Skip to main content
SpringerLink
Log in

Monotherapy versus Combination Therapy as First Line Treatment of Uncomplicated Arterial Hypertension

  • Review Article
  • Published:
Drugs Aims and scope Submit manuscript

Abstract

Mild to moderate hypertension still remains poorly controlled. This relates to multiple factors including low antihypertensive efficacy of single drug therapies, reluctance of primary care physicians to modify/titrate initially chosen therapy to obtain target blood pressure, and poor compliance with medication. Several guidelines for the treatment of high blood pressure now include combination therapy with low doses of 2 drugs as one of the strategies for the initial management of mild/moderate arterial hypertension. Evidence discussed in this article points to superior control of blood pressure by combinations of low doses of 2 drugs as compared with monotherapy in regular doses. This superior effectiveness of combined therapy relates to a better antihypertensive efficacy and higher response rates in the low range of doses as the result of complementary mechanisms of antihypertensive effects, better tolerance as a result of a lower rate of adverse effects in the low dose range, improved compliance from better tolerance and simple drug regimen, and lower cost. Whether increased use of fixed low dose combination therapies would translate to better control of arterial hypertension in the population and thereby further reduction of cardiovascular/cerebrovascular morbidity and mortality caused by hypertension remains to be assessed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Table I

Similar content being viewed by others

References

  1. WHO/ISH Hypertension Guidelines Subcommittee. 1999 WHO-ISH guidelines for the management of hypertension. J Hypertens 1999; 17: 151–83

    Google Scholar 

  2. The sixth report of The Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure. Arch Intern Med 1997; 157: 2413–46

    Article  Google Scholar 

  3. Feldman RD, Campbell N, Larochelle P, et al. 1999 Canadian recommendation for the management of hypertension. CMAJ 1999; 161: S1–7

    PubMed  Google Scholar 

  4. Chockalingam A, Fodor JG. Treatment of raised blood pressure in the population: the Canadian experience. Am J Hypertens 1998; 11: 747–9

    Article  PubMed  CAS  Google Scholar 

  5. Burt VL, Whelton P, Roccella EJ. Prevalence of hypertension in the US adult population. Results from the Third National Health and Nutrition Examination Survey, 1988–1991. Hypertension 1995; 25: 305–13

    Article  PubMed  CAS  Google Scholar 

  6. Coca A. Actual blood pressure control: are we doing things right? J Hypertens 1998; 16: S45–51

    Article  CAS  Google Scholar 

  7. Mancia G, Sega R, Milesi C, et al. Blood pressure control in the hypertensive population. Lancet 1997; 349: 454–7

    Article  PubMed  CAS  Google Scholar 

  8. Colhoun HM, Dong W, Poulter NR. Blood pressure screening, management and control in England: results from the health survey for England 1994. J Hypertens 1998; 16: 747–52

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  10. Philipp T, Anlauf M, Distler A, et al. Randomized, double blind, multicentre comparison of hydrochlorothiazide, atenolol, nitrendipine, and enalapril in antihypertensive treatment: results of the HANE Trial Research Group. BMJ 1997; 315: 154–9

    Article  PubMed  CAS  Google Scholar 

  11. Brown MJ, Castaigne A, de Leeuw PW, et al. Influence of diabetes and type of hypertension on response to antihypertensive treatment. Hypertension 2000; 35: 1038–42

    Article  PubMed  CAS  Google Scholar 

  12. Dickerson JEC, Hingorani AD, Ashby MJ, et al. Optimisation of antihypertensive treatment by crossover rotation of four major classes. Lancet 1999; 353: 2008–13

    Article  PubMed  CAS  Google Scholar 

  13. Attwood S, Bird R, Burch K, et al. Within-patient correlation between the antihypertensive effects of atenolol, lisinopril, and nifedipine. J Hypertens 1994; 12: 1053–60

    Article  PubMed  CAS  Google Scholar 

  14. Van Hoogdalem P, Donker AJM, Leenen FHH. Angiotensin II blockade before and after marked sodium depletion in patients with hypertension. Clin Sci Mol Med 1978; 54: 75–83

    PubMed  Google Scholar 

  15. Frishman WH, Bryzinski BS, Coulson LR, et al. A multifactorial trial design to assess combination therapy in hypertension. Treatment with bisoprolol and hydrochlorothiazide. Arch Intern Med 1994; 154: 1461–8

    Article  PubMed  CAS  Google Scholar 

  16. Chrysant SG, The Lisinopril-Hydrochlorothiazide Group. Antihypertensive effectiveness of low-dose lisinopril-hydrochlorothiazide combination. Arch Intern Med 1994; 154: 737–43

    Article  PubMed  CAS  Google Scholar 

  17. MacKay JH, Arcuri KE, Goldberg AI, et al. Losartan and low-dose hydrochlorothiazide in patients with essential hypertension. Arch Intern Med 1996; 156: 278–85

    Article  PubMed  CAS  Google Scholar 

  18. Myers MG, Asmar R, Leenen FHH, et al. Fixed low-dose combination therapy in hypertension — a dose response study of. perindopril and indapamide. J Hypertens 2000; 18: 317–25

