慢性稳定性心绞痛治疗英文

1、慢性稳定性心绞痛治疗英文The Goals of Therapy in CADTo improve quality of life (symptoms)To reduce mortalityTo reduce morbidityTo reduce progression of disease and induce regression.Treatment of Chronic Stable AnginaMedicalRevascularizationPCIACBGMEDICAL THERAPYANTIPLATELETSBETA BLOCKERSNITRATESCALCIUM ANTAGONIS

2、TACEISTATINSNEW THERAPIESANTIPLATELET AGENTSASAPhysicians Health StudySwedish Angina Pectoris TrialTICLOPIDINECLOPIDOGRELCAPRICUREReceptor GP IIb-IIIa: The Final Common Pathway to Platelet AggregationWhite HD. Am J Cardiol 1997; 80:2B-10B.Schafer A. J Clin Invest 1986; 78:73-79.DeJong MJ, et al. Cri

3、tical 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 a

4、nd thrombosisGP IIb-IIIa inhibitors prevent platelet activation by blocking GP IIb-IIa (outside-in signaling)High-dose heparin stimulates PAF which activates plateletsPHYSICIANS HEALTH STUDYA randomized, double-blind, placebo controlled trial designed to test the effects of low-dose aspirin and beta

5、-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

6、 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 degenerationPrimary EndpointsPHYSICIANS HEALTH STUDYThe trials Data and Safety Monitoring Board

7、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%

8、(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)1. Aspirin in the absence of contraindications A2. Beta-blockers as initial therapy in the absence of co

9、ntraindications in patients with prior myocardial infarction or without prior myocardial infarction A,B3. ACE inhibitor in all patients with CAD who also have diabetes and/or LV systolic dysfunction A4. LDL-lowering therapy in patients with documented or suspected CAD and LDL cholesterol 130 mg/dl,

10、with a target LDL of 100 mg/dl A5. Sublingual nitroglycerin or nitroglycerin spray for the immediate relief of angina B6. Calcium antagonists or long-acting nitrates as initial therapy for reduction of symptoms when beta blockers are contraindicated B7. Calcium antagonists or long-acting nitrates in

11、 combination with beta blockers when initial treatment with beta blockers is not successful B8. Calcium antagonists and long-acting nitrates as a substitute for beta blockers if initial treatment with beta blockers leads to unacceptable side effectsPharmacotherapy for Chronic Stable Angina (class II

12、a)1. Clopidogrel when aspirin is absolutely contraindicated 2. Long-acting non-dihydropyridine calcium antagonists instead of beta blockers as initial therapy B3. In patients with documented or suspected CAD and LDL cholesterol 100129 mg/dl, several therapeutic options are available: Ba. Lifestyle a

13、nd/or drug therapies to lower LDL to 100 mg/dlb. Weight reduction and increased physical activity in persons with the metabolic syndromec. 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 cholestero

14、l4. ACE inhibitor in patients with CAD or other vascular diseasePharmacotherapy for Chronic Stable AnginaIIb (weak supportive evidence)Low-intensity anticoagulation with warfarin in addition to aspirin BIII (not indicated)1. Dipyridamole B2. Chelation therapy BCUREApproach to the treatment of chest

15、pain OXYGEN DEMANDDouble product = (Heart Rate) (systolic blood pressure)BETA BLOCKERSEffects of -blockade on ischemic 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

16、from: Drugs for the Heart 2007 Elsevier Contraindications to -blockade Printed from: Drugs for the Heart 2007 Elsevier BETA BLOCKERS STUDIESTIBET (Total Ischemic Burden European Trial)APSIS (The Angina Prognosis Study In Stockholm)ASIST (Atenolol Silent Ischemia Trial)TIBBS (Total Ischemic Burden Bi

17、soprolol Study)IMAGE (International Multicenter Angina Exercise Study)BB for clinical useACC/AHA 2002 Guideline 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 ElsevierCARDIAC VS. VASCU

18、LARPrinted from: Drugs for the Heart 2007 ElsevierMechanisms of anti-ischemic effects of calcium channel blockers Printed from: Drugs for the Heart 2007 ElsevierVerapamil and diltiazem have a broad spectrum of therapeutic effects. Printed from: Drugs for the Heart 2007 ElsevierContraindications to v

19、erapamil or diltiazem Printed from: Drugs for the Heart 2007 ElsevierContraindications to dihydropyridines Printed from: Drugs for the Heart 2007 ElsevierProperties of CCB in clinical useSchematic diagram of effects of nitrate on the circulation Printed from: Drugs for the Heart 2007 Elsevier Effect

20、s of nitrates in generating NO and stimulating guanylate cyclase to cause vasodilation Printed from: 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 He

21、art 2007 ElsevierNitrates in AnginaEffect of simvastatin on cardiovascular events among patients 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 Elsevie

22、rPost-infarction remodeling Printed from: Drugs for the Heart 2007 ElsevierACC/AHA Guidelines for Treatment 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 re

23、habilitation program (including exercise) B5. LDL-lowering therapy in patients with documented or 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 CACC/AHA Guidelin

24、es for Treatment of Risk Factors (class IIa)1. In patients with documented or suspected CAD and 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

25、obese patients in the absence of hypertension, hyperlipidemia, or diabetes mellitus CACC/AHA Guidelines 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

26、 C3. Intervention directed at psychosocial stress reduction CACC/AHA Guidelines for Treatment of Risk Factors (class III)1. Initiation of hormone replacement therapy in postmenopausal women for the purpose of reducing cardiovascular risk A2. Vitamins C and E supplementation A3. Chelation therapy C4.

