Are+all+sartans+equal

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  • When examining the interaction between the RAAS and the SNS, it can be seen that both play an integral part in vascular adaptive processes. Hyperactivity of the SNS is known to stimulate the secretion of renin, which is the first component of the RAAS system. High levels of plasma renin activity (PRA) have been linked to metabolic imbalances such as hyperlipidemia and hyperinsulinemia, both of which are risk factors for CVD. When sympathetic activity is blocked in renin-dependent hypertension patients, it has been shown to inhibit RAAS activity. The heightened secretion of norepinephrine (NE) by the SNS has also shown a link to CVD. A large scale clinical trial demonstrated that NE levels of >900 pg/mL were correlated with shortened life expectancy in patients with severe congestive heart failure (CHF). Cody RJ. The sympathetic nervous system and the renin-angiotensin-aldosterone system in cardiovascular disease. Am J Cardiol . 1997;80:9J-14J.
  • The ON going T elmisartan A lone and in combination with R amipril G lobal E ndpoint T rial (ONTARGET) randomized 25,620 high-risk patients to telmisartan 80 mg, ramipril 10 mg, or their combination. Eligible subjects were ≥ 55 years of age with coronary, cerebrovascular, or peripheral vascular disease, or with diabetes plus evidence of end-organ damage. The primary end point is a composite of CV death, nonfatal MI, nonfatal stroke, or hospitalization for congestive heart failure. New-onset diabetes is one of the secondary end points. Patients will be followed for up to 5.5 years. Recruitment ended in 2003. ONTARGET: Study design
  • Are+all+sartans+equal

    1. 1. Are all ARBs equal?
    2. 2. Roadmap <ul><li>Introduction to RAAS </li></ul><ul><li>RAAS modulators </li></ul><ul><li>Angiotensin II Receptor blockers </li></ul><ul><li>Clinical Trials </li></ul><ul><li>Summary </li></ul>
    3. 3. Modifiable Risk Factors Associated with Adverse Cardiovascular and Renal Events in Chronic Kidney Disease <ul><li>Hypertension </li></ul><ul><li>Albuminuria </li></ul><ul><li>RAAS </li></ul><ul><li>Dyslipidemia </li></ul><ul><li>Anemia </li></ul><ul><li>Smoking </li></ul><ul><li>Glycemia </li></ul><ul><li>Calcium-phosphorus product </li></ul><ul><li>Others </li></ul>Sarnak et al. Hypertension. 2003;42;1050-1065.
    4. 4. Angiotensinogen (Liver) Renin (kidney) Angiotensin I Non ACE Pathway ACE Pathway Angiotensin II AT1 receptors AT2 receptors Increase Aldosterone. Increase Na + and H 2 O retention. Increase Venous return. Increase Preload Increase Stimulation of SNS. Thus heart rate and CO Increase Increase Cell growth Physiology of RAAS Increase Vasoconstriction ( PVR)
    5. 5. Inappropriate RAAS Activation as a Cause of Impaired Vascular and Metabolic Health Angiotensin II Atherosclerosis Impaired Adipogenesis Elevated BP Endothelial Dysfunction Vascular Remodeling Glucose Intolerance Brasier et al. Arterioscler Thromb Vasc Biol. 2002;22:1257-1266; Dzau. J Hypertens. 2005;23(suppl 1):S9-S17; Engeli et al. Int J Biochem Cell Biol. 2003;35:807-825; Taniyama et al. Hypertension. 2003;43:1075-1081.
    6. 6. Angiotensin II effect in target organ damage McFarlane SI et al. Am J Cardiol . 2003;91(suppl):30H-7. Angiotensinogen Angiotensin I Angiotensin II Renin ACE Aldosterone (Adrenal/CV tissues) Stroke HF Kidney failure  BP VSMC Fat cells Reduced baroreceptor sensitivity
    7. 7. Angiotensin II as a Cardiac and Renal Toxin Chymase Cathepsin G Carboxypeptidase Reactive O 2 Species Cell Growth Renal Na + , H 2 O Collagen Sympathetic Activation Aldosterone Vasoconstriction CHF Cardiac, Vascular, Renal Hypertrophy Bradykinin Inactive Fragments Ang II Ang I Angiotensin Renin AT 1 R Carey et al. Endocr Rev . 2003;24:261-271 .
