Cardiovascular diseases are among the largest global concern, given it’s prevalence, incidence, mortality, hospital setting and economic impact.
Angina is the main clinical manifestation of chronic coronary heart disease. Among grading classifications of angina, the most accepted worldwide is the Canadian Cardiovascular Society Angina Classification (CCSAC), which is the most reproducible classification.
Table 1. Classification of angina pectoris (CCSAC), according to Canadian Cardiovascular Society.
I - Ordinary physical activities (e.g. walking, climbing stairs) do not cause angina, this occurs only after fast, prolonged and strenuous exercise during work or recreation.
II - Slight limitation to ordinary activities. Angina occurs when climbing stairs rapidly, walking uphill, walking or climbing stairs after meals, in cold weather, with wind conditions or under emotional stress, or during the first hours after waking, when walking more than two blocks on a flat surface, or climbing more than one flight of stairs at normal rhythm and conditions.
III - Significant limitation of ordinary physical activity. Angina occurs when walking one or two blocks on a flat surface or climbing a flight of stairs at normal rhythm and conditions.
IV - Inability to perform any physical activity without discomfort, symptoms of angina may be present at rest.
Despite appropriate identification, diagnosis, stratification and treatment, a subgroup of patients with coronary disease have refractory ischemic symptoms and intractability of their clinical condition, not responding both to conventional pharmacological therapy and available revascularization techniques.
The European Cardiology Society, in consensus committee, defined refractory angina pectoris as a "chronic condition characterized by the presence of angina caused by coronary insufficiency in the presence of coronary artery disease, which cannot be controlled by the combination of pharmacological therapy, angioplasty and myocardial revascularization surgery. The presence of reversible myocardial ischemia should be clinically established as the cause of symptoms. Angina classification as chronic is defined as lasting more than three months."
Two criteria need to be met before patients are diagnosed as suffering from refractory angina pectoris: Objective myocardial ischemia must produce severe anginal symptoms; and all known conventional therapies have been thoroughly tried and exhausted. The scientific literature calls them "no-option patients".
As a result of constant scientific and technological advances in the cardiovascular area, this subgroup of patients with refractory angina is growing rapidly.
More than 100,000 patients annually are diagnosed as having refractory angina. Of 500 consecutive angiograms performed in the "Cleveland Clinic" in 1998, 59 (12%) had evidence of ischemia and were not candidates for conventional revascularization techniques9. The European Society of Cardiology estimates that 15% of patients who have angina can be characterized as presenting it in refractory type11. Data from the "Mayo Clinic" of 2005 indicates that approximately 150,000 to 250,000 patients per year diagnosed with Class III and IV angina are considered refractory.
Surprisingly, and of paramount importance to the proposition of any treatment modalities, the ventricular function of patients with refractory angina remains relatively preserved despite the refractoriness of their disease.
We can conclude, then, from the above, that the greatest challenge for patients with refractory angina is the very persistent angina and poor quality of life.
The pharmacological treatment always presents itself as a first and supportive option despite the addition of any other types of treatments. It is primary and indispensable the use of acetylsalicylic acid (ASA), beta blockers, angiotensin-converting enzyme (ACE) inhibitors, calcium channel blockers and long-acting nitrates in the highest tolerated doses. Administration of sublingual nitrates (nitroglycerin) provides immediate relief of acute angina symptoms. Statins are also indicated, because they improve endothelial function, besides having anti-inflammatory activity.
Guidelines of the "American Heart Association/American College of Cardiology" provides little information about refractory angina treatment. Among guidelines, there are transmyocardial revascularization "LASER" (Class IIa, Level of Evidence A); maximized external counterpulsation (Class IIb, Level of Evidence B) and spinal cord stimulation - neuromodulation (Class IIb, Level of Evidence B). None of these treatments have sustained efficacy in randomized trials.