27、 Garlic C5. Acupuncture C6. Coenzyme Q CSpecific Goals for Risk Reduction Strategies in Patients with Chronic Stable AnginaSmoking Complete cessationBlood pressure 140/90 or 130/85 mm Hg if heart failure or renal insufficiency; 130/85 mm Hg if diabetesLipid management Primary goal: LDL 100 mg/dlSeco

28、ndary goal: If triglycerides 200 mg/dl, then non-HDL should be 130 mg/dlPhysical activity Minimum goal: 30 min 3 or 4 d/wOptimal goal: dailyWeight management BMI 18.524.9 kg/m2Diabetes management HbA1c 7%Specific Goals for Risk Reduction Strategies in Patients with Chronic Stable Angina Antiplatelet

29、 agents/anticoagulants : All patients: indefinite use of aspirin 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 indic

30、ated or for those not able to take aspirin or clopidogrelACE 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). Conside

31、r 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 patientsBeta blockers: Start in all post-myocardial infarction and acute patients (arrhythmia, LV dysfunction, inducible ischemia)

32、at 528 days. Continue 6 mo minimum. Observe usual contraindications. Use as needed to manage angina, rhythm, or blood pressure in all patientsACC/AHA Guidelines for Echocardiography, Treadmill Exercise Testing, Stress Radionuclide Imaging, Stress Echocardiography Studies, and Coronary Angiography Du

33、ring Patient Follow-Up 1. Chest radiograph for patients with evidence of new 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

34、 or ECG C3. Echocardiography for evidence of new or worsening valvular heart disease C4. 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. 5ACC/AHA Gu

35、idelines for Echocardiography, Treadmill Exercise Testing, Stress Radionuclide Imaging, Stress Echocardiography Studies, and Coronary Angiography During Patient Follow-Up5. Stress radionuclide imaging or stress echocardiography procedures for patients without prior revascularization who have a signi

36、ficant change in clinical status and are unable to exercise or have one of the following ECG abnormalities: Ca. Preexcitation (Wolff-Parkinson-White) syndromeb. Electronically paced ventricular rhythmc. More than 1 mm of rest ST depressiond. Complete left bundle branch block6. Stress radionuclide im

37、aging 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 C7. Stress radionuclide imaging or stress echocardiography procedu

38、res for patients with prior revascularization who have a significant change in clinical status C8. Coronary angiography in patients with marked limitation of ordinary activity (CCS class III) despite maximal medical therapyChronic stable anginaNEW THERAPIESMyocardial ischemia:Sites of action of anti

39、-ischemia medicationRanolazineConsequences of ischemia Electrical instability Myocardial dysfunction ( systolic function/ diastolic stiffness)Conventionalanti-ischemicmedications blockers Nitrates Ca+ blockersCompressionof nutritiveblood vesselsIschemia(Ca2+ overload) O2 demand Heart rate Blood pres

40、sure Preload Contractility O2 supplyDevelopment 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 m

41、alfunction)Increase ATP consumptionDecrease ATP formationOxygen supply and demand Abnormal contraction and relaxation diastolic tension(LV wall stiffness)Mechanicaldysfunction Early after potentials Beat-to-beat APD Arrhythmias (VT)ElectricalinstabilityDiastolic relaxation failure increases oxygen c

42、onsumption and reduces oxygen supplyIncreased myocardial tension during diastole:Increases myocardial O2 consumptionCompresses intramural small vesselsReduces myocardial blood flow Worsens ischemia and anginaRanolazine: Mechanism of actionIschemia Late INaNa+ overloadDiastolic relaxation failure(inc

43、reased diastolic tension)Extravascular compressionCa2+ overloadRanolazineinhibits the late inwardNa currentMonotherapy with ranolazine increases exercise performance at trough and peak: MARISAn=175, *p 0.01 vs placebo; *p 0.001 vs. placeboPeakTrough*Placebo500 mg bid1000 mg bid1500 mg bidChaitman et

44、 al JACC 2004;43:1375Change from baseline, secn=791*p 0.05; *p 0.01; *p 0.001 vs placebo.PeakTrough*Placebo750 mg bid1000 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;291:309Effect of ranolazine in pa

45、tients withrefractory angina despitemaximum amlodipine therapy: ERICA0123456Amlodipine+PlaceboAmlodipine+Ranolazinep=0.028BaselineOn placeboOn ranolazineAmlodipine+PlaceboAmlodipine+Ranolazinep=0.014p=0.180.01.02.03.04.05.05.50.51.52.53.54.5Stone et al. Circulation 2005;112:II-748Angina episodes/wee

46、kNumber of angina episodes/weekNTG consumption/weekp=0.48Number of NTGs consumed/weekTMRSurgicalsurgeons use the laser to make between 20 and 40 tiny (one-millimeter-wide)Percutaneous TMRPercutaneousRationaleimproved perfusion by stimulation of angiogenesispotential placebo effectanesthetic effect m

47、ediated by the destruction of sympathetic nerves carrying pain-sensitive afferent fibersPeri-procedural infarction. EECPEECPIncreases arterial blood pressure and retrograde aortic blood flow during diastole (diastolic augmentation).Cuffs are wrapped around the patients legs and sequential pressure (300mmHg) is applied in early diastole.Patient selectionAngina class III/IV Refractory to medical therapyReversible ischemia of the free wallnot amenable f