Society guidelines
Management of Patients With Refractory Angina: Canadian Cardiovascular Society/Canadian Pain Society Joint Guidelines

https://doi.org/10.1016/j.cjca.2011.07.007Get rights and content

Abstract

Refractory angina (RFA) is a debilitating disease characterized by cardiac pain resistant to conventional treatments for coronary artery disease including nitrates, calcium-channel and β-adrenoceptor blockade, vasculoprotective agents, percutaneous coronary interventions, and coronary artery bypass grafting. The mortality rate of patients living with RFA is not known but is thought to be in the range of approximately 3%. These individuals suffer severely impaired health-related quality of life with recurrent and sustained pain, poor general health status, psychological distress, impaired role functioning, and activity restriction. Effective care for RFA sufferers in Canada is critically underdeveloped. These guidelines are predicated upon a 2009 Canadian Cardiovascular Society (CCS) Position Statement which identified that underlying the problem of RFA management is the lack of a formalized, coordinated, interprofessional strategy between the cardiovascular and pain science/clinical communities. The guidelines are therefore a joint initiative of the CCS and the Canadian Pain Society (CPS) and make practice recommendations about treatment options for RFA that are based on the best available evidence. Concluding summary recommendations are also made, giving direction to future clinical practice and research on RFA management in Canada.

Résumé

L'angine de poitrine réfractaire (APR) est une maladie débilitante caractérisée par une douleur cardiaque résistant aux traitements traditionnels de la maladie coronarienne incluant les nitrates, le canal calcique et le blocage des récepteurs β-adrénergiques, les agents vasculoprotecteurs, les interventions coronariennes percutanées et le pontage aortocoronarien. Le taux de mortalité des patients vivant avec une APR n'est pas connu, mais est présumé se situer à environ 3 %. Ces individus souffrent sévèrement de leur qualité de vie liée à leur santé déficiente, dont une douleur récurrente et soutenue, un mauvais état de santé général, une détresse psychologique, un déficit de fonctionnement et une restriction d'activité. Au Canada, l'efficacité des soins offerts aux patients souffrant d'une APR est dramatiquement sous-développée. Ces lignes directrices s'appuient sur un énoncé de position de la Société canadienne de cardiologie (SCC) 2009 qui déterminait que le problème sous-jacent de la gestion de l'APR est le manque de stratégies interprofessionnelles, coordonnées et formalisées, entre les communautés clinique et scientifique dans les domaines cardiovasculaire et de la douleur. Les lignes directrices sont par conséquent une initiative conjointe de la SCC et de la Société canadienne de la douleur (SCD) et font des recommandations pratiques sur les options de traitement de l'APR qui sont basées sur les meilleures preuves disponibles. Des recommandations sont aussi faites, donnant une direction à la pratique clinique future et à la recherche sur la gestion de l'APR au Canada.

Section snippets

Pathophysiology: Production and Persistence of Cardiac Pain

Most events that trigger anginal pain do so by changing myocardial oxygen demand; these triggers may be physical, emotional, or metabolic.20 The beneficial effects of most conventional anti-anginal treatments may be explained through their ability to correct determinants of myocardial oxygen supply and demand. However, by definition, RFA patients are resistant to all conventional treatments for ischemia.15 In RFA, there is an important link between mechanisms of chronic/recurrent myocardial

Definition of RFA

Commensurate with the understanding that both ischemic and persistent pain mechanisms underlie the problem, the 2009 CCS position statement put forth the following definition of RFA, adapted from the 2002 ESC Joint Study Group definition:1

Refractory angina is a persistent, painful condition characterized by the presence of angina caused by coronary insufficiency in the presence of coronary artery disease which cannot be controlled by a combination of medical therapy, angioplasty/percutaneous

Inclusion Criteria

These guidelines included systematic reviews, single randomized controlled trials (RCTs), and quasi-experimental and pre-post studies. Observational/descriptive, retrospective, and case studies did not meet our criteria for systematic review. We reviewed 3 classes of interventions including invasive, noninvasive, and pharmacologic therapies. Our specific outcomes were patient-centred, including chest pain, nitrate use, HRQL, morbidity (myocardial infarction [MI], heart transplant,

Guidelines Development Process

A detailed description of our development process including search methods, consensus-building procedure, appraisal of methodologic quality, and data synthesis (meta-analysis) is available as a slide kit on the CCS Web site (http://www.ccs.ca/consensus_conferences/cc_library_e.aspx).

