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,B3. ACE inhibitor in all patients wi
10、th 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 A5. Sublingual nitroglycerin or nitroglycerin spray for the immediate relief of angina B 6. Calcium antago
11、nists or long-acting nitrates as initial therapy for reduction of symptoms when beta blockers are contraindicated B7. 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 nit
12、rates 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 bl
13、ockers 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 sy
14、ndrome 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 supportive
15、evidence) Low-intensity anticoagulation with warfarin in addition to aspirin B III (not indicated) 1. Dipyridamole B2. 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 ischemic
16、 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 Elsevier
17、,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 Guideline
18、 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 blo
19、ckers,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 dihydropyridine
20、s,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: Dr
21、ugs 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 with
22、 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 for T
23、reatment of Risk Factors (class I),1. Treatment of hypertension according to Joint National Conference VI guidelines A2. Smoking cessation therapy B3. Management of diabetes C4. Comprehensive cardiac rehabilitation program (including exercise) B5. LDL-lowering therapy in patients with documented or
24、suspected CAD and LDL cholesterol 130 mg/dl, with a target LDL of 100 mg/dl A6. 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 CAD and
25、LDL cholesterol 100129 mg/dl, several therapeutic options are available: Ba. Lifestyle and/or drug therapies to lower LDL to 200 mg/dl, with a target non-HDL cholesterol 130 mg/dl B3. Weight reduction in obese patients in the absence of hypertension, hyperlipidemia, or diabetes mellitus C,ACC/AHA Gu
26、idelines for Treatment of Risk Factors (class IIb),1. Folate therapy in patients with elevated homocysteine levels C2. Identification and appropriate treatment of clinical depression to improve CAD outcomes C3. Intervention directed at psychosocial stress reduction C,ACC/AHA Guidelines for Treatment
27、 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 Strategies i
28、n 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/dl Physical
29、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 75325 mg per
30、 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 inhibitors: Tre
31、at 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 vascular dis
32、ease 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 contraindications. Use as
33、 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 evidence of n
34、ew or worsening CHF C2. 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 C3. Echocardiography for evidence of new or worsening valvular hea
35、rt 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, Stress Radion
36、uclide 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 exercise or have one
37、 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 patients who have
38、a significant change in clinical status and required a stress imaging procedure on their initial evaluation because of equivocal or intermediate-risk treadmill results C7. Stress radionuclide imaging or stress echocardiography procedures for patients with prior revascularization who have a significa
39、nt change in clinical status C8. 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),Consequences associated wit
40、h 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 reduces oxygen supply,
41、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 diastolic tension) E
42、xtravascular 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;43:1375,Change from bas
43、eline, 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 ranolazine in patients
44、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 et al. Circulation 2
45、005;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 stimulation of angiogenes
46、is 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).Cuffs are wrapped
47、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,ACC/AHA Guidelines for
48、 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 fraction 0.50)A3. CABG for
49、 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 A4. Percutaneous coronary intervention for patients with double-or triple-vessel disease with significant proximal LAD CAD, who have anatomy suitable for catheter-based therapy and normal LV function and who do not have treated diabetes B,