    8. 8. Interactions Between RAAS and SNS <ul><li>A-II </li></ul><ul><ul><li>Central SNS activation </li></ul></ul><ul><ul><li>Increased NE release </li></ul></ul><ul><li>Renal sympathetic nerves </li></ul><ul><ul><li>Renin release: b1 </li></ul></ul><ul><ul><li>Vasoconstriction: a1 </li></ul></ul><ul><ul><li>Na/H 2 0 retention: a1 </li></ul></ul><ul><ul><li>Vascular remodeling: a1 </li></ul></ul>A-II renin SNS Activity NE SNS=sympathetic nervous system; NE=norepinephrine; A-II=angiotensin II. Cody. Am J Cardiol . 1997;80:9J-14J.
    9. 9. Potential role of RAAS activation in metabolic syndrome and diabetes Adapted from Henriksen EJ, Jacob S. J Cell Physiol. 2003;196:171-9. Paul M et al. Physiol Rev. 2006;86:747-803. RAAS activation Skeletal muscle Pancreatic β cells  MetS  T2DM MetS = metabolic syndrome T2DM = type 2 diabetes Obesity
    10. 10. RAAS activation contributes to obesity-related hypertension Obesity Volume expansion Arterial hypertension Sharma AM. Hypertension . 2004;44:12-19.  Leptin Renal medullary compression  RAAS activation Sodium reabsorption Renal vasodilation  SNS activation SNS = sympathetic nervous system
    11. 11. So, inappropriate activation of RAAS leads to… <ul><li>Hypertension </li></ul><ul><li>Diabetes </li></ul><ul><li>Obesity </li></ul><ul><li>Heart Failure </li></ul><ul><li>Renal diseases </li></ul><ul><li>Metabolic Syndrome </li></ul>
    12. 12. Management
    13. 13. RAAS Modulators <ul><li>Angiotensin Converting Enzyme Inhibitors </li></ul><ul><li>Ramipril </li></ul><ul><li>Enalapril </li></ul><ul><li>Lisinopril </li></ul><ul><li>Perindopril </li></ul><ul><li>Angiotensin Receptor Blockers </li></ul><ul><li>Losartan </li></ul><ul><li>Valsartan </li></ul><ul><li>Candesartan </li></ul><ul><li>Telmisartan </li></ul><ul><li>Irbesartan </li></ul><ul><li>Olmesartan </li></ul><ul><li>Direct Renin Inhibitors </li></ul><ul><li>Aliskerin </li></ul>
    14. 14. Angiotensinogen (Liver) Renin (kidney) Angiotensin I Non ACE Pathway ACE Pathway Angiotensin II AT1 receptors AT2 receptors Increase Aldosterone. Increase Na + and H 2 O retention. Increase Venous return. Increase Preload Increase Stimulation of SNS. Thus heart rate and CO Increase Increase Cell growth RAAS Modulators Increase Vasoconstriction ( PVR) ACE’s ARB’s Direct Renin Inhibitors MECHANISM OF ACTION
    15. 15. Role of RAAS Modulators <ul><li>Inhibition of RAAS </li></ul><ul><li>Decreased release of non-epinephrine </li></ul><ul><li>Increased formation of Bradykinin </li></ul><ul><li>Decreased Na + retention from reduced secretion of aldosterone </li></ul>Role in Hypertension Role in Congestive Heart Failure <ul><li>More pronounced changes in BP </li></ul><ul><li>Cardiac Output and Coronary filling period indicating improved left ventricular function </li></ul>
    16. 16. Role of RAAS Modulators (CONTD…) Role in Renal Impairment <ul><li>Renal blood flow </li></ul><ul><li>Reduces intra-glomerular capillary pressure </li></ul><ul><li>Retards the development of hypertensive nephropathy </li></ul>Role in Post Myocardial Infarction <ul><li>Prevents ventricular remodeling in post MI patients and thus prevents left ventricle dystrophy </li></ul>
    17. 17. RAAS modulators – The past & The present <ul><li>In the 1980s - the angiotensin-converting enzyme (ACE) inhibitors demonstrated the first clear benefit of blocking conversion of AngiotensinI to AngiotensinII in Cardiovascular events. </li></ul><ul><li>Development of AngiotensinII receptor blockers (ARBs) in the1990s promised more complete inhibition of the RAAS by blockade of the angiotensin II type 1 (AT1) receptor. </li></ul><ul><li>Combination therapy with an ARB and ACE inhibitor also showed improved Cardiovascular outcomes in HF patients and reduction in mortality. </li></ul>Cardiology Review JUNE 2007 • Vol 24 No 6 (Suppl)
    18. 18. Development of ARB’s Became the first successful Ang II antagonist drug Valsartan –nonheterocyclic ARB Candesartan – Prodrug have stronger blood pressure lowering effects than and losartan. Irebesartan - longer acting than valsartan & losartan Telmisartan - longest elimination half-life of the ARBs or about 24 hours Olmesartan - Newest ARB on the market, marketed in 2002
