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Cardiovascular Drug Therapy in Elderly Patients

Specific Age-Related Pharmacokinetic, Pharmacodynamic and Therapeutic Considerations

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Abstract

An increasing number of elderly patients are exposed to cardiovascular drugs for the treatment of acute and/or chronic conditions. This is a result of the progressive aging of the population, a common feature in most industrialised countries, and an improvement in primary and secondary cardiovascular prevention strategies with increased survival rates. Traditionally, most elderly patients receiving cardiovascular drugs had advanced cardiac, liver and kidney disease that significantly influenced drug pharmacokinetic and pharmacodynamic parameters. Currently, however, many patients without significant organ impairment receive cardiovascular therapy for primary or early secondary prevention (i.e. increased vascular risk, asymptomatic left ventricular dysfunction, poststroke phase, type 2 diabetes mellitus), highlighting the need for a better understanding of specific age-related pharmacokinetic and pharmacodynamic effects.

A systematic review has been conducted on the specific effects of aging, in the absence of major co-morbidities, on the pharmacokinetic and pharmacodynamic properties of traditional and newer cardiovascular drugs. Currently, the evidence available is poor or nonexisting for several drugs and mainly derived from very small and underpowered studies, thus limiting data interpretation. In particular, there is very little information on patients >80 years of age, thus raising important concerns about the correct use of these drugs in this constantly growing population.

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References

  1. American Heart Association. Heart disease and stroke statistics: 2005 update. Dallas (TX): American Heart Association, 2004

    Google Scholar 

  2. Australian Institute of Health and Welfare (AIHW) and Heart Foundation. Heart, stroke and vascular diseases: Australian facts 2004. AIHW Cat. No. CVD 27. Canberra (ACT): Australian Institute of Health and Welfare and the National Heart Foundation of Australia, 2004: 18–26

    Google Scholar 

  3. Shah RR. Drug development and use in the elderly: search for the right dose and dosing regimen (Parts I and II). Br J Clin Pharmacol 2004; 58: 452–69

    Article  PubMed  Google Scholar 

  4. Swift CG. The clinical pharmacology of ageing. Br J Clin Pharmacol 2003; 56: 249–53

    Article  PubMed  CAS  Google Scholar 

  5. Routledge PA, O’Mahony MS, Woodhouse KW. Adverse drug reactions in elderly patients. Br J Clin Pharmacol 2004; 57: 121–6

    Article  PubMed  CAS  Google Scholar 

  6. Sokol SI, Cheng A, Frishman WH, et al. Cardiovascular drug therapy in patients with hepatic diseases and patients with congestive heart failure. J Clin Pharmacol 2000; 40: 11–30

    Article  PubMed  CAS  Google Scholar 

  7. Matzke GR, Frye RF. Drug administration in patients with renal insufficiency: minimising renal and extrarenal toxicity. Drug Saf 1997; 16: 205–31

    Article  PubMed  CAS  Google Scholar 

  8. Vrhovac B, Sarapa N, Bakran I, et al. Pharmacokinetic changes in patients with oedema. Clin Pharmacokinet 1995; 28: 405–18

    Article  PubMed  CAS  Google Scholar 

  9. Rodighiero V. Effects of liver disease on pharmacokinetics: an update. Clin Pharmacokinet 1999; 37: 399–431

    Article  PubMed  CAS  Google Scholar 

  10. Pichette V, Leblond FA. Drug metabolism in chronic renal failure. Curr Drug Metab 2003; 4: 91–103

    Article  PubMed  CAS  Google Scholar 

  11. Barbour MM, McKindley DS. Pharmacology and pharmacotherapy of cardiovascular drugs in patients with chronic renal disease. Semin Nephrol 2001; 21: 66–78

    Article  PubMed  CAS  Google Scholar 

  12. Westphal JF, Brogard JM. Drug administration in chronic liver disease. Drug Saf 1997; 17: 47–73

    Article  PubMed  CAS  Google Scholar 

  13. Reetze-Bonorden P, Bohler J, Keller E. Drug dosage in patients during continuous renal replacement therapy: pharmacokinetic and therapeutic considerations. Clin Pharmacokinet 1993; 24: 362–79

    Article  PubMed  CAS  Google Scholar 

  14. Lakatta EG, Levy D. Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises: Part I. Aging arteries: a ‘set up’ for vascular disease. Circulation 2003; 107: 139–46

    Article  PubMed  Google Scholar 

  15. Lakatta EG, Levy D. Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises: Part II. The aging heart in health: links to heart disease. Circulation 2003; 107: 346–54

    Article  PubMed  Google Scholar 

  16. Lakatta EG. Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises: Part III. Cellular and molecular clues to heart and arterial aging. Circulation 2003; 107: 490–7

    Article  PubMed  Google Scholar 

  17. Moore A, Mangoni AA, Lyons D, et al. The cardiovascular system. B J Clin Pharmacol 2003; 56: 254–60

    Article  CAS  Google Scholar 

  18. Burgess ML, McCrea JC, Hedrick HL. Age-associated changes in cardiac matrix and integrins. Mech Ageing Dev 2001; 122: 1739–56

    Article  PubMed  CAS  Google Scholar 

  19. Goor D, Lillehei CW, Edwards JE. The ‘sigmoid septum’: variation in the contour of the left ventricular outlet. Am J Roentgenol Radium Ther Nucl Med 1969; 107: 366–76

    PubMed  CAS  Google Scholar 

  20. Lyons D, Roy S, Patel M, et al. Impaired nitric oxide-mediated vasodilatation and total body nitric oxide production in healthy old age. Clin Sci (Lond) 1997; 93: 519–25

    CAS  Google Scholar 

  21. Saetrum OO, Ytterberg HT, Saxena PR, et al. Influence of ageing on vasomotor responses of human epicardial coronary arteries. Pharmacol Toxicol 2000; 86: 183–91

    Article  Google Scholar 

  22. Andrawis N, Jones DS, Abernethy DR. Aging is associated with endothelial dysfunction in the human forearm vasculature. J Am Geriatr Soc 2000; 48: 193–8

    PubMed  CAS  Google Scholar 

  23. Hogikyan RV, Supiano MA. Arterial alpha-adrenergic responsiveness is decreased and SNS activity is increased in older humans. Am J Physiol 1994; 266: E717–24

