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Management of Primary Hypertension

The Potential Role of Losartan

  • Drugs in Disease Management
  • Published:
Disease Management & Health Outcomes

Summary

Hypertension is a major independent risk factor for cardiovascular events and death. Moreover, it generally occurs in conjunction with other cardiovascular risk factors (e.g. dyslipidaemia, diabetes, obesity, left ventricular hypertrophy) which greatly increase the overall risk of adverse cardiovascular outcomes.

Diet and lifestyle modifications are recommended for all patients with hypertension; however, most will also require pharmacological therapy. To date, only diuretic- and β-blocker-based regimens have been shown to reduce cardiovascular morbidity and mortality in long term outcome studies; therefore, these agents are the preferred first-line drugs in patients with hypertension according to most expert committee guidelines. Newer agents (i.e. ACE inhibitors, calcium antagonists, α1-blockers) show antihypertensive efficacy equivalent to diuretics and β-blockers, but long term outcome data are not yet available for the newer drugs. The newer drugs also appear to have important roles in the treatment of hypertensive patients with concomitant disorders (e.g. ACE inhibitors in patients with congestive heart failure).

Losartan (losartan potassium) is the first angiotensin II antagonist available for clinical use. It has been shown to be as effective as the well established agents atenolol, enalapril, amlodipine and long-acting formulations of felodipine and nifedipine in reducing blood pressure in patients with hypertension. It has additive effects when used in combination with hydrochlorothiazide. Losartan has been well tolerated in clinical trials to date and, in contrast with ACE inhibitors, does not cause cough. However, the results of ongoing long term studies, as well as studies in special patient populations, are needed to clarify the role of losartan in the management of hypertension. Pending these results, losartan should have the same positioning as ACE inhibitors, calcium antagonists and α1-blockers in most management protocols for hypertension, i.e., as an alternative first-line agent to diuretics and β-blockers and for patients who are not adequately managed with, or who are intolerant of, their current therapy. It is likely that losartan will find a particular niche in patients unable to tolerate ACE inhibitors because of persistent cough.

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References

  1. Goa KL, Wagstaff AJ. Losartan potassium: a review of its pharmacology, clinical efficacy and tolerability in the management of hypertension. Drugs 1996 May; 51: 820–45

    Article  PubMed  CAS  Google Scholar 

  2. Joint National Committee on Detection Evaluation and Treatment of High Blood Pressure. The Fifth Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC V). Arch Intern Med 1993 Jan 25; 153: 154–83

    Article  Google Scholar 

  3. Guidelines Sub-Committee. 1993 Guidelines for the management of mild hypertension: memorandum from a World Health Organization/International Society of Hypertension meeting. J Hypertens 1993; 11: 905–18

    Article  Google Scholar 

  4. Ogilvie RI, Burgess ED, Cusson JR, et al. Report of the Canadian Hypertension Society Consensus Conference: 3. Pharmacological treatment of essential hypertension. Can Med Assoc J 1993; 149: 575–84

    CAS  Google Scholar 

  5. Sever P, Beevers G, Bulpitt C, et al. Management guidelines in essential hypertension: report of the second working party of the British Hypertension Society. BMJ 1993 Apr 10; 306: 983–7

    Article  PubMed  CAS  Google Scholar 

  6. Jackson R, Barham P, Bills J, et al. Management of raised blood pressure in New Zealand: a discussion document. BMJ 1993 Jul 10; 307: 107–10

    Article  PubMed  CAS  Google Scholar 

  7. Australian Consensus Panel. The management of hypertension: a consensus statement. Med J Aust 1994; 160 Suppl.: S1–S16

    Google Scholar 

  8. Kannel WB. Blood pressure as a cardiovascular risk factor: prevention and treatment. JAMA 1996 May 22–29; 275: 1571–6

    Article  PubMed  CAS  Google Scholar 

  9. Pyörälä K, De Backer G, Graham I, et al. Prevention of coronary heart disease in clinical practice: recommendations of the Task Force of the European Society of Cardiology, European Atherosclerosis Society and European Society of Hypertension. Atherosclerosis 1994 Oct; 110: 121–61

    Article  PubMed  Google Scholar 

  10. Burt VL, Cutler JA, Higgins M, et al. Trends in the prevalence, awareness, treatment, and control of hypertension in the adult US population. Data from the health examination surveys, 1960 to 1991. Hypertension 1995; 26: 60–9

    Article  PubMed  CAS  Google Scholar 

  11. Kaplan NM. Systemic hypertension: mechanisms and diagnosis. In: Braunwald E, editor. Heart disease: a textbook of cardiovascular medicine. 4th ed. Vol. 1. Philadelphia: W.B. Saunders, 1992: 817–48

