Heart and Metabolism

Diagnosis, incidence, epidemiology, and treatment of refractory angina

M.R. Chester
Cardiothoracic Centre and National Refractory Angina Centre, Liverpool, UK

Correspondence: Dr M. Chester, National Refractory Angina Centre, Liverpool L14 3PE, UK. Tel: +44 151 2932448/2244, fax: +44 151 2932269, e-mail: ali@angina.org

Abstract

Angina that is refractory to the orthodox cardiac management paradigm is becoming a significant clinical problem. The chronic refractory angina patient is usually a major burden on their family, their family doctors and ‘clog up’ secondary and tertiary service providers. Such recidivist patients who do not improve using conventional models of care commonly earn the epithet “heart-sink”. Faced with such patients the physician is faced with two options. Abandon the conventional paradigm or abandon the patient. The future for these expanding group patients is grim unless we do the right thing. This article sets out a simple, pragmatic and unorthodox approach that merits serious consideration.-Heart Metabol. 2002;16:9–14.

Key words: Angina, patient centered, holistic, multidisciplinary, guidelines

Introduction
Stable angina that persists despite optimal conventional treatment is a major clinical headache. In the past the terminology used to describe this condition included: intractable angina, therapy-resistant angina, uncontrolled angina, and refractory angina. This made any attempt to define the epidemiology of the problem difficult. In 1997, the UK National Refractory Angina Guideline Group recommended that the term chronic refractory angina should be used to describe all patients with a clinical diagnosis of stable angina pectoris that is not controllable with optimal medication and where revascularization is unfeasible
or the risks cannot be justified [1]. It does not included syndrome X. This definition was presented at both the World Congress of Pain meeting in 1999 and the European Congress of Cardiology in 1999 and 2000. The term “intractable angina” is best reserved for the tiny minority of patients with continuous unremitting angina.

Prevalence
The prevalence of chronic refractory angina is unknown; however, in a given population it is likely to be related to the size of the main at-risk population, namely CABG patients. In our own series of over 500 patients with chronic refractory angina, over 95% were referred with recurrent angina following revascularization, the remaining 5% being patients with inoperable disease from the outset. The majority of patients (80%) had previously undergone CABG, many of whom had also undergone angioplasty (PTCA) to native disease or vein graft. Only 15% had undergone PTCA only. Eight patients had undergone the now largely discredited transmyocardial laser procedure.
Data from key angioplasty vs coronary artery surgery studies reveal that more than 20% of angioplasty patients and more than 10% of bypass surgery patients have angina a year after the procedure, often despite repeat revascularization [2, 3]. Vein graft attrition [4], native disease progression [5], and long-term survival [6–8] combine to ensure a steady increase in recurrent angina over time until the death rate matches or exceeds the rate of recurrence. Data from post-CABG angiogram activity and disposal in our own center confirm that there is a strong correlation between the prevalence of post-CABG recurrent angina and the number of CABG survivors multiplied by time after surgery [9].

Management of recurrent angina
Angina recurrence rates and the proportion of patients undergoing repeat revascularization in key PTCA vs CABG trials are shown in Table I.

Table I. Percentage of patients with recurrent angina in angioplasty vs coronary bypass studies.

In these trials the decision to revascularize for recurrent angina was at the clinician’s discretion; comparison with registry data reveals a consistent pattern of practical decision-making. Thus, repeat revascularization rates at 7 years for angioplasty and surgery were 60% and 12%, respectively, and were the same in the BARI trial and registry patients [13]. It is clear from the data that most cardiologists are comfortable with managing recurrent angina whilst angioplasty or surgery is an option. In the absence of any comparative trial data, the preference for PTCA over repeat CABG is based on extrapolation, supported by audit [15], that PTCA is safer though less effective than CABG in the management of postrevascularization recurrent angina.
The lack of prospective clinical trials represents a major challenge for evidence-based cardiology and cardiac surgical practice in determining when repeat revascularization is justified and when alternatives should be tried. There is growing evidence of the safety and efficacy of low-risk nonrevascularization strategies, and the dogged attachment to the anti-ischemia revascularization approach is becoming increasingly hard to justify especially when high-risk palliative procedures are under consideration. Clearly, availability and clinical confidence in the alternatives will vary between centers. In our center the number of patients referred for repeat CABG has fallen dramatically as patients are instead referred to the refractory angina program for outpatient management. Consequently, the prevalence of clinically defined chronic refractory angina will be partly reflected by the availability of low-risk alternatives.

Management of chronic refractory angina
There are a number of nonrevascularization treatment options available for the management of chronic refractory angina and they vary enormously in terms of cost, safety, efficacy, and evidence. The lack of a coherent treatment strategy and consequent gross variation in clinical practice prior to 1998 prompted the inauguration of the UK National Chronic Refractory Angina Guideline Group. This group, jointly commissioned by the UK Pain Society and the British Cardiac Society, has formal representation from the Royal College of General Practitioners, the British Cardiac Patients’ Association, and the International Association for the Study of Pain, and meets regularly to review the guideline in the light of new evidence. In the absence of comparative trials, therapies are ordered pragmatically according to relative risk, reversibility, and simplicity of application. Relative cost is used when therapies are otherwise equally ranked. The first consultation guideline document was produced in November 1998 and was endorsed by the British Cardiovascular Interventional Society, forming the basis for the European Society of Cardiology Refractory Angina Study Group document [16]. The guideline was first published in the British Journal of Cardiology [1] and is available at www.angina.org.

