慢性稳定性心绞痛的治疗（英文）

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 lTo improve quality of life (symptoms) lTo reduce mortality lTo reduce morbidity lTo reduce progression of disease and induce regression. Treatment of Chronic Stable Angina Medical Revascularization PCI ACBG MEDICAL THERAPY lANTIPLATELETS lBETA BLOCKERS lNITRATES lCALCIUM ANTAGONIST lACEI lSTATINS lNEW THERAPIES ANTIPLATELET AGENTS lASA Physicians Health Study Swedish Angina Pectoris Trial lTICLOPIDINE lCLOPIDOGREL CAPRI CURE Receptor GP IIb-IIIa: The Final 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;80(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 activates 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 were 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 cancer Cardiovascular disease Eye disease Cataract Macular degeneration Primary Endpoints PHYSICIANS HEALTH STUDY l 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 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 mortality Pharmacotherapy for Chronic Stable Angina (class I) l 1. Aspirin in the absence of contraindications A l 2. Beta-blockers as initial therapy in the absence of contraindications in patients with prior myocardial infarction or without prior myocardial infarction A,B l 3. ACE inhibitor in all patients with CAD who also have diabetes and/or LV systolic dysfunction A l 4. LDL-lowering therapy in patients with documented or suspected CAD and LDL cholesterol 130 mg/dl, with a target LDL of 200 mg/dl, with a target non-HDL cholesterol 130 mg/dl B l 3. Weight reduction in obese patients in the absence of hypertension, hyperlipidemia, or diabetes mellitus C ACC/AHA Guidelines for Treatment of Risk Factors (class IIb) l1. Folate therapy in patients with elevated homocysteine levels C l 2. Identification and appropriate treatment of clinical depression to improve CAD outcomes C l 3. Intervention directed at psychosocial stress reduction C ACC/AHA Guidelines for Treatment of Risk Factors (class III) l 1. Initiation of hormone replacement therapy in postmenopausal women for the purpose of reducing cardiovascular risk A l 2. Vitamins C and E supplementation A l 3. Chelation therapy C l 4. Garlic C l 5. Acupuncture C l 6. Coenzyme Q C Specific Goals for Risk Reduction Strategies in Patients with Chronic Stable Angina l Smoking Complete cessation l Blood pressure 140/90 or 130/85 mm Hg if heart failure or renal insufficiency; 130/85 mm Hg if diabetes l Lipid management Primary goal: LDL 100 mg/dl Secondary goal: If triglycerides 200 mg/dl, then non-HDL should be 130 mg/dl l Physical activity Minimum goal: 30 min 3 or 4 d/w Optimal goal: daily l Weight management BMI 18.524.9 kg/m2 l Diabetes management HbA1c 7% Specific Goals for Risk Reduction Strategies in Patients with Chronic Stable Angina l Antiplatelet agents/anticoagulants : All patients: indefinite use of aspirin 75 325 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 l ACE inhibitors: 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 vascular disease unless contraindicated. Use as needed to manage blood pressure or symptoms in all other patients l 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 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 l 1. Chest radiograph for patients with evidence of new or worsening CHF C l 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 l 3. Echocardiography for evidence of new or worsening valvular heart disease C l 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 Radionuclide Imaging, Stress Echocardiography Studies, and Coronary Angiography During Patient Follow-Up l 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 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 l 6. Stress radionuclide imaging or stress echocardiography procedures for patients 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 l 7. Stress radionuclide imaging or stress echocardiography procedures for patients with prior revascularization who have a significant change in clinical status C l 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 Ranolazine Consequences of ischemia Electrical instability Myocardial dysfunction ( systolic function/ diastolic stiffness) Conventional anti-ischemic medications blockers Nitrates Ca+ blockers Compression of nutritive blood vessels Ischemia (Ca2+ overload) O2 demand Heart rate Blood pressure Preload Contractility O2 supply Development of ischemia (Stone, 2004) Consequences 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) Increase ATP consumption Decrease ATP formation Oxygen supply and demand Abnormal contraction and relaxation diastolic tension (LV wall stiffness) Mechanical dysfunction Early after potentials Beat-to-beat APD Arrhythmias (VT) Electrical instability Diastolic relaxation failure increases oxygen consumption and reduces oxygen supply Increased myocardial tension during diastole: Increases myocardial O2 consumption Compresses intramural small vessels l Reduces myocardial blood flow Worsens ischemia and angina Ranolazine: Mechanism of action Ischemia Late INa Na+ overload Diastolic relaxation failure (increased diastolic tension) Extravascular compression Ca2+ overload Ranolazine inhibits the late inward Na current Monotherapy with ranolazine increases exercise performance at trough and peak: MARISA n=175, *p 0.01 vs placebo; *p 0.001 vs. placebo PeakTrough * * * * * * * * * * * * * * * * Placebo 500 mg bid 1000 mg bid 1500 mg bid Chaitman et al JACC 2004;43:1375 Change from baseline, sec n=791 *p 0.05; *p 0.01; *p 0.001 vs placebo. PeakTrough * * * * * * * * 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 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 2005;112:II-748 Angina episodes/week Number of angina episodes/week NTG consumption/week p=0.48 Number of NTGs consumed/week TMR lSurgical lsurgeons use the laser to make between 20 and 40 tiny (one-millimeter-wide) Percutaneous TMR lPercutaneous Rationale limproved perfusion by stimulation of angiogenesis lpotential placebo effect lanesthetic effect mediated by the destruction of sympathetic nerves carrying pain-sensitive afferent fibers lPeri-procedural infarction. EECP EECP lIncreases arterial blood pressure and retrograde aortic blood flow during diastole (diastolic augmentation). lCuffs are wrapped around the patients legs and sequential pressure (300mmHg) is applied in early diastole. Patient selection lAngina class III/IV Refractory to medical therapy Reversible ischemia of the free wall not amenable for revascularization lExcluded if LVEF20% or had current major illness ACC/AHA Guidelines for Revascularization with PCI and CABG in Patients with Stable Angina (class I) l 1. CABG for patients with significant left main coronary disease A l 2. CABG for patients with triple-vessel disease. The survival benefit is greater in patients with abnormal LV function (ejection fraction 0.50)A l 3. CABG for patients with doubl