    Google Scholar 

  12. Reaven GM. Insulin resistance and compensatory hyperinsulinemia: role in hypertension, dyslipidemia and coronary heart disease. Am Heart J 1991; 121: 1283–8

    Article  PubMed  CAS  Google Scholar 

  13. Timmermans PB, Wong PC, Chiu AT, et al. Angiotensin II receptors and angiotensin II receptor antagonists. Pharmacol Rev 1993 Jun; 45: 205–51

    PubMed  CAS  Google Scholar 

  14. Cody RJ. The clinical potential of renin inhibitors and angiotensin antagonists. Drugs 1994 Apr; 47: 586–98

    Article  PubMed  CAS  Google Scholar 

  15. Sytkowski PA, D’Agostino RB, Belanger AJ, et al. Secular trends in long-term sustained hypertension, long-term treatment, and cardiovascular mortality. The Framingham Heart Study 1950 to 1990. Circulation 1996 Feb 15; 93: 697–703

    Article  PubMed  CAS  Google Scholar 

  16. Johannesson M, Jonsson B. A review of cost effectiveness analyses of hypertension treatment. Pharmacoeconomics 1992; 1: 250–64

    Article  PubMed  CAS  Google Scholar 

  17. Kannel WB. Hypertension as a risk factor for cardiac events-epidemiologic results of long-term studies. J Cardiovasc Pharmacol 1993; 21Suppl. 2: S27–37

    Article  PubMed  Google Scholar 

  18. Hanes DS, Weir MR, Sowers JR. Gender considerations in hypertension pathophysiology and treatment. Am J Med 1996 Sep 30; 101Suppl. 3A: 10S–21S

    Article  PubMed  CAS  Google Scholar 

  19. Ford ES, Cooper RS. Risk factors for hypertension in a national cohort study. Hypertension 1991; 18: 598–606

    Article  PubMed  CAS  Google Scholar 

  20. MacMahon S, Peto R, Cutler J, et al. Blood pressure, stroke, and coronary heart disease. Part 1, prolonged differences in blood pressure: prospective observational studies corrected for the regression dilution bias. Lancet 1990; 335: 765–74

    Article  PubMed  CAS  Google Scholar 

  21. Levy D, Larson MG, Vasan RS, et al. The progression from hypertension to congestive heart failure. JAMA 1996; 275(20): 1557–62

    Article  PubMed  CAS  Google Scholar 

  22. Stamler J, Stamler R, Neaton J. Blood pressure, systolic and diastolic, and cardiovascular risks. US population data. Arch Intern Med 1993; 153: 598–615

    Article  PubMed  CAS  Google Scholar 

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

    Article  Google Scholar 

  24. American Heart Association. Heart and stroke facts. Dallas: American Heart Association, 1994

    Google Scholar 

  25. Elliot WJ. The costs of treating hypertension. What are the long-term realities of cost containment and pharmacoeconomics? Postgrad Med 1996; 99: 241–52

    Google Scholar 

  26. Nissinen A, Tuomilehto J, Kottke E, et al. Cost-effectiveness of the North Karelia Hypertension Program 1972–1977. Med Care 1986; 24: 767–80

    Article  PubMed  CAS  Google Scholar 

  27. Kawachi I, Malcolm LA. The cost-effectiveness of treating mild-to-moderate hypertension: a reappraisal. J Hypertens 1991 Mar; 9: 199–208

    Article  PubMed  CAS  Google Scholar 

  28. Fletcher A. Economics of hypertension control: a statement by the World Hypertension League. J Hum Hypertens 1994 Oct; 8: 789–95

    PubMed  CAS  Google Scholar 

  29. Fletcher A. Cost effective analyses in the treatment of high blood pressure. J Hum Hypertens 1992 Dec; 6: 437–45

    PubMed  CAS  Google Scholar 

  30. Johannesson M. The cost effectiveness of hypertension treatment in Sweden. Pharmacoeconomics 1995; 7(3): 242–50

    Article  PubMed  CAS  Google Scholar 

  31. Hilleman DE, Mohiuddin SM, Lucas Jr BD, et al. Cost-minimization analysis of initial antihypertensive therapy in patients with mild-to-moderate essential diastolic hypertension. Clin Ther 1994 Jan–Feb; 16: 88–102 (discussion 87)

    PubMed  CAS  Google Scholar 

  32. McVeigh GE, Flack J, Grimm R. Goals of antihypertensive therapy. Drugs 1995 Feb; 49: 161–75

    Article  PubMed  CAS  Google Scholar 

  33. Chalmers J. Treatment guidelines in hypertension: current limitations and future solutions. J Hypertens 1996; 14Suppl. 4: S3–8

