Chronic Refractory Angina

Development of a clinical management guideline for chronic refractory angina: The UK National Refractory Angina Guideline Group experience1997-1999.

The case for a coherent approach to refractory angina management is overwhelming. In this document I will briefly review the general approach to guideline development and I will outline the UK national refractory angina guideline groups experience over the past 2 years.

Background to general guideline development

Definition of terms

Practice guidelines are ‘systematically developed statements to assist practitioner and patient decisions about appropriate health care for specific clinical circumstances (Field & Lohr 1992). Thus a clear consensus on the definition of the specific clinical condition or disease state is a pre requisite (this is of special importance in chronic refractory angina, see below).

The UK Regional Group on Clinical Protocols and Guidelines recommend that the following factors should be considered when selecting topics for guideline development. All of these are pertinent to a guideline for chronic refractory angina.

Assessment of evidence and formulation of recommendations

There are 4 guideline development methods.

* The informal consensus guideline approach is simplest and cheapest guideline development tool and therefore the most widely used in the UK. The choice of methodology clearly involves consideration of the state of the evidence base.

Core working group

A preliminary core working group must be convened to make the initial assessment of the evidence base and initiate the subsequent steps. The core group should familiarise themselves with the clinical issues involved in refractory angina management and clinical guideline development through a combination of literature review and direct personal contacts with experts in the field before embarking on subsequent stages of the process.

Guideline Group development (Report of the Clinical Guidelines Working Group., 1995).

A guideline group must be assembled in order to carry out the tasks required for guideline development and group design is important. It is essential that the group has adequate expert representation in each of the relevant areas including users (Bond 1995). The range of therapies and disciplines involved in RAP means that a large multidisciplinary group design is required. Consequently the problems of bias inherent in small groups not an issue (Scott 1990; Newton 1992 ).

Multidisciplinary groups have special problems that need to be addressed at the outset (Bond 1995). Guideline groups should have leaders "whose disinterested position is unquestioned by any of the concerned parties but whose expertise in co ordinating groups of health professionals is accepted by all (Fink 1984). The role of the co ordinator is to ensure that the group adequately addresses its tasks. The starting point must be reinterpretation of the task of the group and to arrive at a consensus about aims and objectives (Bond 1995).

Wider consultation

Peer review and consultation is essential and the guideline design should be able to take account of feedback in reaching the final stage of the guideline document. A number of consultation approaches are available and includes consensus conferences, focus groups and surveys. Piloting guidelines locally can be a useful method of further evaluating the guideline in practice.

Desirable attributes of a clinical guideline

(adapted from Grimshaw 1993)

The UK national refractory angina guideline group experience 1997-1999

The Liverpool Cardiothoracic Centre (CTC) serves a population of 2.8 million patients and performs over 2,000 revascularisation procedures annually. This is around 5% of the total UK angina activity. Despite tremendous technical advances which enable interventional cardiologists and cardiac surgeons to treat more and more complex disease there are patients who cannot be treated by revascularisation. Audit of activity over the past decade has revealed a steady growth in a number of patients presenting with refractory angina at the CTC. In response to this problem in 1996 the CTC set up the first multi-disciplinary angina research and treatment programme in the UK.

As part of the clinical management policy at the hospital we developed a process for producing practical local clinical guidelines. An essential part of that process involved a systematic literature review and consultation with colleagues both locally and at other specialist centres elsewhere in the UK and beyond. In 1997 we audited management strategies offered to refractory angina sufferers in the UK cardiologists and pain specialists. This revealed gross variation in clinical practice with little or no interaction between the clinical disciplines. Thus an individual patient presenting with RAP might be offered 8 different therapies depending on the interests and expertise of their consultant ranging from simple counselling through neuromodulation to cardiac transplantation. More importantly these therapies vary enormously in terms of cost, safety and efficacy. This variation in clinical practice is clearly unacceptable and properly developed and enacted practice guidelines should be the most effective way to improve this situation. Before Dec 1998 no practice guideline existed and a recent survey revealed that the vast majority of UK cardiologists and pain specialists who responded agreed that a practice guideline for refractory angina is desirable.

