最近の降圧治療 ARBとACEI ONTARGETをとおして

1 HATORI CLINIC 11101110--11 http:// CLINIC II ACE ARB Val-HeFT 4) vs ACE ARB1) N Engl J Med1987; 316: 1429-1435, 2) N Engl J Med1991; 325: 293-302, 3) JAMA1995; 273: 1450-1456, 4) N Engl J Med2001; 345: 1667-1675, 5) Lancet2003: 362; 759-766 ACE /ARB 95 2) vs Garg 3) vs CHARM-Overall 5) vs AHA ACE ARB Hunt SA, et al: Circulation 2005; 112: e154-235 A B C D ACE /ARB / A ACE /ARB A/B ACE ARB / A/B/C / inotropes / ACE ARB Val-HeFT /CHARM-Added ACE ACE 1 95 1 Cohn JN, et al: N Engl J Med 2001: 345: 1667-16752 McMurray JJV, et al: Lancet 2003.

2 362: 3034 p 95 + ACE ACE 2 / BMJ ARB !? Verma S BMJ2004;329;1248-1249 BPLTTC BPLTTC Blood Pressure Lowering Treatment Trialists Collaboration WHO ISH ACE ARB 15 2005J Hypertens. 2007; 25: 951-8 Circulation ARB ? vs ? Martin H Circulation2006;114;838-854 ARB ACE HATORI CLINICHATORI CLINIC BPLTTC BPLTTC 2005 15 2 ACE ARB 2005 15 2000 Lancet 1 2000 Lancet 1 2003 Lancet 362 2 2003 Lancet 362 2 2003 Lancet 2 2003 Lancet 2 Blood Pressure Lowering Treatment Trialists CollaborationSecond cycle of overview analysesInstituteforInternationalHealthB lood Pressure Lowering Treatment Trialists CollaborationSecond cycle of overview analysesInstituteforInternationalHealth ACE Ca HATORI CLINICBPLTTC BPLTTC 2.

3 WHO ISH CLINICS tafford RS Hypertension 2006;48:213-218 HATORI CLINIC ACE 02004006008001,0001,2001,4001,6001,8002, 0002001 2002 2003 2004 2005 ( ) ( ) ( ) Hanon S., et Renin Angiotensin Aldosterone Syst 2000;1:147 150; Chen R., et 2003;42:542 547; Hurairah H., et J Clin Pract 2004;58:173 183;Steckelings , et al. Peptides 2005;26:1401 1409 /NO I IIAT1 AT2 ACE tPA II ACE AT1 Hanon S., et Renin Angiotensin Aldosterone Syst 2000;1:147 150; Chen R., et 2003;42:542 547; Hurairah H.

4 , et J Clin Pract 2004;58:173 183; Steckelings , et al. Peptides 2005;26:1401 1409 I II ?NO?ACE tPA AT2 AT1 ARB /NOHanon S., et Renin Angiotensin Aldosterone Syst 2000;1:147 150; Chen R., et 2003;42:542 547; Hurairah H., et J Clin Pract 2004;58:173 183;Steckelings , et al. Peptides 2005;26:1401 1409 ACE /ARB AT1 ACEI nhibitor ?NO?ARB /NO I II tPA AT2 II HATORI CLINICARB PDR 2005 PDR 2005 losartanCOZAAR valsartan ACE ARB candesartan ARB ACE telmisartan ARB ACE olmesartan ACE ARB PDR Physicians Desk ReferenceHATORI CLINIC n=750 vs ACE n=1,500 vs HCTZ.

5 Reno-protectionReno-protectionVascular-p rotectionand blood pressuremanagementVascular-protectionand blood pressuremanagement n=450 vs n=750 +HCTZ vs +HCTZ / n=800 +HCTZ vs +HCTZARB n=800 +HCTZ vs +HCTZ n=750 vs PROBE Program of Research tO show TelmisartanEnd-organ proteCTION 5,5005,500 n=87 vs n=250 vs HATORI CLINICDzau V, et al.; Am Heart J 121 : 1244-1263, 1991 / / / / / / / / HATORI CLINIC ACEACE FDAFDA ACEACE Am J Health Syst Pharm 2000; Suppl 1: S27 AllDeath fromCV causesMIStroke-27%P= reduction for treatment with Ramipril vs.

