Refractory angina (RA) is a growing clinical problem. Long-term mortality is better than expected and focus has shifted to improving symptoms, quality of life and psychological morbidity. We established a dedicated multi-disciplinary care pathway for patients with RA and assessed its effect on psychological outcomes, quality of life and polypharmacy. We reviewed electronic health records to capture demographics, changes in medication use, and patient-related outcome measures (Seattle Angina Questionnaire [SAQ] and Hospital Anxiety and Depression Scale) before and after enrolment.
One hundred and ninety patients were referred to our service. Pre- and post-questionnaire data were available in 83 patients. Anxiety and depression scores significantly improved (p<0.05) as well as quality of life and all subcategories of the SAQ (p<0.0001). Patients were most commonly on three or four anti-anginal drugs. In patients with no demonstrable reversible ischaemia, there was a significant reduction in anti-anginal usage (mean reduction of two drugs) after completion of our pathway (p<0.025).
In conclusion, a dedicated multi-disciplinary pathway for RA is associated with improvements in quality of life, mental health and polypharmacy. An ischaemia-driven method to rationalise medication may reduce polypharmacy in patients with RA, particularly in patients with no demonstrable ischaemia.
Refractory angina (RA) is an increasingly common clinical problem due to improved survival from coronary artery disease (CAD) and an ageing population. It is defined as chronic angina-type chest pain (≥3 months in duration) due to myocardial ischaemia in the setting of CAD that persists despite optimal medical therapy, angioplasty or bypass surgery. In the US, between 600,000 and 1.8 million people are living with RA.1,2 Annually, it is estimated that 75,000 new cases are diagnosed in the US and 30,000 to 50,000 in Europe.
Long-term outcomes are better than previously estimated (nine-year life expectancy is 71.6%).3 With persistent symptomatology and associated decline in mental wellbeing, focus has shifted to managing a multi-factorial ‘chronic chest pain syndrome’ and addressing psychological morbidity and quality of life using a multi-disciplinary approach.3-5
Studies to date have been limited by their lack of specificity to RA and few psychosocial end points. Importantly, the role of multi-disciplinary specialised services, which are able to provide the variety of treatments available, has been poorly examined.4-6 There are only three dedicated centres for RA in the UK (Royal Brompton Hospital, Bradford Royal Infirmary and Liverpool Heart and Chest Hospital). Consequently, there is a significant unmet clinical need, given the limited provision of specialist services for what is likely to be a larger number of patients with RA than estimated. In our centre, we established a dedicated multi-disciplinary care pathway for patients with RA (figure 1).6 This included clinical assessment by a cardiologist, followed by a nurse-led programme of education and rehabilitation, relevant further investigations, multi-disciplinary team discussion and a range of therapies as needed, including interventional, neuromodulatory or psychological options. In this study, we created a registry of patients who had gone through this pathway and sought to assess the efficacy of our model and its effect on psychological outcomes, quality of life and medication usage.
We reviewed electronic health records of patients that had been treated in our multi-disciplinary pathway to capture demographics, changes in medication use and patient-related outcome measures (Seattle Angina Questionnaire [SAQ] and Hospital Anxiety and Depression Scale [HADS] scores), before and after enrolment of patients referred between 23 January 2003 and 6 June 2016. Data were collected for anti-anginal medications (e.g. calcium channel blocker, long-acting nitrate, nicorandil, ivabradine and ranolazine) whereas secondary prevention medications (e.g. beta blocker, angiotensin-converting enzyme inhibitor [ACEI]/angiotensin-receptor blocker [ARB], statins and antiplatelet) were also included in this study as an internal negative control. For the patients included in the medication subgroup analysis, changes in ischaemia on functional testing were recorded. Patients lost to follow-up or who had incomplete follow-up data were excluded.
Chi-squared tests were performed to compare categories of HADS scores (normal: 0–7; borderline: 8–10; affected: 11–21) and the percentage of patients on cardiovascular medications. Wilcoxon signed-rank tests were used for non-parametric analyses. Statistical significance was considered at p<0.05. All collation and data analysis was performed on Microsoft Excel and GraphPad Prism version 7. As data were anonymised, collected retrospectively and a part of routine care, no consent was obtained.
