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A. Overview of Conditions navigator

  1. Classification of Myocardial Ischemia
    1. Stable angina - intermittant angina on exertion relieved by rest
    2. Acute coronary syndromes (ACS): unstable angina and myocardial infarction (MI)
    3. Unstable angina (USA) was originally defined as angina at rest
    4. USA now includes new onset angina and accelerating angina
    5. Angina with increasing frequency is called accelerating or crescendo angina
    6. USA also includes new pulmonary edema, valvular changes, hypotension
    7. Myocardial ischemia with normal coronary vessels (~15%) is microvascular angina [51]
    8. MI is myocardial infarction, actual death of heart tissue
  2. Myocardial Ischemia / Stable Angina Epidemiology [3,45]
    1. Incidence 2/100 in men, 1.9/100 in women in USA
    2. Overall risk of cardiovascular (CV) events ~4% in 1 year for established atherosclerosis
    3. With multiple CV risk factors, risk of CV events in 1 year ~2%
    4. With established cerebrovascular disease (CVD), 1 year CV event rate 6%
  3. MI versus USA and Myocardial Ischemia
    1. In MI, cardiomyocyte cell death always occurs (versus damaged cells in USA)
    2. Electrocardiographic (ECG) evaluation is critical in evaluation of MI and USA
    3. MI is divided into subendocardial (usually non-Q wave) and transmural (Q wave) MI
    4. MI diagnosis requires both increased cardiac enzymes and consistent ECG changes
  4. Pathogenesis Overview
    1. ~90% of myocardial ischemia is due to atherosclerosis
    2. ~10% is due to vasospasm and abnormal subendocardial perfusion
    3. Normal or non-obstructive coronary lesions in 10% of women, 6% of men with MI [1]
    4. Congenital coronary artery abnormalities
    5. Vasculitis involving coronary arteries
    6. Interruption of blood flow to the epicardial cardiac arteries leads to symptoms
    7. Failure to relieve ischemic symptoms either by rest or other means leads to MI
  5. Pathogenic Correlates of Ischemia
    1. Stable Angina - partial coronary artery occlusion, demand on exertion exceeds supply
    2. Unstable Angina - acute (partial) occlusion of artery; demand exceeds supply at rest
    3. Non-Q Wave Infarction - partial occlusion of artery with death of myocardial cells
    4. Q-Wave Infarction - complete occlusion of coronary artery, transmural myocardial death
    5. Sudden cardiac death - acute ischemia on susceptible tissue leads to fatal arrhythmia

B. Risks for Coronary Artery Disease (CAD) [2] navigator

  1. A large number of risk factors for CAD and MI have been identified (see above)
  2. Framingham CAD Prediction Score is the best validated simple prediction method [2]
    1. Consists of 6 parameters for predicting CAD events
    2. Age
    3. Blood Pressure (BP)
    4. Current Smoking
    5. Diabetes (DM)
    6. Total Cholesterol (chol)
    7. HDL chol
    8. These parameters are weighted and prediction scores calculated
  3. Ankle-Brachial Index (ABI) [93]
    1. ABI adds independent predictive value to Framingham score
    2. ABI <0.9 associated with overall >2X increase in cardiovascular events as well as mortality over 10 years
  4. C-Reactive Protein (CRP) [44]
    1. CRP elevation associated with increased cardiac events [34,65]
    2. Normal CRP <1mg/L; moderate risk 1-3mg/L; high risk >3mg/L [78]
    3. Adding CRP to Framingham score helps assess risk inintermediate risk patients [68,69]
  5. Cardiovascular (CV) Risk in Women [37]
    1. Simplified model includes age, systolic BP, HbA1c in DM, smoking, chol, CRP, parentlal history of MI prior to age 60 years
    2. This model allows reclassification of ~50% of intermediate risk women to high or low risk
  6. Uppsala Longitudinal Study of Adult Men (ULSAM) [43]
    1. Study of biomarkers to predict >10 year CV morbidity and mortality in adult men
    2. Combination of biomarkers more accurate than any one alone in predicting clinical outcomes
    3. Adult men with or without pre-existing cardiovascular disease
    4. Four independent markers were validated:
    5. Troponin I - myocardial damage
    6. N-terminal pro-brain ntatriuetic peptide (NT pro-BNP) - left ventricular dysfunction
    7. Cystatin C - renal dysfunction
    8. C-reactive protein (CRP) - inflammation
    9. These markers were all independent of known, existing CV risk factors
  7. Mediterranean Diet [70]
    1. Rich in omega-3 fatty acids; reduces overall chol, blood pressure
    2. Associated with reduced overall, coronary, and cancer mortality [71]
  8. Major depression assocated with primary and secondary CAD [55]
  9. Low risk CV profile associated with ~5-10 year increased lifespan
  10. Carotid bruits associated with >2X risk of future MI and 2.3X risk of cardiovascular death versus patients without carotid bruits [91]
  11. Subclinical (abnormal TSH level) thyroid disease carries >20% increased cardiac event risk [92]

