On the management of chronic stable and refractory angina. A review.

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The objectives in treating angina are relief of pain and prevention of disease progression through risk factor reduction. Traditional anti-anginal agents include nitrates, β-blockers, and calcium channel blockers. The method by which angina is relieved is well understood and includes the following mechanisms:

Cardiovascular effects of nitrates, CCBs, and β-blockers in angina
Variable Nitrates CCBs β-blockers
Collateral blood flow ↑↑ ↑↑
Endomyocardial to epimyocardial flow ↑↑
Heart rate ↑ (reflex) ↑↓ (reflex) ↓↓
Left ventricular wall tension ↓↓ ↑→
Myocardial contractility ↑ (reflex) ↑ ↓→ (reflex) ↓↓
Cardiac work ↓↓ ↓↓ ↓↓
Abbreviation: CCBs, calcium channel blockers

Of course, these only relieve symptoms by improving the blood supply somewhat and reducing the cardiac work load. Traditional risk factors for Coronary Artery Disease (CAD) that include smoking, hypertension, dyslipidemia, diabetes, and obesity are not modified by these drugs.

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The Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial showed however, that in patients with stable angina, coronary intervention (PCI) with medical therapy was no better than optimal medical therapy alone in preventing myocardial infarction and death.

For patients who are unstable, with very high risk, with left main coronary artery lesions, or in whom medical therapy fails, and in those with Acute Coronary Syndromes (ACS), PCI or CABG is indicated. In many asymptomatic patients with CAD or those with stable angina, interventions may be safely deferred without additional risk with optimum medical therapy.

For many patients, especially those with diabetes, reduced left ventricular function and with three vessel disease, coronary artery bypass surgery offers the treatment.

Optimal medical therapy, percutaneous coronary intervention, and surgery are not competing therapies, but are complementary and should fill an important need in comprehensive management of CAD.

The prevalence of cardiovascular disease means that 45% of the adult population In the United States has at least one of the three major risk factors, hypertension, diabetes, or dyslipidemia.

The incubation time for development of atherosclerosis and CAD is at least 10 years. Under ideal circumstances, lifestyle modifications should be optimized during this period. A modest change in health behavior is associated with a 25% reduction in risk of death!

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In a new AHA report, Cardiovascular health can be determined by the following criteria:

  • Never having smoked or quitting over a year ago.
  • Keeping BMI < 25 kg/m2.
  • Exercising at moderate intensity $150 minutes (or 75 minutes at vigorous intensity) each week.
  • Eating a “healthy diet”: adhering to 4 of 5 important dietary components.

o   sodium intake ,1.5 g/d

o   sugar-sweetened beverage intake ,36 oz weekly

o   ≥ 4.5 cups of fruits and vegetables/d

o   ≥ three 1 oz servings of fiber-rich whole grains/d

o   ≥ two 3.5 oz servings of oily fish/week.

  • Maintaining total cholesterol ,200 mg/dL.
  • Keeping BP , 120/80 mm Hg.
  • Keep fasting blood glucose < 100 mg/dL.

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Revascularization is a mechanical treatment for flow-limiting coronary obstructive lesions in order to relieve myocardial ischemia. In 2006, about 1,313,000 PCI procedures and 448,000 CABG surgeries were performed in the United States. Many cardiologists, surgeons, and patients believe that for angina and Acute Coronary Syndrome (ACS), revascularization with PCI or CABG, when appropriate, are the preferred treatments. There is little question that in high-risk ACS patients a routine invasive strategy produces the best outcomes, but thresholds have been unclear for some patients with chronic angina.

About 85% of the PCIs performed are elective, 25% are in patients with chronic stable angina. Estimates of asymptomatic patients range from 12% to 25%. In 2004, only 44% of elderly patients underwent a noninvasive study prior to referral for PCI.

ACC/AHA recommendations for PCI in patients with chronic stable angina
  • 2-vessel or 3-vessel disease with significant proximal LAD lesions, with anatomy enabling catheter-based therapy and normal LVF; diabetics under treatment excluded.
  • 1-vessel or 2-vessel disease without significant proximal LAD lesions, with high risk on noninvasive testing and a large area of viable myocardium.
  • Prior PCI with either recurrence of stenosis or high risk on noninvasive testing.
  • Failure of optimum medical therapy and with acceptable risk for revascularization procedure.
Abbreviations: ACC/AHA, American College of Cardiology/American Heart Association;
PCI, percutaneous coronary intervention; LOE, level of evidence;
LAD, left anterior descending coronary artery; LVF, left ventricular function

Survival rates of patients with CAD are associated with both severity and location of lesions. Although medical therapy has advanced significantly and is reflected in improved survival, the relationship between severity of obstructions and prognosis remains valid.

Extent of CAD and 5-year survival rate (%)
Extent of CAD 5-year survival (%)
1-vessel disease, 75% 93
1-vessel disease,≥ 95% 91
2-vessel disease 88
2-vessel disease, both≥ 95% 86
1-vessel disease, ≥ 95% proximal LAD 83
2-vessel disease, ≥ 95% LAD 83
2-vessel disease, $95% proximal LAD 79
3-vessel disease 79
3-vessel disease, ≥ 95% in at least 1 73
3-vessel disease, 75% proximal LAD 67
3-vessel disease, ≥ 95% proximal LAD 59
Abbreviations: CAD, coronary artery disease; LAD, Left anterior descending.