    PubMed  CAS  Google Scholar 

  24. McDonald A, MacDonald E, Fulton JD, et al. No evidence for a general change in contractile responsiveness of the mesenteric artery with aging. J Gerontol A Biol Sci Med Sci 1995; 50A: B20–5

    Article  PubMed  CAS  Google Scholar 

  25. Taddei S, Virdis A, Mattei P, et al. Aging and endothelial function in normotensive subjects and patients with essential hypertension. Circulation 1995; 91: 1981–7

    Article  PubMed  CAS  Google Scholar 

  26. Ignarro LJ, Cirino G, Casini A, et al. Nitric oxide as a signaling molecule in the vascular system: an overview. J Cardiovasc Pharmacol 1999; 34: 879–86

    Article  PubMed  CAS  Google Scholar 

  27. Ahlers BA, Parnell MM, Chin-Dusting JP, et al. An age-related decline in endothelial function is not associated with alterations in L-arginine transport in humans. J Hypertens 2004; 22: 321–7

    Article  PubMed  CAS  Google Scholar 

  28. Kedziora-Kornatowska K, Czuczejko J, Pawluk H, et al. The markers of oxidative stress and activity of the antioxidant system in the blood of elderly patients with essential arterial hypertension. Cell Mol Biol Lett 2004; 9: 635–41

    PubMed  CAS  Google Scholar 

  29. Lakatta EG. Cardiovascular reserve capacity in healthy older humans. Aging (Milano) 1994; 6: 213–23

    CAS  Google Scholar 

  30. Parati G, Frattola A, Di Rienzo M, et al. Effects of aging on 24-h dynamic baroreceptor control of heart rate in ambulant subjects. Am J Physiol 1995; 268: H1606–12

    PubMed  CAS  Google Scholar 

  31. Olsen H, Vernersson E, Lanne T. Cardiovascular response to acute hypovolemia in relation to age: implications for orthostasis and hemorrhage. Am J Physiol Heart Circ Physiol 2000; 278: H222–32

    PubMed  CAS  Google Scholar 

  32. Rubin PC, Scott PJ, McLean K, et al. Noradrenaline release and clearance in relation to age and blood pressure in man. Eur J Clin Invest 1982; 12: 121–5

    Article  PubMed  CAS  Google Scholar 

  33. Sundlof G, Wallin BG. Human muscle nerve sympathetic activity at rest: relationship to blood pressure and age. J Physiol 1978; 274: 621–37

    PubMed  CAS  Google Scholar 

  34. Davy KP, Seals DR, Tanaka H. Augmented cardiopulmonary and integrative sympathetic baroreflexes but attenuated peripheral vasoconstriction with age. Hypertension 1998; 32: 298–304

    Article  PubMed  CAS  Google Scholar 

  35. Wing LM, Tonkin AL. Orthostatic blood pressure control and ageing. Aust N Z J Med 1997; 27: 462–6

    Article  PubMed  CAS  Google Scholar 

  36. Gabbett T, Gass G, Gass E, et al. Norepinephrine and epinephrine responses during orthostatic intolerance in healthy elderly men. Jpn J Physiol 2000; 50: 59–66

    Article  PubMed  CAS  Google Scholar 

  37. Stratton JR, Levy WC, Caldwell JH, et al. Effects of aging on cardiovascular responses to parasympathetic withdrawal. J Am Coll Cardiol 2003; 41: 2077–83

    Article  PubMed  Google Scholar 

  38. Ng AV, Callister R, Johnson DG, et al. Sympathetic neural reactivity to stress does not increase with age in healthy humans. Am J Physiol 1994; 267: H344–53

    PubMed  CAS  Google Scholar 

  39. O’Mahony D, Bennett C, Green A, et al. Reduced baroreflex sensitivity in elderly humans is not due to efferent autonomic dysfunction. Clin Sci (Lond) 2000; 98: 103–10

    Article  Google Scholar 

  40. Taylor JA, Hand GA, Johnson DG, et al. Augmented forearm vasoconstriction during dynamic exercise in healthy older men. Circulation 1992; 86: 1789–99

    Article  PubMed  CAS  Google Scholar 

  41. Esler M, Lambert G, Kaye D, et al. Influence of ageing on the sympathetic nervous system and adrenal medulla at rest and during stress. Biogerontology 2002; 3: 45–9

    Article  PubMed  CAS  Google Scholar 

  42. Kekki M, Samloff IM, Ihamaki T, et al. Age- and sex-related behaviour of gastric acid secretion at the population level. Scand J Gastroenterol 1982; 17: 737–43

    Article  PubMed  CAS  Google Scholar 

  43. Evans MA, Triggs EJ, Cheung M, et al. Gastric emptying rate in the elderly: implications for drug therapy. J Am Geriatr Soc 1981; 29: 201–5

    PubMed  CAS  Google Scholar 

  44. Bender AD. The effect of increasing age on the distribution of peripheral blood flow in man. J Am Geriatr Soc 1965; 13: 192–8

    PubMed  CAS  Google Scholar 

  45. Corazza GR, Frazzoni M, Gatto MR, et al. Ageing and small-bowel mucosa: a morphometric study. Gerontology 1986; 32: 60–5

    Article  PubMed  CAS  Google Scholar 

  46. Gainsborough N, Maskrey VL, Nelson ML, et al. The association of age with gastric emptying. Age Ageing 1993; 22: 37–40

    Article  PubMed  CAS  Google Scholar 

  47. Husebye E, Engedal K. The patterns of motility are maintained in the human small intestine throughout the process of aging. Scand J Gastroenterol 1992; 27: 397–404

    Article  PubMed  CAS  Google Scholar 

  48. Anantharaju A, Feller A, Chedid A. Aging Liver: a review. Gerontology 2002; 48: 343–53

    Article  PubMed  CAS  Google Scholar 

  49. Castleden CM, George CF. The effect of ageing on the hepatic clearance of propranolol. Br J Clin Pharmacol 1979; 7: 49–54

    Article  PubMed  CAS  Google Scholar 

  50. Kelly JG, McGarry K, O’Malley K, et al. Bioavailability of labetalol increases with age. Br J Clin Pharmacol 1982; 14: 304–5