C. Symptoms navigator

  1. Typical Anginal Symptoms
    1. Sensation in chest of squeezing, heaviness, pressure, weight, tightness, aching
    2. Radiation to shoulder, neck, jaw, inner arm, epigastrium, band like-discomfort
    3. Relatively predictable onset with exertion (stable angina) or at rest (unstable angina)
    4. Stable angina with pain at rest is well document and due to high grade stenosis
    5. Shortness of breath, diaphoresis
    6. Abates when stressor is gone or nitroglycerin is taken
    7. Nitroglycerin respone does not distinguish active CAD from other chest pain causes [41]
  2. Non-Classical
    1. Includes pleuritic, sharp, prickling or knife-like
    2. Involves chest wall, is positional, tender to palpation, variable response to nitroglycerin
    3. Rule out cardiac causes and then evaluate for reflux esophagitis (GERD)
    4. No symptoms (silent ischemia)
  3. Severity of Angina
    1. Class I: no angina with ordinary physical activity; angina with strenous or plonged exertion
    2. Class II: early-onset limitation of ordinary activity, or with emotional stress
    3. Class III: marked limitation of ordinary activity
    4. Class IV: inability to carrout any physical activity without chest discomfort; angina at rest
  4. Silent Ischemia [4]
    1. Most common in diabetics and women [2]; often coexists with symptomatic ischemia
    2. May be associated with poorer prognosis compared with symptomatic ischemica in CAD
    3. Preinfarction angina correlated with reduced risk of right ventricular infarction
    4. Patients with heart transplants have no somatic pain inputs from new heart
    5. Both peripheral and central nervous systems are involved in lack of pain sensation
    6. Frontal cortical activation is present in patients with pain, absent without pain
    7. Difficult diagnosis; careful evaluation must be performed to understand MI risk
  5. Depression [72]
    1. Prominent finding in ~20% of CAD patients
    2. Depressive symptoms strongly associated with quality of life
    3. Detection and treatment of depression is key component of care

