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1、GUIDELINES FOR THE MANAGEMENT OF CHRONIC STABLE ANGINA,American College of Cardiology, Puerto Rico Chapter, February 6, 2007,GAP,The Goals of Therapy in CAD,To improve quality of life (symptoms) To reduce mortality To reduce morbidity To reduce progression of disease and induce regression.,Treatment
2、 of Chronic Stable Angina,Medical,Revascularization,PCI,ACBG,MEDICAL THERAPY,ANTIPLATELETS BETA BLOCKERS NITRATES CALCIUM ANTAGONIST ACEI STATINS NEW THERAPIES,ANTIPLATELET AGENTS,ASA Physicians Health Study Swedish Angina Pectoris Trial TICLOPIDINE CLOPIDOGREL CAPRI CURE,Receptor GP IIb-IIIa: The F
3、inal Common Pathway to Platelet Aggregation,White HD. Am J Cardiol 1997; 80:2B-10B. Schafer A. J Clin Invest 1986; 78:73-79. DeJong MJ, et al. Critical Care Nursing Clin of N Am 1999; 11:355-371. Moser M, et al. J Cardiovasc Pharmacol 2003;41:586-592. Phillips DR, Scarborough RM. Am J Cardiol 1997;8
4、0(4A):11B-20B.,GP IIb-IIIa inhibitors displace fibrinogen in existing thrombi to disaggregate thrombus and prevent further platelet cross-linking and thrombosis,GP IIb-IIIa inhibitors prevent platelet activation by blocking GP IIb-IIa (outside-in signaling),High-dose heparin stimulates PAF which act
5、ivates platelets,PHYSICIANS HEALTH STUDY,A randomized, double-blind, placebo controlled trial designed to test the effects of low-dose aspirin and beta-carotene in the primary prevention of CVD and cancer among 22,071 US male physicians, aged 40 to 84 at baseline in 1982. Baseline blood specimens we
6、re collected and frozen for later analyses from 14,916 participants. Using a 2x2 factorial design: 325 mg of aspirin (Bufferin, supplied by Bristol-Myers Products on alternate days) 50 mg of beta-carotene (Lurotin, supplied by BASF AG on alternate days),PHYSICIANS HEALTH STUDY, Total cancer Prostate
7、 cancer Cardiovascular disease Eye disease Cataract Macular degeneration,Primary Endpoints,PHYSICIANS HEALTH STUDY,The trials Data and Safety Monitoring Board stopped the aspirin arm of the PHS several years ahead of schedule because it was clear that aspirin had a significant effect on the risk of
8、a first myocardial infarction. As reported in the July 20, 1989 New England Journal of Medicine, aspirin reduced the risk of first myocardial infarction by 44% (P less than 0.00001). There were too few strokes or deaths upon which to base sound clinical judgment regarding aspirin and stroke or morta
9、lity,Pharmacotherapy for Chronic Stable Angina (class I),1. Aspirin in the absence of contraindications A 2. Beta-blockers as initial therapy in the absence of contraindications in patients with prior myocardial infarction or without prior myocardial infarction A,B 3. ACE inhibitor in all patients w
10、ith CAD who also have diabetes and/or LV systolic dysfunction A 4. LDL-lowering therapy in patients with documented or suspected CAD and LDL cholesterol 130 mg/dl, with a target LDL of 100 mg/dl A 5. Sublingual nitroglycerin or nitroglycerin spray for the immediate relief of angina B 6. Calcium anta
11、gonists or long-acting nitrates as initial therapy for reduction of symptoms when beta blockers are contraindicated B 7. Calcium antagonists or long-acting nitrates in combination with beta blockers when initial treatment with beta blockers is not successful B 8. Calcium antagonists and long-acting
12、nitrates as a substitute for beta blockers if initial treatment with beta blockers leads to unacceptable side effects,Pharmacotherapy for Chronic Stable Angina (class IIa),1. Clopidogrel when aspirin is absolutely contraindicated 2. Long-acting non-dihydropyridine calcium antagonists instead of beta