    Article  PubMed  CAS  Google Scholar 

  51. Davies RO, Gomez HJ, Irvin JD, et al. An overview of the clinical pharmacology of enalapril. Br J Clin Pharmacol 1984; 18Suppl. 2: 215S–29S

    Article  PubMed  Google Scholar 

  52. Todd PA, Fitton A. Perindopril: a review of its pharmacological properties and therapeutic use in cardiovascular disorders. Drugs 1991; 42: 90–114

    Article  PubMed  CAS  Google Scholar 

  53. Brenner SS, Klotz U. P-glycoprotein function in the elderly. Eur J Clin Pharmacol 2004; 60: 97–102

    Article  PubMed  CAS  Google Scholar 

  54. Fulop Jr T, Worum I, Csongor J, et al. Body composition in elderly people: II. Comparison of measured and predicted body composition in healthy elderly subjects. Gerontology 1985; 31: 150–7

    Article  PubMed  Google Scholar 

  55. Fulop Jr T, Worum I, Csongor J, et al. Body composition in elderly people: I. Determination of body composition by multi-isotope method and the elimination kinetics of these isotopes in healthy elderly subjects. Gerontology 1985; 31: 6–14

    Article  PubMed  Google Scholar 

  56. Cusack B, Kelly J, O’Malley K, et al. Digoxin in the elderly: pharmacokinetic consequences of old age. Clin Pharmacol Ther 1979; 25: 772–6

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  58. Benet LZ, Hoener BA. Changes in plasma protein binding have little clinical relevance. Clin Pharmacol Ther 2002; 71: 115–21

    Article  PubMed  CAS  Google Scholar 

  59. Kasiske BL. Relationship between vascular disease and age-associated changes in the human kidney. Kidney Int 1987; 31: 1153–9

    Article  PubMed  CAS  Google Scholar 

  60. Back SE, Ljungberg B, Nilsson-Ehle I, et al. Age dependence of renal function: clearance of iohexol and p-amino hippurate in healthy males. Scand J Clin Lab Invest 1989; 49: 641–6

    Article  PubMed  CAS  Google Scholar 

  61. Rowe JW, Andres R, Tobin JD, et al. The effect of age on creatinine clearance in men: a cross-sectional and longitudinal study. J Gerontol 1976; 31: 155–63

    Article  PubMed  CAS  Google Scholar 

  62. Somogyi A, Hewson D, Muirhead M, et al. Amiloride disposition in geriatric patients: importance of renal function. Br J Clin Pharmacol 1990; 29: 1–8

    Article  PubMed  CAS  Google Scholar 

  63. Tsang P, Gerson B. Understanding digoxin use in the elderly patient. Clin Lab Med 1990; 10: 479–92

    PubMed  CAS  Google Scholar 

  64. Rigby JW, Scott AK, Hawksworth GM, et al. A comparison of the pharmacokinetics of atenolol, metoprolol, oxprenolol and propranolol in elderly hypertensive and young healthy subjects. Br J Clin Pharmacol 1985; 20: 327–31

    Article  PubMed  CAS  Google Scholar 

  65. Fliser D, Bischoff I, Hanses A, et al. Renal handling of drugs in the healthy elderly. Creatinine clearance underestimates renal function and pharmacokinetics remain virtually unchanged. Eur J Clin Pharmacol 1999; 55: 205–11

    Article  PubMed  CAS  Google Scholar 

  66. Mathew TH. Chronic kidney disease and automatic reporting of estimated glomerular filtration rate: a position statement. Med J Aust 2005; 183: 138–41

    PubMed  Google Scholar 

  67. Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976; 16: 31–41

    Article  PubMed  CAS  Google Scholar 

  68. Hallan S, Asberg A, Lindberg M, et al. Validation of the Modification of Diet in Renal Disease formula for estimating GFR with special emphasis on calibration of the serum creatinine assay. Am J Kidney Dis 2004; 44: 84–93

    Article  PubMed  Google Scholar 

  69. Kinirons MT, O’Mahony MS. Drug metabolism and ageing. Br J Clin Pharmacol 2004; 57: 540–4

    Article  PubMed  CAS  Google Scholar 

  70. Schmucker DL. Liver function and phase I drug metabolism in the elderly: a paradox. Drugs Aging 2001; 18: 837–51

    Article  PubMed  CAS  Google Scholar 

  71. Miners JO, Penhall R, Robson RA, et al. Comparison of paracetamol metabolism in young adult and elderly males. Eur J Clin Pharmacol 1988; 35: 157–60

    Article  PubMed  CAS  Google Scholar 

  72. Greenblatt DJ, Divoll M, Harmatz JS, et al. Oxazepam kinetics: effects of age and sex. J Pharmacol Exp Ther 1980; 215: 86–91

    PubMed  CAS  Google Scholar 

  73. Rostami-Hodjegan A, Kroemer HK, Tucker GT. In-vivo indices of enzyme activity: the effect of renal impairment on the assessment of CYP2D6 activity. Pharmacogenetics 1999; 9: 277–86

    Article  PubMed  CAS  Google Scholar 

  74. Yuan R, Venitz J. Effect of chronic renal failure on the disposition of highly hepatically metabolized drugs. Int J Clin Pharmacol Ther 2000; 38: 245–53

    PubMed  CAS  Google Scholar 

  75. Oberbauer R, Krivanek P, Turnheim K. Pharmacokinetics and pharmacodynamics of the diuretic bumetanide in the elderly. Clin Pharmacol Ther 1995; 57: 42–51

    Article  PubMed  CAS  Google Scholar 

  76. Andreasen F, Hansen U, Husted SE, et al. The pharmacokinetics of frusemide are influenced by age. Br J Clin Pharmacol 1983; 16: 391–7

    Article  PubMed  CAS  Google Scholar 

  77. Williams RL, Thornhill MD, Upton RA, et al. Absorption and disposition of two combination formulations of hydrochlorothiazide and triamterene: influence of age and renal function. Clin Pharmacol Ther 1986; 40: 226–32

    Article  PubMed  CAS  Google Scholar 

  78. Sabanathan K, Castleden CM, Adam HK, et al. A comparative study of the pharmacokinetics and pharmacodynamics of atenolol, hydrochlorothiazide and amiloride in normal young and elderly subjects and elderly hypertensive patients. Eur J Clin Pharmacol 1987; 32: 53–60

