminogen activator. Strong positive recommendation, moderate quality evidence.
!! ⊕⊕⊕
Emergency care and hospitalization
40 University of Antioquia
7.9. Drug-‐eluting stents compared with conventional stents
In patients older than 18 years who present with ACS, does the implantation of a drug-‐eluting stent reduce the rate of reinfarction, need for vessel revascularization, and death at one year compared with conventional stent?
Recommendation We recommend using a drug eluting stent only to decrease the rate of repeat revascularization, particularly in patients with small vessels (< 3 mm in diameter) and/or long lesions (> 15 mm in length). There are no differences between bare metal and drug eluting stents in mortality rate, reinfarction, or stent thrombosis. Strong positive recommendation, moderate quality evidence.
!! ⊕⊕⊕
8. Three-‐vessel or left main coronary artery disease
In patients older than 18 years presenting with ACS and 3-‐vessel or left main trunk disease, does percutaneous coronary intervention improve the quality of life and reduce the incidence of nonfatal myocardial infarction, repeat revascularization, cerebrovascular events, and death at one year compared with bypass surgery?
Recommendations
We recommend coronary artery bypass graft surgery (CABG) in patients with ACS with 3-‐vessel or left main coronary artery disease with high SYNTAX score, with or without diabetes mellitus. Strong positive recommendation, low quality evidence.
!! ⊕⊕##
We recommend individualizing the myocardial revascularization strategy (CABG vs PCI) in patients with ACS with 3-‐vessel or left main disease with low or moderate SYNTAX score, based on clinical judgment and patient preference. Strong positive recommendation, low quality evidence.
!! ⊕⊕##
Ministry of Health and Social Protectionl -‐ Colciencias 39
ome Coronario Agudo
uía para el Síndr
referencia rápida. G
Guía de
Secondary prevention 9. Drug therapy in secondary prevention
9.1. Beta blockers
In patients older than 18 years with a history of an acute coronary event, does treatment with beta blockers reduce the likelihood of a new coronary event, the rate of re-‐hospitalization, heart failure, and mortality at one year compared with not administering them?
Recommendation
We recommend continuing long-‐term treatment with betablockers after an ACS. Strong positive recommendation, moderate quality evidence.
!!
⊕⊕⊕#
9.2. Inhibitors of the renin-‐angiotensin-‐aldosterone system, ACE inhibitors In patients older than 18 years with a history of an acute coronary event, does treatment with ACE inhibitors reduce the likelihood of a new coronary event, the rate of re-‐hospitalization, heart failure, and mortality at one year compared with not administering them?
Recommendation
We recommend long-‐term treatment with angiotensin-‐converting enzyme inhibitors after an ACS. Strong positive recommendation, moderate quality evidence.
!!
⊕⊕⊕# #
40 University of Antioquia
Secondary prevention
9.3. Angiotensin II receptor blockers, ARBs
In patients older than 18 years with a history of an acute coronary event, does administering treatment with ARBs reduce the likelihood of a new coronary event, the rate of re-‐hospitalization, heart failure, and mortality at one year compared with not administering them?
Recommendation
We recommend using angiotensin II receptor blockers after an ACS only when there is intolerance to angiotensin-‐converting enzyme inhibitors. Strong positive recommendation, low quality evidence.
!! ⊕##
9.4. Statins a. Consumption of statins irrespective of cholesterol levels
In patients older than 18 years with a history of an acute coronary event, does statin use (regardless of cholesterol levels) reduce the possibility of having a new coronary event compared with not using them?
Recommendation
We recommend the use of statins to achieve LDL < 100 mg/dl (ideally in high-‐risk patients, less than 70 mg/dl) or reach at least 30% decrease in LDL (low-‐density lipoprotein cholesterol) in patients with a history of ACS provided there are no documented contraindications or adverse effects. Strong positive recommendation, moderate quality evidence.
!! ⊕⊕⊕#
a. Combination of statins with nicotinic acid and/or fibrates In patients older than 18 years with ACS and dyslipidemia that, despite having reached the LDL goal with statins, continue to present with low high-‐density lipoprotein (HDL) cholesterol and high triglycerides, does the combination of statins with nicotinic acid and/or fibrates reduce the likelihood of having a new coronary event compared with statins alone?
