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The Role of Angiotensin II Type 1 Receptor Antagonists in Elderly Patients with Hypertension

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Abstract

Hypertension is a major risk factor for stroke and coronary events in elderly people and clinical trials have shown that treatment of hypertension with various drugs can result in a substantial reduction in cerebrovascular and cardiovascular events. The angiotensin II type 1 (AT1) receptor antagonists are the newest class of antihypertensive agents to be used widely in clinical practice. AT1 receptor antagonists can generally be given once-daily. They are also extremely well tolerated with minimal first-dose hypotension and an incidence of adverse effects similar to that seen with placebo. Adverse event rates are significantly lower than with other classes of antihypertensive drugs including ACE inhibitors. These factors result in improved compliance and increased rates of continuance on therapy. AT1 receptor antagonists show similar efficacy in lowering blood pressure to other classes of antihypertensive agents and their antihypertensive effect is potentiated when they are given concomitantly with low-dose thiazide diuretics. AT1 receptor antagonists are eliminated predominantly by the hepatic route but most are not subject to extensive metabolism and interactions with other drugs are uncommon. This is an advantage in the elderly, who are often receiving multiple medications which increases the risk for adverse drug interactions. Dose adjustments are not usually required in the elderly unless there is plasma volume depletion. Although plasma AT1 receptor antagonist concentrations are generally higher in the elderly than in younger subjects, this pharmacokinetic difference may be balanced by decreased activation of the circulating renin-angiotensin-aldosterone system in the elderly.

Recent clinical studies in high-risk hypertensive patients with left ventricular hypertrophy or in patients with diabetic nephropathy or heart failure have demonstrated that AT1 receptor antagonists can improve clinical outcomes to a similar or sometimes greater extent than other antihypertensive agents. Many of these studies have included large numbers of older patients and have confirmed the excellent tolerability profile of these drugs. Thus, AT1 receptor antagonists should be considered as a possible first-line treatment or as a component of combination therapy in patients with type 2 diabetes mellitus and microalbuminuria or nephropathy and as an alternative or additional treatment to ACE inhibitors in patients with heart failure or left ventricular dysfunction. AT1 receptor antagonists also appear to reduce the onset of new diabetes compared with some other antihypertensive drugs. The benefits in terms of organ protection have mainly been seen in studies using higher doses of particular AT1 receptor antagonists and it is not certain at present whether these results can be extrapolated to other members of the class.

As the elderly are more likely to have developed organ damage related to hypertension or to have heart failure or diabetes as concomitant conditions, AT1 receptor antagonists represent an appropriate option for many elderly patients. The main disadvantage of these drugs is the cost of the medication but this may be offset by their improved tolerability with fewer adverse reactions and thus increased compliance, resulting in better blood pressure control and fewer clinical events. Overall, AT1 receptor antagonists are well tolerated and efficacious for blood pressure-lowering when given as a single daily dose in elderly patients and have many potential benefits in high-risk hypertensive subjects.

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References

  1. Hajjar I, Kotchen TA. Trends in prevalence, awareness, treatment, and control of hypertension in the United States, 1988–2000. JAMA 2003; 290: 199–206

    Article  PubMed  Google Scholar 

  2. Chobanian AV, Bakris GL, Black HR, et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA 2003; 289: 2560–72

    Article  PubMed  CAS  Google Scholar 

  3. Staessen JA, Gasowski J, Wang JG, et al. Risks of untreated and treated isolated systolic hypertension in the elderly: meta-analysis of outcome trials. Lancet 2000; 355: 865–72

    Article  PubMed  CAS  Google Scholar 

  4. Rajkumar C. Hypertension in the elderly. In: Birkenhager WH, Reid JL, Bulpitt CJ, editors. Handbook of hypertension. London: Elsevier Science, 2000: 106–14

    Google Scholar 

  5. Guidelines Committee. 2003 European Society of Hypertension—European Society of Cardiology guidelines for the management of arterial hypertension. J Hypertens 2003; 21: 1011–53

    Article  Google Scholar 

  6. Eastern Stroke and Coronary Heart Disease Collaborative Research Group. Blood pressure, cholesterol and stroke in eastern Asia. Lancet 1998; 352: 1801–7

    Article  Google Scholar 

  7. Lewington S, Clarke R, Qizilbash N, et al. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet 2002; 360: 1903–13

    Article  PubMed  Google Scholar 

  8. SHEP Cooperative Research Group. Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension: final results of the Systolic Hypertension in the Elderly Program (SHEP). JAMA 1991; 265: 3255–64

    Article  Google Scholar 

  9. Dahlof B, Lindholm LH, Hansson L, et al. Morbidity and mortality in the Swedish Trial in Old Patients with Hypertension (STOP-Hypertension). Lancet 1991; 338: 1281–5

    Article  PubMed  CAS  Google Scholar 

  10. MRC Working Party. Medical Research Council trial of treatment of hypertension in older adults: principal results. BMJ 1992; 304: 405–12

    Article  Google Scholar 

  11. Staessen JA, Fagard R, Thijs L, et al. Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension. Lancet 1997; 350: 757–64

    Article  PubMed  CAS  Google Scholar 

  12. Wang JG, Staessen JA, Gong L, et al., for the Systolic Hypertension in China (Syst-China) Collaborative Group. Chinese trial on isolated systolic hypertension in the elderly. Arch Intern Med 2000; 160: 211–20

    Article  PubMed  CAS  Google Scholar 

  13. Hansson L, Lindholm LH, Ekbom T, et al. Randomised trial of old and new antihypertensive drugs in elderly patients: cardiovascular mortality and morbidity: the Swedish Trial in Old Patients with Hypertension-2 study. Lancet 1999; 354: 1751–6

    Article  PubMed  CAS  Google Scholar 

  14. The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA 2002; 288: 2981–97

    Article  Google Scholar 

  15. Guidelines Subcommittee. 1999 World Health Organization-International Society for Hypertension guidelines for the management of hypertension. J Hypertens 1999; 17: 151–83

    Google Scholar 

  16. Turnbull F, Blood Pressure Lowering Treatment Trialists’ Collaboration. Effects of different blood-pressure-lowering regimens on major cardiovascular events: results of prospectively-designed overviews of randomised trials. Lancet 2003; 362: 1527–35

    Article  PubMed  CAS  Google Scholar 

  17. Israili ZH, Hall WD. ACE inhibitors: differential use in elderly patients with hypertension. Drugs Aging 1995; 7: 355–71

    Article  PubMed  CAS  Google Scholar 

  18. Svanborg A. Age-related changes in cardiac physiology. Can they be postponed or treated by drugs? Drugs Aging 1997; 10: 463–72