D. Evaluation [7,46] navigator

  1. Evaluation of borderline cases in a chest-pain observation unit in an emergency department is safe and effective
  2. Initial Evaluation [8]
    1. History, especially cardiac risk factors, previous cardiac events
    2. Targetted physical exam - jugular venous distension, lungs, heart, extremities (edema)
    3. Comorbid conditions: stroke, peripheral vascular disease, renovascular disease
    4. Vital signs including pulse-oximetry or arterial blood gas
    5. Electrocardiogram (ECG) should be perfomed on ANY patient with chest pain
    6. Old ECG is very helpful for interpretation of ECG abnormalities
    7. Rapid Cardiac Troponin T or I level now essential for ruling out MI
    8. Consider Chest Radiograph
    9. Women should be evaluated similar to men, particularly post-menopausal patients [2]
    10. Consider panic attacks in initial differential diagnosis
    11. Consider RV infarction in patients with evidence of ischemia without angina
    12. Relief of chest pain after nitroglycerin does not distinguish coronary from other causes [41]
  3. CAD Risks
    1. Particularly important in patients with history of CAD [8]
    2. Management in that population is multifactorial
    3. Special attention to homocysteine levels, HDL chol levels
    4. Elevated CRP (see above)
    5. Elevated N-terminal-BNP associated with increase MI and death risk in CAD patients [23]
    6. Consider recreational drug abuse (particularly in younger persons)
    7. Strongly consider aortic dissection and pulmonary embolism in differential of angina
    8. Electron beam or multidetector CT to determine calcium score as a strong predictor of cardiac events across racial and ethnic groups, independent of other risk factors [90]
  4. Recreational Drug Abuse
    1. Cocaine and other amphetamines cause vasoconstriction and can precipitate MI [10]
    2. Cocaine also increases inotropy and chronotropy, increasing cardiac oxygen demand
    3. Amyl nitrate inhalation can mimic cardiac ischemia: increased pulse and blood pressure
  5. Various algorithms have been developed to aide in decision to admit specific patients [8]
  6. Evaluation of Patients with Prolonged Chest Pain [8]
    1. In patients presenting to emergency room, full "rule-out" MI protocol should be done
    2. Usually consists of history (risk factors), physical exam (especially for murmers)
    3. ECG with comparison to (asymptomatic) baseline is essential in rule-out MI protocol
    4. Troponin T or I levels allow rule-out MI in 6 hours
    5. Serial creatinine kinase (CK) MB fractions every 4-6 hours for 12 hours
    6. Patients with initial negative evaluation should undergo ETT
    7. This protocol has a 98% negative predictive value (NPV)
    8. Positive predictive value (PPV) is only 16% for true CAD (confirmed by angiography)

E. ECG Changes and Other Diagnostics navigator

  1. Up to 50% of patients with chronic stable angina and CAD will have normal resting ECG [46]
  2. Reversible ST segment depression
    1. Down-sloping depression most specific
    2. Horizontal depression is less specific
    3. Up-sloping (with J point) is most likely a normal variant
  3. Variant Angina (Prinzmetal's)
    1. ST segment elevation may indicate vessel occlusion or spasm
    2. Variant angina is vasospasm induced, relieved when spasm stops
    3. May be due to underlying plaque / thrombus which is variably lodged / dislodged
    4. Must rule out unstable angina or myocardial infarction (CK, troponins)
    5. Other vasospastic diseases are commonly found (eg. migraine, Raynaud's Disease)
  4. In general, any ST or T segment changes from baseline ECG with symptoms should be fully evaluated [9]
  5. ECG-gated single photon emission computed tomography (GSPECT) can be used in patients with chest pain to rule out cardiac cause (99m-Tc-based perfusion test)
  6. Rapid serum troponin T or I levels critical for early evaluation for MI
  7. Echocardiography (wall motion abnormalities) during ischemia can help document ischemia
  8. Magnetic Resonance Imaging (MRI)
    1. Improvements allowing real-time imaging likely available soon
    2. Can be used to evaluate healed MI [11]
    3. Can be used to evaluate subendocardial response to adenosine [12]
  9. Coronary Angiography
    1. Strong recommendation for early evaluation for CAD with angiography
    2. Abnormal (CAD) with likely causative lesion identified in >80% of patients
    3. Can also detect congenital abnormalities or vasculitic changes
    4. ~15% of patients with true cardiac angina have normal coronary arteriograms
    5. These patients likely have microvascular angina (see below)
  10. Ultrafast (electron-beam) CT not recommended for angina evaluation