    Article  CAS  Google Scholar 

  34. Krakoff LR. Ambulatory blood pressure monitoring can improve cost-effective management of hypertension. Am J Hypertens 1993 Jun; 6 (6 Pt 2): 220S–4S

    PubMed  CAS  Google Scholar 

  35. Zanchetti A, Chalmers J, Arakawa K, et al. Summary of 1993 World Health Organisation-International Society of Hypertension guidelines for the management of mild hypertension. BMJ 1993 Dec 11; 307: 1541–6

    Article  Google Scholar 

  36. Rudd P. Clinicians and patients with hypertension: unsettled issues about compliance. Am Heart J 1995 Sep; 130 (3 Pt 1): 572–9

    Article  PubMed  CAS  Google Scholar 

  37. Girvin B, Johnston GD. The implications of noncompliance with antihypertensive medication. Drugs 1996 Aug; 52: 186–95

    Article  PubMed  CAS  Google Scholar 

  38. Ramsay LE, Yeo WW, Chadwick IG, et al. Non-pharmacological management of hypertension. Neth J Med 1993; 43: S44–51

    PubMed  Google Scholar 

  39. Kaplan NM, Gifford Jr RW. Choice of initial therapy for hypertension. JAMA 1996 May 22–29; 275: 1577–80

    Article  PubMed  CAS  Google Scholar 

  40. Freis ED, Papademetriou V. Current drug treatment and treatment patterns with antihypertensive drugs. Drugs 1996 Jul; 52: 1–16

    Article  PubMed  CAS  Google Scholar 

  41. Mogensen CE. Angiotensin converting enzyme inhibitors and diabetic nephropathy: their effects on proteinuria may be independent of their effects on blood pressure. BMJ 1992; 304: 327–8

    Article  PubMed  CAS  Google Scholar 

  42. Lewis EJ, Hunsicker HG, Bain RP, et al. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. N Engl J Med 1993; 329: 1456–62

    Article  PubMed  CAS  Google Scholar 

  43. Donnelly R. Angiotensin-Converting enzyme inhibitors and insulin sensitivity: metabolic effects in hypertension, diabetes and heart failure. J Cardiovasc Pharmacol 1992; 20Suppl. 11: S38–44

    Article  PubMed  Google Scholar 

  44. Dahlöf B, Pennert K, Hansson L. Reversal of left ventricular hypertrophy in hypertensive patients: a meta-analysis of 109 treatment studies. Am J Hypertens 1992; 5: 95–110

    PubMed  Google Scholar 

  45. Leonetti G, Cuspidi C. Choosing the right ACE inhibitor: a guide to selection. Drugs 1995 Apr; 49: 516–35

    Article  PubMed  CAS  Google Scholar 

  46. Collins R, Peto R, MacMahon S, et al. Blood pressure, stroke, and coronary heart disease. Pt 2, short-term reductions in blood pressure: overview of randomised drug trials in their epidemiological context. Lancet 1990; 335: 827–38

    Article  PubMed  CAS  Google Scholar 

  47. Dahlöf 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  Google Scholar 

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

    Article  Google Scholar 

  49. Neutel JM, Black HR, Weber MA. Combination therapy with diuretics: an evolution of understanding. Am J Med 1996 Sep 30; 101Suppl. 3A: 61S–70S

    Article  PubMed  CAS  Google Scholar 

  50. Neutel JM. Metabolic manifestations of low-dose diuretics. Am J Med 1996 Sep 30; 101Suppl. 3A: 71S–82S

    Article  PubMed  CAS  Google Scholar 

  51. Moser M. Management of hypertension, Parti [see comments]. Am Fam Physician 1996 May 15; 53: 2295–302

    PubMed  CAS  Google Scholar 

  52. Karlberg BE. Cough and inhibition of the renin-angiotensin system. J Hypertens Suppl 1993 Apr; 11: S49–52

    Article  PubMed  CAS  Google Scholar 

  53. Lacourcière Y, Lefebvre J. Modulation of the renin-angiotensin-aldosterone system and cough. Can J Cardiol 1995 Aug; 11Suppl. F: 33F–9F

    PubMed  Google Scholar 

  54. Fletcher AE, Palmer AJ, Bulpitt CJ. Cough with angiotensin converting enzyme inhibitors: how much of a problem? J Hypertens 1994; 12Suppl. 2: S43–7

    CAS  Google Scholar 

  55. Epstein M. Calcium antagonists should continue to be used for first-line treatment of hypertension [see comments]. Arch Intern Med 1995 Nov 13; 155: 2150–6