    Article  PubMed  CAS  Google Scholar 

  19. Bulpitt CJ, Cameron JD, Rajkumar C, et al. The effect of age on vascular compliance in man: which are the appropriate measures? J Hum Hypertens 1999; 13: 753–8

    Article  PubMed  CAS  Google Scholar 

  20. Beckett NS, Connor M, Sadler JD, et al. Orthostatic fall in blood pressure in the very elderly hypertensive: results from the hypertension in the very elderly trial (HYVET) — pilot. J Hum Hypertens 1999; 13: 839–40

    Article  PubMed  CAS  Google Scholar 

  21. Cleophas TJ, van Marum R. Age-related decline in autonomic control of blood pressure: implications for the pharmacological management of hypertension in the elderly. Drugs Aging 2003; 20: 313–9

    Article  PubMed  CAS  Google Scholar 

  22. Weidmann P, De Myttenaere-Bursztein S, Maxwell MH, et al. Effect on aging on plasma renin and aldosterone in normal man. Kidney Int 1975; 8: 325–33

    Article  PubMed  CAS  Google Scholar 

  23. Tsunoda K, Abe K, Goto T, et al. Effect of age on the renin-angiotensin-aldosterone system in normal subjects: simultaneous measurement of active and inactive renin, renin substrate, and aldosterone in plasma. J Clin Endocrinol Metab 1986; 62: 384–9

    Article  PubMed  CAS  Google Scholar 

  24. Belmin J, Lévy BI, Michel J-B. Changes in the renin-angiotensin-aldosterone axis in later life. Drugs Aging 1994; 5: 391–400

    Article  PubMed  CAS  Google Scholar 

  25. Nakamaru M, Ogihara T, Higaki J, et al. Effect of age on active and inactive plasma renin in normal subjects and in patients with essential hypertension. J Am Geriatr Soc 1981; 29: 379–82

    PubMed  CAS  Google Scholar 

  26. Takeda R, Morimoto S, Uchida K, et al. Effect of age on plasma aldosterone response to exogenous angiotensin II in normotensive subjects. Acta Endocrinol 1980; 94: 552–8

    PubMed  CAS  Google Scholar 

  27. Unger T. The role of the renin-angiotensin system in the development of cardiovascular disease. Am J Cardiol 2002; 89: 3A–9A

    Article  PubMed  CAS  Google Scholar 

  28. Schiffrin EL, Touyz RM. Multiple actions of angiotensin II in hypertension: benefits of AT1 receptor blockade. J Am Coll Cardiol 2003; 42: 911–3

    Article  PubMed  Google Scholar 

  29. The ACE Inhibitors in Diabetic Nephropathy Trialist Group. Should all patients with type 1 diabetes mellitus and microalbuminuria receive angiotensin-converting enzyme inhibitors? A meta-analysis of individual patient data. Ann Intern Med 2001; 134: 370–9

    Google Scholar 

  30. Yusuf S, Sleight P, Pogue J, et al. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients: the Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med 2000; 342: 145–53

    Article  PubMed  CAS  Google Scholar 

  31. Jafar TH, Schmid CH, Landa M, et al. Angiotensin-converting enzyme inhibitors and progression of nondiabetic renal disease: a meta-analysis of patient-level data. Ann Intern Med 2001; 135: 73–87

    PubMed  CAS  Google Scholar 

  32. Tomlinson B, Young RP, Chan JCN, et al. Pharmacoepidemiology of ACE inhibitor-induced cough. Drug Safety 1997; 16: 150–1

    Article  PubMed  CAS  Google Scholar 

  33. Lacourciere Y. A multicenter, randomized, double-blind study of the antihypertensive efficacy and tolerability of irbesartan in patients aged > or = 65 years with mild to moderate hypertension. Clin Ther 2000; 22: 1213–24

    Article  PubMed  CAS  Google Scholar 

  34. Pitt B, Segal R, Martinez FA, et al. Randomised trial of losartan versus captopril in patients over 65 with heart failure (Evaluation of Losartan In The Elderly Study, ELITE). Lancet 1997; 349: 747–52

    Article  PubMed  CAS  Google Scholar 

  35. McInnes GT, O’Kane KP, Istad H, et al. Comparison of the AT1-receptor blocker, candesartan cilexetil, and the ACE inhibitor, lisinopril, in fixed combination with low dose hydrochlorothiazide in hypertensive patients. J Hum Hypertens 2000; 14: 263–9

    Article  PubMed  CAS  Google Scholar 

  36. Juillerat L, Nussberger J, Menard J, et al. Determinants of angiotensin II generation during converting enzyme inhibition. Hypertension 1990; 16: 564–72

    Article  PubMed  CAS  Google Scholar 

  37. Hollenberg NK. AT(l)-receptor blockade and the kidney: importance of non-ACE pathways in health and disease. J Hum Hypertens 2002; 16Suppl. 3: S59–63

    Article  PubMed  CAS  Google Scholar 

  38. Hollenberg NK, Fisher ND, Price DA. Pathways for angiotensin II generation in intact human tissue: evidence from comparative pharmacological interruption of the renin system. Hypertension 1998; 32: 387–92

    Article  PubMed  CAS  Google Scholar 

  39. Pitt B, Poole-Wilson P, Segal R, et al. Effects of losartan versus captopril on mortality in patients with symptomatic heart failure: rationale, design, and baseline characteristics of patients in the Losartan Heart Failure Survival Study — ELITE II. J Card Fail 1999; 5: 146–54

    Article  PubMed  CAS  Google Scholar 

  40. Kaschina E, Unger T. Angiotensin AT1/AT2 receptors: regulation, signalling and function. Blood Press 2003; 12: 70–88

    Article  PubMed  CAS  Google Scholar 

  41. Matsubara H. Pathophysiological role of angiotensin II type 2 receptor in cardiovascular and renal diseases. Circ Res 1998; 83: 1182–91

    Article  PubMed  CAS  Google Scholar 

  42. Johren O, Dendorfer A, Dominiak P. Cardiovascular and renal function of angiotensin II type-2 receptors. Cardiovasc Res 2004; 62: 460–7

    Article  PubMed  CAS  Google Scholar 

  43. Henrion D, Kubis N, Levy BI. Physiological and pathophysiological functions of the AT(2) subtype receptor of angiotensin II: from large arteries to the microcirculation. Hypertension 2001; 38: 1150–7

    Article  PubMed  CAS  Google Scholar 

  44. Schneider MD, Lorell BH. AT(2), judgment day: which angiotensin receptor is the culprit in cardiac hypertrophy? Circulation 2001; 104: 247–8

