The Burden of Chronic Angina

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Chronic angina is traditionally recognized as the cardinal symptom or manifestion of coronary artery disease (CAD), and worsening angina symptoms signal progression of the underlying pathology.1 Whereas the value of monitoring angina frequency and severity as a metric to identify disease progression is widely accepted, this long-held tradition may have paradoxically obscured the tremendous impact chronic angina pain or discomfort imposes on the daily lives of patients with CAD.

According to the American College of Cardiology/American Heart Association (ACC/AHA) 2002 Guideline Update for the Management of Patients with Chronic Stable Angina, the goals of chronic angina management are two-fold: to reduce morbidity and mortality; and to reduce symptoms. The reduction of symptoms should include complete or nearly complete elimination of angina chest pain or discomfort and a return to normal activities.1 The authors note that it is the reduction of symptoms that is of greater concern when viewed from the perspective of patients with angina. Essentially, patients should return to as normal a life as possible, given their individual circumstances.2

Unfortunately, a significant number of Americans continue to suffer from chronic angina attacks despite medical advances. Because of the intermittent and sometimes unpredictable pattern of chronic angina, patients must often downscale their lives to avoid attacks, which in turn may lead to reduced productivity in the workplace, increased bouts of depression, increased medical costs, and higher out-of-pocket expenses. These, in turn, may increase levels of patient anxiety and lead to angina attacks of greater frequency and severity - essentially sending patients into a downward spiral of worsening angina symptoms and decrements in physical and social functioning despite interventions. Ultimately, patients may have unacceptable quality of life during an era in which medical advances have increased the quantity of their lives.

The AHA reports that 6.8 million patients in the US suffer from angina, and approximately 400,000 new cases of angina are reported annually.3 According to the US Census Bureau, 59.6 million people in the US were 55 years of age or older in March 2002.4 Therefore, based on the estimated prevalence of chronic angina, approximately 9.0% of the group that is 55 years of age or older may be suffering from debilitating chronic angina attacks.

According to the ACC/AHA guidelines, beta-blockers are considered first-line treatment for chronic angina not only because of their documented anti-anginal efficacy but also because of their proven mortality benefit post-myocardial infarction (MI). If beta-blockers are not fully effective or not tolerated by the patient, it is suggested that calcium channel blockers be the next choice of therapy, either to replace beta-blockers, or to be added to them. Patients who are unable to tolerate one or both of these agents, or who do not receive relief from angina, may have a long-acting nitroglycerin agent added to their regimen. Sublingual nitroglycerin in tablet or spray formulations is indicated for the immediate relief of acute angina attacks.1

A large cohort of a contemporary population of non-hospitalized patients who have angina (N = 5,125) was evaluated in 1990 by Pepine et al.5 Patients were not excluded for any type of anti-anginal use other than the need to continually administer nitrates. Despite the use of traditional anti-anginal agents (beta-blockers, calcium channel blockers, and nitrates), as well as mechanical revascularization, patients still reported an average of two angina attacks per week, even though two-thirds of patients were receiving more than one cardiovascular medication. Therefore, using current AHA statistics (6.8 million), an estimated 13.6 million angina attacks are occurring weekly, equivalent to 1,350 angina attacks throughout the US each minute. A meta-analysis of chronic angina medications has also revealed that regardless of whether patients were taking beta-blockers, calcium antagonists, and/or long-acting nitrates, they continued to experience frequent episodes of angina per week and required the same amounts of sublingual nitroglycerin.6

Focal interventions at target lesions do not treat the underlying systemic disease and, despite innovations in revascularization over the past decade, many patients continue to have chronic angina symptoms.The results of the National Heart, Lung, and Blood Institute (NHLBI) Dynamic Registry of Coronary Interventions demonstrated that one year after percutaneous coronary intervention (PCI) 25.6% of all patients reported chronic angina symptoms, and 77.7% were at Canadian Cardiovascular Society Angina Classification (CCS) grades II-IV despite medical and interventional therapy.7

Coronary artery bypass grafts (CABGs), percutaneous transluminal coronary angioplasty (PTCA), and PCI (with stent) are associated with low rates of angina occurrence immediately after the procedure. By as little as six months after the intervention, however, patients had worsening angina symptoms and needed additional interventions.8-9 For example, Serruys et al. found that, at the one-year follow-up, 21% of patients receiving stents and 3.8% of patients who had a CABG required revascularization, 21.1% of stent patients and 10.5% of CABG patients were not angina-free at one year, and 78.9% and 58.5% of stent and surgery patients, respectively, still required anti-anginal medication.10