F. Stable Angina [7]navigator

  1. Definition
    1. Angina on exertion, relieved by resting ± nitrates
    2. Cardiac etiology confirmed usually by ECG or exercise treadmill test (ETT)
    3. Most patients have demonstrable epicardial CAD
  2. Etiology
    1. Epicardial CAD present in most patients
    2. Stable atherosclerotic plaques present in majority
    3. True cardiac angina with normal epicardial vessels is microvascular angina (see below)
  3. Evaluation of Stable Angina [46,62]
    1. Medical history and level of angina suggestive of CAD
    2. This provides a pre-test probability of coronary disease (CAD)
    3. Tests are done to rule out CAD and avoid unnecessary cardiac angiography
    4. Concommitant risk factors - hypertension (HTN), smoking
    5. Exercise Treadmill Test (ETT) with ECG - in men, best predictor of overall mortality [79]
    6. ETT with Bruce protocol and Duke treadmill score is usually first diagnostic test
    7. Exercise or pharmacologic (such as dobutamine or adenosine) echocardiography
    8. Angiography for high risk patients who are candidates for PTCA or cardiac surgery
    9. The most important part of evaluation is patient's history and cardiac risk factors
    10. Electron Beam Computerized Tomography (CT) can detect high grade stenoses [9]
  4. Hybernating Myocardium
    1. Chronically ischemic, non-scarred, dysfunctional heart muscle with functional potential
    2. Under normal conditions, hybernating myocardium does not contract
    3. Hypokinetic, akinetic and/or dyskinetic areas may be seen on echocardiography
    4. Acute, fully reversible myocardial stunning can occur with severe emotional stress [36]
    5. Chronically stunned myocardium may be a component of hypernating myocardium
    6. Stimulation with vasodilators (dobutamine) or with epinephrine can induce contraction
    7. Revascularization (CABG, PTCA) can return function to hybernating myocardium