    Article  PubMed  CAS  Google Scholar 

  45. de Gasparo M, Siragy HM. The AT2 receptor: fact, fancy and fantasy. Regul Pept 1999; 81: 11–24

    Article  PubMed  Google Scholar 

  46. Siragy HM. The role of the AT2 receptor in hypertension. Am J Hypertens 2000; 13: 62S–7S

    Article  PubMed  CAS  Google Scholar 

  47. Levy BI. Can angiotensin II type 2 receptors have deleterious effects in cardiovascular disease? Implications for therapeutic blockade of the renin-angiotensin system. Circulation 2004; 109: 8–13

    Article  PubMed  Google Scholar 

  48. Israili ZH. Clinical pharmacokinetics of angiotensin II (AT1) receptor blockers in hypertension. J Hum Hypertens 2000; 14: S73–86

    Article  PubMed  CAS  Google Scholar 

  49. Unger T. Pharmacology of AT1-receptor blockers. Blood Press 2001; 10Suppl. 3: 5–10

    Article  Google Scholar 

  50. Lip GY, Beevers DG. More evidence on blocking the renin-angiotensin-aldosterone system in cardiovascular disease and the long-term treatment of hypertension: data from recent clinical trials (CHARM, EUROPA, ValHEFT, HOPE-TOO and SYST-EUR2). J Hum Hypertens 2003; 17: 747–50

    Article  PubMed  CAS  Google Scholar 

  51. Dickson TZ, Zagrobelny J, Lin CC, et al. Pharmacokinetics, safety, and antihypertensive efficacy of losartan in combination with hydrochlorothiazide in hypertensive patients with renal impairment. J Clin Pharmacol 2003; 43: 591–603

    PubMed  CAS  Google Scholar 

  52. Mallion JM, Carretta R, Trenkwalder P, et al. Valsartan/hydrochlorothiazide is effective in hypertensive patients inadequately controlled by valsartan monotherapy. Blood Press 2003; 12Suppl. 1: 36–43

    Article  CAS  Google Scholar 

  53. Wing LM, Arnolda LF, Upton J, et al. Candesartan and hydrochlorothiazide in isolated systolic hypertension. Blood Press 2003; 12: 246–54

    Article  PubMed  Google Scholar 

  54. Cody RJ. Physiological changes due to age. Implications for drug therapy of congestive heart failure. Drugs Aging 1993; 3: 320–34

    Article  PubMed  CAS  Google Scholar 

  55. Fu A, Sreekumaran Nair K. Age effect on fibrinogen and albumin synthesis in humans. Am J Physiol 1998; 275: E1023–30

    PubMed  CAS  Google Scholar 

  56. Israili ZH, Dayton PG. Human alpha-1-glycoprotein and its interactions with drugs. Drug Metab Rev 2001; 33: 161–235

    Article  PubMed  CAS  Google Scholar 

  57. Mangoni AA. Cardiovascular drug therapy in elderly patients: specific age-related pharmacokinetic, pharmacodynamic and therapeutic considerations. Drugs Aging 2005; 22: 913–41

    Article  PubMed  CAS  Google Scholar 

  58. Gillis JC, Markham A. Irbesartan: a review of its pharmacodynamic and pharmacokinetic properties and therapeutic use in the management of hypertension. Drugs 1997; 54: 885–902

    Article  PubMed  CAS  Google Scholar 

  59. Markham A, Goa KL. Valsartan: a review of its pharmacology and therapeutic use in essential hypertension. Drugs 1997; 54: 299–311

    Article  PubMed  CAS  Google Scholar 

  60. McClellan KJ, Markham A. Telmisartan. Drugs 1998; 56: 1039–44

    Article  PubMed  CAS  Google Scholar 

  61. McClellan KJ, Balfour JA. Eprosartan. Drugs 1998; 55: 713–8

    Article  PubMed  CAS  Google Scholar 

  62. Markham A, Spencer CM, Jarvis B. Irbesartan: an updated review of its use in cardiovascular disorders. Drugs 2000; 59: 1187–206

    Article  PubMed  CAS  Google Scholar 

  63. Plosker GL, Foster RH. Eprosartan: a review of its use in the management of hypertension. Drugs 2000; 60: 177–201

    Article  PubMed  CAS  Google Scholar 

  64. Simpson KL, McClellan KJ. Losartan: a review of its use, with special focus on elderly patients. Drugs Aging 2000; 16: 227–50

    Article  PubMed  CAS  Google Scholar 

  65. Sharpe M, Jarvis B, Goa KL. Telmisartan: a review of its use in hypertension. Drugs 2001; 61: 1501–29

    Article  PubMed  CAS  Google Scholar 

  66. Warner GT, Jarvis B. Olmesartan medoxomil. Drugs 2002; 62: 1345–53

    Article  PubMed  CAS  Google Scholar 

  67. Burnier M, Brunner HR. Angiotensin II receptor antagonists. Lancet 2000; 355: 637–45

    Article  PubMed  CAS  Google Scholar 

  68. Bottorff MB, Tenero DM. Pharmacokinetics of eprosartan in healthy subjects, patients with hypertension and special populations. Pharmacotherapy 1999; 19: 73S–8S

    Article  PubMed  CAS  Google Scholar 

  69. Marino MR, Langenbacher KM, Raymond RH, et al. Pharmacokinetics and pharmacodynamics of irbesartan in patients with hepatic cirrhosis. J Clin Pharmacol 1998; 38: 347–56

    PubMed  CAS  Google Scholar 

  70. Tenero D, Martin D, Chapelsky M, et al. Effect of hepatic disease on the pharmacokinetics and plasma protein binding of eprosartan. Pharmacotherapy 1998; 18: 42–50

    PubMed  CAS  Google Scholar 

  71. Stangier J, Su CA, Schondorfer G, et al. Pharmacokinetics and safety of intravenous and oral telmisartan 20mg and 120mg in subjects with hepatic impairment compared with healthy volunteers. J Clin Pharmacol 2000; 40: 1355–64

    PubMed  CAS  Google Scholar 

  72. Thurmann PA. Valsartan: a novel angiotensin type 1 receptor antagonist. Expert Opin Pharmacother 2000; 1: 337–50

    Article  PubMed  CAS  Google Scholar 

  73. Gleiter CH, Morike KE. Clinical pharmacokinetics of candesartan. Clin Pharmacokinet 2002; 41: 7–17

    Article  PubMed  CAS  Google Scholar 

  74. Waldmeier F, Flesch G, Muller P, et al. Pharmacokinetics, disposition and biotransformation of [14C]-radiolabelled valsartan in healthy male volunteers after a single oral dose. Xenobiotica 1997; 27: 59–71