Long-term studies have also revealed that many patients failed to maintain prolonged benefit with original revascularization strategies. Weintraub et al. evaluated patients with ischemic heart disease who received CABG between 1973 and 1979.Twenty years after the index procedure, 40.1% of patients overall in the study had required repeat CABG.11 Van Domburg et al. evaluated patients who underwent their first elective CABG between 1970 and 1980, and those who received PTCA between 1980 and 1985. More than one-quarter (27%) of the CABG group required revascularization during follow-up and 65% of PTCA patients also required revascularization. Neither CABG nor PTCA provided any survival advantage over the long-term.12

Drug-eluting stents have the potential to reduce post-intervention stenosis by a significant degree. Outcomes at one year for both the sirolimus- and paclitaxel-eluting stents have demonstrated major adverse cardiac event (MACE)-free survival rates in excess of 90%, while MACE-free rates with bare metal stents approximate 80%.13,14 While the need for target vessel revascularization was significantly reduced by drug-eluting stents, their impact on angina recurrence, frequency, and severity at one year have not yet been reported.

A noninvasive strategy is enhanced external counterpulsation (EECP), which uses pneumatic cuffs placed around the lower extremities that inflate sequentially with each diastole, causing aortic counterpulsation, diastolic augmentation, and increased venous return. It is believed to result in improved endothelial function, requires 35 hours over several weeks to complete the full treatment, and is typically reserved for patients refractory to other treatments, most of whom are not eligible for repeat revascularization and are still experiencing angina symptoms classified as CCS III or IV.

Though data from the International EECP Patient Registry showed that approximately three-quarters of patients benefit from the procedure with reductions in angina frequency and sublingual nitroglycerin use, at two years post-intervention this effect diminishes over time, a trend also seen with traditional medical and revascularization strategies.15

Persistence of chronic angina despite intervention may be multi-factorial. Mechanical intervention may be incomplete, either by choice or because of complicated vasculature. Restenosis and reocclusion may occur, though certainly the use of stents (and now drug-eluting stents) in PCI, and the use of internal mammary artery grafts rather than saphenous vein grafts in CABG, have helped reduce the incidence of target vessel revascularization. Finally, disease progression in native vessels cannot be ruled out. Microvascular dysfunction may also play a role in angina persistence.16

When both angina frequency and severity are evaluated in tandem, symptom distress and relief can have a significant impact on both the decline and improvement in patient quality of life (QOL).17 Furthermore, when the condition is so severe that physical functioning is impaired, patient perception of a good quality of life can be negatively affected.18

The burden of angina on patientÔÇÖs lives is often compounded by the burden of additional comorbidities. Several studies have reported the presence of comorbidities such as diabetes, reactive airway disease, peripheral vascular disease (PVD), heart failure and depression.19-23 Each of these conditions compromises patient health and well-being. As a new comorbidity is diagnosed, physical and social functioning are likely to decline further over time.

The downward spiral of worsening angina symptoms and physical and social functioning can be accelerated by the presence of depression. Acute angina attacks can prevent patients from participating in many of their usual activities and may lead to restriction of pleasurable social functions and relationships. Anticipatory anxiety of future attacks and the onset of depression related to the loss of various levels of independence can increase sympathetic tone and decrease parasympathetic activity.

Sequelae of depression may include increased angina frequency and severity, greater platelet reactivity, and higher mortality rates post-MI.24 Symptoms of depression often go under-recognized and under-treated. The resulting increase in angina activity can impose a heavier angina burden and potentially lead to further reduction in physical function, ability to perform daily activities, and socialization.

The burden of chronic angina can be significant, and physical functioning and limitation are critical determinants of overall QOL, even in the presence of comorbidities. Patients are most concerned with reducing angina frequency and severity, and improving physical functioning. If achieved, these outcomes have the potential to dramatically improve the quality of the extended lifespan of patients with chronic angina. Despite many innovations, the pain and discomfort of chronic angina still plagues many patients. Chronic angina is a significant, life-altering condition that continues to be less than optimally managed. Many people who suffer from the chronic and sometimes unpredictable pain or discomfort of chronic angina also experience the additional burden of other chronic illnesses. Patients with chronic angina continue to be challenged by their condition despite medical innovations.

References
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