1. Contemporary Management of Myocardial Ischemia
As the population ages, ischemic heart disease is projected to be a major public health concern.
Traditional concepts about the pathophysiology of myocardial ischemia have recently been challenged and new insights into the mechanisms causing this condition have been postulated.
New anti-ischemic and antianginal medications are emerging with novel mechanisms of action; their potential role in patient management is the subject of this slide kit.

2. Epidemiology of chronic ischemia (angina)
6.5–16.5 million Americans suffer with angina pectoris
Despite therapeutic advances
>13 million episodes of angina per week in the US
>1000 episodes of angina every minute
Growing prevalence of chronic ischemia (angina) due to residual CAD after PCI and CABG
Improved treatment of recurring ischemia (angina) is an important goal
Epidemiology of chronic ischemia (angina)
Estimates of the number of individuals with symptomatic ischemia range widely from 6.5 million (most recent AHA statistics) to 16.5 million (ACC/AHA guidelines).
The higher figure is extrapolated from data suggesting that approximately one half of patients with myocardial infarction (MI) have preceding angina and that the rate of MI in patients with stable angina is approximately 3%.
Given that patients treated with traditional antianginal agents continue to experience anginal episodes, a conservative estimate is that at least 13 million episodes occur weekly (1000 every minute).
AHA. Heart Disease and Stroke Statistics–2006 Update. Gibbons RJ et al. ACC/AHA 2002 guidelines.
Pepine CJ et al. Am J Cardiol. 1994;74:

3. Persistent ischemia (angina) despite current drug therapy
Despite use of traditional antianginal agents (-blockers, CCBs, and nitrates), patients reported a median of 2 anginal attacks/week
A significant percentage of patients have relative intolerance to full doses of -blockers, CCBs, and nitrates
-blockers and many CCBs have similar depressive effects on BP, HR and/or AV nodal conduction
Antianginal drugs without these limitations are needed
Persistent ischemia (angina) despite current drug therapy
Many patients continue to experience anginal episodes despite antianginal drugs.
However, dose titration or addition of another agent are not options for many patients.
Patients such as the elderly and those with left ventricular dysfunction cannot tolerate maximal doses of traditional agents.
In addition, since beta-blockers and many CCBs have similar effects, their use in combination is limited because of increased risk for hypotension or bradycardia.
Thus, there is a need for new antianginal drugs.
Gibbons RJ et al. ACC/AHA 2002 guidelines.
Pepine CJ et al. Am J Cardiol. 1994;74:

4. Persistent ischemia (angina) despite PCI
N = 1620 consecutive NHLBI Dynamic Registry patients; 1 year post-PCI
Despite adjunctive antianginal therapy, 26% of patients reported recent angina
Persistent ischemia (angina) despite PCI
1620 patients underwent elective or urgent PCI. At 1-year follow-up, 26% reported experiencing angina within the previous 6 weeks, despite relatively extensive use of adjunctive antianginal therapy.
Holubkov R et al. Am Heart J. 2002;144:

5. Persistent ischemia (angina) despite optimal revascularization
Arterial Revascularization Therapies Study
~60% to 80% taking antianginal medication
~10 to 20% had angina
Persistent ischemia (angina) despite optimal revascularization
A study of patients who underwent PCI or coronary artery bypass surgery (CABG) for treatment of ischemia (stable or unstable, symptomatic or asymptomatic) found that a high proportion were still taking anginal medications 1 year later.
*1 year after optimal revascularization (stenting or surgery) for ischemia relief (not to prolong survival)
Serruys PW et al. N Engl J Med. 2001;344:

6. Myocardial ischemia: Significant clinical burden
Coronary artery disease
Hypertension
Hypertrophic cardiomyopathy
Valvular heart disease
6.5–16.5 million patients with stable angina1,2
≥ $1.9 billion in direct costs3
Myocardial ischemia: Significant clinical burden
In summary, chronic ischemia (angina) imposes a significant clinical and economic burden.
As the following slides demonstrate, it also imposes a significant burden on quality of life.
1. AHA. Heart Disease and Stroke Statistics–2006 Update. 2. Gibbons RJ et al. ACC/AHA 2002 guidelines.
3. Javitz HS et al. Am J Manag Care. 2004;10(suppl):S

7. Myocardial ischemia diminishes quality of life
N = 934 post-PCI/CABG Assessment of general health status during follow-up visits 50 40
Health status: excellent/ very good (% of patients) 30 20
Myocardial ischemia diminishes quality of life 10
During a 5-year follow-up of patients who had undergone coronary revascularization, the presence of angina was associated with reduction in several quality of life (QOL) measures, including general health status (data shown) and the Duke Activity Status Index and RAND Mental Health Inventory (data not shown).
The investigators concluded that angina exerted a substantial negative effect on QOL throughout the course of the study. 1 5 10
Follow-up (years)
Free from angina
Angina
Hlatky MA et al. Circulation. 2004;110:

8. Coexistence of myocardial ischemia and depression
N = 1957; 7 months post-discharge following MI/UA
History of depression* (%)
Coexistence of myocardial ischemia and depression
In a population composed almost exclusively (98%) of older men (mean age 65.2 years), a history of depression was associated with more frequent angina (adjusted odds ratio, 2.4; 95% CI, 1.86–3.10; P < 0.001).
Depression was assessed using the Seattle Angina Questionnaire.
While it is plausible that diminished quality of life associated with more frequent angina contributed to the development of depression, it is also possible that depression itself may trigger symptomatic myocardial ischemia.
Angina frequency
*Seattle Angina Questionnaire
Rumsfeld JS et al. Am Heart J. 2003;145:493-9.