G. Treatment of Stable Angina [7,14,15] navigator

  1. Goals are reduce morbidity and mortality from CAD and control angina
  2. Control of Cardiac Risk Factors
    1. HTN itself can induce angina
    2. Chol reduction is critical
    3. Diabetes control
    4. Tobacco abuse
    5. Moderate (1-2 drinks) per day alcohol reduces angina and MI
    6. Excercise reduces many risk factors, improves endothelial function [16]
    7. Exercise program associated with ~20% reduced overall mortality in coronary artery disease (CAD) patients [6]
    8. Increased intake of N-3 polyunsaturated fatty acids [17]
  3. Interventions to Reduce Angina
    1. Pharmacologic therapy - for mild to moderate stable angina
    2. Revascularization leads to symptom control in most patients
    3. Percutaneous coronary interventions (PCI) or coronary artery bypass grafting (CABG)
  4. Clearly Beneficial Pharmacologic Agents [15]
    1. Antiplatelet agents - mainly aspirin (ASA), clopidogrel (Plavix®)
    2. Control pulse and blood pressure (rate-pressure product)
    3. ß-adrenergic antagonists are first line
    4. ACE inhibitors (ACE-I) or angiotensin II receptor blockers (ARB) are 2nd line
    5. ACE-I added to standard therapy of no benefit in stable CAD with normal LV function [77]
    6. Calcium channel blockers (CCB) and nitrates are third line and reduce symptoms only
    7. Chol Reduction - statins strongly preferred first line (may add absorption inhibitors)
    8. Homocysteine Reduction - very likely beneficial with no harm
  5. Heart Rate Control
    1. ß-blockers have been proven to reduce mortality in angina as well as MI
    2. ß-blockers reduce sympathetic tone (stress) and reduce arrhythmia and first MI
    3. Use rate slowing CCB (verapamil, diltiazem) only when ß-Blockers are not tolerated
    4. CCB reduce anginal symptoms but do not slow disease progression or reduce mortality
    5. CCB for rate control include verapamil and diltiazem
    6. Only long-acting CCB are used
  6. Blood Pressure (BP) Control
    1. ß-blockers and ACE-I or ARB are first for BP control
    2. ACE-I / ARB also reduce progression of atherosclerosis
    3. ACE-I first line for HTN, with any renal disease, and in diabetics
    4. ACE-I also reduce LVH
    5. ACE-I / ARB improve CHF progression
    6. ARB are recommended in ACE-I intolerant patients
    7. CCB are also effective for angina and blood pressure, but do not reduce mortality
    8. Long acting nitrates reduce anginal symptoms but do not reduce mortality
    9. Goal diastolic BP no lower than 75-80mm Hg in CAD with HTN [84]
  7. Platelet Inhibition
    1. All patients should be ASA aspirin (75-325mg po qd) if tolerated [20,21]
    2. Clopidigrel (75mg po qd) should be used in place of ASA in ASA intolerant patients
    3. For primary event prevention, clopidogrel+ASA is not superior to ASA alone [13]
    4. In ACS, clopidogrel should be combined with ASA 81-162mg/day [22]
    5. For secondary prevention, ASA+clopidogrel is superior to ASA alone [13]
  8. Chol Reduction (see below)
    1. Both primary and secondary prevention (post-ischemic event) are highly beneficial
    2. Chol reduction is absolutely indicated in all patients with CAD, particularly in age >65 years, even with normal chol levels [49,50]
    3. Aggressive chol reduction leads to regression of coronary atherosclerosis [52]
    4. Statins reduce CV events and mortality in CAD patients [18]
    5. Persons with normal lipids and elevated CRP benefit from statins which reduce acute coronary events by 25% [24]
    6. Goal LDL for primary prevention <100-130mg/dL; total chol <200mg/dL
  9. Homocysteine Reduction
    1. Reducing homocysteine with vitamins has no primary prevention benefit [27,28]
    2. Vitamins B6 + B12 + folate may reduce restenosis [29]
  10. PCI for Angina and Stable CAD
    1. Stable CAD usually with fixed stenotic lesions (versus unstable, rupture-prone plaques)
    2. PCI, usually with stents, may be recommended for severe or refractory angina
    3. PCI added to optimal medical therapy does not change outcomes in stable CAD [32]
    4. PCI/Stenting superior to medications with symptomatic angina, including in elderly [32,33]
    5. Meta-analysis showed PCI had less angina (53% versus 70%) but more CABG (7.6% versus 4.1%) compared with medical therapy
    6. Transmyocardial lasar revascularization was not beneficial in refractory angina
  11. Coronary Artery Bypass Grafting (CABG) [25]
    1. Patients with 2 or 3 vessel disease and reduced left ventricular function benefit from bypass surgery (CABG) or PCI over pharmacologic therapy
    2. Subsequent revascularization is always higher with PCI±stent compared with CABG
    3. Post-procedure angina usually somewhat higher with PCI±stent compared with CABG
  12. Refractory Angina
    1. Mainly applies to patients not controlled on one or two medications
    2. Further evaluation of angina may be indicated
    3. Patients with high risk ETT results should undergo coronary angiography
    4. Other causes of angina should be considered
    5. PCI added to medical therapy superior to medications alone in refractory angina [32,33]

H. Microvascular Angina [1,51] navigator

  1. Definition
    1. Chest pain
    2. Abnormal ECG and ETT with ST depressions
    3. No significant CAD on angiography (clean or non-obstructive coronary lesions)
    4. ~10% of patients with angina will have microvascular form
    5. 10% of women and 6% of men with MI have normal or non-obstructed coronary arteries
    6. Suspect in patients with symptoms out of proportion to anatomical CAD
  2. Etiology [12]
    1. Vasospasm versus microvascular disease
    2. Abnormal arterial dilatory responses (inadequate vasodilator reserve)
    3. Role of hyperinsulinemia, insulin resistance, and dyslipidemia is debated
    4. Minimal atheroscerotic plaque may lead to endothelial dysfunction
    5. Abnormal subendocardial perfusion after adenosine simulation demonstrated
    6. Adenosine challenge provoked pain in 95% of patients with microvascular angina
    7. Ischemia in microvascular angina is non-transmural, so risk of ACS is minimal
  3. Treatment
    1. No specific therapy for preventing microvascular angina (versus usual angina)
    2. ACE inhibitors, ß-blockers, statins and exercise may relieve symptoms
    3. Aspirin should probably be used as described below
    4. Tricyclic antidepressants may have efficacy (such as Imipramine 25-50mg po qhs)
    5. Prognosis is poorer than originally reported with 2% risk of death or MI within 30 days