Grading of Evidence and Practice Recommendations

The quality of the evidence that supports each practice recommendation was rated according to GRADE criteria16, 17, 18, 19 as follows:

  • High: Further research is very unlikely to change our confidence in the estimate of effect.

  • Moderate: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.

  • Low: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the

Establishing a Diagnosis of RFA and Ongoing Evaluation of Symptoms

Consistent with the definition of RFA employed in these guidelines, the presence of myocardial ischemia must first be established.15 A thorough evaluation of patients' cardiovascular status is required as well as a review of current pharmacotherapy to ensure maximally-tolerated and appropriate medical management; conventional revascularization procedures should also have been exhausted.1, 25, 34, 35 In addition to standard CAD assessment, Table 1 lists originating sources of chest pain (as

Transmyocardial laser revascularization

Transmyocardial laser revascularization (TMLR) is a surgical treatment, developed in the 1980s,42 aimed at reducing anginal symptoms through the creation of transmural channels via a CO2, holmium yttrium-aluminum-garnet (Ho:YAG), or XeCL excimer lasers.43, 44, 45, 46, 47, 48 By way of thoracotomy or sternotomy, laser energy is directed to the epicardial surface of the left ventricle in order create a series of transmural channels in targeted regions of viable myocardium; a variety of protocols

Enhanced external counter-pulsation

Enhanced external counter-pulsation (EECP) is a noninvasive therapy that employs the application of compressive cuffs to the calves, lower thighs, and upper thighs. The cuffs are synchronized to inflate in a distal to proximal sequence during early diastole and to simultaneously deflate at the onset of systole.103, 104 The hemodynamic effect of the treatment augments diastolic pressure, presumably resulting in increased coronary perfusion during cuff inflation.105 The rapid cuff deflation

Pharmacologic Therapies

Level of access in Canada to pharmacologic therapies reviewed varies (eg, widely available, approved for use in clinical trials, not available). Readers are referred to the Health Canada Drug Product Database (http://www.hc-sc.gc.ca/dhp-mps/prodpharma/databasdon/index-eng.php) for drug availability status and related information.

Emerging Therapies

Emerging therapies for RFA include shock wave therapy,178, 179 coronary sinus reducer,180, 181 and myocardial cryotherapy.182 The evidence for these therapies remains limited and does not meet our inclusion for review; practice recommendations cannot yet be made (Table 2).

Implications for Practice and Research

RFA is a debilitating condition characterized by severe, unremitting cardiac pain caused by coronary insufficiency in the presence of CAD.1, 15 While the presence of myocardial ischemia must be clinically established to be the root cause, the pain experienced may arise or persist with or without ischemia.15 The ischemic and neuropathophysiological mechanisms underlying RFA are complex and pose unique management challenges. Given the complexity of the mechanisms at play, establishing the

Funding Sources

These guidelines were funded by the Canadian Institutes of Health Research, #188445.

Publication and distribution of this article are supported by Servier Canada and the Heart and Stroke Foundation of Ontario.

Disclosures

M.M. and H.M.A. have received honoraria/consulting fees from Servier. P.L.L. has received honoraria/consulting fees from AstraZeneca, Sanofi-Aventis, Eli Lilly, Merck Schering, Novartis, and Pfizer. E.M.J. has received honoraria/consulting fees from Gilead, Servier Canada, Lilly, and AstraZeneca and participated in clinical trials sponsored by Gilead, AstraZeneca, GlaxoSmithKline, and Neovasc Inc. N.S. has received honoraria/consulting fees from Medtronic. J.N. has received honoraria/consulting

Acknowledgements

The authors are grateful to Anne Ferguson, Carolyn Pullen, Dr Michelle Graham, and members of the CCS and CPS executive committees. We also thank our RFA patient collaborators for their valuable insights.