    19. 19. Key trends in ARB’s <ul><li>Losartan: The only medicine in its class proven to lower the chance of stroke. </li></ul><ul><li> Only ARB that has been shown to reduce serum uric acid levels. </li></ul><ul><li> Only ARB approved by the FDA for treating nephropathy in patients withT2DM </li></ul><ul><li>Valsartan: First ARB to receive approval in Heart Failure </li></ul><ul><li> Reverses ventricular remodeling and Improves survival outcome in HF </li></ul><ul><li>Telmisartan: Highly selective inhibition of the angiotensin II receptor 1 (AT1) </li></ul><ul><li> Has the longest plasma half-life and largest volume of distribution of any ARB </li></ul><ul><li> Powerful 24-hour action, curbing the morning surge in blood pressure </li></ul><ul><li>compared to other leading ARB’s </li></ul><ul><li> Has PPAR-gamma activity and hence improves Insulin sensitivity </li></ul><ul><li>Olmesartan: Significant mean double-digit blood pressure (BP) reductions vs baseline at </li></ul><ul><li> the starting dose </li></ul>
    20. 20. AT 1 affinity The specific AT1 affinity relates to how specificially attracted the medicine is for the correct receptor. http://en.wikipedia.org/wiki/Angiotensin_II_receptor_antagonist#AT1_affinity valsartan > olmesartan > candesartan > Irbesartan > telmisartan > losartan * * Andrew Whittaker .A Review of Olmesartan Medoxomil -- A New Angiotensin II Receptor Blocker . Br J Cardiol. 2005;12(2):125-129.
    21. 21. Recent Guidelines <ul><li>British Hypertension Society state that </li></ul><ul><ul><li>ACE inhibitor intolerance, </li></ul></ul><ul><ul><li>Diabetic nephropathy </li></ul></ul><ul><ul><li>Hypertension with left ventricular hypertrophy, </li></ul></ul><ul><ul><li>Heart failure in ACE inhibitor-intolerant patients post-MI </li></ul></ul><ul><ul><li>are all 'compelling indications' for the use of ARBs </li></ul></ul>Williams B, Poulter NR, Brown MJ et al . British Hypertension Society guidelines for hypertension management 2004 (BHS-IV): summary. BMJ 2004;328:634-40.
    22. 22. Drug comparison and pharmacokinetics 1. Sankyo Pharma Inc (US). Expanding the Paradigm for Hypertension Management with a New Angiotensin II Receptor Blocker. Benicar® (Olmesartan Medoxomil) [product monograph]. New York: Advantage Communications, 2002. 2. Olin BR, ed. Drug Facts and Comparisons. St. Louis: JB Lippincott Co, 2002:514–518.
    23. 23. Dosing schedule* (QD indicates once a day; BID, twice a day) *Olin BR, ed. Drug Facts and Comparisons. St. Louis: JB Lippincott Co, 2002:514–518. * Burnier M. Angiotensin II type 1 receptor blockers. Circulation 2001;103:904– 912. † Some patients will require the total daily dose to be split into twice-daily dosing
    24. 24. ARB in Reducing BP and CV events 1. Dahlöf B, Devereux RB, Kjeldsen SE et al . Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet 2002;359:995-1003. 2. Dickstein K, Kjekshus J. Effects of losartan and captopril on mortality and morbidity in high-risk patients after acute myocardial infarction: the OPTIMAAL randomised trial. Lancet 2002;360:752-60. Name Patient population Drugs/follow up Results LIFE 1 (Losartan Intervention For Endpoint Reduction in Hypertension Study) 9,193 patients aged 55-80 yr with hypertension and LVH Losartan, 50-100 mg qd, vs atenolol, 50-100 mg qd Mean follow-up: 4.8 yr Losartan decreased the composite end point (cardiovascular mortality, MI, and stroke), stroke, and new-onset diabetes significantly more than atenolol for a similar reduction in blood pressure OPTIMAAL 2 (Optimal Trial In Myocardial Infarction with the Angiotensin Receptor Blocker Losartan) 5,477 European patients aged over 50 with confirmed acute MI and heart failure. Losartan, 50 mg qd, vs captopril, 50 mg tid Mean follow-up: 2.7 yr No significant difference in overall mortality between the groups. The ARB was better tolerated than the ACE inhibitor, with significantly fewer withdrawals due to adverse effects.
