HTN: 80 mg once daily 23,f 80 mg once daily 23,f Hypertension 40, 80 mg $82.66 (80 mg once daily) HTN: 8-32 mg daily in one or two divided doses 1

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1 Detail-Document # This Detail-Document accompanies the related article published in PHARMACIST S LETTER / PRESCRIBER S LETTER March 2010 ~ Volume 26 ~ Number Comparison of Angiotensin Receptor Blockers (Full update February 2012) Abbreviations: ACEI = angiotensin-converting enzyme inhibitor; CHF = congestive heart failure; CrCl = creatinine clearance; CV = cardiovascular; DM = diabetes mellitus; HCT = hydrochlorothiazide; HTN = hypertension; LVH = left ventricular hypertrophy; MI = myocardial infarction Azilsartan (Edarbi) HTN: 80 mg once daily 23,f 80 mg once daily 23,f Hypertension 40, 80 mg $82.66 (80 mg once With chlorthalidone (Edarbyclor; not for volume-depleted patients): 40/12.5, 40/25 27 Candesartan (Atacand) HTN: 16 mg once daily 1,b CHF: 4 mg once daily 1,b HTN: 8-32 mg daily in one or two divided doses 1 CHF: 32 mg once daily 1 Hypertension 1 Heart Failure 1 CHF: Reduces risk of CV death or CHF hospitalization 1 Diabetic retinopathy: reduces incidence (type 1 DM) and improves mild to moderate retinopathy (type 2 DM) 2,3 DM): reduces microalbuminuria 14 4, 8, 16, 32 mg 1 $ (32 mg once With HCT (Atacand HCT; not for initial therapy; not recommended if CrCl <30 ml/min): 16/12.5, 32/12.5, 32/25 mg 4

2 (Detail-Document #260301: Page 2 of 7) Eprosartan (Teveten) 600 mg once daily 5,c mg daily in one or two divided doses 5 Hypertension 5 400, 600 mg 5 $98.66 (600 mg once Irbesartan (Avapro) HTN: 150 mg once daily 7,d HTN: mg once daily 7 DM): 300 mg once daily 7 Hypertension 7 Nephropathy (type 2 DM) 7 DM): reduces rate of progression 7 With HCT (Teveten HCT; not for initial therapy): 600/12.5, 600/25 mg 6 75, 150, 300 mg 7 $108 (300 mg once With HCT (Avalide; not for volume-depleted patients; not recommended if CrCl <30 ml/min): 150/12.5, 300/ Losartan (Cozaar, generics) Continued HTN: 50 mg once daily 9,e HTN with LVH: 50 mg once daily 9,e DM): 50 mg once daily 9,e CHF: 12.5 mg once daily (not currently taking an ARB) or 25 mg once daily (switching HTN: mg daily in one or two divided doses 9 HTN/LVH: mg once daily (plus HCT if needed) 9 DM): 100 mg once daily 9 Hypertension 9 Hypertension with LVH 9 Nephropathy (type 2 DM) 9 CHF: Reduces risk of CV death or CHF hospitalization; 10 mortality similar to captopril 34 HTN with LVH: reduces stroke risk (may not benefit African-Americans) 9 25, 50, 100 mg 9 $79.55 (100 mg once With HCT (Hyzaar; indicated for HTN and HTN with LVH only; not for volume-depleted patients; not recommended if CrCl <30 ml/min): 50/12.5, 100/12.5, 100/25 mg 11

3 (Detail-Document #260301: Page 3 of 7) Losartan, cont. from another ARB) 10 (Off-label use) Olmesartan (Benicar) CHF: 150 mg once daily 10 (Off-label) 20 mg once daily 12,g mg once daily 12 Hypertension 12 DM): reduces rate of progression 9 Type 2 DM: delays onset of microalbuminuria, but with increased risk of fatal CV events among patients with coronary artery disease 28 5, 20, 40 mg 12 $ (40 mg once With HCT (Benicar HCT; not for initial therapy; not recommended if CrCl <30 ml/min): 20/12.5, 40/12.5, 40/25 mg 13 With amlodipine (Azor): 5/20, 10/20, 5/40, 10/40 mg 21 With HCT and amlodipine (Tribenzor; not for initial therapy; not for volumedepleted patients; avoid if CrCl <30 ml/min): 20/5/12.5, 40/5/12.5, 40/5/25, 40/10/12.5, 40/10/25 mg 22 Telmisartan (Micardis) Continued HTN: 40 mg once daily 15,i CV risk reduction (in patients unable to take ACE HTN: mg once Hypertension 15 daily 15 CV risk reduction in High CV risk: reduces risk of CV events 15 20, 40, 80 mg 15 $ (80 mg once