    Article  PubMed  CAS  Google Scholar 

  19. Chalmers J, Castaigne A, Morgan T, et al. Long-term efficacy of a new, fixed, very-low-dose angiotensin-converting enzyme-inhibitor/diuretic combination as first-line therapy in elderly hypertensive patients. J Hypertens 2000; 18: 327–37

    Article  PubMed  CAS  Google Scholar 

  20. Myers MG. A dose-response study of perindopril in hypertension: effects on blood pressure 6 and 24 hours after dosing. Can J Cardiol 1996; 12: 1191–6

    PubMed  CAS  Google Scholar 

  21. Chanudet X, de Champvallins M. Antihypertensive efficacy and tolerability of low-dose perindopril plus indapamide compared with losartan in the treatment of essential hypertension. Int J Clin Pract 2001 May; 55(4): 233–9

    PubMed  CAS  Google Scholar 

  22. Berlowitz DR, Ash AS, Hickey EC, et al. Inadequate management of blood pressure in a hypertensive population. N Engl J Med 1998; 339: 1957–63

    Article  PubMed  CAS  Google Scholar 

  23. Hanson L, Zanchetti A. The Hypertension Optimal Treatment (HOT) Study: randomization, risk profiles and early blood pressure results. Blood Press 1994; 3: 322–7

    Article  Google Scholar 

  24. Caro JJ, Salas M, Speckman JL, et al. Persistence with treatment for hypertension in actual practice. CMAJ 1999; 160: 31–7

    PubMed  CAS  Google Scholar 

  25. Myers MG. Compliance in hypertension: why don’t patients take their pills? CMAJ 1999; 160: 64–5

    PubMed  CAS  Google Scholar 

  26. Fagan TC. Remembering the lessons of basic pharmacology. Arch Intern Med 1994; 154: 1430–1

    Article  PubMed  CAS  Google Scholar 

  27. Franse LV, Pahor M, Di Bari M, et al. Hypokalemia associated with diuretic use and cardiovascular events in the Systolic Hypertension in the Elderly Program. Hypertension 2000; 35: 1025–30

    Article  PubMed  CAS  Google Scholar 

  28. Carlsen J, Kober L, Torp-Pedersen C, et al. Relation between dose of bendofluazide, antihypertensive effect, and adverse biochemical effects. BMJ 1990; 300: 975–8

    Article  PubMed  CAS  Google Scholar 

  29. Jounela AJ, Lilja M, Lumme J, et al. Relation between low dose hydrochlorothiazide, antihypertensive effect and adverse effects. Blood Press 1994; 3: 231–5

    Article  PubMed  CAS  Google Scholar 

  30. Haria M, Plosker GL, Markham A. Felodipine/Metoprolol: a review of the fixed dose controlled release formulation in the management of essential hypertension. Drugs 2000; 59: 141–57

    Article  PubMed  CAS  Google Scholar 

  31. Leenen FHH for the Canadian Felodipine Study Group. Antihypertensive efficacy of the calcium-antagonist felodipine in patients with persisting hypertension on beta-adrenoreceptor blocker therapy. Br J Clin Pharmacol 1988; 26: 535–45

    Article  Google Scholar 

  32. Kloner RA, Vetrovec GW, Materson BJ, et al. Safety of long-acting dihydropyridine calcium channel blockers in hypertensive patients. Am J Cardiol 1998; 81: 163–9

    Article  PubMed  CAS  Google Scholar 

  33. Weinberger MH. Blood pressure and metabolic response to hydrochlorothiazide, captopril and the combination in black and white mild to moderate hypertensive patients. J Cardiovasc Pharmacol 1985; 7: S52–5

    Article  PubMed  Google Scholar 

  34. Holland OB, Kuhnert L, Campbell WB, et al. Synergistic effect of captopril with hydrochlorothiazide for the treatment of low-renin hypertensive black patients. Hypertension 1983; 4: 235–9

    Article  Google Scholar 

  35. Bakris GL, Wilson DM, Burnett Jr JC. The renal, forearm and humoral responses to standing in the presence and absence of propranolol. Circulation 1988; 74: 1061–5

    Article  Google Scholar 

  36. Frishman W, Silverman R. Clinical pharmacology of the new beta-adrenergic blocking drugs part 2: physiologic and metabolic effects. Am Heart J 1979; 97: 797–807

    Article  PubMed  CAS  Google Scholar 

  37. Garrett BN, Kaplan NM. Plasma renin activity suppression: duration after withdrawal from β-adrenergic blockade. Arch Intern Med 1980; 140: 1316–8

    Article  PubMed  CAS  Google Scholar 

  38. Chrysant SG, Chappel C, Farnham DJ, et al. Antihypertensive and metabolic effects of single and combined atenolol regimens. J Clin Pharmacol 1992; 32: 61–5

    PubMed  CAS  Google Scholar 

  39. Prisant LM, Weir MR, Papademetriou V, et al. Low-dose combination therapy: an alternative first-line approach to hypertension treatment. Am Heart J 1995; 130: 359–66