I. Summary of Pharmacologic Agents [7] navigator

  1. Aspirin (ASA) and Clopidogrel [20]
    1. Primary Prevention: ASA 325mg po qod or 81mg qd
    2. Treatment of USA or possible MI: ASA 325mg po qd
    3. Secondary prevention: ASA 325mg qd
    4. Clopidogrel (Plavix®) 75mg po qd in ASA intolerant patients
    5. For ASA, monitor symptoms of gastritis or ulcer
    6. ASA for primary CAD event prevention: ~15% in men, ~12% stroke reduction in women [85]
  2. Glycoprotein (gp) 2b/3a Inhibitors [42]
    1. Potent anti-platelet agents target major platelet adhesion receptor gp 2b/3a
    2. Intravenous gp2b/3a inhibitors are indicated in ACS but not for stable angina
    3. Abciximab, eptifibitide, and tirofiban are intravenous (IV) platelet gp2b/3a inhibitors
    4. In patients with ACS given ASA, gp2b/3a inhibitors generally more effective than heparin
  3. Heparin
    1. Heparin bolus then drip for 2-3 days in all patients with USA or rule out MI
    2. Consider warfarin in patients with PTCA, diabetes, high risk of MI or ASA intolerant
    3. Enoxaparin, LMW heparin, is as effective as heparin in USA with fewer side effects
    4. Dalteparin (LMW heparin) use for 3 months for USA may reduce complications
    5. ASA must be given before heparin is stopped or recurrent USA likely to occur
    6. Direct thrombin inhibitors should be considered in patients with thrombocytopenia
    7. Chronic antianginals (but not aspirin) can be reduced or stopped after PCI
  4. ß-Blockers
    1. Excellent anti-ischemic agents (anti-inotropic, anti-chronotropic)
    2. In stable angina, as good as calcium blockers and nitrates for reduction of angina
    3. Also reasonable good anti-arrhythmic activity
    4. Demonstrated benefit on survival post-MI and for HTN; reduce atherosclerotic plaque [88]
    5. Relative contraindications: bronchospasm, diabetes, low-EF states, impotence
    6. Suggest Metoprolol 50-100mg bid-tid or Atenolol 50-100mg qd (both oral)
    7. Patients with CAD should receive ß-blockers perioperatively if tolerated
    8. ß-blockers are first line recommended therapy in patients with angina
  5. ACE-I or ARB [58]
    1. Effective and safe in patients with COPD, arrhythmias, peripheral vascular disease
    2. Ramipril (ACE-I) reduced mortality and CV events in high risk patients [19]
    3. Telmisartan (ARB) equivalent to ramipril in reducing mortality and CV events in patients at high risk for vascular events; no benefit to combination of both [58]
    4. Perindopril, an ACE inhibitor, reduced new CV events by 20% over 4 years in patients with stable coronary atherosclerosis without CHF [66]
    5. Enalapril 20mg qd showed non-significant trend to reduction in CV events in patients with CAD and normal blood pressure [76]
    6. ACE-I and ARB are increasingly considered similar; ACE-I cause more side effects including cough and angioedema [58]
    7. Likely ACE-I reduce atherosclerosis progression and ACS [47]
  6. Nitrates
    1. Good antianginal activity but no benefit on CV or mortality endpoints
    2. Nitroglycerin (IV or paste) is short acting, primarily coronary artery and venodilator
    3. Isosorbide Dinitrate (Isordil®): long acting vasodilator but tolerance develops
    4. Isosorbide Mononitrate (Ismo®): major active metabolite of dinitrate with reduced tolerance and rebound compared to isosorbide dinitrate
    5. Isosorbide mononitrate is >100% bioavailable
  7. Calcium Antagonists [48]
    1. These are excellent for symptomatic angina and for HTN
    2. These are not first line for severe CAD
    3. Act on cardiac conduction system, cardiac muscle, and/or vascular smooth muscle
    4. Verapamil has potent anti-inotropic and anti-chronotropic activities
    5. Verapamil useful for hypertrophic cardiomyopathies when ß-blockers are not used
    6. Diltiazem excellent for slowing heart rate; less anti-inotropic activity than verapamil
