慢性稳定性心绞痛的治疗英文

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1、Treatment of Chronic Stable AnginaMedicalRevascularizationPCIACBGWhite 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

2、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

3、activates plateletsPHYSICIANS HEALTH STUDYA 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

4、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 Card

5、iovascular disease Eye disease Cataract Macular degenerationPrimary EndpointsPHYSICIANS HEALTH STUDYDouble product=(Heart Rate)(systolic blood pressure)Printed from:Drugs for the Heart 2007 Elsevier Printed from:Drugs for the Heart 2007 Elsevier Printed from:Drugs for the Heart 2007 Elsevier ACC/AHA

6、 2002 Guideline Update for the Management of Patients With Chronic Stable Angina Printed from:Drugs for the Heart 2007 ElsevierPrinted from:Drugs for the Heart 2007 ElsevierPrinted from:Drugs for the Heart 2007 ElsevierPrinted from:Drugs for the Heart 2007 ElsevierPrinted from:Drugs for the Heart 20

7、07 ElsevierPrinted from:Drugs for the Heart 2007 ElsevierPrinted from:Drugs for the Heart 2007 Elsevier Printed from:Drugs for the Heart 2007 Elsevier Printed from:Drugs for the Heart 2007 Elsevier Printed from:Drugs for the Heart 2007 ElsevierPrinted from:Drugs for the Heart 2007 ElsevierPrinted fr

8、om:Drugs for the Heart 2007 ElsevierRanolazineConsequences of ischemia Electrical instability Myocardial dysfunction (systolic function/diastolic stiffness)Conventionalanti-ischemicmedications blockers Nitrates Ca+blockersCompressionof nutritiveblood vesselsIschemia(Ca2+overload)O2 demand Heart rate

9、 Blood pressure Preload Contractility O2 supplyDevelopment of ischemia(Stone,2004)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 formationOxy

10、gen supply and demand Abnormal contraction and relaxation diastolic tension(LV wall stiffness)Mechanicaldysfunction Early after potentials Beat-to-beat APD Arrhythmias(VT)ElectricalinstabilityIschemia Late INaNa+overloadDiastolic relaxation failure(increased diastolic tension)Extravascular compressi

11、onCa2+overloadRanolazineinhibits the late inwardNa currentn=175,*p 0.01 vs placebo;*p 0.001 vs.placeboPeakTrough*Placebo500 mg bid1000 mg bid1500 mg bidChaitman et 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

12、 regimen of ranolazine with:Atenolol 50 mg qd,or Diltiazem 120 mg qd,or Amlodipine 5 mg qd(CARISA)Chaitman et al.JAMA 2004;291:3090123456Amlodipine+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/weekNumber of angina episodes/weekNTG consumption/weekp=0.48Number of NTGs consumed/week