    Article  PubMed  CAS  Google Scholar 

  75. Chung O, Unger T. Pharmacology of angiotensin receptors and AT1 receptor blockers. Basic Res Cardiol 1998; 93Suppl. 2: 15–23

    Article  PubMed  CAS  Google Scholar 

  76. Yasar UMD, Forslund-Bergengren CMD, Tybring GP, et al. Pharmacokinetics of losartan and its metabolite E-3174 in relation to the CYP2C9 genotype. Clin Pharmacol Ther 2002; 71: 89–98

    Article  PubMed  CAS  Google Scholar 

  77. Hallberg P, Karlsson J, Kurland L, et al. The CYP2C9 genotype predicts the blood pressure response to irbesartan: results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation vs Atenolol (SILVHIA) trial. J Hypertens 2002; 20: 2089–93

    Article  PubMed  CAS  Google Scholar 

  78. Uchida S, Watanabe H, Nishio S, et al. Altered pharmacokinetics and excessive hypotensive effect of candesartan in a patient with the CYP2C91/3 genotype. Clin Pharmacol Ther 2003; 74: 505–8

    Article  PubMed  CAS  Google Scholar 

  79. Miners JO, McKinnon RA, Mackenzie PI. Genetic polymorphisms of UDP-glucuronosyltransferases and their functional significance. Toxicology 2002; 181–182: 453–6

    Article  PubMed  Google Scholar 

  80. Mallion JM, Siche JP, Lacourciere Y. ABPM comparison of the antihypertensive profiles of the selective angiotensin II receptor antagonists telmisartan and losartan in patients with mild-to-moderate hypertension. J Hum Hypertens 1999; 13: 657–64

    Article  PubMed  CAS  Google Scholar 

  81. White WB, Anwar YA, Mansoor GA, et al. Evaluation of the 24-hour blood pressure effects of eprosartan in patients with systemic hypertension. Am J Hypertens 2001; 14: 1248–55

    Article  PubMed  CAS  Google Scholar 

  82. Sioufi A, Marfil F, Jaouen A, et al. The effect of age on the pharmacokinetics of valsartan. Biopharm Drug Dispos 1998; 19: 237–44

    Article  PubMed  CAS  Google Scholar 

  83. Hubner R, Hogemann AM, Sunzel M, et al. Pharmacokinetics of candesartan after single and repeated doses of candesartan cilexetil in young and elderly healthy volunteers. J Hum Hypertens 1997; 11: S19–25

    PubMed  CAS  Google Scholar 

  84. Tenero DM, Martin DE, Miller AK, et al. Effect of age and gender on the pharmacokinetics of eprosartan. Br J Clin Pharmacol 1998; 46: 267–70

    Article  PubMed  CAS  Google Scholar 

  85. Vachharajani NN, Shyu WC, Smith RA, et al. The effects of age and gender on the pharmacokinetics of irbesartan. Br J Clin Pharmacol 1998; 46: 611–3

    Article  PubMed  CAS  Google Scholar 

  86. von Bergmann K, Laeis P, Puchler K, et al. Olmesartan medoxomil: influence of age, renal and hepatic function on the pharmacokinetics of olmesartan medoxomil. J Hypertens Suppl 2001; 19Suppl. 1: S33–40

    Google Scholar 

  87. Brousil JA, Burke JM. Olmesartan medoxomil: an angiotensin II-receptor blocker. Clin Ther 2003; 25: 1041–55

    Article  PubMed  CAS  Google Scholar 

  88. Schepke M, Werner E, Biecker E, et al. Hemodynamic effects of the angiotensin II receptor antagonist irbesartan in patients with cirrhosis and portal hypertension. Gastroenterology 2001; 121: 389–95

    Article  PubMed  CAS  Google Scholar 

  89. Weir MR. Are drugs that block the renin-angiotensin system effective and safe in patients with renal insufficiency? Am J Hypertens 1999; 12: 195S–203S

    Article  PubMed  CAS  Google Scholar 

  90. Belz GG, Butzer R, Kober S, et al. Time course and extent of angiotensin II antagonism after irbesartan, losartan, and valsartan in humans assessed by angiotensin II dose response and radioligand receptor assay. Clin Pharmacol Ther 1999; 66: 367–73

    Article  PubMed  CAS  Google Scholar 

  91. Mclnnes GT. Clinical advantage of valsartan. Cardiology 1999; 91Suppl. 1: 14–8

    Article  Google Scholar 

  92. Burrell LM, Johnston CI. Angiotensin II receptor antagonists: potential in elderly patients with cardiovascular disease. Drugs Aging 1997; 10: 421–34

    Article  PubMed  CAS  Google Scholar 

  93. Mclnnes GT, O’Kane KP, Jonker J, et al. The efficacy and tolerability of candesartan cilexetil in an elderly hypertensive population. J Hum Hypertens 1997; 11Suppl. 2: S75–80

    Google Scholar 

  94. Okereke CE, Messerli FH. Efficacy and safety of angiotensin II receptor blockers in elderly patients with mild to moderate hypertension. Am J Geriatr Cardiol 2001; 10: 42–9

    Article  PubMed  CAS  Google Scholar 

  95. Brunner HR, Laeis P. Clinical efficacy of olmesartan medoxomil. J Hypertens Suppl 2003; 21Suppl. 2: S43–6

    PubMed  CAS  Google Scholar 

  96. Chrysant SG. Fixed combination therapy of hypertension: focus on valsartan/hydrochlorothiazide combination (Diovan®/HCT). Expert Rev Cardiovasc Ther 2003; 1: 335–43

    Article  PubMed  CAS  Google Scholar 

  97. Bohm M, Sachse A. Safety and tolerability of eprosartan in combination with hydrochlorothiazide. Drug Saf 2002; 25: 599–611

    Article  PubMed  Google Scholar 

  98. Kulbertus H. Kinzalkomb, a fixed telmisartan-hydrochlorothiazide combination for the treatment of hypertension [in French]. Rev Med Liege 2003; 58: 580–4

    PubMed  CAS  Google Scholar 

  99. Lacourciere Y, Gil-Extremera B, Mueller O, et al. Efficacy and tolerability of fixed-dose combinations of telmisartan plus HCTZ compared with losartan plus HCTZ in patients with essential hypertension. Int J Clin Pract 2003; 57: 273–9

    PubMed  CAS  Google Scholar 

  100. Lacourciere Y, Neutel JM, Schumacher H. Comparison of fixed-dose combinations of telmisartan/hydrochlorothiazide 40/12.5mg and 80/12.5mg and a fixed-dose combination of losartan/hydrochlorothiazide 50/12.5mg in mild to moderate essential hypertension: pooled analysis of two multicenter, prospective, randomized, open-label, blinded-end point (PROBE) trials. Clin Ther 2005; 27: 1795–805

