慢性穩(wěn)定性心絞痛的治療英文

1、 Treatment of Chronic Stable Angina Medical Revascularization PCIACBG 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, Scarborou

2、gh 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 hepa

3、rin 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.

4、 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

5、STUDY Total cancer Prostate cancer Cardiovascular disease Eye disease Cataract Macular degeneration Primary Endpoints PHYSICIANS HEALTH STUDY Double product = (Heart Rate) (systolic blood pressure) Printed from: Drugs for the Heart 2007 Elsevier Printed from: Drugs for the Heart 2007 Elsevier Printe

6、d from: Drugs for the Heart 2007 Elsevier ACC/AHA 2002 Guideline Update for the Management of Patients With Chronic Stable Angina Printed 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 th

7、e 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 Elsevier Printed from: Drugs for the Heart 2007 Elsevier Printed from: Drugs for the Heart 2007 Elsevier Printed from: Drugs for the Heart 2007

8、 Elsevier Printed from: Drugs for the Heart 2007 Elsevier Printed from: Drugs for the Heart 2007 Elsevier Ranolazine Consequences of ischemia Electrical instability Myocardial dysfunction ( systolic function/ diastolic stiffness) Conventional anti-ischemic medications blockers Nitrates Ca+ blockers

9、Compression of nutritive blood vessels Ischemia (Ca2+ overload) O2 demand Heart rate Blood pressure Preload Contractility O2 supply Development of ischemia (Stone, 2004) Diseases (eg, ischemia, heart failure) Pathological milieu (reactive O2 species, ischemic metabolites) Toxins and drugs (eg, ATX-I

10、I, 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 instabilit

11、y Ischemia Late INa Na+ overload Diastolic relaxation failure (increased diastolic tension) Extravascular compression Ca2+ overload Ranolazine inhibits the late inward Na current n=175, *p 0.01 vs placebo; *p 0.001 vs. placebo PeakTrough * * * * * * * * * * * * * * * * * Placebo500 mg bid 1000 mg bi

12、d1500 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 * * * * * * * * 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

13、 al. JAMA 2004;291:309 0 1 2 3 4 5 6 Amlodipine + Placebo Amlodipine + Ranolazine p=0.028 BaselineOn placeboOn 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 o

14、f angina episodes/week NTG consumption/week p=0.48 Number of NTGs consumed/week 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,

15、 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

16、 alternate days) Printed from: Drugs for the Heart 2007 Elsevier ACC/AHA 2002 Guideline Update for the Management of Patients With Chronic Stable Angina Printed from: Drugs for the Heart 2007 Elsevier Ranolazine Consequences of ischemia Electrical instability Myocardial dysfunction ( systolic functi

17、on/ 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) 0 1 2 3 4 5 6 Amlodipine + Placebo Amlodipine + Ranolazine p=0.028 BaselineOn placebo