13、 blockers as initial therapy B 3. In patients with documented or suspected CAD and LDL cholesterol 100129 mg/dl, several therapeutic options are available: B a. Lifestyle and/or drug therapies to lower LDL to 100 mg/dl b. Weight reduction and increased physical activity in persons with the metabolic
14、 syndrome c. Institution of treatment of other lipid or non-lipid risk factors; consider use of nicotinic acid or fibric acid for elevated triglycerides or low HDL cholesterol 4. ACE inhibitor in patients with CAD or other vascular disease,Pharmacotherapy for Chronic Stable Angina,IIb (weak supporti
15、ve evidence) Low-intensity anticoagulation with warfarin in addition to aspirin B III (not indicated) 1. Dipyridamole B 2. Chelation therapy B,CURE,Approach to the treatment of chest pain,OXYGEN DEMAND,Double product = (Heart Rate) (systolic blood pressure),BETA BLOCKERS,Effects of -blockade on isch
16、emic heart,Printed from: Drugs for the Heart 2007 Elsevier,Cardiac effects of -adrenergic blocking drugs at the levels of the SA node, AV node, conduction system, and myocardium,Printed from: Drugs for the Heart 2007 Elsevier,Contraindications to -blockade,Printed from: Drugs for the Heart 2007 Else
17、vier,BETA BLOCKERS STUDIES,TIBET (Total Ischemic Burden European Trial) APSIS (The Angina Prognosis Study In Stockholm) ASIST (Atenolol Silent Ischemia Trial) TIBBS (Total Ischemic Burden Bisoprolol Study) IMAGE (International Multicenter Angina Exercise Study),BB for clinical use,ACC/AHA 2002 Guide
18、line Update for the Management of Patients With Chronic Stable Angina,Comparison of hemodynamic effects of -blockers and of CCBs,Printed from: Drugs for the Heart 2007 Elsevier,CARDIAC VS. VASCULAR,Printed from: Drugs for the Heart 2007 Elsevier,Mechanisms of anti-ischemic effects of calcium channel
19、 blockers,Printed from: Drugs for the Heart 2007 Elsevier,Verapamil and diltiazem have a broad spectrum of therapeutic effects.,Printed from: Drugs for the Heart 2007 Elsevier,Contraindications to verapamil or diltiazem,Printed from: Drugs for the Heart 2007 Elsevier,Contraindications to dihydropyri
20、dines,Printed from: Drugs for the Heart 2007 Elsevier,Properties of CCB in clinical use,Schematic diagram of effects of nitrate on the circulation,Printed from: Drugs for the Heart 2007 Elsevier,Effects of nitrates in generating NO and stimulating guanylate cyclase to cause vasodilation,Printed from
21、: Drugs for the Heart 2007 Elsevier,Current proposals for therapy of nitrate tolerance.,Printed from: Drugs for the Heart 2007 Elsevier,A serious nitrate drug interaction,Printed from: Drugs for the Heart 2007 Elsevier,Nitrates in Angina,Effect of simvastatin on cardiovascular events among patients
22、with and without coronary heart disease (CHD) in the Heart Protection Study,Dual role of ACE inhibitors, both preventing and treating cardiovascular disease,Printed from: Drugs for the Heart 2007 Elsevier,Post-infarction remodeling,Printed from: Drugs for the Heart 2007 Elsevier,ACC/AHA Guidelines f
23、or Treatment of Risk Factors (class I),1. Treatment of hypertension according to Joint National Conference VI guidelines A 2. Smoking cessation therapy B 3. Management of diabetes C 4. Comprehensive cardiac rehabilitation program (including exercise) B 5. LDL-lowering therapy in patients with docume
24、nted or suspected CAD and LDL cholesterol 130 mg/dl, with a target LDL of 100 mg/dl A 6. Weight reduction in obese patients in the presence of hypertension, hyperlipidemia, or diabetes mellitus C,ACC/AHA Guidelines for Treatment of Risk Factors (class IIa),1. In patients with documented or suspected
25、 CAD and LDL cholesterol 100129 mg/dl, several therapeutic options are available: B a. Lifestyle and/or drug therapies to lower LDL to 200 mg/dl, with a target non-HDL cholesterol 130 mg/dl B 3. Weight reduction in obese patients in the absence of hypertension, hyperlipidemia, or diabetes mellitus C