    Article  PubMed  CAS  Google Scholar 

  101. Lorell BH, Carabello BA. Left ventricular hypertrophy: pathogenesis, detection, and prognosis. Circulation 2000; 102: 470–9

    Article  PubMed  CAS  Google Scholar 

  102. Verdecchia P, Carini G, Circo A, et al. Left ventricular mass and cardiovascular morbidity in essential hypertension: the MAVI study. J Am Coll Cardiol 2001; 38: 1829–35

    Article  PubMed  CAS  Google Scholar 

  103. Verdecchia P, Porcellati C, Reboldi G, et al. Left ventricular hypertrophy as an independent predictor of acute cerebrovascular events in essential hypertension. Circulation 2001; 104: 2039–44

    Article  PubMed  CAS  Google Scholar 

  104. Vakili BA, Okin PM, Devereux RB. Prognostic implications of left ventricular hypertrophy. Am Heart J 2001; 141: 334–41

    Article  PubMed  CAS  Google Scholar 

  105. Levy D, Anderson KM, Savage DD, et al. Echocardiographically detected left ventricular hypertrophy: prevalence and risk factors. The Framingham Heart Study. Ann Intern Med 1988; 108: 7–13

    PubMed  CAS  Google Scholar 

  106. Verdecchia P, Schillaci G, Borgioni C, et al. Prognostic significance of serial changes in left ventricular mass in essential hypertension. Circulation 1998; 97: 48–54

    Article  PubMed  CAS  Google Scholar 

  107. Verdecchia P, Angeli F, Borgioni C, et al. Changes in cardiovascular risk by reduction of left ventricular mass in hypertension: a meta-analysis. Am J Hypertens 2003; 16: 895–9

    Article  PubMed  Google Scholar 

  108. Lorell BH. Role of angiotensin AT1, and AT2 receptors in cardiac hypertrophy and disease. Am J Cardiol 1999; 83: 48H–52H

    Article  PubMed  CAS  Google Scholar 

  109. Kim S, Iwao H. Molecular and cellular mechanisms of angiotensin II-mediated cardiovascular and renal diseases. Pharmacol Rev 2000; 52: 11–34

    PubMed  CAS  Google Scholar 

  110. Schmieder RE, Martus P, Klingbeil A. Reversal of left ventricular hypertrophy in essential hypertension: a meta-analysis of randomized double-blind studies. JAMA 1996; 275: 1507–13

    Article  PubMed  CAS  Google Scholar 

  111. Klingbeil AU, Schneider M, Martus P, et al. A meta-analysis of the effects of treatment on left ventricular mass in essential hypertension. Am J Med 2003; 115: 41–6

    Article  PubMed  Google Scholar 

  112. Mancia G, Zanchetti A, Agabiti-Rosei E, et al. Ambulatory blood pressure is superior to clinic blood pressure in predicting treatment-induced regression of left ventricular hypertrophy: SAMPLE Study Group. Study on Ambulatory Monitoring of Blood Pressure and Lisinopril Evaluation. Circulation 1997; 95: 1464–70

    Article  PubMed  CAS  Google Scholar 

  113. Dahlof 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

    Article  PubMed  CAS  Google Scholar 

  114. 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: 2022–31

    Article  PubMed  CAS  Google Scholar 

  115. Pfeffer MA, McMurray JJ, Velazquez EJ, et al. Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both. N Engl J Med 2003; 349: 1893–906

    Article  PubMed  CAS  Google Scholar 

  116. Mclnnes GT. Angiotensin II antagonism in clinical practice: experience with valsartan. J Cardiovasc Pharmacol 1999; 33Suppl. 1: S29–32

    Article  Google Scholar 

  117. Pool JL, Guthrie RM, Littlejohn 3rd TW, et al. Dose-related antihypertensive effects of irbesartan in patients with mild-to-moderate hypertension. Am J Hypertens 1998; 11: 462–70

    Article  PubMed  CAS  Google Scholar 

  118. Hedner T, Oparil S, Rasmussen K, et al. A comparison of the angiotensin II antagonists valsartan and losartan in the treatment of essential hypertension. Am J Hypertens 1999; 12: 414–7

    Article  PubMed  CAS  Google Scholar 

  119. Man in’t Veld AJ. Clinical overview of irbesartan: expanding the therapeutic window in hypertension. J Hypertens 1997; 15 Suppl.: S27–33

    Google Scholar 

  120. Chan JCN, Critchley JAJH, Tomlinson B, et al. Antihypertensive and antialbuminuric effects of losartan potassium and felodipine in Chinese elderly hypertensive patients with or without non-insulin-dependent diabetes mellitus. Am J Nephrol 1997; 17: 72–80

    Article  PubMed  CAS  Google Scholar 

  121. Argenziano L, Trimarco B. Effect of eprosartan and enalapril in the treatment of elderly hypertensive patients: subgroup analysis of a 26-week, double-blind, multicentre study. Eprosartan Multinational Study Group. Curr Med Res Opin 1999; 15: 9–14

    Article  PubMed  CAS  Google Scholar 

  122. Conlin PR, Elkins M, Liss C, et al. A study of losartan, alone or with hydrochlorothiazide vs nifedipine GITS in elderly patients with diastolic hypertension. J Hum Hypertens 1998; 12: 693–9

    Article  PubMed  CAS  Google Scholar 

  123. Conlin PR, Spence JD, Williams B, et al. Angiotensin II antagonists for hypertension: are there differences in efficacy? Am J Hypertens 2000; 13: 418–26

    Article  PubMed  CAS  Google Scholar 

  124. Conlin PR. Angiotensin II antagonists in the treatment of hypertension: more similarities than differences. J Clin Hypertens (Greenwich) 2000; 2: 253–7

    CAS  Google Scholar 

  125. Critchley JAJH, Gilchrist N, Ikeda L, et al. A randomized, double-masked comparison of the antihypertensive efficacy and safety of combination therapy with losartan and hydrochlorothiazide versus captopril and hydrochlorothiazide in elderly and younger patients. Curr Ther Res 1996; 57: 392–407

    Article  CAS  Google Scholar 

  126. Giles TD, Bakris GL, Smith DH, et al. Defining the antihypertensive properties of the angiotensin receptor blocker telmisartan by a practice-based clinical trial. Am J Hypertens 2003; 16: 460–6

    Article  PubMed  CAS  Google Scholar 

  127. Roden DM, Brown NJ. Preprescription genotyping: not yet ready for prime time, but getting there. Circulation 2001; 103: 1608–10