    Article  PubMed  CAS  Google Scholar 

  79. Ismail Z, Triggs EJ, Smithurst BA, et al. The pharmacokinetics of amiloride-hydrochlorothiazide combination in the young and elderly. Eur J Clin Pharmacol 1989; 37: 167–71

    Article  PubMed  CAS  Google Scholar 

  80. Ho PC, Bourne DW, Triggs EJ, et al. Comparison of plasma levels of canrenone and metabolites after base hydrolysis in young and elderly subjects following single and multiple doses of spironolactone. Eur J Clin Pharmacol 1984; 27: 435–9

    Article  PubMed  CAS  Google Scholar 

  81. Andreasen F, Hansen U, Husted SE, et al. The influence of age on renal and extrarenal effects of frusemide. Br J Clin Pharmacol 1984; 18: 65–74

    Article  PubMed  CAS  Google Scholar 

  82. Chaudhry AY, Bing RF, Castleden CM, et al. The effect of ageing on the response to frusemide in normal subjects. Eur J Clin Pharmacol 1984; 27: 303–6

    Article  PubMed  CAS  Google Scholar 

  83. Wilson TW, McCaulay FA, Waslen TA. Effects of aging on responses to furosemide. Prostaglandins 1989; 38: 675–87

    Article  PubMed  CAS  Google Scholar 

  84. Rowlands DB, Glover DR, Young MA, et al. Once daily indapamide in the treatment of the elderly and young hypertensive. Eur J Clin Pharmacol 1984; 27: 397–405

    Article  PubMed  CAS  Google Scholar 

  85. 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

  86. Chobanian AV, Bakris GL, Black HR, et al. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension 2003; 42: 1206–52

    Article  PubMed  CAS  Google Scholar 

  87. Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6,105 individuals with previous stroke or transient ischaemic attack. Lancet 2001; 358: 1033–41

    Google Scholar 

  88. Fogari R, Zoppi A. Effect of antihypertensive agents on quality of life in the elderly. Drugs Aging 2004; 21: 377–93

    Article  PubMed  CAS  Google Scholar 

  89. Waeber B. Very-low-dose combination: a first-line choice for the treatment of hypertension? J Hypertens Suppl 2003; 21Suppl. 3: S3–10

    PubMed  CAS  Google Scholar 

  90. Singh H, Johnson ML. Prescribing patterns of diuretics in multidrug antihypertensive regimens. J Clin Hypertens (Greenwich) 2005; 7: 81–7

    Article  Google Scholar 

  91. Gupta S, Neyses L. Diuretic usage in heart failure: a continuing conundrum in 2005. Eur Heart J 2005; 26: 644–9

    Article  PubMed  CAS  Google Scholar 

  92. Gheorghiade M, Filippatos G. Reassessing treatment of acute heart failure syndromes: the ADHERE Registry. Eur Heart J 2005; 7Suppl. B: B13–9

    Google Scholar 

  93. Pitt B, Zannad F, Remme WJ, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med 1999; 341: 709–17

    Article  PubMed  CAS  Google Scholar 

  94. Stewart PM. Mineralocorticoid hypertension. Lancet 1999; 353: 1341–7

    Article  PubMed  CAS  Google Scholar 

  95. Vasan RS, Evans JC, Larson MG, et al. Serum aldosterone and the incidence of hypertension in nonhypertensive persons. N Engl J Med 2004; 351: 33–41

    Article  PubMed  CAS  Google Scholar 

  96. Juurlink DN, Mamdani MM, Lee DS, et al. Rates of hyperkalemia after publication of the Randomized Aldactone Evaluation Study. N Engl J Med 2004; 351: 543–51

    Article  PubMed  CAS  Google Scholar 

  97. Rubin PC, Scott PJ, McLean K, et al. Atenolol disposition in young and elderly subjects. Br J Clin Pharmacol 1982; 13: 235–7

    Article  PubMed  CAS  Google Scholar 

  98. Sowinski KM, Forrest A, Wilton JH, et al. Effect of aging on atenolol pharmacokinetics and pharmacodynamics. J Clin Pharmacol 1995; 35: 807–14

    PubMed  CAS  Google Scholar 

  99. Gretzer I, Alvan G, Duner H, et al. Beta-blocking effect and pharmacokinetics of pindolol in young and elderly hypertensive patients. Eur J Clin Pharmacol 1986; 31: 415–8

    Article  PubMed  CAS  Google Scholar 

  100. Hitzenberger G, Fitscha P, Beveridge T, et al. Effects of age and smoking on the pharmacokinetics of pindolol and propranolol. Br J Clin Pharmacol 1982; 13: 217S–22S

    Article  PubMed  CAS  Google Scholar 

  101. Ishizaki T, Hirayama H, Tawara K, et al. Pharmacokinetics and pharmacodynamics in young normal and elderly hypertensive subjects: a study using sotalol as a model drug. J Pharmacol Exp Ther 1980; 212: 173–81

    PubMed  CAS  Google Scholar 

  102. Briant RH, Dorrington RE, Ferry DG, et al. Bioavailability of metoprolol in young adults and the elderly, with additional studies on the effects of metoclopramide and probanthine. Eur J Clin Pharmacol 1983; 25: 353–6

    Article  PubMed  CAS  Google Scholar 

  103. Kendall MJ, Quarterman CP. The effect of age on the pharmacokinetics of oxprenolol. Int J Clin Pharmacol Ther Toxicol 1982; 20: 101–4

    PubMed  CAS  Google Scholar 

  104. Quarterman CP, Kendall MJ, Jack DB. The effect of age on the pharmacokinetics of metoprolol and its metabolites. Br J Clin Pharmacol 1981; 11: 287–94

    Article  PubMed  CAS  Google Scholar 

  105. Morgan T, Anderson A, Cripps J, et al. Pharmacokinetics of carvedilol in older and younger patients. J Hum Hypertens 1990; 4: 709–15

    PubMed  CAS  Google Scholar 

  106. Abernethy DR, Schwartz JB, Plachetka JR, et al. Comparison in young and elderly patients of pharmacodynamics and disposition of labetalol in systemic hypertension. Am J Cardiol 1987; 60: 697–702

    Article  PubMed  CAS  Google Scholar 

  107. Rocci Jr ML, Vlasses PH, Cressman MD, et al. Pharmacokinetics and pharmacodynamics of labetalol in elderly and young hypertensive patients following single and multiple doses. Pharmacotherapy 1990; 10: 92–9