6 Placebo Ramipril : n=1,808, Placebo : n=1,769 %-40-35-30-25-20-15-10-50 MICRO-HOPE Study Primary Outcomes The HOPE Study Investigators : Lancet 355 : 253, 2000 HATORI CLINICP ilote L, et al: Ann Intern Med 141: 102-112, 2004 7,512 027080901004681012 ACE ACEACE HATORI CLINIC 14 5 HATORI CLINIC ARB ONgoingTelmisartan Alone andin combination with Ramipril Global Endpoint TrialHATORI CLINIC The ONTARGET/TRANSCEND Investigators: Am Heart J 148: 52-61, 2004 ARB+ACE ARB vs. ACE ONTARGET ONTARGET TRANSCEND 2 HATORI CLINIC 55 25,620 40 733 80mg 10mg 80mg 10mg56 2 The ONTARGET Investigators: N Engl J Med 358: 1547-1559, 2008 HATORI CLINICARBARB 31,546 VALUEHOPELIFECHARMCASE-JJIKEI-HEART10,00 0 20,000 30,000 15,2459,2979,1937,6014,7033,081=1,000 25,620 HATORI CLINICThe ONTARGET/TRANSCEND Investigators: Am Heart J 148: 52-61, 2004, The ONTARGET Investigators: N Engl Med 358.

7 1547-1559, 2008 z z z z ACE 6,000 25,620 80mg/80mg/ 8,5428,542 10mg/10mg/ 8,5768,576 80mg/80mg/ 3,0003,000 3,0003,000 80mg/80mg/ 10mg/10mg/ 8,5028,502 HATORI CLINIC n=284 OGTTn=4,000 n=7,000 ABPMn=1,000 MRI n=350 n=12,000 n=1,500n= 25,620n= 5,926 n= 31,546 Sleight P: Acta Diabetol 42 Suppl 1: S50-S56, 2005 HATORI CLINIC 66 vs. vs. SBPSBP mmHgmmHg mmHgmmHg mmHgmmHg mmHgmmHg 10mg10mg 80mg80mg The ONTARGET Investigators: N Engl J Med 358: 1547-1559, 2008 HATORI CLINIC 20 80mg 10mg025310155 41 9595 The ONTARGET Investigators: N Engl J Med 358: 1547-1559, 2008 HATORI CLINIC 8080mgmg N=8,542N=8,542 10mg10mg N=8,576N=8,576 1,4231,423 1,4121,412 HOPEHOPE 1,1901,190 1,2101,210 95 The ONTARGET Investigators.

8 N Engl J Med 358: 1547-1559, < HATORI CLINIC 66 vs. vs. SBPSBP mmHgmmHg mmHgmmHg mmHgmmHg mmHgmmHg 10mg10mg The ONTARGET Investigators: N Engl J Med 358: 1547-1559, 2008 HATORI CLINIC 20 10mg51015502341 The ONTARGET Investigators: N Engl J Med 358: 1547-1559, 2008 (( )) 9595 HATORI CLINIC N=8,502N=8,502 10mg10mg N=8,576N=8,576 PP Hypotensive symptomsHypotensive symptoms 4064061491491515360360121225256060< < SyncopeSyncope CoughCough DiarrheaDiarrhea 3939< < AngioedemaAngioedema Renal impairmentRenal impairment 9494< < The ONTARGET Investigators: N Engl J Med 358.

9 1547-1559, 2008 HATORI ACEACE BPLTTCBPLTTC ARBARB ONTARGETONTARGET HATORI CLINICHATORI CLINICHATORI CLINICHATORI CLINICHATORI CLINICHATORI CLINIC ACEACE JNCJNC--77 ACEACEARBARBCCBCCB HATORI CLINIC ACEACE JNCJNC--77 JNCJNC--88 ACEACEARBARBCCBCCB ONTARGONTARGETET

10 ONTARGONTARGETET PRoFESSPRoFESS HATORI CLINIC Diuretics in the management of essential hypertension (DIME) study Diuretics in the management of essential hypertension (DIME) studyThe DIME Study Group & HATORI BendrofliazideBendrofliazide (mmHg) 1mg1mg2mg 4mg2mg 25mg 25mg 50mg100mg100mgHATORI CLINIC Dual Benefit PPAR Kurtz TW, et al.; J Hypertens 22 : 2253-2261, 2004 HATORI CLINIC HOOC O NHSOOAT1 PPAR Kurtz TW, et al.; J Hypertens 22 : 2253-2261, 2004