    Article  PubMed  CAS  Google Scholar 

  56. Furberg CD, Psaty BM. Should dihydropyridines be used as first-line drugs in the treatment of hypertension? The con side [see comments]. Arch Intern Med 1995 Nov 13; 155: 2157–61

    Article  PubMed  CAS  Google Scholar 

  57. Hoes AW, Grobbee DE, Lubsen J, et al. Diuretics, β-blockers, and the risk of sudden cardiac death in hypertensive patients. Ann Intern Med 1995; 123: 481–7

    PubMed  CAS  Google Scholar 

  58. Siscovick DS, Raghunathan TE, Psaty BM, et al. Diuretic therapy for hypertension and the risk of primary cardiac arrest. N Engl J Med 1994; 330: 1852–7

    Article  PubMed  CAS  Google Scholar 

  59. Multiple Risk Factor Intervention Trial Research Group. Exercise electrocardiogram and coronary heart disease mortality in the Multiple Risk Factor Intervention Trial. Am J Cardiol 1985; 55: 16–24

    Article  Google Scholar 

  60. Insua JT, Sacks HS, Tai-Shing L, et al. Drug treatment of hypertension in the elderly: a meta-analysis. Ann Intern Med 1994; 121: 355–62

    PubMed  CAS  Google Scholar 

  61. MacMahon S, Cutler JA, Furberg CD, et al. The effects of drug treatment for hypertension on morbidity and mortality from cardiovascular disease: a review of randomized controlled trials. Prog Cardiovasc Dis 1986; 29Suppl. 1: 99–118

    Article  PubMed  CAS  Google Scholar 

  62. Lenfant C. High blood pressure. Some answers, new questions and continuing challenges [editorial]. JAMA 1996; 275(90): 1604–6

    Article  PubMed  CAS  Google Scholar 

  63. Robertson JIS. Guidelines for the treatment of hypertension: a critical review. Cardiovasc Drugs Ther 1994 Aug; 8: 665–72 (discussion 673–5)

    Article  PubMed  CAS  Google Scholar 

  64. Gavras H, Gavras I. On the JNC V report. A different point of view [editorial]. Am J Hypertens 1994 Mar; 7: 288–93

    PubMed  CAS  Google Scholar 

  65. Neaton JD, Grimm Jr RH. Treatment of mild hypertension study. Final results. JAMA 1993; 270: 713–24

    Article  PubMed  CAS  Google Scholar 

  66. Materson BJ, Reda DJ, Cushman WC, et al. Single-drug therapy for hypertension in men: a comparison of six anti-hypertensive agents with placebo. N Engl J Med 1993; 328: 914–21

    Article  PubMed  CAS  Google Scholar 

  67. Francis CK. Hypertension, cardiac disease, and compliance in minority patients. Am J Med 1991; 91Suppl. 1A: 29S–36S

    Article  PubMed  CAS  Google Scholar 

  68. Neaton JD, Grimm Jr RH, Prineas RJ, et al. Treatment of mild hypertension study (TOMHS): final results. JAMA 1993; 270: 713–24

    Article  PubMed  CAS  Google Scholar 

  69. Psaty BM, Smith NL, Siscovick DS, et al. Health outcomes associated with antihypertensive therapies used as first-line agents. A systematic review and meta-analysis. JAMA 1997 Mar 5; 277(9): 739–45

    Article  PubMed  CAS  Google Scholar 

  70. Psaty BM, Heckbert SR, Koepsell TD, et al. The risk of myocardial infarction associated with antihypertensive drug therapy. JAMA 1995; 274: 620–5

    Article  PubMed  CAS  Google Scholar 

  71. Pahor M, Guralnik JM, Corti M-C, et al. Long-term survival and use of antihypertensive medications in older persons. J Am Geriatr Soc 1995; 43: 1191–7

    PubMed  CAS  Google Scholar 

  72. Furberg C, Psaty B, Meyer JV. Nifedipine: dose-related increase in mortality in patients with coronary heart disease. Circulation 1995; 92: 1326–31

    Article  PubMed  CAS  Google Scholar 

  73. Timmermans PBMWM, Wong PC, Chiu AT, et al. The preclinical basis of the therapeutic evaluation of losartan. J Hypertens 1995 Jul; 13Suppl. 1: 1–13

    Article  Google Scholar 

  74. Schaefer KL, Porter JA. Angiotensin II receptor antagonists: the prototype losartan. Ann Pharmacother 1996 Jun; 30: 625–36