    Article  PubMed  CAS  Google Scholar 

  40. Neutel JM, Rolf CN, Valentine SN, et al. Low-dose combination therapy as first line treatment of mild to moderate hypertension: the efficacy and safety of bisoprolol/HCTZ versus amlodipine, enalapril, and placebo. Cardiovasc Rev Rep 1996; 17: 1–9

    Google Scholar 

  41. Fenichel RC, Lipicky RJ. Combination products as first-line pharmacotherapy. Arch Intern Med 1994; 154: 1429–30

    Article  PubMed  CAS  Google Scholar 

  42. Zusman RM. Effects of converting enzyme inhibitors on the renin-angiotensin, aldosterone, bradykinin, and arachidonic acid-prostaglandin systems: correlation of chemical structure and biologic activity. Am J Kidney Dis 1987; 10: S13–23

    Google Scholar 

  43. Lund-Johansen P, Omvik P. Central hemodynamic changes of calcium antagonists at rest and during exercise in essential hypertension. J Cardiovasc Pharmacol 1987; 10: S139–48

    Article  PubMed  Google Scholar 

  44. Redgrave JE, Rabinowe SL, Hollenberg NK, et al. Correction of abnormal renal blood flow response to angiotensin II by converting enzyme inhibition. J Clin Invest 1985; 75: 1285–90

    Article  PubMed  CAS  Google Scholar 

  45. Romero JC, Raij L, Granger JP, et al. Multiple effects of calcium entry blockers on renal function in hypertension. Hypertension 1987; 10: 140–51

    Article  PubMed  CAS  Google Scholar 

  46. Frishman WH, Ram VS, McMahon FG, et al. Comparison of amlodipine and benazepril monotherapy to amlodipine plus benazepril in patients with systemic hypertension: a randomized, double-blind, placebo-controlled, parallel-group study. J Clin Pharmacol 1995; 35: 1060–6

    PubMed  CAS  Google Scholar 

  47. Cappuccio FP, Markandu ND, Singer DRJ, et al. Amlodipine and lisinopril in combination for the treatment of essential hypertension: efficacy and predictors of response. J Hypertens 1993; 11: 839–48

    Article  PubMed  CAS  Google Scholar 

  48. Morgan T, Anderson A, Hopper J. Enalapril and nifedipine in essential hypertension: synergism of the hypotensive effects in combination. Clin Exp Hypertens 1988; 10: 719–89

    Google Scholar 

  49. De Quattro V, Lee D, The Trandolapril Study Group. Fixed-dose combination therapy with trandolapril and verapamil SR is effective in primary hypertension. Am J Hypertens 1997; 10: 138S–45S

    Article  Google Scholar 

  50. Dahlof B, Hosie J. Antihypertensive efficacy and tolerability of a fixed combination of metoprolol and felodipine in comparison with the individual substances in monotherapy. The Swedish/United Kingdom Study Group. J Cardiovasc Pharmacol 1990; 16: 910–6

    Article  PubMed  CAS  Google Scholar 

  51. Dahlof B, Jonsson L, Borgholst O, et al. Improved antihypertensive efficacy of the felodipine-metoprolol extended-release tablet compared with each drug alone. Blood Press 1993; 1: 37–45

    CAS  Google Scholar 

  52. Waeber B, Detry JM, Dahlof B, et al. Felodipine-metoprolol combination tablet: a valuable option to initiate antihypertensive therapy? Am J Hypertens 1999; 12: 915–20

    Article  PubMed  CAS  Google Scholar 

  53. Hoffman J. Comparison of a felodipine-metoprolol combination tablet vs each component alone as antihypertensive therapy. The German Multicentre Study Group. Blood Press 1993; 1: 30–6

    Google Scholar 

  54. Smith DH, Neutel JM, Jankelow D, et al. A comparative study of atenolol, nifedipine and their combination in the treatment of hypertension. S Afr Med J 1991; 79: 12–5

    PubMed  CAS  Google Scholar 

  55. Anderton JL, Vallance BD, Stanley NN, et al. Atenolol and sustained release nifedipine alone and in combination in hypertension. A randomised, double-blind, crossover study. Drugs 1988; 35 Suppl. 4: S22–6

    Article  Google Scholar 

  56. Mancia G, Omboni S, Grassi G. Combination treatment in hypertension. The VeraTran Study. Am J Hypertens 1997; 10 (7 Pt 2): 153S–8S

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Internal Medicine, University of Ottawa, Ottawa, Ontario, Canada

    Marcel Ruzicka

  2. Hypertension Unit, Department of Cardiology, University of Ottawa Heart Institute, Room H360, 1053 Carling Avenue, Ottawa, Ontario, K1Y 4W7, Canada

    Frans H. H. Leenen (Director)

Authors
  1. Marcel Ruzicka
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Frans H. H. Leenen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Frans H. H. Leenen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ruzicka, M., Leenen, F.H.H. Monotherapy versus Combination Therapy as First Line Treatment of Uncomplicated Arterial Hypertension. Drugs 61, 943–954 (2001). https://doi.org/10.2165/00003495-200161070-00004

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003495-200161070-00004

Keywords

Search

Navigation