Chronic stable angina is a fairly common clinical syndrome. In the United States, it has been reported that the annual incidence of angina in patients older than 30 years is 213 per 100,000.1 It has also been estimated that currently 16.5 million Americans have stable angina.2 The incidence of stable angina from chronic ischemic heart disease is likely to increase in the future because of an aging population and improved survival of patients with acute coronary syndromes. The World Health Organization projects that in the year 2020 coronary artery disease will still remain a major disease burden, accounting for 5.9% of the total global disease burden and 11.2% of that in developed countries.3
In approximately 50% of patients with ischemic heart disease, chronic stable angina is the initial manifestation.2 Chronic stable angina is not a benign clinical entity. It is associated with considerable morbidity and mortality. The rate of myocardial infarction (MI) is about 3% to 3.5% in patients with angina, affecting approximately 1 million patients per year in the United States.
The economic burden is also considerable. The annual Medicare payments for the evaluation and management of stable angina are approximately $7.5 billion, with total hospitalization costs including non-Medicare patients being almost twice this amount. Thus, future studies should address how to reduce the morbidity, mortality, and economic burden associated with treating patients with chronic stable angina. Drs. Janarthanan and Alpert lucidly describe the pathophysiologic mechanisms of stable angina that result from myocardial ischemia, which is caused by an imbalance between myocardial oxygen demand and oxygen supply. Myocardial ischemia may occur from an excessive increase in myocardial oxygen demand or from a primary decrease in oxygen supply because of decreased coronary blood flow. The principal abnormality inducing myocardial ischemia, however, may not be the same in all the clinical subsets of stable angina (table).4 In patients with classic angina (angina of effort), an excessive increase in myocardial oxygen demand is the principal mechanism (demand ischemia). In patients with vasospastic angina, a focal spasm of an epicardial coronary artery decreases coronary blood flow and induces myocardial ischemia (supply ischemia). In those with linked angina, walk-through angina, postprandial angina, and syndrome X, increased coronary vascular resistance decreasing coronary blood flow is the principal mechanism of myocardial ischemia. In some clinical subsets, such as mixed angina, increased myocardial oxygen demand and increased coronary vascular resistance contribute to myocardial ischemia. An understanding of the mechanisms of myocardial ischemia in the various clinical subsets of angina is necessary for appropriate management. Future studies that delineate the precise mechanisms of dynamic changes in myocardial oxygen demand and coronary vascular tone will improve treatment of patients with chronic stable angina.
Drs. Janarthanan and Alpert’s detailed review of the management of stable angina shows two major objectives of treatment. The first is to decrease the risks of death and MI, and the second is to relieve myocardial ischemia and its major symptom, angina. Antiplatelet drugs, such as aspirin and clopidogrel,
and angiotensin-converting enzyme inhibitors, beta-adrenergic antagonists, and lipid-lowering agents (HMG-CoA reductase inhibitors [statins]), have been proved to decrease morbidity and mortality. All patients with ischemic heart disease should receive these therapies.
Concomitant therapies to modify risk factors (diabetes, hypertension, obesity, and smoking) should be implemented. Clinicians should understand that the treatments presently available are only partially successful in reducing risks of death and MI. Research must continue to develop newer treatments to further reduce morbidity and mortality. A promising treatment, infusion of apolipoprotein MILANO, has been reported to cause rapid regression of atherosclerotic plaque.
The conventional pharmacotherapy for relief of angina and myocardial ischemia, as outlined by Drs. Janarthanan and Alpert, consists of beta-adrenergic antagonists, nitrates, and calcium channel blocking agents. Nonpharmacotherapy is catheter-based or surgical revascularization. Because the incidence of refractory angina is increasing, research must continue to discover newer treatments for angina. Enhanced external counterpulsation is already an approved therapy for refractory angina.
Several pharmacologic agents are undergoing clinical trials and a few appear promising. Nicorandil, a potassium channel activator, not only decreases myocardial oxygen demand and improves myocardial perfusion, but also possesses cardioprotective effects. Ranolazine, a partial inhibitor of free fatty acid oxidation, reduces myocardial ischemia by increasing myocardial oxygen supply without increasing coronary blood flow or changing myocardial oxygen demand. Angiogenic gene therapy with adenovirus 5 fibroblast growth factor-4 also shows potential for treating angina.5 These promising new therapies indicate it is reasonable to be optimistic about the future management of myocardial ischemia and angina.