Skip to main content
SpringerLink
Log in

Fixed-Dose Combinations as Initial Therapy for Hypertension

A Review of Approved Agents and a Guide to Patient Selection

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

Abstract

Recent guidelines recommend initiation of antihypertensive therapy with fixed-dose combinations in high-risk patients because such patients usually need two or more blood pressure (BP)-lowering agents in order to normalize their BP. Agents that block the renin-angiotensin system (ACE inhibitors or angiotensin II receptor antagonists [angiotensin receptor blockers; ARBs]) are preferred for the management of hypertension in most patients exhibiting subclinical target organ damage, or established cardiovascular or renal diseases. Unless contraindicated they should be one of the components of fixed-dose combinations, whereas the other component may be either a calcium channel antagonist or a thiazide diuretic. Fixed-dose combinations containing an ACE inhibitor or ARB plus a calcium channel antagonist appear particularly effective in preventing complications of coronary heart disease.

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
Table I
Fig. 3
Fig. 4
Table II
Table III
Table IV
Table V

Similar content being viewed by others

References

  1. Ezzati M, Lopez AD, Rodgers A, et al. Selected major risk factors and global and regional burden of disease. Lancet 2002; 360: 1347–60

    Article  PubMed  Google Scholar 

  2. Kearney PM, Whelton M, Reynolds K, et al. Global burden of hypertension: analysis of worldwide data. Lancet 2005; 365: 217–23

    PubMed  Google Scholar 

  3. 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 

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

    Article  PubMed  Google Scholar 

  5. Turnbull F, Neal B, Algert C, et al. Effects of different blood pressure-lowering regimens on major cardiovascular events in individuals with and without diabetes mellitus: results of prospectively designed overviews of randomized trials. Arch Intern Med 2005; 165: 1410–9

    Article  PubMed  Google Scholar 

  6. Turnbull F, Neal B, Ninomiya T, et al. Effects of different regimens to lower blood pressure on major cardiovascular events in older and younger adults: meta-analysis of randomised trials. BMJ 2008; 336: 1121–3

    Article  PubMed  CAS  Google Scholar 

  7. 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 

  8. Mancia G, De Backer G, Dominiczak A, et al. 2007 Guidelines for the Management of Arterial Hypertension: the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens 2007; 25: 1105–87

    Article  PubMed  CAS  Google Scholar 

  9. Brunner HR, Menard J, Waeber B, et al. Treating the individual hypertensive patient: considerations on dose, sequential monotherapy and drug combinations. J Hypertens 1990; 8: 3–11

    Article  PubMed  CAS  Google Scholar 

  10. Zanchetti A. Angiotensin converting enzyme inhibition in clinical practice: a re-examination of stepped-care: a retrospective and a prospective. J Cardiovasc Pharmacol 1985; 7 Suppl. 1: S126–31

    Article  PubMed  Google Scholar 

  11. Marques-Vidal P, Tuomilehto J. Hypertension awareness, treatment and control in the community: is the ‘rule of halves’ still valid? J Hum Hypertens 1997; 11: 213–20

    Article  PubMed  CAS  Google Scholar 

  12. Wolf-Maier K, Cooper RS, Kramer H, et al. Hypertension treatment and control in five European countries, Canada, and the United States. Hypertension 2004; 43: 10–7

    Article  PubMed  CAS  Google Scholar 

  13. Wang YR, Alexander GC, Stafford RS. Outpatient hypertension treatment, treatment intensification, and control in Western Europe and the United States. Arch Intern Med 2007; 167: 141–7

    Article  PubMed  Google Scholar 

  14. Mancia G, Pessina AC, Trimarco B, et al. Blood pressure control according to new guidelines targets in low- to high-risk hypertensives managed in specialist practice. J Hypertens 2004; 22: 2387–96

    Article  PubMed  CAS  Google Scholar 

  15. Banegas JR, Segura J, Ruilope LM, et al. Blood pressure control and physician management of hypertension in hospital hypertension units in Spain. Hypertension 2004; 43: 1338–44

    Article  PubMed  CAS  Google Scholar 

  16. Amar J, Vaur L, Perret M, et al. Hypertension in high-risk patients: beware of the under use of effective combination therapy (results of the PRATIK study). J Hypertens 2002; 20: 779–84

    Article  PubMed  Google Scholar 

  17. Ruzicka M, Leenen FH. Monotherapy versus combination therapy as first line treatment of uncomplicated arterial hypertension. Drugs 2001; 61: 943–54

    Article  PubMed  CAS  Google Scholar 

  18. White WB. Improving blood pressure control and clinical outcomes through initial use of combination therapy in stage 2 hypertension. Blood Press Monit 2008; 13: 123–9