26、,ACC/AHA Guidelines for Treatment of Risk Factors (class IIb),1. Folate therapy in patients with elevated homocysteine levels C 2. Identification and appropriate treatment of clinical depression to improve CAD outcomes C 3. Intervention directed at psychosocial stress reduction C,ACC/AHA Guidelines
27、for Treatment of Risk Factors (class III),1. Initiation of hormone replacement therapy in postmenopausal women for the purpose of reducing cardiovascular risk A 2. Vitamins C and E supplementation A 3. Chelation therapy C 4. Garlic C 5. Acupuncture C 6. Coenzyme Q C,Specific Goals for Risk Reduction
28、 Strategies in Patients with Chronic Stable Angina,Smoking Complete cessation Blood pressure 140/90 or 130/85 mm Hg if heart failure or renal insufficiency; 130/85 mm Hg if diabetes Lipid management Primary goal: LDL 100 mg/dl Secondary goal: If triglycerides 200 mg/dl, then non-HDL should be 130 mg
29、/dl Physical activity Minimum goal: 30 min 3 or 4 d/w Optimal goal: daily Weight management BMI 18.524.9 kg/m2 Diabetes management HbA1c 7%,Specific Goals for Risk Reduction Strategies in Patients with Chronic Stable Angina,Antiplatelet agents/anticoagulants : All patients: indefinite use of aspirin
30、 75325 mg per day if not contraindicated. Consider clopidogrel as an alternative if aspirin is contraindicated. Manage warfarin to international normalized ratio = 2.0 to 3.0 in patients after myocardial infarction when clinically indicated or for those not able to take aspirin or clopidogrel ACE in
31、hibitors: Treat all patients indefinitely after myocardial infarction; start early in stable high-risk patients (anterior myocardial infarction, previous myocardial infarction, Killip class II S3 gallop, rales, radiographic CHF). Consider chronic therapy for all other patients with coronary or other
32、 vascular disease unless contraindicated. Use as needed to manage blood pressure or symptoms in all other patients Beta blockers: Start in all post-myocardial infarction and acute patients (arrhythmia, LV dysfunction, inducible ischemia) at 528 days. Continue 6 mo minimum. Observe usual contraindica
33、tions. Use as needed to manage angina, rhythm, or blood pressure in all patients,ACC/AHA Guidelines for Echocardiography, Treadmill Exercise Testing, Stress Radionuclide Imaging, Stress Echocardiography Studies, and Coronary Angiography During Patient Follow-Up,1. Chest radiograph for patients with
34、evidence of new or worsening CHF C 2. Assessment of LV ejection fraction and segmental wall motion by echocardiography or radionuclide imaging in patients with new or worsening CHF or evidence of intervening myocardial infarction by history or ECG C 3. Echocardiography for evidence of new or worseni
35、ng valvular heart disease C 4. Treadmill exercise test for patients without prior revascularization who have a significant change in clinical status, are able to exercise, and do not have any of the ECG abnormalities listed in No. 5,ACC/AHA Guidelines for Echocardiography, Treadmill Exercise Testing
36、, Stress Radionuclide Imaging, Stress Echocardiography Studies, and Coronary Angiography During Patient Follow-Up,5. Stress radionuclide imaging or stress echocardiography procedures for patients without prior revascularization who have a significant change in clinical status and are unable to exerc
37、ise or have one of the following ECG abnormalities: C a. Preexcitation (Wolff-Parkinson-White) syndrome b. Electronically paced ventricular rhythm c. More than 1 mm of rest ST depression d. Complete left bundle branch block 6. Stress radionuclide imaging or stress echocardiography procedures for pat
