Treatment of chronic refractory angina pectoris--light at the end of the tunnel?

Despite increasing number of coronary interventions over recent years, there is still a considerable number of patients suffering from chronic refractory angina pectoris. The volume of no option patients is not exactly known, but has been suggested to be 30 per million inhabitants per year; other estimates are 2.5–5% of coronary angiography procedures. The group of no option patients includes those who have angina despite optimal medical therapy; they may not have been offered PCI or CABG because of severe diffuse coronary artery disease, or they who continue to experience severe angina after CABG, PCI, or both. A considerable number of therapeutic strategies have been investigated to treat severe chronic angina, such as transcutaneous electric nerve stimulation (TENS), left stellate ganglion blockade (LSGB), endoscopic thoracoscopic symathectomy (ETS), thoracic epidural anaesthesia (TEDA), external balloon counter pulsation (EECP), stem cell therapy, and finally myocardial laser revascularization by surgical (TMR) or percutaneous (PMR) technique or spinal cord stimulation (SCS). These interventions have been suggested to have primary effect on pain; there is no valid evidence that any of these procedures reduces any clinical major cardiac endpoints. Only a few of these options have undergone the test of randomized studies, so the impact of a placebo effect on pain is largely not known. When trying to orientate in the jungle of mechanical or implant options to decide on how to advice patients, it may be helpful to look at the natural course of chronic refractory angina. We know that this group of patients often are in agony with severe coronary artery disease. It is therefore natural to first look at the data on mortality with drug therapy only. The suggestion of a mortality over 1-year of up to 17% is often quoted, however, there is other evidence suggesting that this figure may be too high. If we look at the medically treated placebo groups of previous myocardial laser studies that did not allow crossover, the 1-year mortality was 1–5% for percutaneous myocardial laser studies and 4–8% for surgical myocardial laser, and 3-year mortality of up to 24%. Spontaneous remissions of even severe angina do occur. Again, looking at the medically treated groups of randomized studies, between 0–19% of patients included in PMR trials and 0–32% for TMR studies had a reduction of at least two CCS angina classes over 12 months, and 0–44% at 3 years. About 7–69% of patients may expect to be re-admitted to hospital for cardiac causes during the first 12 months, but there is no consistent finding in the studies that re-admissions may be reduced by intervention beyond drug therapy. Thus, when considering treatment options that may have their own inherent complications and may be mortality, this must be weighed up against the possible therapeutic benefit and data on the natural course of the disease. We may learn from the past studies that chronic refractory angina is probably not an inert situation but rather has a large variation in symptoms over time. McNab et al. report the results of an open label, single centre, parallel group randomized comparison of SCS and percutaneous myocardial laser (SPIRIT trial). The primary goal was to compare exercise treadmill time; secondary goals were comparison of angina functional class and quality-of-life measurements. They found no difference after 12 months between the two treatments in the main endpoint exercise time, nor in the secondary angina endpoint. PMR/SCS-related events during 12 months were 3 vs. 27, respectively. There were no serious events related to therapy. Neither of the two treatment options used in the study is widely used, both treatment procedures carry a certain risk. SCS procedure requires co-operation between anaesthetists and cardiologist, and the study was conducted in a tertiary referral centre. Consequently, the study population is rather small, but the statistical power calculation must be accepted; hence, we accept the main conclusion that there is little evidence of a difference between the two therapies. The interpretation of the comparison of angina is not so clear because the impact of placebo or the validation of interpretation of angina after a one-time procedure vs. a permanent implant may be uncertain. Another drawback with this trial is that it was