    25. 25. ARB in Reducing BP and CV events <ul><li>Pfeffer MA, Swedberg K, Granger CB et al . Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-Overall programme. Lancet 2003;362:759-66. </li></ul><ul><li>Granger CB, McMurray JJV, Yusuf S et al . Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function intolerant to angiotensin-converting-enzyme inhibitors: the CHARM-Alternative trial. Lancet 2003;362:772-6. </li></ul><ul><li>Yusuf S, Pfeffer MA, Swedberg K et al . Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARM-Preserved Trial. Lancet 2003;362:777-81. </li></ul>Name Patient population Drugs/follow up Results CHARM 1 (Candesartan in Heart failure Assessment of Reduction in Mortality and morbidity) study 7,601 patients with chronic heart failure (CHF) Candesartan with placebo Mean follow-up: At least 2 years Candesartan significantly reduced the primary outcome of cardiovascular deaths and hospital admissions for heart failure (20% candesartan vs. 24% placebo) CHARM-Alternative study 2 2,028 patients with CHF who were intolerant of ACE inhibitors Candesartan In this group the hazard ratio for candesartan was 0.70 for cardiovascular death or hospital admission for CHF CHARM-Preserved trial 3 3,023 patients with CHF and preserved left ventricular ejection fraction Candesartan Hazard ratio of 0.89 for the primary outcome but no difference in cardiovascular deaths between the candesartan and placebo groups
    26. 26. ARB’s in MI & Heart Failure <ul><li>The Optimal Trial in Myocardial Infarction With the Angiotensin II Antagonist Losartan (OPTIMAAL) and the V alsartan in A cute M yocardial I nfarction T rial (VALIANT) have assessed whether ARBs are equivalent or superior to ACE inhibitors after MI. </li></ul>Postgrad Med 2004;116(2):31-41
    27. 27. ARB’s in AMI & Heart Failure 1. Pfeffer et al., N Engl J Med 349(20):1893-1906 November 13, 2003. 2.Cohn JN, Tognoni G. A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. N Engl J Med 2001;345: 1667-75. Name Patient population Drugs/follow up Results VALIANT (VALsartan In Acute myocardial iNfarcTion) 14,703 patients aged > 18 yr with acute MI complicated by left ventricular dysfunction or heart failure Valsartan, 160 mg bid, vs captopril, 50 mg tid, vs valsartan, 80 mg bid, plus captopril, 50 mg tid Median follow-up: 24.7 mo Valsartan was as effective as captopril at decreasing all-cause mortality and a composite of cardiovascular death, MI, and heart failure hospitalization ; combination of valsartan and captopril offered no additional benefit but increased the rate of adverse events Val-HeFT 5,010 patients aged > 18 yr with NYHA class II-IV heart failure Valsartan, 160 mg bid, vs placebo (open ACE inhibitor) Mean follow-up: 23 mo Valsartan significantly reduced mortality and morbidity and improved clinical signs and symptoms when added to prescribed therapy. An adverse effect on mortality and morbidity was observed in the subgroup receiving valsartan, an ACEI + beta-blocker
    28. 28. ARB’s in AMI & Heart Failure * Postgrad Med 2004;116(2):31-41 Name Patient population Drugs/follow up Results ELITE* 722 patients aged > 65 yr with NYHA class II-IV heart failure Losartan, 50 mg qd, vs captopril, 50 mg tid Losartan and captopril had similar effects on renal dysfunction (primary end point); all-cause mortality was significantly lower with losartan than captopril ELITE II* 3,152 patients aged > 60 yr with NYHA class II-IV heart failure Losartan, 50 mg qd, vs captopril, 50 mg tid Median follow-up: 79.3 wk Nonsignificant trend in favor of captopril for all-cause mortality, sudden death or resuscitated cardiac arrest, and a composite of all-cause mortality and hospitalization
    29. 29.