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Recommendations for CABG surgery include patients with left main coronary lesions, symptomatic 3-vessel disease, critical (>75%) stenoses in all 3 major coronary arteries and LVEF< 50%, diabetics with multivessel disease, and very complex lesions. Generally, CABG produces lower rates of repeat revascularization and longer survival times than PCI. The risks of CABG surgery include 1%–3% death, a

5%–10% peri operative MI and a 10%–20% vein graft failure (first year), and a low risk of peri operative stroke and cognitive dysfunction. About 75% of patients remain angina-free or free of cardiac events after 5 years.

Guidelines recommending PCI or CABG (ACC/AHA)
PCI indicated, actual procedure Either PCI or CABG indicated, Actual procedure CABG indicated, Actual procedure Neither PCI nor CABG indicated
94% 93% PCI 53% CABG, 34% PCI 21% PCI
Guidelines for revascularization with CABG
  • Significant left main coronary disease. Triple-vessel disease; survival benefit is greater in patients with LVEF< 50%.
  • 1- or 2-vessel disease without significant proximal LAD lesions, with high risk on noninvasive testing and a large area of viable myocardium.
  • 1- or 2-vessel disease without significant proximal LAD lesions who have survived SCD or sustained VT.
  • Failure of optimum medical therapy and with acceptable risk for a revascularization procedure.
  • 1- or 2-vessel disease without significant proximal LAD Lesions, but with a moderate area of viable myocardium and demonstrable ischemia on noninvasive testing.
  • Single vessel disease with significant proximal LAD disease.
Abbreviations: ACC/AHA, American College of Cardiology/American Heart
Association; CABG, coronary artery bypass surgery; LAD, Left anterior descending;
LVEF, left ventricular ejection fraction; SCD, sudden cardiac death; VT, ventricular Tachycardia

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  • Some patients do not respond to drug therapy, life style modification but are not candidates for any interventional therapy. For this sub group, two options for refractory angina treatment, enhanced external counter pulsation (EECP) and spinal cord stimulation (SCS) may be a solution.
  • Patient should know that no pill or surgical procedure will reverse the problem, but that lifestyle changes will influence the course of the disease in the most fundamental way and are preferred. Lifestyle modification is efficacious, widely available, innocuous, and an inexpensive form of management of angina and coronary artery disease (CAD), but is underused and unsupported.
  • Refractory angina refers to patients who have continued angina, and objective evidence of ischemia despite optimum medical therapy, but who are not candidates for revascularization. In the United States, as many as 1.7 million patients are believed to have refractory angina, usually in the setting of advanced heart disease. Patients have a bleak future, with an annual rate of non-fatal MI of 3.2% and annual mortality of 1.8%. Treatment options for refractory angina are limited and include spinal cord stimulation (SCS) (invasive and multi mechanistic), enhanced external counter pulsation (EECP) to raise myocardial perfusion, and angiogenesis through extracorporeal cardiac shock wave therapy (noninvasive), trans myocardial laser revascularization (invasive), or stem cell/gene therapy (invasive and preclinical).
  • EECP consists of the application of 3 pairs of pneumatic cuffs placed on the lower extremities at the levels of the calves and lower and upper thighs. Cuff inflation and deflation are synchronized with the ECG. At the onset of diastole, the cuffs are sequentially inflated from the calves proximally to the lower and upper thighs. Before the onset of systole, all cuffs are simultaneously deflated. The pressure created during inflation increases venous return and diastolic blood flow in the coronary arteries and other vascular beds in a manner similar to intra-aortic balloon counter pulsation. The simultaneous pre-systolic decompression in the cuffs reduces afterload so that the ejection fraction (EF) improves, whereas the work of the heart diminishes.
  • EECP provides a noninvasive, effective alternative for treatment of refractory angina and is capable of improving ventricular function, systolic BP, coronary perfusion, myocardial oxygen balance, and exercise tolerance. The treatment lowers the number of anginal episodes and spares nitrate use in an impressive proportion of patients, which may endure for years.
  • SCS involves implantation of an epidural electrode between levels C7 and. The electrode is connected to an stimulator.  A magnetic hand-held control device turns the unit on and off and adjusts stimulation intensity within programmed parameters.
  • Originally, it was thought that stimulating large afferent fibers in the dorsal columns simply blocked impulses from afferent nerves carrying cardiac pain signals, according to the gate control hypothesis. SCS lowers catecholamine levels, and inhibits sympathetic tone that may dilate coronary microvasculature, increasing myocardial perfusion and hence myocardial oxygen consumption.

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Cardiovascular disease is the leading cause of death in the United States, yet it is a preventable disease. The current epidemic of obesity threatens to reverse recent advances in controlling this foe. For this reason, bold proposals and calls for implementation of population-wide lifestyle and environmental changes are being made.

(From: Recent advances in the management of chronic stable angina II. Anti-ischemic therapy, options for refractory angina, risk factor reduction, and revascularization, Richard Kones, The Cardiometabolic Research Institute, Houston, Texas, USA. Vascular Health and Risk Management Vascular Health and Risk Management, August, 2010)

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  • Never having smoked or quitting over a year ago.
  • Keeping BMI < 25 kg/m2.
  • Exercising at moderate intensity $150 minutes (or 75 minutes at vigorous intensity) each week.
  • Eating a “healthy diet”: adhering to 4 of 5 important dietary components.
  1. sodium intake ,1.5 g/d;
  2. sugar-sweetened beverage intake ,36 oz weekly;
  3. ≥ 4.5 cups of fruits and vegetables/d;
  4. ≥ three 1 oz servings of fiber-rich whole grains/d;
  5. ≥ two 3.5 oz servings of oily fish/week.
  • Maintaining total cholesterol ,200 mg/dL.
  • Keeping BP , 120/80 mm Hg.
  • Keep fasting blood glucose < 100 mg/dL.

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