A total of 190 patients were referred to our service (male: 81.1%; female: 18.9%). Most patients had Canadian Cardiovascular Society (CCS) class II–III angina (0: 0%; I: 13%; II: 37%; III: 43%; IV: 7%). Mean treatment duration was 259 days. Overall use of the angina plan was high (80.5%; n=153) and 38.9% of patients (n=74) had an onward referral for specialist pain management. Further analysis focused on patients with available complete pre- and post-intervention data.
Quality of life and SAQ domains
Total SAQ score improved by a median of +19 points (p<0.0001) with significant improvements in each domain: physical limitation (Δ score: +8), treatment satisfaction (Δ score: +25) and frequency and perception of symptoms (Δ score: +18) (all p<0.0001) (table 1).
Table 1. Pre and post Seattle Angina Questionnaire (SAQ) scores showing an improvement in each domain
|Outcome||Total (quality of life)||Physical limitation||Frequency and perception||Treatment satisfaction|
|No. of patients||84||83||83||83|
|Median difference (IQR)||+19 (0.25 to 29)||+8 (–3 to 25)||+18 (0 to 35)||+25 (0 to 42)|
|Key: IQR = interquartile range|
Table 2. Pre and post Hospital Anxiety and Depression Scale (HADS) scores showing distribution of scores
|No. of patients||85||85|
|Median difference (IQR)||–1 (–4 to 1)||–1 (–2.5 to 2)|
|Distribution of scores (%)|
|Key: IQR = interquartile range|
Significant improvements in anxiety and depression were observed (n=85) (table 2).
For anxiety, the proportion of patients at baseline with normal, borderline and affected categories were 41%, 24% and 35%, respectively. Following participation, these were 47%, 33% and 20%, respectively (p=0.008), suggesting a significant improvement. For depression, the proportion of patients at baseline with normal, borderline and affected categories were 51%, 32% and 18%, respectively. Following participation, these were 62%, 21% and 17%, respectively, suggesting a trend towards improvement (p=0.067).
Patients with complete medication records on entry to and completion of our pathway were analysed (n=72). The use of disease-modifying secondary prevention medications was high and remained unchanged: statins (89% [pre] vs. 83% [post]), antiplatelets (94% vs. 94%) and ACEI/ARB (79% vs. 83%) (all p>0.05). Analysis of anti-anginal medications showed no change in beta blockers (75% [pre] vs. 65% [post]), calcium channel blockers (63% vs. 56%) or long-acting nitrates (56% vs. 50%). Nicorandil use reduced (51% vs. 39%; p=0.033), while ivabradine (7% vs. 19%; p<0.001) and ranolazine increased (10% vs. 26%; p<0.001).
At baseline, patients were most commonly on three or four anti-anginal drugs (zero: 1%; one: 21%; two: 21%; three: 32%; four: 22%; five: 1%; six: 1%). To assess the relationship between reversible ischaemia on functional testing and anti-anginal use, we stratified patients according to whether they had 1) an increase or 2) no change/reduction in their medication. Reversible ischaemia was assessed predominantly via myocardial perfusion scintigraphy (65% of patients), while dobutamine stress echocardiography (11%) and perfusion cardiac magnetic resonance imaging (MRI) (13%) were also performed. In those with an increase (n=34), there was a significantly increased burden of reversible ischaemia (none: 20%; minor/mild: 50%; moderate: 17%; severe: 13%), compared with those with no change/reduction in their medication (n=38) (none: 44%; minor/mild: 47%; moderate: 9%; severe: 0%) (p<0.001). Importantly, in patients with no ischaemia, we found a significant reduction in anti-anginal usage (mean reduction of two drugs) after completion of our pathway (p<0.025).
Our experience suggests that a multi-disciplinary pathway for patients with RA improves quality of life, psychological outcomes and medication use. Furthermore, a significant proportion of patients with no ischaemia were able to reduce their anti-anginal medications. These preliminary results suggest that an ischaemia-graded strategy can guide and rationalise medication.
