SCS for the treatment of refractory angina

Spinal cord stimulation (SCS) is well-established for the treatment of common conditions such as failed back surgery syndrome (FBSS) and complex regional pain syndrome (CRPS).1 It was identified as an efficacious treatment for refractory angina in 1987, but high-powered randomised controlled trials (RCT) providing strong cost, safety and efficacy data have been lacking. The potential use of SCS as a routine treatment option for refractory angina is still under investigation.2

SCS involves the implantation of electrodes into the epidural space near the source of pain. The electrodes, stimulated by an external or internal power source, emit a current that stimulates the dorsal columns and produces a level of paraesthesia. SCS has also been associated with increased and redistributed blood flow as well as normalisation of the intrinsic cardiac nervous system. Though these are not confirmed methods of action for the positive effects seen in refractory angina patients, they are thought to play a role in decreasing the severity of ischaemic changes observed during ECG recording.²

Chronic refractory angina is estimated to affect 100,000 people in Europe and similarly in the US.³In Australia, refractory angina is thought to affect 2% of the population.⁴

A/Prof Brendan McQuillan, Consultant Cardiologist and Medical Director of Virtual Cardiac Centre, said, "While chronic stable angina affects approximately 7 to 10% of the adult population, only a minority suffer truly refractory angina – perhaps 5 to 10 per thousand."

Dr McQuillan said, "It is essential that a management plan for angina patients includes careful assessment of the underlying cause of their symptoms: not all chest pain in subjects with known coronary artery disease is angina. Failure to do this is a common reason for ongoing angina among patients with coronary artery disease. That said, for the relatively few patients with truly refractory angina pectoris, a range of potential therapies are emerging."

Pharmacotherapies and procedures to treat heart disease and coronary events are improving, and so are survival rates for this patient population. With this, the numbers of people with refractory angina are increasing. Accordingly, there is a need to review cost and efficacy for the therapy options indicated for its treatment.²

Cardiologist at Sir Charles Gardiner Hospital and Clinical Professor at the University of Western Australia Peter Thompson believes the current treatment options are in most cases successful in treating refractory angina. He said, "Coronary revascularisation (CABG or PCI) has a high patient satisfaction rate. Medical treatment s may require lifestyle modification – such as restriction of exercise and avoidance of some activities – which may be unacceptable to some patients. Some treatments cause significant side effects. For example, nitrates cause headache, beta blockers cause cold peripheries, and calcium channel blockers cause constipation. But most people can return to a normal lifestyle."

Professor Thompson said, "If [coronary revascularisation] fails, a review of medication by an experienced cardiologist can often recognise significant undertreatment with standard therapies such as beta blockers, nitrates and calcium channel blockers, and prophylactic use of nitroglycerin. When these fail, the use of treatments without a large evidence base is considered."

The first meta-analysis for SCS in the treatment of refractory angina was published recently. The results for SCS were positive but not conclusive.²

Methods

Authors conducted a search of the literature for RCTs that investigated the use of SCS for the treatment of refractory angina. Comparator treatments included either percutaneous myocardial laser revascularisation (PMR) or coronary artery bypass grafting (CABG). Studies were also selected if they compared the use of SCS (SCS-ON) with no SCS or SCS when switched off (SCS-OFF). Seven RCTs were analysed, totalling 270 patients.²

The outcomes measured in the trials included:²

Exercise capacity, including exercise duration, maximum oxygen uptake and peak workload;
Frequency and magnitude of ST-depression, termed ischaemic burden, measured via prolonged ECG monitoring;
Nitrate drug consumption;
Functional class;
Health-related quality of life; and
Adverse events and SCS-related complications.

The outcomes were compared within-group and between-group, and the standardised mean difference was calculated for outcomes that measured the same parameter in different ways.²

Results

Compared to no stimulation, SCS significantly improved exercise capacity, similarly to improvements seen in PMR or CABG.²

No significant differences were found between any of the comparators for ischaemic burden, although a slight trend was identified for a decrease in burden in SCS-ON versus SCS-OFF. Further studies will need to confirm the significance of this trend.²

Directly following the relevant procedure, SCS was found to decrease nitrate drug consumption for the first 6 months of treatment.²

Canadian Cardiovascular Class was found to be lower for SCS patients at 3 and 12 months post-implant, compared to those receiving PMR.²

SCS, PMR and CABG all similarly increased health-related quality of life scores within-group. No significant between-group differences were found.²

The adverse events for SCS included infections, lead migration and lead fracture. The risk analysis for adverse events for SCS was not significantly different from those associated with PMR.²

Cost-effectiveness analysis

Only one trial selected for the analysis reported costs. SCS patients required less days in hospital than patients with the comparator treatment, CABG. Taking this into account as well as associated follow up costs, SCS was significantly less expensive.²

Conclusions

Compared to no SCS or an inactive control, SCS improves exercise capacity and health-related quality of life for refractory angina patients. SCS was just as effective and safe as PMR or CABG.However, the study authors caution that more evidence is required before any conclusive statements can be made regarding the potential for SCS as a primary treatment option for refractory angina.²

There were several limitations to this study. Firstly, there is no stand out first-line treatment for refractory angina, which makes comparing SCS difficult. Studies investigating SCS for refractory angina treatment use various comparator treatments, which makes gaining enough power for meta-analysis difficult. Furthermore, no SCS study can be sufficiently "placebo-controlled". Although some trials use the inactive control SCS-OFF, due to the nature and intensity of the paraesthesia experienced, patients will always know whether their SCS device is switched on or off.²

Rod Taylor, first author on the paper under review, commented on current and further research needed in the area. "In the UK, the National Institute for Health and Clinical Excellence (NICE) concluded that the current evidence was insufficient to recommend SCS as routine treatment for refractory angina. NICE called for real world randomised controlled trials that assess the impact of SCS in the context of best supportive care. Such studies need to collect data on healthcare utilisation and costs so that the clinical and cost effectiveness of SCS for refractory angina can be fully assessed."^2,5

References

Simpson EL, Duenas A, Holmes MW, Papaioannou D, Chilcott J. Spinal cord stimulation for chronic pain of neuropathic or ischaemic origin: systematic review and economic evaluation. Health Technol Assess. 2009; 13(17): 1-154.
Taylor RS, De Vries J, Buchser E, DeJongste MJL. Spinal cord stimulation in the treatment of refractory angina: systematic review and meta-analysis of randomised controlled trials. BMC Cardiovasc Disord. 2009; 9: 13.
DeJongste MJL, Tio RA, Foreman RD. Chronic therapeutically refractory angina pectoris. Heart. 2004; 90(2): 225-30.
Kumar P, Clark M. Clinical Medicine. 5^th ed. Sydney: WB Saunders; 2002.
National Institute for Health and Clinical Excellence. Spinal cord stimulation for chronic pain of neuropathic or ischaemic origin [online]. 14 October 2008. [cited 2 November 2009]. Available from URL: http://guidance.nice.org.uk/TA159/Guidance/pdf/English