4 (Detail-Document #260301: Page 4 of 7) Telmisartan, cont. inhibitors): CV risk reduction: patients unable 80 mg once daily 15,i 80 mg once daily 15 to take ACEI 15 DM): reduces microalbuminuria, 16 slows progression as well as enalapril, 32 and reduces proteinuria in patients with HTN 29,30 With HCT (Micardis HCT; not for initial therapy; not for volume-depleted patients; not recommended if CrCl <30 ml/min): 40/12.5, 80/12.5, 80/25 mg 17 Hemodialysis patients with CHF: added to ACEI, reduces all-cause and CV mortality, and heart failure hospitalization 24 Valsartan (Diovan) Continued HTN: mg once daily 18,j,k CHF: 40 mg twice daily 18,k Post-MI: 20 mg twice daily 18,k HTN: mg once daily 18 CHF: mg twice daily (target 160 mg twice 18 Post-MI: mg twice daily (target 160 mg twice 18 Hypertension Heart Failure (Class II to IV) Post-MI with left ventricular dysfunction/ failure CHF: reduces hospitalization 18 Post-MI with left ventricular dysfunction/failure: reduces CV mortality 18 DM): reduces microalbuminuria, 19 and proteinuria in patients with HTN 30 40, 80, 160, 320 mg 18 $128 (320 mg once With HCT (Diovan HCT; not for volume-depleted patients; not recommended if CrCl <30 ml/min.): 80/12.5, 160/12.5, 160/25, 320/12.5, 320/25 mg 20 With amlodipine (Exforge; indicated for HTN only): 5/160, 10/160, 5/320,

5 (Detail-Document #260301: Page 5 of 7) Valsartan, cont. HTN with high CV risk: reduces CV morbidity/mortality about as well as amlodipine 33 10/320 mg 25 With amlodipine and HCT (Exforge HCT; indicated for HTN only; not for initial therapy; not for volume-depleted patients; avoid if CrCl <30 ml/min): 5/160/12.5, 10/160/12.5, 5/160/25, 10/160/25, 10/320/25 mg 26 With aliskiren (Valturna; not for volume-depleted patients): 150/160, 300/320 mg 31 a. Indications, dosing, and clinical benefit for adult patients. b. Consider lower starting dose for moderate hepatic impairment or volume-depleted patients. 1 c. Recommended initial dose for monotherapy in patients who are not volume-depleted. Do not exceed 600 mg daily in moderate or severe renal impairment. 5 d. Initial dose of 75 mg once daily recommended for volume/sodium-depleted patients. 7 e. Starting dose for volume/sodium-depleted patients or patients with (or with a history of) hepatic impairment is 25 mg once daily. 9 f. Starting dose for volume/sodium-depleted patients is 40 mg once daily. 23 g. Consider lower starting dose for volume-depleted patients. 12 h. Evidence level A; high-quality randomized controlled trials. i. Use lower starting dose for hepatic impairment or volume/sodium-depleted patients. 15 j. Recommended initial dose for monotherapy in patients who are not volume-depleted. 18 k. Dose cautiously in hepatic or severe renal impairment. 18 L. Cost is for 30-day supply of brand (or generic, if available), per at time of writing. Users of this document are cautioned to use their own professional judgment and consult any other necessary or appropriate sources prior to making clinical judgments based on the content of this document. Our editors have researched the information with input from experts, government agencies, and national organizations. Information and Internet links in this article were current as of the date of publication.