    30. 30. Renal Protection in Diabetes with ARBs <ul><li>Lewis EJ, Hunsicker LG, Clarke WR et al . Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med 2001;345:851-60. </li></ul><ul><li>Parving H-H, Lehnert H, Bröchner-Mortensen J, Gomis R, Andersen S, Arner P. The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. N Engl J Med 2001;345:870-8. </li></ul>Name Patient population Drugs/follow up Results IDNT 1 (The Irbesartan Diabetic Nephropathy Trial) 1,715 patients aged 30-70 yr with type 2 diabetes, proteinuria, and hypertension Irbesartan, 300 mg qd, vs amlodipine, 10 mg qd, vs placebo Mean follow-up: 2.6 yr Risk of a doubling of serum creatinine was 33% lower in the irbesartan group than in the placebo group and 37% lower than in the amlodipine group IRMA II 2 590 patients aged 30-70 yr with type 2 diabetes, microalbuminuria, and hypertension Irbesartan, 150 mg qd, vs irbesartan, 300 mg qd, vs placebo Median follow-up: 2 yr Irbesartan prevented progression of microalbuminuria to overt proteinuria and restored normal albumin excretion in more patients than placebo (significant at the 300-mg dose only); these effects were above and beyond the effect on BP
    31. 31.
    32. 32. Renal Protection in Diabetes with ARBs <ul><li>Brenner BM, Cooper ME, de Zeeuw D et al . Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 2001;345: 861-9. </li></ul><ul><li>Postgrad Med 2004;116(2):31-41 </li></ul>RENAAL 1 (Reduction of Endpoints in NIDDM with the ARB Losartan) 1,513 patients aged 31-70 yr with type 2 diabetes and nephropathy Losartan, 50-100 mg qd, vs placebo in addition to 'conventional‘ antihypertensives such as beta blockers Mean follow-up: 3.4 yr Losartan reduced the occurrence of proteinuria, doubling of serum creatinine concentration and end-stage renal disease by 35%, 25% and 28% respectively. MARVAL 2 (M icro A lbuminuria R eduction with VAL sartan) 332 patients aged 35-75 yr with type 2 diabetes and microalbuminuria Valsartan, 80-160 mg/day, vs amlodipine, 5-10 mg/day Follow-up: 24 wk Valsartan improved the urinary albumin excretion rate significantly more than amlodipine and restored normal albumin excretion in significantly more patients
    33. 33. Anti-inflammatory effects of olmesartan
    34. 34. European Trial on Olmesartan and Pravastatin in Inflammation and Atherosclerosis (EUTOPIA) <ul><li>The study comprised of 199 patients, of whom 100 were treated with olmesartan and 99 were in the placebo treatment group. </li></ul><ul><li>Both treatment groups were comparable with regard to age, gender, and body mass index, but the placebo treatment group comprised significantly more patients with known type 2 diabetes mellitus. </li></ul>
    35. 35. Results & Conclusion Circulation2004;110;1103-1107 Conclusion <ul><li>Treatment with the Ang II receptor antagonist olmesartan significantly reduces biochemical markers of(vascular) inflammation in patients with essential hypertension by as early as week 6 of therapy . </li></ul><ul><li>These anti-inflammatory properties of Ang II receptor antagonists may have beneficial cardiovascular effects in addition to their blood pressure lowering action. </li></ul>Inflammatory markers After 6weeks with olmesartan After12 weeks with olmesartan & Pravastatin . C-reactive protein -15.1%;(p<0.05) -21.1%;(p<0.02) Tumor necrosis factor- α -8.9%;(p<0.02) -13.6%;(p<0.01) Interleukin-6 -14.0%;(p<0.05) -18.0%;(p<0.01) Monocyte chemotactic protein -6.5%;(p<0.01) _