    PubMed  Google Scholar 

  108. Lalonde RL, Tenero DM, Burlew BS, et al. Effects of age on the protein binding and disposition of propranolol stereoisomers. Clin Pharmacol Ther 1990; 47: 447–55

    Article  PubMed  CAS  Google Scholar 

  109. Zhou HH, Whelan E, Wood AJ. Lack of effect of ageing on the stereochemical disposition of propranolol. Br J Clin Pharmacol 1992; 33: 121–3

    Article  PubMed  CAS  Google Scholar 

  110. Scott M, Castleden CM, Adam HK, et al. The effect of ageing on the disposition of nifedipine and atenolol. Br J Clin Pharmacol 1988; 25: 289–96

    Article  PubMed  CAS  Google Scholar 

  111. Buell JC, Eliot RS, Plachetka JR, et al. Hemodynamic effects of labetalol in young and older adult hypertensives. J Clin Pharmacol 1988; 28: 327–31

    PubMed  CAS  Google Scholar 

  112. Tenero DM, Bottorff MB, Burlew BS, et al. Altered beta-adrenergic sensitivity and protein binding to 1-propranolol in the elderly. J Cardiovasc Pharmacol 1990; 16: 702–7

    Article  PubMed  CAS  Google Scholar 

  113. Colangelo PM, Blouin RA, Steinmetz JE, et al. Age and beta-adrenergic receptor sensitivity to S(−)- and R,S(+/−)-propra-nolol in humans. Clin Pharmacol Ther 1992; 51: 549–54

    Article  PubMed  CAS  Google Scholar 

  114. European Society of Hypertension-European Society of Cardiology guidelines for the management of arterial hypertension. J Hypertens 2003; 21: 1011–1053

    Article  Google Scholar 

  115. Packer M, Coats AJ, Fowler MB, et al. Effect of carvedilol on survival in severe chronic heart failure. N Engl J Med 2001; 344: 1651–8

    Article  PubMed  CAS  Google Scholar 

  116. Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF). Lancet 1999; 353: 2001–7

    Google Scholar 

  117. Deedwania PC, Gottlieb S, Ghali JK, et al. Efficacy, safety and tolerability of beta-adrenergic blockade with metoprolol CR/XL in elderly patients with heart failure. Eur Heart J 2004; 25: 1300–9

    Article  PubMed  CAS  Google Scholar 

  118. Elliott HL, Meredith PA, Reid JL, et al. A comparison of the disposition of single oral doses of amlodipine in young and elderly subjects. J Cardiovasc Pharmacol 1988; 12Suppl. 7: S64–6

    Article  PubMed  CAS  Google Scholar 

  119. Abernethy DR. An overview of the pharmacokinetics and pharmacodynamics of amlodipine in elderly persons with systemic hypertension. Am J Cardiol 1994; 73: 10A–7A

    Article  PubMed  CAS  Google Scholar 

  120. Landahl S, Edgar B, Gabrielsson M, et al. Pharmacokinetics and blood pressure effects of felodipine in elderly hypertensive patients: a comparison with young healthy subjects. Clin Pharmacokinet 1988; 14: 374–83

    Article  PubMed  CAS  Google Scholar 

  121. Robertson DR, Waller DG, Renwick AG, et al. Age-related changes in the pharmacokinetics and pharmacodynamics of nifedipine. Br J Clin Pharmacol 1988; 25: 297–305

    Article  PubMed  CAS  Google Scholar 

  122. Abernethy DR, Montamat SC. Acute and chronic studies of diltiazem in elderly versus young hypertensive patients. Am J Cardiol 1987; 60: 1161–201

    Article  Google Scholar 

  123. Montamat SC, Abernethy DR. Calcium antagonists in geriatric patients: diltiazem in elderly persons with hypertension. Clin Pharmacol Ther 1989; 45: 682–91

    Article  PubMed  CAS  Google Scholar 

  124. Bianchetti G, Billy S, Ascalone V, et al. Multicenter studies on the pharmacokinetic profile of sustained-release oral diltiazem (300 mg) after once a day repeated administration: influence of age. Int J Clin Pharmacol Ther 1996; 34: 195–201

    PubMed  CAS  Google Scholar 

  125. Schwartz JB. Aging alters verapamil elimination and dynamics: single dose and steady-state responses. J Pharmacol Exp Ther 1990; 255: 364–73

    PubMed  CAS  Google Scholar 

  126. Schwartz JB, Capili H, Daugherty J. Aging of women alters S-verapamil pharmacokinetics and pharmacodynamics. Clin Pharmacol Ther 1994; 55: 509–17

    Article  PubMed  CAS  Google Scholar 

  127. Gupta SK, Atkinson L, Tu T, et al. Age and gender related changes in stereoselective pharmacokinetics and pharmacodynamics of verapamil and norverapamil. Br J Clin Pharmacol 1995; 40: 325–31

    Article  PubMed  CAS  Google Scholar 

  128. Sasaki M, Tateishi T, Ebihara A. The effects of age and gender on the stereoselective pharmacokinetics of verapamil. Clin Pharmacol Ther 1993; 54: 278–85

    Article  PubMed  CAS  Google Scholar 

  129. Carosella L, Menichelli P, Alimenti M, et al. Verapamil disposition and cardiovascular effects in elderly patients after single intravenous and oral doses. Cardiovasc Drugs Ther 1989; 3: 417–25

    Article  PubMed  CAS  Google Scholar 

  130. Ahmed JH, Meredith PA, Elliott HL. The influence of age on the pharmacokinetics of verapamil. Pharmacol Res 1991; 24: 227–33

    Article  PubMed  CAS  Google Scholar 

  131. Kloner RA, Sowers JR, DiBona GF, et al. Sex- and age-related antihypertensive effects of amlodipine. The Amlodipine Cardiovascular Community Trial Study Group. Am J Cardiol 1996; 77: 713–22

    Article  PubMed  CAS  Google Scholar 

  132. Kuwajima I, Suzuki Y, Shimosawa T, et al. Effect of nifedipine tablets on ambulatory blood pressure in patients aged less than 60 and greater than 65 years with systemic hypertension. Am J Cardiol 1991; 68: 1351–6