Below is a brief description of the treatment stages. Patients advance through successive stages until they have achieved their objectives or are unwilling to proceed.

A best management stepwise algorithm for patients suffering from chronic refractory angina
Diagnosis
1a Requires a cardiological and cardiothoracic surgical opinion that the patient has angina of ischemic origin and that revascularization is unfeasible or the risks unjustifiable. Regular angiographic review is recommended to exclude the development of “new” revascularizable disease.
1b Outpatient assessment to include:
– review of pain history, drug history, and physical exam;
– evaluation of additional/complicating noncardiac causes of pain (common);
– assessment of functional impairment;
– consideration of depression as a component of the patient’s total pain experience;
– realistic and achievable “treatment targets” should be agreed at this and each subsequent stage.
1c Outpatient therapy to include:
– (re)-education;
– standard risk factor modification;
– explanation of management plan;
– medication optimization.
2 Rehabilitation based on recommended guidelines involving a combination of education, modification of mistaken beliefs in the patient and carer, stress management, and an individually tailored graduated exercise program [17].
3 Transcutaneous electrical nerve stimulation [18].
4 Temporary sympathectomy, stellate ganglion block [19, 20], T3/4 paravertebral block [21], or high thoracic epidural [22].
5 Spinal cord stimulation (SCS) [23–25]: implant data and outcome should be recorded in a registry. Note: Although SCS is licensed for use in “pain,” it does not yet have approval for use in angina in the USA. Conversely, SCS has a grade A SERNIP classification for use in angina in the UK and is in widespread use across the European Union.
6 Opiate analgesia: there is limited evidence of the effectiveness of strong analgesics in refractory angina. Introducing opiates requires extensive pretreatment counseling and careful follow-up. Opiates should be avoided in patients with a history of addiction. Trial of epidural followed by intrathecal opioids may be beneficial if side effects are intolerable [26].
7 Destructive sympathectomy [27].
8 External enhanced counterpulsation [28] undoubtedly has a role in refractory angina management and is currently under review.

Whilst all therapies require further evaluation in clinical trials, the therapies in the following section were considered too high-risk to justify their use in routine clinical practice. We recommend that these therapies should only be undertaken as part of a formal clinical trial except in experienced centers in exceptional circumstances.

1 Myocardial (percutaneous or transmyocardial) laser [29–33].
2 Gene therapy.

Cardiac transplantation has no place in routine management.

Practical tip
There is no doubt that psychology plays a major part in the syndrome, and the starting point of successful management often hinges on an in-depth understanding of how the angina is affecting the life of the individual patient. This takes time and is not suited to a routine follow-up appointment in a busy clinic. By the time the diagnosis is reached, the typical patient will have been revascularized at least once and have been through the mill of cardiological investigations following angina recurrence. It is worth seeing the patient afresh with plenty of time in a new patient clinic. Extra time is needed because by definition the chronic refractory angina patient is unresponsive to the conventional ischemia-centered approach, and a different and unfamiliar holistic patient-centered approach is required.
Since 1997 we have treated over 550 patients with chronic refractory angina in a multidisciplinary clinic, and a useful and illuminating trick is to consider angina as an entity, the primary purpose of which is to erode the patient’s (and his or her carer’s) quality of life. In nearly all patients, angina uses a relatively small number of tools: pain, fear, avoidance behavior (“it hurt so I won’t do it again”), and vicarious avoidance behavior (“it hurts him so I won’t let him do it again”). Understanding which is the dominant tool in a particular clinical situation helps to direct therapy. Anxiety and avoidance behavior are almost always influenced by misconceptions about angina and it is important to address the angina beliefs of the patient and main carers at the initial clinic visit. For example, it is commonly believed that each episode of angina permanently damages the heart and that the patient’s heart must therefore be dangerously weak. Many patients complain that their lives are ruined by angina because they cannot function normally, whereas the truth is that they rarely attempt to function normally for fear of further damaging their already dangerously weakened heart. On the rare occasion that they do try to do something, their spouses, certain that they will do themselves harm, stop them. When such patients, who are usually obese and very unfit, present at the clinic, clinicians often wrongly assume that their condition is the result of laziness rather than of a genuine, though misguided, belief that they will live longer if they do not provoke the angina through regular exercise.
A thorough explanation of the cardiac-neurological-psychological interactions that produce the angina syndrome is invaluable and enables the patient and carer to understand the logic behind the therapies and the order in which they are offered.
Ask one or two patients how they felt when they were told that they were “inoperable.”

Summary
All the available evidence indicates that the size of the chronic refractory angina population will grow inexorably to present a major clinical problem within a decade. Faced with patients who are refractory to the conventional treatment paradigm, the cardiologist can either admit defeat or change strategy. A significant minority of patients will improve once their irrational fears have been identified and confronted. The UK National Refractory Angina Consensus Guideline sets out a logical order in which alternative therapies should be tried, based on the available evidence, and recommends the provision of complex treatment within a patient-centered multidisciplinary framework. The provision of refractory angina management programs makes clinical and economic sense, especially in centers
with relatively high rates of palliative repeat CABG surgery and complex graft
angioplasty.

REFERENCES
1. Chester MR. Chronic refractory angina: time to sort out a neglected and growing problem. Br J Cardiol. 2000;7:108–111.

2: J Am Coll Cardiol 1999 Nov 15;34(6):1750-9