1、GAPTreatment of Chronic Stable AnginaMedicalRevascularizationPCIACBGWhite HD.Am J Cardiol 2019;80:2B-10B.Schafer A.J Clin Invest 1986;78:73-79.DeJong MJ,et al.Critical Care Nursing Clin of N Am 2019;11:355-371.Moser M,et al.J Cardiovasc Pharmacol 2019;41:586-592.Phillips DR,Scarborough RM.Am J Cardi
2、ol 2019;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 whi
3、ch 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 we
4、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 cancer C
5、ardiovascular disease Eye disease Cataract Macular degenerationPrimary EndpointsDouble product=(Heart Rate)(systolic blood pressure)Printed from:Drugs for the Heart 2019 Elsevier Printed from:Drugs for the Heart 2019 Elsevier Printed from:Drugs for the Heart 2019 Elsevier ACC/AHA 2019 Guideline Upda
6、te for the Management of Patients With Chronic Stable Angina Printed from:Drugs for the Heart 2019 ElsevierPrinted from:Drugs for the Heart 2019 ElsevierPrinted from:Drugs for the Heart 2019 ElsevierPrinted from:Drugs for the Heart 2019 ElsevierPrinted from:Drugs for the Heart 2019 ElsevierPrinted f
7、rom:Drugs for the Heart 2019 ElsevierPrinted from:Drugs for the Heart 2019 Elsevier Printed from:Drugs for the Heart 2019 Elsevier Printed from:Drugs for the Heart 2019 Elsevier Printed from:Drugs for the Heart 2019 ElsevierPrinted from:Drugs for the Heart 2019 ElsevierPrinted from:Drugs for the Hea
8、rt 2019 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 Blood pressure Prel
9、oad Contractility O2 supplyDevelopment of ischemia(Stone,2019)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 formationOxygen supply and deman
10、d 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 compressionCa2+overloadRanola
11、zineinhibits 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 2019;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 ranolazi
12、ne with:Atenolol 50 mg qd,or Diltiazem 120 mg qd,or Amlodipine 5 mg qd(CARISA)Chaitman et al.JAMA 2019;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 2019;112:II-748Angina episodes/weekNumber of angina episodes/weekNTG consumption/weekp=0.48Number of NTGs consumed/week