    Article  PubMed  CAS  Google Scholar 

  133. Grossman E, Messerli FH. Calcium antagonists. Prog Cardiovasc Dis 2004; 47: 34–57

    Article  PubMed  CAS  Google Scholar 

  134. Lees KR, Reid JL. Age and the pharmacokinetics and pharmacodynamics of chronic enalapril treatment. Clin Pharmacol Ther 1987; 41: 597–602

    Article  PubMed  CAS  Google Scholar 

  135. Lees KR, Green ST, Reid JL. Influence of age on the pharmacokinetics and pharmacodynamics of perindopril. Clin Pharmacol Ther 1988; 44: 418–25

    Article  PubMed  CAS  Google Scholar 

  136. MacDonald NJ, Sioufi A, Howie CA, et al. The effects of age on the pharmacokinetics and pharmacodynamics of single oral doses of benazepril and enalapril. Br J Clin Pharmacol 1993; 36: 205–9

    Article  PubMed  CAS  Google Scholar 

  137. Hockings N, Ajayi AA, Reid JL. Age and the pharmacokinetics of angiotensin converting enzyme inhibitors enalapril and enalaprilat. Br J Clin Pharmacol 1986; 21: 341–8

    Article  PubMed  CAS  Google Scholar 

  138. Gautam PC, Vargas E, Lye M. Pharmacokinetics of lisinopril (MK521) in healthy young and elderly subjects and in elderly patients with cardiac failure. J Pharm Pharmacol 1987; 39: 929–31

    Article  PubMed  CAS  Google Scholar 

  139. Meyer BH, Muller FO, Badian M, et al. Pharmacokinetics of ramipril in the elderly. Am J Cardiol 1987; 59: 33D–7D

    Article  PubMed  CAS  Google Scholar 

  140. Arner P, Wade A, Engfeldt P, et al. Pharmacokinetics and pharmacodynamics of trandolapril after repeated administration of 2 mg to young and elderly patients with mild-to-moderate hypertension. J Cardiovasc Pharmacol 1994; 23Suppl. 4: S44–9

    PubMed  Google Scholar 

  141. Cummings DM, Amadio Jr P, Taylor Jr EJ, et al. The antihypertensive response to lisinopril: the effect of age in a predominantly black population. J Clin Pharmacol 1989; 29: 25–32

    PubMed  CAS  Google Scholar 

  142. Saalbach R, Wochnik G, Mauersberger H, et al. Antihypertensive efficacy, tolerance, and safety of ramipril in young vs old patients: a retrospective study. J Cardiovasc Pharmacol 1991; 18Suppl. 2: S134–6

    PubMed  Google Scholar 

  143. Bertrand ME. Provision of cardiovascular protection by ACE inhibitors: a review of recent trials. Curr Med Res Opin 2004; 20: 1559–69

    Article  PubMed  CAS  Google Scholar 

  144. Dahlof B, Pennert K, Hansson L. Regression of left ventricular hypertrophy: a meta-analysis. Clin Exp Hypertens A 1992; 14: 173–80

    Article  PubMed  CAS  Google Scholar 

  145. 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 

  146. 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 

  147. Fox KM. Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: randomised, double-blind, placebo-controlled, multicentre trial (the EUROPA study). Lancet 2003; 362: 782–8

    Article  PubMed  CAS  Google Scholar 

  148. Wing LM, Reid CM, Ryan P, et al. A comparison of outcomes with angiotensin-converting-enzyme inhibitors and diuretics for hypertension in the elderly. N Engl J Med 2003; 348: 583–92

    Article  PubMed  CAS  Google Scholar 

  149. Reid JL, Macfadyen RJ, Squire IB, et al. Blood pressure response to the first dose of angiotensin-converting enzyme inhibitors in congestive heart failure. Am J Cardiol 1993; 71: 57E–60E

    Article  PubMed  CAS  Google Scholar 

  150. Ahmed A. Use of angiotensin-converting enzyme inhibitors in patients with heart failure and renal insufficiency: how concerned should we be by the rise in serum creatinine? J Am Geriatr Soc 2002; 50: 1297–300

    Article  PubMed  Google Scholar 

  151. Loboz KK, Shenfield GM. Drug combinations and impaired renal function: the ‘triple whammy’. Br J Clin Pharmacol 2005; 59: 239–43

    Article  PubMed  CAS  Google Scholar 

  152. Bicket DP. Using ACE inhibitors appropriately. Am Fam Physician 2002; 66: 461–8

    PubMed  Google Scholar 

  153. Packer M, Poole-Wilson PA, et al. Comparative effects of low and high doses of the angiotensin-converting enzyme inhibitor, lisinopril, on morbidity and mortality in chronic heart failure: ATLAS Study Group. Circulation 1999; 100: 2312–8

    Article  PubMed  CAS  Google Scholar 

  154. Massie BM, Armstrong PW, Cleland JG, et al. Toleration of high doses of angiotensin-converting enzyme inhibitors in patients with chronic heart failure: results from the ATLAS trial. The Assessment of Treatment with Lisinopril and Survival. Arch Intern Med 2001; 161: 165–71

    Article  PubMed  CAS  Google Scholar 

  155. Manyemba J, Mangoni AA, Pettingale KW, et al. Determinants of failure to prescribe target doses of angiotensin-converting enzyme inhibitors for heart failure. Eur J Heart Fail 2003; 5: 693–6

    Article  PubMed  CAS  Google Scholar 

  156. 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 

  157. 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 

  158. Vachharajani NN, Shyu WC, Smith RA. The effect of age on the pharmacokinetics of irbesartan [abstract]. J Clin Pharmacol 1997; 37: 872

    Google Scholar 

  159. 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 

  160. Meier P, Maillard M, Burnier M. The future of angiotensin II inhibition in cardiovascular medicine. Curr Drug Targets Cardiovasc Haematol Disord 2005; 5: 15–30

    Article  PubMed  CAS  Google Scholar 

  161. Burnier M. Angiotensin II type 1 receptor blockers. Circulation 2001; 103: 904–12

    Article  PubMed  CAS  Google Scholar 

  162. 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 

  163. 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 

  164. Lee VC, Rhew DC, Dylan M, et al. Meta-analysis: angiotensinreceptor blockers in chronic heart failure and high-risk acute myocardial infarction. Ann Intern Med 2004; 141: 693–704