An important starting point in the development of refractory angina guidelines must be an agreed definition of terms. Several interchangeable terms are in use: intractable angina, end stage angina, resistant angina and refractory angina. In order to avoid the confusion generated by this in March 1999 we proposed that the following definition should be adopted.

Aim: The aim of the group is to improve the standard of care of patients with refractory angina through the development of a pragmatic clinical guideline

The first step involved an evaluation of published literature and guideline recommendations by the core group consisting of Dr. A Leach pain specialist, Dr C Hammond cardiology research fellow and myself in consultation with local colleagues.

We took account of these recommendations in designing the refractory angina guideline process. The primary objective of clinical guideline development is that the guidelines produced should lead to an improvement in care. Clearly it is essential that colleagues who manage such patients are comfortable adopting a new treatment algorithm. This requires confidence in the process and that practical benefits will accrue for the patients in their care.

Guideline development methodology is a rapidly moving area and important initiatives (i.e. NICE) are underway within the NHS. Therefore the guideline process was designed to accommodate new pertinent guideline recommendations. Subsequently we have consulted recognised guideline specialists e.g. Prof. M. Eccles Senior Lecturer, University of Newcastle and Dr. F. Cluzeau Lecturer, Healthcare Evaluation Unit at St George’s Hospital Medical School.

Refractory angina management is unusually complex and none of the multiple refractory angina therapies in use have been compared directly and when treatments have been adequately studied different disciplines tend to measure different end points thus rendering standardised comparison between treatments difficult. Moreover since the primary objective of treatment is the improvement of quality of life through the amelioration of angina it is of critical importance that with the exception of one small study in 1965 none of the treatments have been evaluated in a randomised placebo controlled trial. In addition the initial systematic review showed that there was insufficient data for a pure evidence linked or evaluative guideline model. We therefore elected to develop the guideline in stages beginning with a formal consensus approach involving structured data presentation to an invited multidisciplinary audience followed by a modified Delphi method of ranking based on subjective evaluation of the quality of the data. In order to assist ranking it was proposed and subsequently agreed that simple, safe and low cost procedures should be ranked high e.g. TENS whereas high risk, high cost procedures such as transmyocardial laser or transplantation should be ranked low.

Having decided on a guideline model, the second step was to build up a network of expert clinicians from whom a guideline group could be drawn. Cardiologists and cardiac surgeon are all members of the British Cardiac Society and Council members were approached for advice on appropriate representatives. Likewise most of the non-cardiac disciplines involved in refractory angina management are members of the Pain Societies. Therefore in 1998 we established a Refractory Angina special interest group (SIG) within the UK Pain Society with support from Council. A refractory angina SIG has also been established within the International Association for the Study of Pain and is based on the UK model.

The third step was to bring together a representative multi disciplinary group of respected UK clinicians to reach a consensus on a management algorithm for the refractory angina within the NHS. These were identified through personal contact, peer recommendation and literature review.

The group includes: Prof. David Brodie (rehabilitation), Dr. Michael Chester (cardiologist and group convenor), Dr. Alf Collins (pain specialist), Dr. Mark DeBelder (cardiologist) Mr. Brian Fabri (cardiac surgery), Dr. Austin Leach (pain specialist), Prof. Bob Lewin (psychology & rehabilitation), Mr. Neil Moat (cardiac surgery), Dr. David Ramsdale (cardiologist & BCS representative), Mr. Abbas Rashid (cardiac surgery), Dr. Peter Schofield (cardiologist), Dr. Simon Thompson (pain specialist). In May three new members joined the group Dr. Mike Colquhoun representing the Royal College of General Practitioners, Mrs. Eve Knight representing the British Cardiac Patients Association, Dr. Mark Jackson (health service management and health economics).