    Article  PubMed  CAS  Google Scholar 

  128. Carlberg B, Samuelsson O, Lindholm LH. Atenolol in hypertension: is it a wise choice? Lancet 2004; 364: 1684–9

    Article  PubMed  CAS  Google Scholar 

  129. Messerli FH, Grossman E, Fournier A. Losartan vs atenolol in prevention of stroke and cardiovascular disease. JAMA 2003; 289: 700–1

    Article  PubMed  Google Scholar 

  130. Lindholm LH, Ibsen H, Dahlof B, et al. Cardiovascular morbidity and mortality in patients with diabetes in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet 2002; 359: 1004–10

    Article  PubMed  CAS  Google Scholar 

  131. Julius S, Alderman MH, Beevers G, et al. Cardiovascular risk reduction in hypertensive black patients with left ventricular hypertrophy: the LIFE study. J Am Coll Cardiol 2004; 43: 1047–55

    Article  PubMed  Google Scholar 

  132. Devereux RB, Lyle PA. Losartan for the treatment of hypertension and left ventricular hypertrophy: the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study. Expert Opin Pharmacother 2004; 5: 2311–20

    Article  PubMed  CAS  Google Scholar 

  133. Lithell H, Hansson L, Skoog I, et al. The Study on Cognition and Prognosis in the Elderly (SCOPE): principal results of a randomized double-blind intervention trial. J Hypertens 2003; 21: 875–86

    Article  PubMed  CAS  Google Scholar 

  134. Kjeldsen SE, Dahlof B, Devereux RB, et al. Effects of losartan on cardiovascular morbidity and mortality in patients with isolated systolic hypertension and left ventricular hypertrophy: a Losartan Intervention for Endpoint Reduction (LIFE) substudy. JAMA 2002; 288: 1491–8

    Article  PubMed  CAS  Google Scholar 

  135. Papademetriou V, Farsang C, Elmfeldt D, et al. Stroke prevention with the angiotensin II type 1-receptor blocker candesartan in elderly patients with isolated systolic hypertension: the Study on Cognition and Prognosis in the Elderly (SCOPE). J Am Coll Cardiol 2004; 44: 1175–80

    PubMed  CAS  Google Scholar 

  136. 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

    Article  PubMed  CAS  Google Scholar 

  137. 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

    Article  PubMed  CAS  Google Scholar 

  138. Staessen JA, Wang JG, Thijs L. Cardiovascular prevention and blood pressure reduction: a quantitative overview updated until 1 March 2003. J Hypertens 2003; 21: 1055–76

    Article  PubMed  CAS  Google Scholar 

  139. Berl T, Hunsicker LG, Lewis JB, et al. Cardiovascular outcomes in the Irbesartan Diabetic Nephropathy Trial of patients with type 2 diabetes and overt nephropathy. Ann Intern Med 2003; 138: 542–9

    PubMed  CAS  Google Scholar 

  140. Lindholm LH, Persson M, Alaupovic P, et al. Metabolic outcome during 1 year in newly detected hypertensives: results of the Antihypertensive Treatment and Lipid Profile in a North of Sweden Efficacy Evaluation (ALPINE study). J Hypertens 2003; 21: 1563–74

    Article  PubMed  CAS  Google Scholar 

  141. 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

    Article  PubMed  CAS  Google Scholar 

  142. Weber MA, Julius S, Kjeldsen SE, et al. Blood pressure dependent and independent effects of antihypertensive treatment on clinical events in the VALUE Trial. Lancet 2004; 363: 2049–51

    Article  PubMed  CAS  Google Scholar 

  143. Staessen JA, Thijs L, Birkenhager WH. VALUE: analysis of results [letter]. Lancet 2004; 364: 931

    Article  PubMed  Google Scholar 

  144. Williams B. Recent hypertension trials: implications and controversies. J Am Coll Cardiol 2005; 45: 813–27

    Article  PubMed  Google Scholar 

  145. Schrader J, Luders S, Kulschewski A, et al. Morbidity and mortality after stroke, eprosartan compared with nitrendipine for secondary prevention: principal results of a prospective randomized controlled study (MOSES). Stroke 2005; 36: 1218–26

    Article  PubMed  CAS  Google Scholar 

  146. UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes (UKPDS38). BMJ 1998; 317: 703–13

    Article  Google Scholar 

  147. Jover B, Demeilliers B. Angiotensin II type 1 receptor antagonist versus angiotensin I-converting enzyme inhibitor in experimental renal diseases. Fundam Clin Pharmacol 2000; 14: 541–8

    Article  PubMed  CAS  Google Scholar 

  148. Ravid M, Savin H, Jutrin I, et al. Long-term stabilizing effect of angiotensin-converting enzyme inhibition on plasma creatinine and on proteinuria in normotensive type II diabetic patients. Ann Intern Med 1993; 118: 577–81

    PubMed  CAS  Google Scholar 

  149. Parving HH, Lehnert H, Brochner-Mortensen J, et al. The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. N Engl J Med 2001; 345: 870–8

    Article  PubMed  CAS  Google Scholar 

  150. Viberti G, Wheeldon NM. Microalbuminuria reduction with valsartan in patients with type 2 diabetes mellitus: a blood pressure-independent effect. Circulation 2002; 106: 672–8

    Article  PubMed  CAS  Google Scholar 

  151. Gerstein HC. Diabetes and the HOPE study: implications for macrovascular and microvascular disease. Int J Clin Pract Suppl 2001: 8–12

    Google Scholar 

  152. Adler AI, Stevens RJ, Manley SE, et al. Development and progression of nephropathy in type 2 diabetes: the United Kingdom Prospective Diabetes Study (UKPDS 64). Kidney Int 2003; 63: 225–32

    Article  PubMed  Google Scholar 

  153. Donnelly R, Yeung JM, Manning G. Microalbuminuria: a common, independent cardiovascular risk factor, especially but not exclusively in type 2 diabetes. J Hypertens Suppl 2003; 21Suppl. 1: S7–12

    PubMed  CAS  Google Scholar 

  154. Strippoli GF, Craig M, Deeks JJ, et al. Effects of angiotensin converting enzyme inhibitors and angiotensin II receptor antagonists on mortality and renal outcomes in diabetic nephropathy: systematic review. BMJ 2004; 329: 828

    Article  PubMed  CAS  Google Scholar 

  155. Verma S, Strauss M. Angiotensin receptor blockers and myocardial infarction. BMJ 2004; 329: 1248–9

    Article  PubMed  Google Scholar 

  156. Epstein BJ, Gums JG. Angiotensin receptor blockers versus ACE inhibitors: prevention of death and myocardial infarction in high-risk populations. Ann Pharmacother 2005; 39: 470–80