Recommendation
We suggest not administering niacin or fibrates to patients with ACS with dyslipidemia that, despite having reached the LDL goal with statins, continue to present with low HDL and high triglycerides. Weak negative recommendation with moderate quality evidence.
"? ⊕⊕⊕#
Ministry of Health and Social Protectionl -‐ Colciencias 41
Quick Reference Guide. Guidelines for Acute Coronary Syndrome
We suggest administering fibrates as an alternative to administering statins in patients with a history of ACS and dyslipidemia but with an intolerance to statins. Weak positive recommendation, moderate quality evidence.
!?
⊕⊕⊕##
9.5. Dual antiplatelet medicated stent In patients older than 18 years with ACS, is there a difference between the dual antiplatelet time of those who have a medicated stent to reduce the risk of late thrombosis and/or death compared with those receiving a conventional stent?
Recommendations We recommend dual antiplatelet therapy for at least 12 months in patients with a history of ACS who have a stent, regardless of whether it is a drug eluting stent or bare metal stent. Strong positive recommendation, low quality evidence.
We recommend 6 months of dual antiplatelet therapy in patients who received a new generation drug eluting stent if there is a high risk of bleeding and/or non-‐cardiac surgery is required that cannot be postponed. Strong positive recommendation, low quality evidence. We recommend 3 months of dual antiplatelet therapy in patients who received a bare metal (conventional) stent if there is high risk of bleeding and/or surgery is required that cannot be postponed. Strong positive recommendation, low quality evidence.
!!
⊕⊕##
10. Controlling cardiovascular risk factors
In patients older than 18 years with a history of an acute coronary event, does the control of cardiovascular risk factors based on targets (blood pressure, LDL, HDL, triglycerides, glycosylated hemoglobin in diabetics, and smoking control) reduce the probability of having a new coronary event compared with the lack of control?
Recommendation
We recommend controlling risk factors based on targets in patients with ACS: blood pressure < 140/90; LDL <100 mg/dl (ideally less than 70 mg/dL in patients at very high risk); non-‐HDL cholesterol (total cholesterol minus HDL cholesterol) < 130 mg/dl, triglycerides < 150 mg/dl; glycated hemoglobin in diabetics < 7%; and smoking cessation. Strong positive recommendation, low quality evidence.
!! ⊕##
Secondary prevention
42 University of Antioquia
2
11. Nutritional program In patients older than 18 years with a history of an acute coronary event, does attending a nutrition program result in patients quickly acquiring targets to control cardiovascular risk and reduce the probability of a new coronary event compared with those receiving only the recommendations given by the physician at discharge?
Recommendation
We recommend decreasing and controlling fat intake and increasing fruit and vegetable consumption in patients with ACS. Strong positive recommendation, low quality evidence.
!!
⊕⊕##
12. Cardiopulmonary exercise testing
In patients older than 18 years with ACS, for cardiopulmonary exercise testing with direct determination of O2 consumption, is it more accurate to evaluate oxygen consumption, functional capacity, and having a lower risk of heart attack and death compared with the conventional test?
Recommendation
We suggest not using routine cardiopulmonary exercise testing with direct measurement of peak O2 consumption instead of the conventional stress test in patients with a history of an acute coronary event. Weak negative recommendation, very low quality evidence.
!! ⊕##
13. Cardiac rehabilitation 13.1. Electrocardiographic monitoring during exercise
In patients older than 18 years with a history of ACS, undergoing a cardiac rehabilitation program, does performing electrocardiographic monitoring during exercise compared with not doing so improve patient safety during surgery by avoiding reinfarction, re-‐hospitalization rate, and/or death?
Recommendation We suggest electrocardiographic monitoring during exercise in patients with a history of ACS at intermediate and high risk. Weak positive recommendation, low quality evidence.
!!
⊕⊕##
Quick Reference Guide. Guidelines for Acute Coronary Syndrome
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13.2. Cardiac rehabilitation program
In patients older than 18 years with ACS, is a comprehensive cardiac rehabilitation program, directed and requiring classroom attendance (therapeutic exercise, ergonomic and psychological support indications), compared with a program at home or with no exercise, more effective in improving the level of fitness, health-‐related quality of life, exercise adherence and decreasing the rate of re-‐hospitalization, and death in the first year post-‐event?
Recommendation
We recommend a comprehensive cardiac rehabilitation program conducted in ACS patients. Strong positive recommendation, moderate quality evidence.
!! ⊕⊕⊕