A panel of acknowledged experts provided an international perspective: Prof. Gianni Angelini, Dr. Filipo Crea, Dr. Mike DeJongste, Clas Mannheimer and Prof. Patrick Wall.

The guideline group was divided into specialist focus groups and were asked to evaluate and summarise the current evidence base for their speciality. In addition each member of the group was asked to consult locally and produce a pragmatic treatment pathway. Completed proposals were forwarded to the coordinator (MC). The documents were collated and distributed to the group.

The first formal meeting of the group took place at prior to the First International Refractory Angina Workshop meeting on the 5th November 1998. The guideline group came to a consensus view on the definition of refractory angina, confirmed the aims of the initiative and the ranking method. The meeting, expressly designed as a vehicle for the guideline process was widely advertised in specialist newsletters as well as by mailshots and direct invitation. A multi disciplinary audience clinicians involved in refractory angina management attended the workshop. Each expert speaker presented an overview of the evidence base for each treatment modality in use in the UK (including heroic angioplasty, heroic cardiac surgery, multidisciplinary cognitive behavioural therapy, rehabilitation, transcutaneous nerve stimulation, spinal cord stimulation, cardiac sympathectomy (including ganglion blockade, epidurals, destructive sympathectomy and transplantation), opioids, urokinase and laser revascularisation. Note: External counterpulsation is not in use in the UK but will be considered at the next meeting. There was a ten minute discussion period at the end of each presentation. At the end of the meeting the days key points were summarised following which there was a thirty minute period of debate involving all participants. At 17.15 hrs all participants were asked to set out the best treatment algorithm with first line therapy numbered 1 along with relevant comments. The score for each therapy was averaged and this defined its position in the algorithm. The guideline group reached a consensus on the algorithm subsequently published as ‘Draft proposal Dec 1998 based on this information. Dr. Austin Leach as secretary of the Pain society refractory angina SIG has provided a detailed summary of the proceedings. Each presentation has been written up as a series of documents and will be published in the British Journal of Cardiology shortly.

The draft guideline proposal Dec 1998 was widely circulated to all UK cardiologists for peer review. In Feb 1999 the provisional guideline was officially endorsed by the British Cardiovascular Interventional Society. The British Cardiac Society, the Royal College of General Practitioners and the British Cardiac Patients Association have all recognised the guideline group and each has a named representative in the group.

The second guideline meeting took place in May 1999. All participants had reviewed the literature and the meeting was designed to facilitate a review of the guideline and revise the algorithm if necessary. The current May 1999 guideline reflects the minor revisions arising from that meeting and took account of the wide consultation process (including the outcome of the first meeting of the ESC refractory angina study group.

The guideline was adopted as official policy and we have systematically evaluated algorithm in 74 consecutive patients with refractory angina referred to the National refractory angina centre since Jan. 1st 1999. In addition to the Liverpool CTC, the provisional guideline has already been adopted by several of the other major cardiothoracic units in the UK.

The provisional guideline has been lodged with NICE and the guideline was presented at the first meeting of NICE in Harrogate, UK in December 1999.

What follows is the current ‘consensus’ evidence linked treatment algorithm. The final guideline document will be produced following a year long consultation process and clinical pilot in March 2000.

Draft guideline: This document is designed to open the debate to a wide audience on the "best management stepwise algorithm" for patients suffering with chronic refractory angina. The authors stress that it is a draft proposal and that individual practitioners will have to take account of local resource provision.

Diagnosis

1. Requires a cardiological and cardiothoracic surgical opinion that the patient has angina of ischaemic origin and that revascularisation is unfeasible. Regular angiographic review is recommended to exclude the development of ‘new’ revascularisable disease.

