Trials and tribulations associated with angina and traditional therapeutic approaches

Ischemic heart disease is the foremost cause of death in the United States and the developed countries. Stable angina is the initial manifestation of ischemic heart disease in one half of the patients and becomes a recurrent symptom in survivors of myocardial infarction (MI) and other forms of acute coronary syndromes (ACS). There are multiple therapeutic modalities currently available for treatment of anginal symptoms in patients with stable CAD. These include anti-anginal drugs and myocardial revascularization procedures such as coronary artery bypass graft surgery (CABGS), percutaneous transluminal coronary angioplasty (PTCA) and percutaneous coronary intervention (PCI). Anti-anginal drug therapy is based on treatment with nitrates, beta blockers, and calcium channel blockers. A newly approved antianginal drug, ranolazine, is undergoing phase III evaluation. Not infrequently, combination therapy is often necessary for adequate symptom control in some patients with stable angina. However, there has not been a systematic evaluation of individual or combination antianginal drug therapy on hard clinical end points in patients with stable angina. Most revascularization trials that have evaluated treatment with CABGS, PTCA, or PCI in patients with chronic CAD and stable angina have not shown significant improvement in survival or decreased incidence of non-fatal MI compared to medical treatment. In the CABGS trials, various post-hoc analyses have identified several smaller subgroups at high-risk in whom CABGS might improve clinical outcomes. However, there are conflicting findings in different reports and these findings are further compromised due to the heterogeneous groups of patients in these trials. Moreover, no prospective randomized controlled trial (RCT) has confirmed an advantage of CABGS, compared to medical treatment, in reduction of hard clinical outcomes in any of the high-risk subgroups. Based on the available data, it appears reasonable to conclude that for most patients (except perhaps in those with presence of left main disease > 50% stenosis) there is no apparent survival benefit of CABGS compared to medical therapy in stable CAD patients with angina. Although these trial have reported better symptom control associated with the revascularization intervention in most patients, this has not been adequately compared using modern medical therapies. Available data from recent studies also suggest treatment with an angiotensin converting enzyme inhibitor (ACEI), a statin and a regular exercise regimen in patients with stable CAD and angina pectoris.