References (182)

  • S.N. Oesterle et al.

    Percutaneous transmyocardial laser revascularisation for severe angina: the PACIFIC randomised trialPotential class improvement from intramyocardial channels

    Lancet

    (2000)
  • M. Salem et al.

    Usefulness and safety of percutaneous myocardial laser revascularization for refractory angina pectoris

    Am J Cardiol

    (2004)
  • T. Kohmoto et al.

    Physiology, histology, and 2-week morphology of acute transmyocardial channels made with a CO2 laser

    Ann Thorac Surg

    (1997)
  • S.M. Burns et al.

    Quantitative analysis of myocardial perfusion changes with transmyocardial laser revascularization

    Am J Cardiol

    (2001)
  • S. Guzzetti et al.

    Absence of clinical signs of cardiac denervation after percutaneous myocardial laser revascularization

    Int J Cardiol

    (2003)
  • J. Myers et al.

    Do transmyocardial and percutaneous laser revascularization induce silent ischemia?An assessment by exercise testing

    Am Heart J

    (2002)
  • J.F. Beek et al.

    Cardiac denervation after clinical transmyocardial laser revascularization: short-term and long-term iodine 123-labeled meta-iodobenzylguanide scintigraphic evidence

    J Thorac Cardiovasc Surg

    (2004)
  • P.L. Whitlow et al.

    One-year results of percutaneous myocardial revascularization for refractory angina pectoris

    Am J Cardiol

    (2003)
  • T.J. Gray et al.

    Percutaneous myocardial laser revascularization in patients with refractory angina pectoris

    Am J Cardiol

    (2003)
  • M.B. Leon et al.

    A blinded, randomized, placebo-controlled trial of percutaneous laser myocardial revascularization to improve angina symptoms in patients with severe coronary disease

    J Am Coll Cardiol

    (2005)
  • G.W. Stone et al.

    A prospective, multicenter, randomized trial of percutaneous transmyocardial laser revascularization in patients with nonrecanalizable chronic total occlusions

    J Am Coll Cardiol

    (2002)
  • M.J.L. DeJongste

    Efficacy, safety and mechanisms of spinal cord stimulation used as an additional therapy for patients suffering from chronic refractory angina pectoris

    Neuromodulation

    (1999)
  • T. Eliasson et al.

    Spinal cord stimulation in severe angina pectoris–presentation of current studies, indications and clinical experience

    Pain

    (1996)
  • R.W. Hautvast et al.

    Spinal cord stimulation in chronic intractable angina pectoris: a randomized, controlled efficacy study

    Am Heart J

    (1998)
  • M.J. DeJongste et al.

    Efficacy of spinal cord stimulation as adjuvant therapy for intractable angina pectoris: a prospective, randomized clinical studyWorking Group on Neurocardiology

    J Am Coll Cardiol

    (1994)
  • F. Di Pede et al.

    Immediate and long-term clinical outcome after spinal cord stimulation for refractory stable angina pectoris

    Am J Cardiol

    (2003)
  • R. Moore et al.

    Temporary sympathectomy in the treatment of chronic refractory angina

    J Pain Symptom Manage

    (2005)
  • M. Chester et al.

    Long-term benefits of stellate ganglion block in severe chronic refractory angina

    Pain

    (2000)
  • S.G. Blomberg et al.

    Thoracic epidural anaesthesia for treatment of refractory angina pectoris

    Baillieres Clin Anaesthesiol

    (1999)
  • A. Richter et al.

    Effect of thoracic epidural analgesia on refractory angina pectoris: long-term home self-treatment

    J Cardiothorac Vasc Anesth

    (2002)
  • P. Gramling-Babb

    High thoracic epidural analgesia for relief of coronary ischemia syndrome without cardiac surgery

    Tech Reg Anesth Pain Manag

    (2008)
  • P.M. Gramling-Babb et al.