2. Outpatient assessment to include: Review of pain history, drug history and physical exam. It is essential to ensure that the patient has failed to respond to maximum tolerable medication. Poor compliance should be considered and the need for compliance explained. Simplification of the drug regimen is recommended.

3. Exclude non-cardiac causes e.g. costrochondritis, intercostal neuralgia, anaemia, thyrotoxicosis, reflux oesophagitis (consider trial of proton pump inhibitors.

4. It is important that consider the possibility that depressive disease may contribute a significant component to their total pain experience. The HAD questionnaire is a simple screening tool that can help to identify patients who might benefit from psychiatric or psychological assessment.

1. Outpatient counselling to include explanation of management plan, lifestyle advice (diet, smoking, physical activity. A realistic and achievable ‘pain contract’ should be decided on so that the patient, their family and the clinical treatment team have an agreed objective.

2. Rehabilitation. Based on recommended guidelines: involving exercise programme, lifestyle advice, relaxation training.

3. Multidisciplinary cognitive behavioural pain management programme. If appropriate-based on established psychological assessment methods e.g. Hospital Anxiety and Depression score. A formal psychological assessment can be of value especially in determining whether formal psychotherapy may be of value.

4. Transcutaneous electrical nerve stimulation (TENS).

5. Temporary sympathectomy. Stellate ganglion block, T3/4 paravertebral block in stages. High thoracic epidural. Based on the Liverpool protocol

6. Spinal cord stimulation (SCS). Implant data and outcome should be recorded in a registry.

7. Opioids. There is limited evidence of the effectiveness of opioids in refractory angina. In clinical practice oral and transdermal opioids can be effective. Trial of epidural followed by intrathecal opioids might be beneficial.

8. Destructive sympathectomy. Thoracoscopic, surgical, phenol depending on local expertise.

9. Myocardial Laser (percutaneous or transmyocardial). There is insufficient data to support this therapy outside clinical research. We recommend that these therapies should only be undertaken as part of a formal clinical trial.

Angina alone is not an indication for cardiac transplantation

Recommendations

• ‘Refractory angina’ as proposed above is a pragmatic diagnosis in the absence of an agreed definition. A consensus view by the profession will be sought through consultation

• Closer links between cardiologists and pain specialists is essential.

• There is a striking lack of randomised controlled trials (RCTs) in this area. Clearly a great deal of research is required. There is an overwhelming case for comparative studies.

• The UK National refractory angina guideline group are working with overseas organisations to encourage them to adopt these guidelines (EFIC, ESC, APS, IASP, ISC).

References

Bond CM & Grimshaw JM (1995) Multidisciplinary guideline development: a case study from community pharmacy. Health Bulletin 53, 29-36.

Field & Lohr eds (1992) Guidelines for Clinical Practice. From Development to Use. National Academy Press, Institute of Medicine,Washington.

Fink A, Kosecoff J, Chassin M et al. (1984) Consensus methods: characteristics and guidelines for use. American Journal of Public Health 74, 979-83.

Grimshaw J & Russell I (1993) Achieving health gains through clinical guidelines: Developing scientifically valid guidelines. Quality in Health Care 2,243-8

Newton JC, Hutchinson A, Steen IN et al. (1992) Educational potential of medical audit: observations from a study of small groups setting standards. Quality in Health Care 1, 256-9.

Report of the Clinical Guidelines Working Group (1995) The development and Implementation of Clinical Guidelines. Royal College of General Practitioners Ch 2,8-11

Scott EA, Black N (1992) When does consensus exist in expert panels. J Pub Health 13,35-39

Scott M and Marinker ML (1990) Small group work. In Markinker ML (Ed.) Medical Audit and General Practice. London, British Medical Journal, pp. 185-95.

For more information, queries or comments please contact:

Dr. M Chester.

UK National Refractory Angina Guideline Coordinator,

National Refractory Angina Centre,

CTC, Liverpool L14 3PE.

Email: refractory.angina@ccl-tr.nwest.nhs.uk