Society guidelinesManagement of Patients With Refractory Angina: Canadian Cardiovascular Society/Canadian Pain Society Joint Guidelines
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.
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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.
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For a complete list of panelists and collaborators see Appendix I.