    7. Second and later generation dihydropyridines are particularly good for angina and HTN
    8. Amlodipine (Norvasc®) 10mg qd reduced CV events 30% and atherosclerosis progression in patients with CAD and normal blood pressure [76]
    9. Short-acting calcium antagonists are no longer recommended
  8. Ranolazine (Ranexa®) [38]
    1. Blocks fatty acid oxidation, reduces angina
    2. In severe chronic angina, ranolazine improved exercise capacity and reduced symptoms in combination with atenolol, amlodipine, or diltiazem [53]
    3. Ranolazine initial dose 500mg po bid; may increase to 1000mg po bid
    4. Mild QTc prolongation (3-6 msec), constipation, nausea
    5. Reduces angina in ACS, but no effect on cardiac events [86]
    6. Approved for chronic angina inadequately controlled with other agents
  9. Chol Reduction with Statins [24,50]
    1. Aggressive chol reduction (with statins) is essential in all CAD patients
    2. Atorvastatin (Lipitor®) reduced ischemic symptoms and improves cardiac function [67,84]
    3. Atorvastatin 80mg po qd reduced recurrent ischemic events 16% within the 16 weeks after the ACS episode [54]
    4. Atorvastatin 80mg qd reduces lipid and CRP levels and atherosclerotic progression far better than pravastatin 40mg qd [75]
    5. In age >65 with CAD and LDL <130mg/dL, 80mg superior to 10mg atorvastatin for reducing all CV events [87]
    6. Reducing LDL to <80mg/dL in patients with stable CAD with atorvastatin 80mg reduced major CV events but not overall mortality [83]
    7. Pravachol (Pravochol®) reduces risk of initial CAD event even with normal lipids [66]
    8. Pravastatin reduces major CV events in CAD patients, particularly patients >65 years [50]
    9. Statin reduction of CRP levels is independently associated with reduced CV events [79,80]
  10. Consider coronary revascularization for patients with severe symptoms (see above) [12]
  11. Raloxifene (Evista®) reduced CV events 40% in high risk women with osteoporosis [35]
  12. Nicorandil [39]
    1. Nicotinamide ester with dual actions
    2. Open ATP-sensitive postassium channels (Katp) leading to vasodilation
    3. Nitrate moiety dilates systemic veins and epicardial coronary arteries
    4. Reduced combination of CHD death, non-fatal MI, and unplanned hospitalization for cardiac chest pain 17% versus placebo in stable angina patients
    5. Nicorandil of no benefit on infarct size in acute MI treated with reperfusion [89]
    6. Oral or anal ulceration (stomatitis) may occur; resolves with discontinuation of drug [64]
  13. Not Beneficial
    1. Supplemental vitamin E is generally no longer recommended for angina
    2. Chelation therapy with EDTA provides no benefit in ischemic heart disease [56]
    3. Dipyridamole [15]
  14. Gene therapy with angiogenic agents is being developed [57]

J. Transmyocardial Revascularization (TMR) [59,60]navigator

  1. Surgical procedure uses laser to create channels through myocardial wall
  2. These channels connect to ventricular chamber and allow improved blood permeation
  3. Mainly studied on patients with resistant class III and IV angina
  4. Mild reduction in LV EF occurs on echocardiographic assessment
  5. Relatively large studies have demonstrated clear improvement in exercise tolerance, angina scores, myocardial perfusion, and quality of life [61]
  6. Significant reduction in hospitalizations for unstable angina versus medical therapy alone [50]
  7. In a randomized controlled study, patients with severe angina, 44% undergoing TMR had elimination of angina versus 21% for continued medical treatment group [62]
  8. However, a randomized placebo-controlled study showed no overall benefit [63]
  9. Consider this experimental therapy in patients with resistant angina or poor operative candidates

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