    PubMed  CAS  Google Scholar 

  165. Cohn JN, Tognoni G. A randomized trial of the angiotensinreceptor blocker valsartan in chronic heart failure. N Engl J Med 2001; 345: 1667–75

    Article  PubMed  CAS  Google Scholar 

  166. Baruch L, Glazer RD, Aknay N, et al. Morbidity, mortality, physiologic and functional parameters in elderly and non-elderly patients in the Valsartan Heart Failure Trial (Val-HeFT). Am Heart J 2004; 148: 951–7

    Article  PubMed  Google Scholar 

  167. 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 

  168. 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 

  169. 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 

  170. 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 

  171. 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 

  172. 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 

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

    Article  PubMed  CAS  Google Scholar 

  174. 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 

  175. Sica DA. The practical aspects of combination therapy with angiotensin receptor blockers and angiotensin-converting enzyme inhibitors. J Renin Angiotensin Aldosterone Syst 2002; 3: 66–71

    Article  PubMed  CAS  Google Scholar 

  176. Jacobsen P, Parving HH. Beneficial impact on cardiovascular risk factors by dual blockade of the renin-angiotensin system in diabetic nephropathy. Kidney Int Suppl 2004; 92: S108–10

    Article  PubMed  CAS  Google Scholar 

  177. Doulton TW, He FJ, MacGregor GA. Systematic review of combined angiotensin-converting enzyme inhibition and angiotensin receptor blockade in hypertension. Hypertension 2005; 45: 880–6

    Article  PubMed  CAS  Google Scholar 

  178. 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 

  179. Roberto P, Vitaliano B, Donatella P, et al. Disopyramide pharmacokinetics in the elderly after single oral administration. Pharmacol Res Commun 1988; 20: 1025–34

    Article  PubMed  CAS  Google Scholar 

  180. Bonde J, Pedersen LE, Bodtker S, et al. The influence of age and smoking on the elimination of disopyramide. Br J Clin Pharmacol 1985; 20: 453–8

    Article  PubMed  CAS  Google Scholar 

  181. Cusack B, Kelly JG, Lavan J, et al. Pharmacokinetics of lignocaine in the elderly [proceedings]. Br J Clin Pharmacol 1980; 9: 293P–4P

    Article  PubMed  CAS  Google Scholar 

  182. Ochs HR, Greenblatt DJ, Woo E, et al. Reduced quinidine clearance in elderly persons. Am J Cardiol 1978; 42: 481–5

    Article  PubMed  CAS  Google Scholar 

  183. Nation RL, Triggs EJ, Selig M. Lignocaine kinetics in cardiac patients and aged subjects. Br J Clin Pharmacol 1977; 4: 439–48

    Article  PubMed  CAS  Google Scholar 

  184. Grech-Belanger O, Barbeau G, Kishka P, et al. Pharmacokinetics of mexiletine in the elderly. J Clin Pharmacol 1989; 29: 311–5

    PubMed  CAS  Google Scholar 

  185. el Allaf D, Carlier J, Dresse A. Effects of age on the pharmacokinetics of mexiletine. Int J Clin Pharmacol Res 1986; 6: 303–7

    PubMed  Google Scholar 

  186. White M, Leenen FH. Effects of age on cardiovascular responses to adrenaline in man. Br J Clin Pharmacol 1997; 43: 407–14

    Article  PubMed  CAS  Google Scholar 

  187. Rashid MU, Bateman DN. Effect of intravenous atropine on gastric emptying, paracetamol absorption, salivary flow and heart rate in young and fit elderly volunteers. Br J Clin Pharmacol 1990; 30: 25–34

    Article  PubMed  CAS  Google Scholar 

  188. van Brummelen P, Buhler FR, Kiowski W, et al. Age-related decrease in cardiac and peripheral vascular responsiveness to isoprenaline: studies in normal subjects. Clin Sci (Lond) 1981; 60: 571–7

    Google Scholar 

  189. White M, Fourney A, Leenen FH. Age, hypertension, and cardiac responses to beta-agonist in humans. Clin Pharmacol Ther 1998; 63: 663–71

    Article  PubMed  CAS  Google Scholar 

  190. Klein C, Hiatt WR, Gerber JG, et al. Age does not alter human vascular and nonvascular beta 2-adrenergic responses to isoproterenol. Clin Pharmacol Ther 1988; 44: 573–8

    Article  PubMed  CAS  Google Scholar 

  191. Fang MC, Stafford RS, Ruskin JN, et al. National trends in antiarrhythmic and antithrombotic medication use in atrial fibrillation. Arch Intern Med 2004; 164: 55–60

    Article  PubMed  Google Scholar 

  192. Wellens HJ. Cardiac arrhythmias: the quest for a cure: a historical perspective. J Am Coll Cardiol 2004; 44: 1155–63

    PubMed  Google Scholar 

  193. Smith NL, Chan JD, Rea TD, et al. Time trends in the use of beta-blockers and other pharmacotherapies in older adults with congestive heart failure. Am Heart J 2004; 148: 710–7

    Article  PubMed  Google Scholar 

  194. Rathore SS, Curtis JP, Wang Y, et al. Association of serum digoxin concentration and outcomes in patients with heart failure. JAMA 2003; 289: 871–8

    Article  PubMed  CAS  Google Scholar 

  195. Martin PD, Dane AL, Nwose OM, et al. No effect of age or gender on the pharmacokinetics of rosuvastatin: a new HMG-CoA reductase inhibitor. J Clin Pharmacol 2002; 42: 1116–21

    Article  PubMed  CAS  Google Scholar 

  196. Gibson DM, Bron NJ, Richens A, et al. Effect of age and gender on pharmacokinetics of atorvastatin in humans. J Clin Pharmacol 1996; 36: 242–6

    PubMed  CAS  Google Scholar 

  197. Cheng H, Rogers JD, Sweany AE, et al. Influence of age and gender on the plasma profiles of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitory activity following multiple doses of lovastatin and simvastatin. Pharm Res 1992; 9: 1629–33

    Article  PubMed  CAS  Google Scholar 

  198. Miettinen TA, Pyorala K, Olsson AG, et al. Cholesterol-lowering therapy in women and elderly patients with myocardial infarction or angina pectoris: findings from the Scandinavian Simvastatin Survival Study (4S). Circulation 1997; 96: 4211–8