    Article  PubMed  CAS  Google Scholar 

  157. McDonald MA, Simpson SH, Ezekowitz JA, et al. Angiotensin receptor blockers and risk of myocardial infarction: systematic review. BMJ 2005; 331: 873

    Article  PubMed  CAS  Google Scholar 

  158. Verdecchia P, Angeli F, Gattobigio R, et al. Do angiotensin II receptor blockers increase the risk of myocardial infarction? Eur Heart J 2005; 26: 2381–6

    Article  PubMed  CAS  Google Scholar 

  159. Verdecchia P, Reboldi G, Angeli F, et al. Angiotensin-converting enzyme inhibitors and calcium channel blockers for coronary heart disease and stroke prevention. Hypertension 2005; 46(2): 386–92

    Article  PubMed  CAS  Google Scholar 

  160. Teo K, Yusuf S, Sleight P, et al. Rationale, design, and baseline characteristics of 2 large, simple, randomized trials evaluating telmisartan, ramipril, and their combination in high-risk patients: the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial/Telmisartan Randomized Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease (ONTARGET/TRANSCEND) trials. Am Heart J 2004; 148: 52–61

    Article  PubMed  CAS  Google Scholar 

  161. Barnett AH, Bain SC, Bouter P, et al. Angiotensin-receptor blockade versus converting-enzyme inhibition in type 2 diabetes and nephropathy. N Engl J Med 2004; 351: 1952–61

    Article  PubMed  CAS  Google Scholar 

  162. Lacourciere Y, Belanger A, Godin C, et al. Long-term comparison of losartan and enalapril on kidney function in hypertensive type 2 diabetics with early nephropathy. Kidney Int 2000; 58: 762–9

    Article  PubMed  CAS  Google Scholar 

  163. 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: 1440–4

    Article  PubMed  CAS  Google Scholar 

  164. Nakao N, Yoshimura A, Morita H, et al. Combination treatment of angiotensin-II receptor blocker and angiotensin-converting-enzyme inhibitor in non-diabetic renal disease (COOPERATE): a randomised controlled trial. Lancet 2003; 361: 117–24

    Article  PubMed  CAS  Google Scholar 

  165. Taal MW, Brenner BM. Combination ACEI and ARB therapy: additional benefit in renoprotection? Curr Opin Nephrol Hypertens 2002; 11: 377–81

    Article  PubMed  Google Scholar 

  166. Hansson L, Lindholm LH, Niskanen L, et al. Effect of angiotensin-converting-enzyme inhibition compared with conventional therapy on cardiovascular morbidity and mortality in hypertension: the Captopril Prevention Project (CAPPP) randomised trial. Lancet 1999; 353: 611–6

    Article  PubMed  CAS  Google Scholar 

  167. Vermes E, Ducharme A, Bourassa MG, et al. Enalapril reduces the incidence of diabetes in patients with chronic heart failure: insight from the Studies Of Left Ventricular Dysfunction (SOLVD). Circulation 2003; 107: 1291–6

    Article  PubMed  CAS  Google Scholar 

  168. Lindholm LH, Ibsen H, Borch-Johnsen K, et al. Risk of new-onset diabetes in the Losartan Intervention For Endpoint reduction in hypertension study. J Hypertens 2002; 20: 1879–86

    Article  PubMed  CAS  Google Scholar 

  169. Mason JM, Dickinson HO, Nicolson DJ, et al. The diabetogenic potential of thiazide-type diuretic and beta-blocker combinations in patients with hypertension. J Hypertens 2005; 23: 1777–81

    Article  PubMed  CAS  Google Scholar 

  170. Verdecchia P, Reboldi G, Angeli F, et al. Adverse prognostic significance of new diabetes in treated hypertensive subjects. Hypertension 2004; 43: 963–9

    Article  PubMed  CAS  Google Scholar 

  171. Francis GS, Cohn JN, Johnson G, et al. Plasma norepinephrine, plasma renin activity and congestive heart failure: relations to survival and the effects of therapy in V-HeFT II. Circulation 1993; 87Suppl. VI: 40–8

    Google Scholar 

  172. Riegger GAJ, Bouzo H, Petr P, et al. Improvement in exercise tolerance and symptoms of congestive heart failure during treatment with candesartan cilexetil. Circulation 1999; 1000: 2224–30

    Article  Google Scholar 

  173. McKelvie RS, Yusuf S, Pericak D, et al. Comparison of candesartan, enalapril, and their combination in congestive heart failure: randomized evaluation of strategies for left ventricular dysfunction (RESOLVD) pilot study. The RESOLVD Pilot Study Investigators. Circulation 1999; 100: 1056–64

    Article  PubMed  CAS  Google Scholar 

  174. Maggioni AP, Anand I, Gottlieb SO, et al. Effects of valsartan on morbidity and mortality in patients with heart failure not receiving angiotensin-converting enzyme inhibitors. J Am Coll Cardiol 2002; 40: 1414–21

    Article  PubMed  CAS  Google Scholar 

  175. Granger CB, McMurray JJ, Yusuf S, et al. Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function intolerant to angiotensin-con-verting-enzyme inhibitors: the CHARM-Alternative trial. Lancet 2003; 362: 772–6

    Article  PubMed  CAS  Google Scholar 

  176. Pitt B, Poole-Wilson PA, Segal R, et al. Effect of losartan compared with captopril on mortality in patients with symptomatic heart failure: randomised trial — the Losartan Heart Failure Survival Study ELITE II. Lancet 2000; 355: 1582–7

    Article  PubMed  CAS  Google Scholar 

  177. Jong P, Demers C, McKelvie RS, et al. Angiotensin receptor blockers in heart failure: meta-analysis of randomized controlled trials. J Am Coll Cardiol 2002; 39: 463–70

    Article  PubMed  CAS  Google Scholar 

  178. Cohn JN, Tognoni G, for the Val-HeFT Investigators. Effect of the angiotensin receptor blocker valsartan on morbidity and mortality in heart failure: the Valsartan Heart Failure Trial (Val-HeFT). Circulation 2000: 102

    Google Scholar 

  179. McMurray JJ, Ostergren J, Swedberg K, et al. Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function taking angiotensin-converting-enzyme inhibitors: the CHARM-Added trial. Lancet 2003; 362: 767–71

    Article  PubMed  CAS  Google Scholar 

  180. 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

    Article  PubMed  CAS  Google Scholar 

  181. 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. Optimal Trial in Myocardial Infarction with Angiotensin II Antagonist Losartan. Lancet 2002; 360: 752–60