    36. 36. ONTARGET: The ON going T elmisartan A lone and in combination with R amipril G lobal E ndpoint T rial <ul><li>ACE-inhibitors (e.g. ramipril in the HOPE trial) reduces CV death, MI, stroke and HF hosp in those with CVD or DM in the absence of ventricular dysfunction or heart failure </li></ul><ul><li>ACE-inhibitors are not tolerated by 15% to 25% of patients </li></ul><ul><li>Will an ARB (telmisartan) be as effective and better tolerated? </li></ul><ul><li>Is the combination superior? </li></ul>
    37. 37. ONTARGET: Study design ONTARGET/TRANSCEND Investigators. Am Heart J. 2004;148:52-61. Ramipril 10 mg Telmisartan 80 mg ≥ 55 years with coronary, Cerebrovascular, or peripheral vascular disease, or diabetes + end-organ damage Ramipril 10 mg + telmisartan 80 mg Primary end point: CV death, MI, stroke, hosp for HF Secondary end point: Newly diagnosed diabetes N = 25,620 Medical Services
    38. 38. ONTARGET: Primary outcome results N = 25,620 with vascular disease or high-risk diabetes ONTARGET Investigators. N Engl J Med .2008;358:1547-59. Cumulative hazard ratio 0.20 0.15 0.10 0.05 0.00 0 1 2 3 4 5 Follow-up (years) Telmisartan Ramipril Telmisartan plus ramipril
    39. 39. ONTARGET: Incidence of primary outcome and components ONTARGET Investigators. N Engl J Med . 2008;358:1547-59. Outcome Ramipril (n = 8576) Telmisartan (n = 8542) Combination (n = 8502) Telmisartan vs ramipril Combination vs ramipril Primary outcome 16.5% 16.7% 16.3% 1.01 RR (0.94–1.09) 0.99 RR (0.92–1.07) Death from CV causes 7.0% 7.0% 7.3% 1.00 RR (0.89–1.12) 1.04 RR (0.93–1.17) MI 4.8% 5.2% 5.2% 1.07 RR (0.94–1.22) 1.08 RR (0.94–1.23) Stroke 4.7% 4.3% 4.4% 0.91 RR (0.79–1.05) 0.93 RR (0.81–1.07) HF hospital-ization 4.1% 4.6% 3.9% 1.12 RR (0.97–1.29) 0.95 RR (0.82–1.10)
    40. 40. ONTARGET: Secondary outcomes ONTARGET Investigators. N Engl J Med.2008;358:1547-59. * P < 0.001 Medical Services Outcome Ramipril (n = 8576) Telmisartan (n = 8542) Combination (n = 8502) Telmisartan vs ramipril Combination vs ramipril Death from CV causes, MI, stroke 14.1% 13.9% 14.1% 0.99 RR (0.91–1.07) 1.00 RR (0.93–1.09) Revasculari- zation 14.8% 15.1% 15.3% 1.03 RR (0.95–1.11) 1.04 RR (0.97–1.13) Angina hos- pitalization 10.8% 11.2% 11.2% 1.04 RR (0.95–1.14) 1.04 RR (0.95–1.14) Worsening/ New angina 6.6% 6.3% 6.3% 0.95 RR (0.84–1.07) 0.96 RR (0.85–1.08) Any HF 6.0% 6.3% 5.6% 1.05 RR (0.93–1.19) 0.94 RR (0.83–1.07) Renal impairment 10.2% 10.6% 13.5% 1.04 RR (0.96–1.14) 1.33 RR * (1.22–1.44)
    41. 41. Amy barreras, pharmd, and cheryle gurk-turner, rp h. Angiotensin II receptor blockers . Bumc Proceedings 2003;16:123–126 Medical Services
    42. 42. Amy barreras, pharmd, and cheryle gurk-turner, rph. Angiotensin II receptor blockers. Bumc Proceedings 2003;16:123–126 Medical Services
    43. 43. Amy barreras, pharmd, and cheryle gurk-turner, rph. Angiotensin II receptor blockers. Bumc Proceedings 2003;16:123–126 Medical Services
    44. 44. Amy barreras, pharmd, and cheryle gurk-turner, rph. Angiotensin II receptor blockers. Bumc Proceedings 2003;16:123–126 Medical Services
    45. 45. Summary <ul><li>The ARBs have very similar clinical profiles. </li></ul><ul><li>They do, however,have different pharmacokinetic profiles, which may lead to some differences in efficacy. </li></ul><ul><li>The newer agents irbesartan, candesartan,telmisartan, and olmesartan have longer half-lives and durations of action than the older agents losartan and valsartan. </li></ul><ul><li>The ARBs are highly effective in lowering blood pressure and reducing cardiovascular mortality. </li></ul><ul><li>They also appear to provide additional renal protection in patients with diabetes, and this effect is independent of their effect on blood pressure. </li></ul>Rodgers JE, Patterson JH. Angiotensin II-receptor blockers: clinical relevance and therapeutic role. Am J Health Syst Pharm 2001;58:671–683.
    46. 46. Thank You

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