38、ients who have a significant change in clinical status and required a stress imaging procedure on their initial evaluation because of equivocal or intermediate-risk treadmill results C 7. Stress radionuclide imaging or stress echocardiography procedures for patients with prior revascularization who
39、have a significant change in clinical status C 8. Coronary angiography in patients with marked limitation of ordinary activity (CCS class III) despite maximal medical therapy,Chronic stable angina,NEW THERAPIES,Myocardial ischemia: Sites of action of anti-ischemia medication,(Stone, 2004),Consequenc
40、es associated with dysfunction of late sodium current,Diseases (eg, ischemia, heart failure) Pathological milieu (reactive O2 species, ischemic metabolites) Toxins and drugs (eg, ATX-II, etc.),Na+ channel (Gating mechanism malfunction),Diastolic relaxation failure increases oxygen consumption and re
41、duces oxygen supply,Increased myocardial tension during diastole: Increases myocardial O2 consumption Compresses intramural small vessels Reduces myocardial blood flow Worsens ischemia and angina,Ranolazine: Mechanism of action,Ischemia, Late INa,Na+ overload,Diastolic relaxation failure (increased
42、diastolic tension) Extravascular compression,Ca2+ overload,Monotherapy with ranolazine increases exercise performance at trough and peak: MARISA,n=175, *p 0.01 vs placebo; *p 0.001 vs. placebo,Peak,Trough,*,*,*,*,*,*,*,*,*,*,*,*,*,*,*,*,*,*,Placebo,500 mg bid,1500 mg bid,Chaitman et al JACC 2004;43:
43、1375,Change from baseline, sec,n=791 *p 0.05; *p 0.01; *p 0.001 vs placebo.,Peak,Trough,*,*,*,*,*,*,*,*,*,Placebo,750 mg bid,1000 mg bid,*,Combination regimen of ranolazine with: Atenolol 50 mg qd, or Diltiazem 120 mg qd, or Amlodipine 5 mg qd,(CARISA),Chaitman et al. JAMA 2004;291:309,Effect of ran
44、olazine in patients with refractory angina despite maximum amlodipine therapy: ERICA,0,1,2,3,4,5,6,Amlodipine,+,Placebo,Amlodipine,+,Ranolazine,p=0.028,Baseline,On placebo,On ranolazine,Amlodipine,+,Placebo,Amlodipine,+,Ranolazine,p=0.014,p=0.18,0.0,1.0,2.0,3.0,4.0,5.0,5.5,0.5,1.5,2.5,3.5,4.5,Stone
45、et al. Circulation 2005;112:II-748,Angina episodes/week,Number of angina episodes/week,NTG consumption/week,p=0.48,Number of NTGs consumed/week,TMR,Surgical surgeons use the laser to make between 20 and 40 tiny (one-millimeter-wide),Percutaneous TMR,Percutaneous,Rationale,improved perfusion by stimu
46、lation of angiogenesis potential placebo effect anesthetic effect mediated by the destruction of sympathetic nerves carrying pain-sensitive afferent fibers Peri-procedural infarction.,EECP,EECP,Increases arterial blood pressure and retrograde aortic blood flow during diastole (diastolic augmentation
47、). Cuffs are wrapped around the patients legs and sequential pressure (300mmHg) is applied in early diastole.,Patient selection,Angina class III/IV Refractory to medical therapy Reversible ischemia of the free wall not amenable for revascularization Excluded if LVEF20% or had current major illness,A
48、CC/AHA Guidelines for Revascularization with PCI and CABG in Patients with Stable Angina (class I),1. CABG for patients with significant left main coronary disease A 2. CABG for patients with triple-vessel disease. The survival benefit is greater in patients with abnormal LV function (ejection fract
49、ion 0.50)A 3. CABG for patients with double-vessel disease with significant proximal LAD CAD and either abnormal LV function (ejection fraction less than 50%) or demonstrable ischemia on noninvasive testing A 4. Percutaneous coronary intervention for patients with double-or triple-vessel disease with significant proximal LAD CAD, who have anatomy suitable for catheter-b