    Article  PubMed  CAS  Google Scholar 

  182. Garg R, Yusuf S. Overview of randomized trials of angiotensin-converting enzyme inhibitors on mortality and morbidity in patients with heart failure: Collaborative Group on ACE Inhibitor Trials. JAMA 1995; 273: 1450–6

    Article  PubMed  CAS  Google Scholar 

  183. 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

    Article  PubMed  CAS  Google Scholar 

  184. Hall J, Marbury T, Gray J, et al. Long term safety, tolerability and efficacy of valsartan: results from one and two year trials. J Clin Res 1998; 1: 147–59

    Google Scholar 

  185. Chan P, Tomlinson B, Huang TY, et al. Double-blind comparison of losartan, lisinopril, and metolazone in elderly hypertensive patients with previous angiotensin-converting enzyme inhibitor-induced cough. J Clin Pharmacol 1997; 37: 253–7

    PubMed  CAS  Google Scholar 

  186. Siragy HM, Carey RM. Protective role of the angiotensin AT2 receptor in a renal wrap hypertension model. Hypertension 1999; 33: 1237–42

    Article  PubMed  CAS  Google Scholar 

  187. Aronow WS. The ELITE Study. What are its implications for the drug treatment of heart failure? Evaluation of Losartan in the Elderly Study. Drugs Aging 1998; 12: 423–8

    Article  PubMed  CAS  Google Scholar 

  188. Puig JG, Mateos F, Buno A, et al. Effect of eprosartan and losartan on uric acid metabolism in patients with essential hypertension. J Hypertens 1999; 17: 1033–9

    Article  PubMed  CAS  Google Scholar 

  189. Csajka C, Buclin T, Brunner HR, et al. Pharmacokinetic-pharmacodynamic profile of angiotensin II receptor antagonists. Clin Pharmacokinet 1997; 31: 1–29

    Article  Google Scholar 

  190. Calvino J, Lens XM, Romero R, et al. Long-term anti-protein-uric effect of losartan in renal transplant recipients treated for hypertension. Nephrol Dial Transplant 2000; 15: 82–6

    Article  PubMed  CAS  Google Scholar 

  191. Ducloux D, Saint-Hillier Y, Chalopin JM. Effect of losartan on haemoglobin concentration in renal transplant recipients — a retrospective analysis. Nephrol Dial Transplant 1997; 12: 2683–6

    Article  PubMed  CAS  Google Scholar 

  192. el-Agroudy AE, Hassan NA, Foda MA, et al. Effect of angiotensin II receptor blocker on plasma levels of TGF-beta 1 and interstitial fibrosis in hypertensive kidney transplant patients. Am J Nephrol 2003; 23: 300–6

    Article  PubMed  CAS  Google Scholar 

  193. Tepel M, van der Giet M, Zidek W. Efficacy and tolerability of angiotensin II type 1 receptor antagonists in dialysis patients using AN69 dialysis membranes. Kidney Blood Press Res 2001; 24: 71–4

    Article  PubMed  CAS  Google Scholar 

  194. Kon V, Fogo A, Ichikawa I. Bradykinin causes selective efferent arteriolar dilation during angiotensin I converting enzyme inhibition. Kidney Int 1993; 44: 545–50

    Article  PubMed  CAS  Google Scholar 

  195. Lewis EJ, Hunsicker LG, Bain RP, et al. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy: the Collaborative Study Group. N Engl J Med 1993; 329: 1456–62

    Article  PubMed  CAS  Google Scholar 

  196. Maschio G, Alberti D, Janin G, et al. Effect of the angiotensin-converting-enzyme inhibitor benazepril on the progression of chronic renal insufficiency: the Angiotensin-Converting-Enzyme Inhibition in Progressive Renal Insufficiency Study Group. N Engl J Med 1996; 334: 939–45

    Article  PubMed  CAS  Google Scholar 

  197. The GISEN Group. Randomised placebo-controlled trial of effect of ramipril on decline in glomerular filtration rate and risk of terminal renal failure in proteinuric, non-diabetic nephropathy. Lancet 1997; 349: 1857–63

    Article  Google Scholar 

  198. Ahmed A, Kiefe CI, Allman RM, et al. Survival benefits of angiotensin-converting enzyme inhibitors in older heart failure patients with perceived contraindications. J Am Geriatr Soc 2002; 50: 1659–66

    Article  PubMed  Google Scholar 

  199. Routledge HC, Townend JN. ACE inhibition in aortic stenosis: dangerous medicine or golden opportunity? J Hum Hypertens 2001; 15: 659–67

    Article  PubMed  CAS  Google Scholar 

  200. Taavitsainen P, Kiukaanniemi K, Pelkonen O. In vitro inhibition screening of human hepatic P450 enzymes by five angiotensin-II receptor antagonists. Eur J Clin Pharmacol 2000; 56: 135–40

    Article  PubMed  CAS  Google Scholar 

  201. Marino MR, Vachharajani NN. Drug interactions with irbesartan. Clin Pharmacokinet 2001; 40: 605–14

    Article  PubMed  CAS  Google Scholar 

  202. Maillard MP, Wurzner G, Nussberger J, et al. Comparative angiotensin II receptor blockade in healthy volunteers: the importance of dosing. Clin Pharmacol Ther 2002; 71: 68–76

    Article  PubMed  CAS  Google Scholar 

  203. Elliott HL, Mclnnes GT. Special management needs of the elderly hypertensive patient. J Renin Angiotensin Aldosterone Syst 2002; 3Suppl. 1: S25–31

    Article  PubMed  Google Scholar 

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Acknowledgements

Funding from the Hong Kong Research Grants Council Grant CUHK 4438/03M was used to assist in the preparation of this manuscript. Brian Tomlinson has received grants for clinical research and educational activities from Boehringer Ingelheim, Merck Sharp & Dohme, Novartis, Pfizer and Sanofi-Aventis and has served on advisory boards for Merck Sharp & Dohme and Pfizer. G. Neil Thomas and Paul Chan have no conflicts of interest that are directly relevant to the content of this review.

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  1. Department of Community Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China

    G. Neil Thomas

  2. Division of Cardiovascular Medicine, Taipei Medical University-Wan Fang Hospital, Taipe, Taiwan

    Paul Chan

  3. Faculty of Medicine, Macao University of Science and Technology, Taipa, Macao, China

    Paul Chan

  4. Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong, China

    Brian Tomlinson

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Thomas, G.N., Chan, P. & Tomlinson, B. The Role of Angiotensin II Type 1 Receptor Antagonists in Elderly Patients with Hypertension. Drugs Aging 23, 131–155 (2006). https://doi.org/10.2165/00002512-200623020-00004

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