    Article  PubMed  Google Scholar 

  19. Struijker-Boudier HA, Ambrosioni E, Holzgreve H, et al. The need for combination antihypertensive therapy to reach target blood pressures: what has been learned from clinical practice and morbidity-mortality trials? Int J Clin Pract 2007; 61: 1592–602

    Article  PubMed  CAS  Google Scholar 

  20. Rosenthal T, Gavras I. Fixed-drug combinations as first-line treatment for hypertension. Prog Cardiovasc Dis 2006; 48: 416–25

    Article  PubMed  CAS  Google Scholar 

  21. Waeber B. Treatment strategy to control blood pressure optimally in hypertensive patients. Blood Press 2001; 10: 62–73

    Article  PubMed  CAS  Google Scholar 

  22. Bangalore S, Kamalakkannan G, Parkar S, et al. Fixed-dose combinations improve medication compliance: a meta-analysis. Am J Med 2007; 120: 713–9

    Article  PubMed  Google Scholar 

  23. Messerli FH, Williams B, Ritz E. Essential hypertension. Lancet 2007; 370: 591–603

    Article  PubMed  CAS  Google Scholar 

  24. Dickerson CJE, 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 

  25. Law MR, Wald NJ, Morris JK, et al. Value of low dose combination treatment with blood pressure lowering drugs: analysis of 354 randomised trials. BMJ 2003; 326: 1427–31

    Article  PubMed  CAS  Google Scholar 

  26. 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 

  27. Dahlöf B, Sever PS, Poulter NR, et al. Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a multicentre randomised controlled trial. Lancet 2005; 366: 895–906

    Article  PubMed  CAS  Google Scholar 

  28. Yusuf S, Teo KK, Pogue J, et al. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med 2008; 358: 1547–59

    Article  PubMed  CAS  Google Scholar 

  29. Pepine CJ, Handberg EM, Cooper-DeHoff RM, et al. A calcium antagonist vs a non-calcium antagonist hypertension treatment strategy for patients with coronary artery disease. The International Verapamil-Trandolapril Study (INVEST): a randomized controlled trial. JAMA 2003; 290: 2805–16

    CAS  Google Scholar 

  30. 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. JAMA 2002; 288: 2977–81

    Google Scholar 

  31. Dahlöf B, Devereux RB, Kjeldsen SE, et al. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet 2002; 359: 995–1003

    Article  PubMed  Google Scholar 

  32. Cushman WC, Ford CE, Cutler JA, et al. Success and predictors of blood pressure control in diverse North American settings: the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT). J Clin Hypertens 2000; 4: 393–404

    Google Scholar 

  33. Mancia G, Messerli F, Bakris G, et al. Blood pressure control and improved cardiovascular outcomes in the International Verapamil SR-Trandolapril Study. Hypertension 2007; 50: 299–305

    Article  PubMed  CAS  Google Scholar 

  34. Fagard RH, Van den Enden M, Leeman M, et al. Survey on treatment of hypertension and implementation of World Health Organization/International Society of Hypertension risk stratification in primary care in Belgium. J Hypertens 2002; 20: 1297–302

    Article  PubMed  CAS  Google Scholar 

  35. Van der Niepen P, Giot C, van de Borne P. Prevalence of isolated uncontrolled systolic blood pressure among treated hypertensive patients in primary care in Belgium: results of the I-inSYST survey. J Hypertens 2008; 26: 2057–63

    Article  PubMed  CAS  Google Scholar 

  36. Roux O, Chapellier M, Czernichow S, et al. Determinants of hypertension control in a large French population of treated hypertensive subjects. Blood Press 2006; 15: 6–13

    Article  PubMed  Google Scholar 

  37. Steckelings UM, Stoppelhaar M, Sharma AM, et al. HYDRA: possible determinants of unsatisfactory hypertension control in German primary care patients. Blood Press 2004; 13: 80–8

    Article  PubMed  Google Scholar 

  38. Mancia G, Ambrosioni E, Rosei EA, et al. Blood pressure control and risk of stroke in untreated and treated hypertensive patients screened from clinical practice: results of the ForLife study. J Hypertens 2005; 23: 1575–81

    Article  PubMed  CAS  Google Scholar 

  39. Kjeldsen SE, Naditch-Brule L, Perlini S, et al. Increased prevalence of metabolic syndrome in uncontrolled hypertension across Europe: the global cardiometabolic risk profile in patients with hypertension disease survey. J Hypertens 2008; 26: 2064–70

    Article  PubMed  CAS  Google Scholar 

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

    Article  Google Scholar 

  41. Moser M. Diuretics should continue to be one of the preferred initial therapies in the management of hypertension: the argument for. J Clin Hypertens 2005; 7: 111–6

    Article  CAS  Google Scholar 

  42. Sever P. New hypertension guidelines from the National Institute for Health and Clinical Excellence and the British Hypertension Society. J Renin Angiotens Aldoster Sys 2006; 7: 61–3

