M. Mohsen Ibrahim, MD Cardiology Department Cairo University

Transcription

1 BENEFITS OF RAS BLOCKADE IN HYPERTENSION M. Mohsen Ibrahim, MD Cardiology Department Cairo University

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3 Physician Survey 2002/ 3 Drug Prescription EGYPT Thiazide B-Blocker ACE-I Ca Antagonist Combination

4 ANGIOTENSIN PROINFLAMMATORY ACTIONS Endothelial Cell Activation : Leucocyte Binding VSMCs : Growth Migration Monocytes/Macrophages : Transformation Activation

5 ACE INHIBITORS ANTI-ATHEROGENIC ACTIVITY Endothelial Function : NO Prostacyclin VSMCs : Superoxide action (Antioxidant) Growth Proliferation Migration Monocytes : Attraction Adhesion

6 MARVAL: Mean BP Effects in Type 2 Diabetic Patients With Microalbuminuria 0-2 SBP DBP -4 Mean Change From Baseline at 24 Weeks (mm Hg) -6-8 P = NS P = NS Valsartan 80/160mg (n = 146) Amlodipine 5/10 mg (n = 145) Adapted from Viberti G et al. Circulation. 2002;106:

7 ARAs Significantly Reduce Microalbuminuria (MARVAL) 20 Change in UAER From Baseline, % Valsartan Amlodipine Time, weeks ( 8%) P < ( 44%) Adapted from Viberti GC, for the MARVAL Trial. Circulation. 2002;106:

8 AASK Study Cumulative Incidence of Renal Events and Death (%) (GFR Event, ESRD, or Death) Cumulative Incidence (%) Amlodipine Ramipril 38 % RR P = Months Agodoa LY, et al. JAMA. 2001) AASK

9 Effect OF Antihypertensives on Proteinuria And Albuminuria in 2924 Patients With Type 1 & 2 Diabetes log change from baseline proteinuria albuminuria ACE Inhibitors CCB s Beta-Blockers Control Kasiske et al. 1993

10 LIFE: Losartan vs. Atenolol Reduced Carotid Artery Hypertrophy Intima-medial thickness change from baseline at year 3 0 Losartan (n=23) Atenolol (n=22) % Change in intima-medial cross-sectional area % 1.7 % p<0.05

11 mmhg *Mean BP at last visit. Comparable Blood-Pressure Reductions 1 Systolic Diastolic Atenolol Losartan Mean arterial Atenolol mmhg* Losartan mmhg* Atenolol mmhg* Losartan mmhg* Losartan 81.3 mmhg* Atenolol 80.9 mmhg* Time (months) ١١ 1. Dahlöf B et al. Lancet 2002;359:

12 Studies Investigating the Effects of RAS Blockade on the Onset of New Cases of Diabetes Study Drug Control Population CAPP Captopril Conventional HBP HOPE Ramipril Placebo NBP + HBP LIFE Losartan Atenolol HBP + LVH SCOPE Candesartan Conventional Elderly HBP CHARM - Overall Candesartan PlaceboCHF CHF SOLVD Enalapril Placebo LVD/CHF ALLHAT Lisinopril Chlortalidone HBP VALUE Valsartan Amlodipine HBP HBP: High blood pressure; NBP: normal blood pressure; LVH: left ventricular hypertrophy; CHF: congestive heart failure. Modified after Nicholas et al, Journal of Hypertension, 2004

13 VALUE: Incidence of New-onset Diabetes New-Onset Diabetes (% of patients in treatment group) % Valsartan-based Regimen (n = 5094) 23% Risk Reduction With Valsartan P < % Amlodipine-based Regimen (n = 5074) Julius S et al. Lancet. June 2004;363.

14 VALUE: Blood Pressure Changes From Baseline to the End of the Study 0 mmhg SBP DBP 20 Valsartan- Based Regimen Amlodipine- Based Regimen Julius S et al. Lancet. June 2004;363.

15 Reduction in the Risk of Stroke 1 Proportion of patients with first event (%) Fatal and nonfatal stroke Atenolol Losartan Adjusted risk reduction 24.9%, p = Unadjusted risk reduction 25.8%, p = % Risk Reduction Number at risk Losartan (n) Atenolol (n) No significant difference in CV death and MI vs. atenolol. ١٥ 1. Dahlöf B et al. Lancet 2002;359: Time (months) Risk reduction = relative risk vs. atenolol.

16 Effect of candesartan cilexetil on blood pressure and stroke incidence in stroke-prone SHR Blood pressure mmhg SHRsp control Candesartan cilexetil 0.1 mg/kg Candesartan cilexetil 10 mg/kg 125 % Incidence of stroke weeks Time Inada et al 1997

17 Cardiovascular Events - Mortality ACE Inhibitors vs Diuretic or β-blocker Treatment Comparison Entry criteria Follow-up (years) AASK Ramipril vs metoprolol HBP+nephropathy, Afr 4.1 ALLHAT Lisinopril vs chlorthalidone HBP+RF 4.9 ANBP2 Enalapril vs hydrochlorothiazide HBP2, years 4.1 CAPPP Captopril vs β-blocker or diuretic HBP 6.1 STOP2 Enalapril or lisinopril vs atenolol or metoprolol HBP, years 5.0 or pindolol or hydrochlorothiazide + amiloride UKPDS-HDS Captopril vs atenolol HBP+DM 8.4 Blood Pressure Lowering Treatment Trialist Collaboration Lancet 2003;362:1527

18 Cardiovascular Events - Mortality ACE Inhibitors vs Calcium Antagonists Treatment Comparison Entry criteria Follow-up (years) AASK Ramipril vs amlodipine HBP+nephropathy, Afr 3.0 ABCD(H) Enalapril vs nisoldipine HBP+DM 5.3 ALLHAT Lisinopril vs amlodopine HBP+CVD RF 4.9 JMIC-B ACE inhibitor vs nifedipine HBP + CHD 3.0 STOP2 Enalapril or lisinopril vs felodipine or isradipine HBP, years 5.0 Blood Pressure Lowering Treatment Trialist Collaboration Lancet 2003;362:1527

19 RAS blockade is superior to other agents in providing target organ protection and preventing development of diabetes ACEIs are superior to CAs in preventing heart failure and possibly coronary events ARAs are superior to many agents in preventing stroke, heart failure and major cardiovascular events RAS blockade provides no advantage over other agents regarding cardiovascular death and total mortality

20 RAS Blockade in Hypertension Specific Indications Heart failure due to systolic dysfunction Chronic renal failure, both diabetic and nondiabetic After a myocardial infarction High risk patients (associated CVD, diabetes with CVRF) Elderly hypertensives