    Article  PubMed  CAS  Google Scholar 

  199. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994; 344: 1383–9

  200. Sacks FM, Pfeffer MA, Moye LA, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial Investigators. N Engl J Med 1996; 335: 1001–9

    Article  PubMed  CAS  Google Scholar 

  201. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels: the Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. N Engl J Med 1998; 339: 1349–57

  202. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002; 360: 7–22

    Google Scholar 

  203. Shepherd J, Blauw GJ, Murphy MB, et al. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet 2002; 360: 1623–30

    Article  PubMed  CAS  Google Scholar 

  204. Roberts MS, Rumble RH, Wanwimolruk S, et al. Pharmacokinetics of aspirin and salicylate in elderly subjects and in patients with alcoholic liver disease. Eur J Clin Pharmacol 1983; 25: 253–61

    Article  PubMed  CAS  Google Scholar 

  205. Ho PC, Triggs EJ, Bourne DW, et al. The effects of age and sex on the disposition of acetylsalicylic acid and its metabolites. Br J Clin Pharmacol 1985; 19: 675–84

    Article  PubMed  CAS  Google Scholar 

  206. Cuny G, Royer RJ, Mur JM, et al. Pharmacokinetics of salicylates in elderly. Gerontology 1979; 25: 49–55

    Article  PubMed  CAS  Google Scholar 

  207. Denninger MH, Necciari J, Serre-Lacroix E, et al. Clopidogrel antiplatelet activity is independent of age and presence of atherosclerosis. Semin Thromb Hemost 1999; 25Suppl. 2: 41–5

    PubMed  CAS  Google Scholar 

  208. Shah J, Teitelbaum P, Molony B, et al. Single and multiple dose pharmacokinetics of ticlopidine in young and elderly subjects. Br J Clin Pharmacol 1991; 32: 761–4

    PubMed  CAS  Google Scholar 

  209. Shepherd AM, Hewick DS, Moreland TA, et al. Age as a determinant of sensitivity to warfarin. Br J Clin Pharmacol 1977; 4: 315–20

    Article  PubMed  CAS  Google Scholar 

  210. Barrett JS, Gibiansky E, Hull RD, et al. Population pharmacodynamics in patients receiving tinzaparin for the prevention and treatment of deep vein thrombosis. Int J Clin Pharmacol Ther 2001; 39: 431–46

    PubMed  CAS  Google Scholar 

  211. Modi NB, Fox NL, Clow FW, et al. Pharmacokinetics and pharmacodynamics of tenecteplase: results from a phase II study in patients with acute myocardial infarction. J Clin Pharmacol 2000; 40: 508–15

    Article  PubMed  CAS  Google Scholar 

  212. Siguret V, Pautas E, Fevrier M, et al. Elderly patients treated with tinzaparin (Innohep) administered once daily (175 anti-Xa IU/kg): anti-Xa and anti-IIa activities over 10 days. Thromb Haemost 2000; 84: 800–4

    PubMed  CAS  Google Scholar 

  213. Garcia Rodriguez LA, Hernandez-Diaz S. Risk of uncomplicated peptic ulcer among users of aspirin and nonaspirin nonsteroidal antiinflammatory drugs. Am J Epidemiol 2004; 159: 23–31

    Article  PubMed  Google Scholar 

  214. Guslandi M, Pellegrini A, Sorghi M. Gastric mucosal defences in the elderly. Gerontology 1999; 45: 206–8

    Article  PubMed  CAS  Google Scholar 

  215. Pilotto A, Franceschi M, Leandro G, et al. Proton-pump inhibitors reduce the risk of uncomplicated peptic ulcer in elderly either acute or chronic users of aspirin/non-steroidal antiinflammatory drugs. Aliment Pharmacol Ther 2004; 20: 1091–7

    Article  PubMed  CAS  Google Scholar 

  216. Mehta SR, Yusuf S, Peters RJ, et al. Effects of pretreatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary intervention: the PCI-CURE study. Lancet 2001; 358: 527–33

    Article  PubMed  CAS  Google Scholar 

  217. Yusuf S, Zhao F, Mehta SR, et al. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med 2001; 345: 494–502

    Article  PubMed  CAS  Google Scholar 

  218. Sabatine MS, Cannon CP, Gibson CM, et al. Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial infarction with ST-segment elevation. N Engl J Med 2005; 352: 1179–89

    Article  PubMed  CAS  Google Scholar 

  219. Pineo GF, Hull RD. Low-molecular-weight heparin for the treatment of venous thromboembolism in the elderly. Clin Appl Thromb Hemost 2005; 11: 15–23

    Article  PubMed  CAS  Google Scholar 

  220. Haas S. The present and future of heparin, low molecular weight heparins, pentasaccharide, and hirudin for venous thromboembolism and acute coronary syndromes. Semin Vasc Med 2003; 3: 139–46

    Article  PubMed  Google Scholar 

  221. Saigo M, Hsue PY, Waters DD. Role of thrombotic and fibrinolytic factors in acute coronary syndromes. Prog Cardiovasc Dis 2004; 46: 524–38

    Article  PubMed  CAS  Google Scholar 

  222. Cohen N, Almoznino-Sarafian D, Alon I, et al. Warfarin for stroke prevention still underused in atrial fibrillation: patterns of omission. Stroke 2000; 31: 1217–22

    Article  PubMed  CAS  Google Scholar 

  223. Fuster V, Ryden LE, Asinger RW, et al. ACC/AHA/ESC guidelines for the management of patients with atrial fibrillation: executive summary. A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines and Policy Conferences (Committee to Develop Guidelines for the Management of Patients With Atrial Fibrillation): developed in collaboration with the North American Society of Pacing and Electrophysiology. J Am Coll Cardiol 2001; 38: 1231–66

    Article  PubMed  CAS  Google Scholar 

  224. Australian Institute of Health and Welfare (AIHW). Australian Population Patterns and Implications: AIHW Cat. No. DIS-19. Canberra (ACT): Australian Institute of Health and Welfare, 2000: 1–7

    Google Scholar 

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    Arduino A. Mangoni

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Mangoni, A.A. Cardiovascular Drug Therapy in Elderly Patients. Drugs Aging 22, 913–941 (2005). https://doi.org/10.2165/00002512-200522110-00003

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