ARB + Statin

ARB + Statin Evidence from emerging concepts as the rationale

The topics for discussion ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]

The exisiting situation Evidence and observations

The observations ,[object Object],[object Object]

CAD risk by associated risk factors

CAD mortality in metabolic syndrome Lakka HM et al. JAMA 2002;288:2709-2716. Cumulative Hazard (%) 0 2 6 8 12 Follow-up (Years) YES Metabolic Syndrome: NO Cardiovascular Disease Mortality RR (95% CI), 3.55 (1.98–6.43) 4 10

CAD event free survival with CRP levels in metabolic syndrome Ridker PM et al. Circulation 2003;107:391-397. CV Event –F ree Survival Probability Follow-up (Years) 0 CRP < 3 mg/L, No metabolic syndrome 1.00 0.99 0.98 0.97 0.96 0.95 2 4 6 8 CRP ≥ 3 mg/L, No metabolic syndrome CRP < 3 mg/L, Metabolic syndrome CRP ≥ 3 mg/L, Metabolic syndrome

Metabolic syndrome ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]

Traditional Treatment Approach ACEI ARB Diuretic Ca-channel blockers ,[object Object],[object Object],BP Ambulatory BP Insulin Sulfonylureas TZDs ,[object Object],[object Object],Blood sugar Glycosylated hemoglobin Monitor Diet Meds Weight Monitoring? Diet/Exercise? Medications? Type 2 DM Dyslipidemia Hypertension Statins Fibrates Niacin Resins Lipid panels Lipoprotein subsets  Total fat  Cholesterol  Fiber

New Treatment Approach ,[object Object],[object Object],[object Object],[object Object],[object Object], Adipose Tissue Diet Meds ,[object Object],[object Object],[object Object],Hypertension ACEI ARB ,[object Object],[object Object],IGT Metformin Exenatide  O mega-3s  MUFA  Sat fat  Trans fat  Glycemia + ETOH ATP III guidelines: TLC diet Dyslipidemia Statins Fibrate

Cross talk ,[object Object],Kim J, Koh KK, Quon MJ. Arterioscler Thromb Vasc Biol 2005;25:889.

Cross talk ,[object Object],Han SH, Quon MJ, Koh KK. Cur Op Lipidology 2007;18:58 (review) Insulin Resistance Endothelial dysfunction Diabetes, Obesity, Dyslipidemia CAD, Hypertension, Atherosclerosis

Cross talk and ARBs ,[object Object],[object Object],[object Object],[object Object]

The big question? Will ARBs combined with statins be better than monotherapy in a defined section of patients?

Hypercholesterolaemia & hypertension ,[object Object],[object Object],[object Object],[object Object],[object Object],Nippon Rinsho. 2009 Apr;67(4):812-8.

ARB+statin on NO ,[object Object],[object Object],[object Object],Nippon Rinsho. 2009 Apr;67(4):812-8.

ARB+statin on NO ,[object Object],[object Object],[object Object],Nippon Rinsho. 2009 Apr;67(4):812-8. ,[object Object],[object Object],[object Object],[object Object]

ARB+statin & phospholipase ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],European Heart Journal 2008 29(16):1956-1965

ARB & age-related hypercholesterolaemia ,[object Object],[object Object],Hypertension Research (2008) 31, 1495–1497 .

ARB+statin and cross talk ,[object Object],[object Object],[object Object]

ARB+statin on LV remodelling ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Am J Physiol Heart Circ Physiol 291: H1281-H1289, 2006.

ARBs and EPCs ,[object Object],[object Object],[object Object],[object Object],[object Object],Hypertension 2005;45;491-492, 526-529.

ARB+statin on plaque size ,[object Object],[object Object],Hypertension Research (2008) 31, 1199–1208.

Summary ↓ PLAQUE SIZE ↑ EPCs ↓ LV REMODELLING ↓ CROSS TALK ↓ OXI. LDL ↓ PHOSPO LIPASES ↓ LIPID ACCUMULATION ↑ NO ARBITEL-AV

Learnings from animal studies ,[object Object],Weiss et al, Circulation 2001;103:448

Learnings from animal studies ,[object Object],Rodriguez-Porcel et al, Arterioscler Thromb Vasc Biol. 2003;23:885.

ARB+Statin after stenting ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Combined Treatment With Statin and ARB after Stenting for prevention of Coronary Restenosis, NISHIKAWA et al, J Cardiol, VOL.45;NO.3;PAGE.107-113(2005)

ARB after grafting ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Ann Thorac Cardiovasc Surg 2008; 14: 25–28

Statins and kidney disease ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Kidney Int. 2008 Sep;74(5):571-6.

ARBITEL-AV Why Telmisartan as the ARB of choice in the combination of ARB+Statin?

Difference between antihypertensives ,[object Object]

Mechanisms of ARB action Glucose Fatty acid Transcription of insulin-responsive genes PPAR  - RXR Glucose uptake and utilization  Lipoprotein lipase  Adipogenesis lipid accumulation ↓ in Skeletal Muscle ARB  GLUT4  TNF- 

Metabolic Effects of Telmisartan ,[object Object],18 hypertensive patients with type 2 diabetes Valsartan 80 mg/day Candesartan 8 mg/day Telmisartan 40 mg/day 12 weeks >6 months Miura Y et al., Diabetes Care 2005 Mar; 28, 757-758

Effects of Telmisartan on glucose, insulin and TG ,[object Object],Miura Y et al., Diabetes Care 2005 Mar; 28, 757-758 Candesartan/ Valsartan Candesartan/ Valsartan Candesartan/ Valsartan Plasma Glucose TG ( mU/l ) Plasma Insulin 100 120 140 160 ( mg/dl ) Telmisartan NS 0 20 40 60 80 100 120 140 160 Telmisartan ( mg/dl ) * 80 60 40 20 0 0 2 4 6 8 10 12 Telmisartan ** P < 0.01 P < 0.05

Effects of Telmisartan on Adiponectin and hs-CRP Levels ,[object Object],Miura Y et al., Diabetes Care 2005 Mar; 28, 757-758 Adiponectin hs-CRP 0 1 2 3 4 5 6 7 8 9 10 ( mg/dl ) Telmisartan Candesartan/ Valsartan ** 0 0.05 0.1 0.15 0.2 Telmisartan Candesartan/ Valsartan ( mg/dl ) * P < 0.01 P < 0.05

Effects on Hs-CRP& Insulin resistance ,[object Object],[object Object],Rodriguez-Porcel et al, Arterioscler Thromb Vasc Biol. 2003;23:885.

PPAR modulation Adapted from Tenenbaum A et al. Intl J Cardiol. 2004;97:167-72.

Telmisartan Insulin resistance Hypertension Cell inflammation Cell proliferation Oxidative stress Dyslipidemia PPAR  pathways Angiotensin pathways Atherosclerosis Activates Blocks

Who would benefit from combined therapy of ARBs and Statins? ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]

Who would not benefit from combination of ARBs and Statins? ,[object Object],[object Object],[object Object],[object Object]

The target audience ARB & Statin

Arbitel-AV target audience ARB & Statin

ARB + Statin

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