    Preliminary report on high thoracic epidural analgesia: relationship between its therapeutic effects and myocardial blood flow as assessed by stress thallium distribution

    J Cardiothorac Vasc Anesth

    (2000)
  • C. Wettervik et al.

    Endoscopic transthoracic sympathectomy for severe angina

    Lancet

    (1995)
  • C. Mannheimer et al.

    The problem of chronic refractory angina report from the ESC joint study group on the treatment of refractory angina

    Eur Heart J

    (2002)
  • A.B. Bhatt et al.

    Current strategies for the prevention of angina in patients with stable coronary artery disease

    Curr Opin Cardiol

    (2006)
  • T.D. Henry

    A new option for the “no-option” patient with refractory angina?

    Catheter Cardiovasc Interv

    (2009)
  • B. Brorsson et al.

    Quality of life of patients with chronic stable angina before and four years after coronary revascularisation compared with a normal population

    Heart

    (2002)
  • M. McGillion et al.

    Positive shifts in the perceived meaning of cardiac pain following a psychoeducation program for chronic stable angina

    Can J Nurs Res

    (2007)
  • G. Erixson et al.

    Experiences of living with angina pectoris

    Nurs Sci Res Nordic Countries

    (1997)
  • M.H. McGillion et al.

    Learning by heart: a focused group study to determine the self-management learning needs of chronic stable angina patients

    Can J Cardiovasc Nurs

    (2004)
  • C.M. Chow et al.

    Regional variation in self-reported heart disease prevalence in Canada

    Can J Cardiol

    (2005)
  • U. Thadani

    Recurrent and refractory angina following revascularization procedures in patients with stable angina pectoris

    Coron Artery Dis

    (2004)
  • M. McGillion et al.

    Self-management training in refractory angina

    BMJ

    (2008)
  • S.J. Genius

    The proliferation of clinical practice guidelines: professional development or medicine-by-numbers?

    J Am Board Fam Pract

    (2005)
  • D.G. Manuel et al.

    Burden of cardiovascular disease in Canada

    Can J Cardiol

    (2003)
  • S. Stewart et al.

    The current cost of angina pectoris to the national health service in the UK

    Heart

    (2003)
  • G.H. Guyatt et al.

    GRADE: an emerging consensus on rating quality of evidence and strength of recommendations

    BMJ

    (2008)
  • R. Jaeschke et al.

    Use of GRADE grid to reach decisions on clinical practice guidelines when consensus is elusive

    BMJ

    (2008)
  • H.J. Schünemann et al.

    Grading quality of evidence and strength of recommendations for diagnostic tests and strategies

    BMJ

    (2008)
  • R. Kones

    Recent advances in the management of chronic stable angina IIAnti-ischemic therapy, options for refractory angina, risk factor reduction, and revascularization

    Vasc Health Risk Manag

    (2010)
  • Cited by (0)

    See page S36 for disclosure information. The disclosure information of the authors and reviewers is also available from the CCS on the following websites: www.ccs.ca and www.ccsguidelineprograms.ca.

    This statement was developed following a thorough consideration of medical literature and the best available evidence and clinical experience. It represents the consensus of a Canadian panel comprised of multidisciplinary experts on this topic with a mandate to formulate disease-specific recommendations. These recommendations are aimed to provide a reasonable and practical approach to care for specialists and allied health professionals obliged with the duty of bestowing optimal care to patients and families, and can be subject to change as scientific knowledge and technology advance and as practice patterns evolve. The statement is not intended to be a substitute for physicians using their individual judgement in managing clinical care in consultation with the patient, with appropriate regard to all the individual circumstances of the patient, diagnostic and treatment options available and available resources. Adherence to these recommendations will not necessarily produce successful outcomes in every case.

    For a complete list of panelists and collaborators see Appendix I.

    View full text