6 (Detail-Document #260301: Page 6 of 7) Levels of Evidence In accordance with the trend towards Evidence-Based Medicine, we are citing the LEVEL OF EVIDENCE for the statements we publish. Level A B C D Definition High-quality randomized controlled trial (RCT) High-quality meta-analysis (quantitative systematic review) Nonrandomized clinical trial Nonquantitative systematic review Lower quality RCT Clinical cohort study Case-control study Historical control Epidemiologic study Consensus Expert opinion Anecdotal evidence In vitro or animal study Adapted from Siwek J, et al. How to write an evidence-based clinical review article. Am Fam Physician 2002;65: Project Leader in preparation of this Detail- Document: Melanie Cupp, Pharm.D., BCPS References 1. Product information for Atacand. AstraZeneca LP. Wilmington, DE April Sjølie AK, Klein R, Porta M, et al. Effect of candesartan on progression and regression of retinopathy in type 2 diabetes (DIRECT-Protect 2): a randomised placebo-controlled trial. Lancet 2008;372: Chaturvedi N, Porta M, Klein R, et al. Effect of candesartan on prevention (DIRECT-Prevent 1) and progression (DIRECT-Protect 1) of retinopathy in type 1 diabetes: randomised, placebo-controlled trials. Lancet 2008;372: Product information for Atacand HCT. AstraZeneca LP. Wilmington, DE April Product information for Teveten. Abbott Laboratories. North Chicago, IL January Product information for Teveten HCT. Abbott Laboratories. North Chicago, IL January Product information for Avapro. Bristol-Myers Squibb Sanofi Synthelabo Partnership. New York, NY Product information for Avalide. Bristol-Myers Squibb Sanofi Synthelabo Partnership. New York, NY Product information for Cozaar. Merck & Co., Inc. Whitehouse Station, NJ November Konstam MA, Neaton JD, Dickstein K, et al. Effects of high-dose versus low-dose losartan on clinical outcomes in patients with heart failure (HEAAL study): a randomised, double-blind trial. Lancet 2009;374: Product information for Hyzaar. Merck & Co., Inc. Whitehouse Station, NJ November Product information for Benicar. Daiichi Sankyo, Inc. Parsippany, NJ June Product information for Benicar HCT. Daiichi Sankyo, Inc. Parsippany, NJ May Mogensen CE, Neldam S, Tikkanen I, et al. Randomised controlled trial of dual blockade of renin-angiotensin system in patients with hypertension, microalbuminuria, and non-insulin dependent diabetes: the candesartan and lisinopril microalbuminuria (CALM) study. BMJ 2000;321: Product information for Micardis. Boehringer Ingelheim Pharmaceuticals, Inc. Ridgefield, CT Makino H, Haneda M, Babazono T, et al. Prevention of transition from incipient to overt nephropathy with telmisartan in patients with type 2 diabetes. Diabetes Care 2007;30: Product information for Micardis HCT. Boehringer Ingelheim Pharmaceuticals, Inc. Ridgefield, CT Product information for Diovan. Novartis 19. Viberti G, Wheeldon NM, MicroAlbuminuria Reduction with VALsartan (MARVAL) study investigators. Microalbuminuria reduction with valsartan in patients with type 2 diabetes mellitus: a blood pressure-independent effect. Circulation 2002;106: Product information for Diovan HCT. Novartis 21. Product information for Azor. Daiichi Sankyo, Inc. Parsippany, NJ November Product information for Tribenzor. Daiichi Sankyo, Inc. Parsippany, NJ November Product information for Edarbi. Takeda Pharmaceuticals America, Inc. Deerfield, IL December Cice G, Di Benedetto A, D lsa S, et al. Effects of telmisartan added to angiotensin-converting enzyme inhibitors on mortality and morbidity in hemodialysis patients with chronic heart failure a double-blind, placebo-controlled trial. J Am Coll Cardiol 2010;56: Product information for Exforge. Novartis 26. Product information for Exforge HCT. Novartis 27. Product information for Edarbyclor. Takeda Pharmaceuticals America, Inc. Deerfield, IL December Haller H, Ito S, Izzo JL Jr, et al. Olmesartan for the delay or prevention of microalbuminuria in type 2 diabetes. N Engl J Med 2011;364:

7 (Detail-Document #260301: Page 7 of 7) 29. Bakris G, Burgess E, Weir M, et al. Telmisartan is more effective than losartan in reducing proteinuria in patients with diabetic nephropathy. Kidney Int 2008;74: Galle J, Schwedhelm E, Pinnetti S, et al. Antiproteinuric effects of angiotensin receptor blockers: telmisartan versus valsartan in hypertensive patients with type 2 diabetes mellitus and overt nephropathy. Nephrol Dial Transplant 2008;23: Product information for Valturna. Novartis October Barnett AH, Bain SC, Bouter P, et al. Angiotensinreceptor blockade versus converting-enzyme inhibition in type 2 diabetes and nephropathy. N Engl J Med 2004;351: Julius S, Kjeldsen SE, Weber M, et al. Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine: the VALUE randomised trial. Lancet 2004;363: Pitt B, Poole-Wilson PA, Segal R, et al. Effect of losartan compared with captopril on mortality in patients with symptomatic heart failure: randomized trial the Losartan Heart Failure Survival Study ELITE II. Lancet 2000;355: Cite this Detail-Document as follows: Comparison of angiotensin receptor blockers. Pharmacist s Letter/Prescriber s Letter 2010 (Full update February 2012);26(3): Evidence and Advice You Can Trust 3120 West March Lane, P.O. Box 8190, Stockton, CA ~ TEL (209) ~ FAX (209) Copyright 2010 by Therapeutic Research Center Subscribers to Pharmacist s Letter and Prescriber s Letter can get Detail-Documents, like this one, on any topic covered in any issue by going to or