Many patients with anginal chest pain are reported as having no evidence of ischaemia on functional testing. There are several potential explanations. First, these patients may have ischaemia secondary to microvascular dysfunction or coronary vasospasm, which may be diagnosed using advanced quantitative perfusion imaging techniques (positron emission tomography [PET] or cardiac MRI [CMR]) or by invasive coronary physiology assessment with pharmacological challenge, which is currently only available in specialist centres. Second, angina may result from an ischaemia burden that is below the detection limit of current imaging techniques, as it is well known that symptom severity is not proportional to the burden of ischaemia. Patients with RA may have a combination of mechanisms of ischaemia both at the epicardial and microcirculatory levels operating simultaneously. Guideline-directed anti-anginal medications often provide inadequate relief of symptoms in patients with RA, many of whom may have associated microvascular dysfunction. There may be scope for psychological and pain-modulatory interventions to improve symptoms and quality of life in these patients, although further studies are needed.
There are various therapies currently available to manage RA, including drugs,5,6 counterpulsatory,7 neuromodulatory,8 and interventional-based treatments.9 Initial studies have suggested that cognitive-behavioural therapy (CBT) improves quality of life and mood in RA.10,11 An intervention embedded within our current pathway is pragmatic rehabilitation, whereby patients are taught cognitive-behavioural self-management techniques and encouraged to manage their own chest pain. The angina plan is a validated tool whereby patient education can be assessed and negative health beliefs corrected.12 Lewin et al. have previously shown it can significantly improve psychological wellbeing, symptomatology and functional status.12 However, their study investigated angina pectoris and was not specific to RA. In our service, the use of the angina plan was high and around a third of patients were referred to a specialist pain management team.
Not only does psychological morbidity increase medical costs in cardiac patients – 41% higher in patients with depression compared with those without – but patients with RA have been shown to accrue significant healthcare-associated costs (about US$10,000 over a three-year period).11,13,14 Although we did not evaluate any potential reduction in healthcare resources, e.g. hospital attendance, we hypothesise that improved psychological morbidity and quality of life, together with an emphasis on patient-led coping strategies will help reduce this resource burden, as suggested previously by Moore et al.15 Dedicated cost-effectiveness studies are needed, which may, in turn, provide a financial incentive for hospitals to adopt such a model.
It is well established that polypharmacy and poor medication adherence are significant barriers in the management of chronic cardiovascular diseases.16,17 Most patients in our study cohort were on three or four anti-anginal medications. Consequently, interventions that are able to reduce the burden of pharmacotherapy are attractive, particularly in patients who have non-cardiac chest pain, who are likely to derive limited benefit and potentially experience adverse effects. We have shown that a multi-disciplinary pathway is associated with reduced anti-anginal medication and rationalisation of polypharmacy, particularly in patients with no demonstrable ischaemia. Signposting these patients towards strategies such as CBT and neuromodulation may achieve greater improvement in symptoms and quality of life.
Limitations to this study include its small size, its retrospective cohort design and lack of a control group. Consequently, sampling and selection bias may exist. Nevertheless, long-term data on the natural progression of morbidity in patients with RA is limited. Only a small number of studies have assessed long-term mortality, not morbidity, but significant morbidity may be inferred from the high costs of rehospitalisation.14 Patients with severe ongoing symptoms should be considered for referral to a specialist angina service. Furthermore, we have observed an association between the degree of reversible ischaemia and rationalisation of pharmacologic management, which raises the hypothesis that there may be a significant element of non-cardiac chest pain in patients RA. Further work in this area is warranted.
RA represents an increasingly challenging problem for clinicians and is associated with a significant burden of psychological morbidity, reduced quality of life and increased healthcare costs. While novel therapies for RA are being investigated, given the importance of a holistic management approach and the benefit of multi-disciplinary expertise, multi-disciplinary services for RA should be considered.
- Refractory angina is a growing clinical problem and patients are often challenging to manage given that they have exhausted conventional treatment options
- Patients with refractory angina suffer from significant morbidity. Management strategies should focus on reducing symptoms and improving quality of life
- The use of specialist angina services with multi-disciplinary expertise may improve patient-reported outcomes
Conflicts of interest
Data were collected from historical hospital records, which was a part of their routine clinical care, and no ethical approval was required.
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