    PubMed  CAS  Google Scholar 

  75. Anonymous. Losartan prescribing information, Merck & Co., Inc., Wilmington, USA

  76. Anonymous. Losartan prescribing information. Merck Sharp & Dohme Limited, Hoddesdon, UK

  77. Smith RD, Sweet CS, Goldberg A, et al. Losartan potassium (Cozaar™): a nonpeptide antagonist of angiotensin II. Drugs Today 1996; 32Suppl. F: 1–42

    CAS  Google Scholar 

  78. Tikkanen I, Omvik P, Jensen HAE, et al. Comparison of the angiotensin II antagonist losartan with the angiotensin converting enzyme inhibitor enalapril in patients with essential hypertension. Hypertension 1995; 13: 1343–51

    Article  CAS  Google Scholar 

  79. Dahlöf B, Keller SE, Makris L, et al. Efficacy and tolerability of losartan potassium and atenolol in patients with mild to moderate essential hypertension. Am J Hypertens 1995; 8: 578–83

    Article  PubMed  Google Scholar 

  80. Chan JCN, Critchley JAJH, Lappe JT, et al. Randomised, double-blind, parallel study of the anti-hypertensive efficacy and safety of losartan potassium compared with felodipine ER in elderly patients with mild to moderate hypertension. J Hum Hypertens 1995; 9: 765–71

    PubMed  CAS  Google Scholar 

  81. Oparil S, Barr E, Elkins M, et al. Efficacy, tolerability, and effects on quality of life of losartan, alone or with hydrochlorothiazide, versus amlodipine, alone or with hydrochlorothiazide, in patients with essential hypertension. Clin Ther 1996 Jul–Aug; 18: 608–25

    Article  PubMed  CAS  Google Scholar 

  82. Weir MR, Elkins M, Liss C, et al. Efficacy, tolerability, and quality of life of losartan, alone or with hydrochlorothiazide, versus nifedipine GITS in patients with essential hypertension. Clin Ther 1996 May–Jun; 18: 411–28

    Article  PubMed  CAS  Google Scholar 

  83. Soffer BA, Wright Jr JT, Pratt JH, et al. Effects of losartan on a background of hydrochlorothiazide in patients with hypertension. Hypertension 1995; 26(1): 112–7

    Article  PubMed  CAS  Google Scholar 

  84. Himmelmann A, Svensson A, Dahlöf B, et al. Atenolol versus losartan in hypertension — focus on left ventricular morphology [abstract]. J Hypertens 1994; 12Suppl. 3: S98

    Google Scholar 

  85. Dahlöf B, Devereux R, de Faire U, et al. Losartan intervention for endpoint reduction in hypertension (The LIFE Study) [abstract]. Am J Hypertens 1996; 9 (Pt 2): 26A

    Article  Google Scholar 

  86. 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 Mar 15; 349: 747–52

    Article  PubMed  CAS  Google Scholar 

  87. Moan A, Hhieggen A, Seljeflot I, et al. The effect of angiotensin II receptor antagonism with losartan on glucose metabolism and insulin sensitivity. J Hypertens 1996; 14: 1093–7

    Article  PubMed  CAS  Google Scholar 

  88. Goldberg AI, Dunlay MC, Sweet CS. Safety and tolerability of losartan potassium, an angiotensin II receptor antagonist, compared with hydrochlorothiazide, atenolol, felodipine ER, and angiontensin-converting enzyme inhibitors for the treatment of systemic hypertension. Am J Cardiol 1995; 75: 793–5

    Article  PubMed  CAS  Google Scholar 

  89. Edelman JM, Gazdick LP, Epstein RS, et al. Trial of Usual Care for Hypertension (TOUCH): an effectiveness study of newly treated hypertension comparing losartan potassium and usual care in a managed care setting [abstract]. Am J Hypertens 1995 Apr; 8 (Pt 2): 79A

    Article  Google Scholar 

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    Rick Davis & Paul Benfield

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Various sections of the manuscript reviewed by: B. Dahlöf, Department of Medicine, University of Göteborg, Gothenburg, Sweden; G.E. McVeigh, Division of General and Preventative Medicine, University of Minnesota, Minneapolis, Minnesota, USA; L.E. Ramsay, Department of Medicine and Pharmacology, Royal Hallamshire Hospital, Sheffield, England; E.B. Kubenstein, Department of Internal Medicine, University of Texas, Houston, Texas, USA; J.D. Swales, Department of Health, London, England; J.A. Whitworth, Professor of Medicine, University of New South Wales, Kogarah, New South Wales, Australia

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Davis, R., Benfield, P. Management of Primary Hypertension. Dis Manage Health Outcomes 1, 210–222 (1997). https://doi.org/10.2165/00115677-199701040-00004

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