    Article  Google Scholar 

  43. Lithell HO. Effect of antihypertensive drugs on insulin, glucose, and lipid metabolism. Diabetes Care 1991; 14: 203–9

    Article  PubMed  CAS  Google Scholar 

  44. Perez-Stable E, Caralis PV. Thiazide-induced disturbances in carbohydrate, lipid, and potassium metabolism. Am Heart J 1983; 106: 245–51

    Article  PubMed  CAS  Google Scholar 

  45. Brown MJ, Palmer CR, Castaigne A, et al. Morbidity and mortality in patients randomised to double-blind treatment with a long-acting calcium-channel blocker or diuretic in the International Nifedipine GITS study: Intervention as a Goal in Hypertension Treatment (INSIGHT). Lancet 2000; 356: 366–72

    Article  PubMed  CAS  Google Scholar 

  46. Berglund G, Andersson O. Hydrochlorothiazide and spironolactone alone and in a fixed combination in hypertension. Curr Ther Res 1980; 27: 360–4

    Google Scholar 

  47. Bradley HA, Wiysonge CS, Volmink JA, et al. How strong is the evidence for use of beta-blockers as first-line therapy for hypertension? Systematic review and meta-analysis. J Hypertens 2006; 24: 2131–41

    Article  PubMed  CAS  Google Scholar 

  48. Lindholm LH, Carlberg B, Samuelsson O. Should beta blockers remain first choice in the treatment of primary hypertension? A meta-analysis. Lancet 2005; 366: 1545–53

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  50. Mancia G, Grassi G, Zanchetti A. New-onset diabetes and antihypertensive drugs. J Hypertens 2006; 24: 3–10

    Article  PubMed  CAS  Google Scholar 

  51. Williams B, Lacy PS, Thom SM, et al. Differential impact of blood pressure-lowering drugs on central aortic pressure and clinical outcomes: principal results of the Conduit Artery Function Evaluation (CAFE) study. Circulation 2006; 113: 1213–25

    Article  PubMed  CAS  Google Scholar 

  52. Pedersen ME, Cockcroft JR. The latest generation of beta-blockers: new pharmacologic properties. Curr Hypertens Rep 2006; 8: 279–86

    Article  PubMed  CAS  Google Scholar 

  53. Naylor WG. The potential for added benefits with beta-blockers and calcium antagonists in treating cardiovascular disorders. Drugs 1988; 35 Suppl. 4: 1–8

    Article  Google Scholar 

  54. Waeber B. Position of fixed-dose combinations containing an AT(1)-receptor blocker and a thiazide diuretic. Blood Press 2005; 14: 324–36

    Article  PubMed  CAS  Google Scholar 

  55. Waeber B. Combination therapy with ACE inhibitors/angiotensin II receptor antagonists and diuretics in hypertension. Expert Rev Cardiovasc Ther 2003; 1: 43–50

    Article  PubMed  CAS  Google Scholar 

  56. Brunner HR, Waeber B, Nussberger J. Renin secretion responsiveness: understanding the efficacy of reninangiotensin inhibition. Kidney Int 1988; 26: S80–S5

    CAS  Google Scholar 

  57. Hall D, Motoro R, Littlejohn T, et al. Efficacy and tolerability of valsartan in combination with hydrochlorothiazide in essential hypertension. Clin Drug Invest 1998; 16: 203–10

    Article  CAS  Google Scholar 

  58. MacKay JH, Arcuri KE, Goldberg AI, et al. Losartan and low-dose hydrochlorothiazide in patients with essential hypertension: a double-blind, placebo-controlled trial of concomitant administration compared with individual components. Arch Intern Med 1996; 156: 278–85

    Article  PubMed  CAS  Google Scholar 

  59. Kochar M, Guthrie R, Triscari J, et al. Matrix study of irbesartan with hydrochlorothiazide in mild-to-moderate hypertension. Am J Hypertens 1999; 12: 797–805

    Article  PubMed  CAS  Google Scholar 

  60. Weinberger MH. Blood pressure and metabolic responses to hydrochlorothiazide, captopril, and the combination in black and white mild-to-moderate hypertensive patients. J Cardiovasc Pharmacol 1985; 7: S52–S5

    Article  PubMed  Google Scholar 

  61. Malini PL, Strocchi E, Ambrosioni E, et al. Long-term antihypertensive, metabolic and cellular effects of enalapril. J Hypertens 1984; 2: S101–S5

    CAS  Google Scholar 

  62. Alderman M, Aiyer KJ. Uric acid: role in cardiovascular disease and effects of losartan. Curr Med Res Opin 2004; 20: 369–79

    Article  PubMed  CAS  Google Scholar 

  63. Johnson RJ, Kivlighn SD, Kim YG, et al. Reappraisal of the pathogenesis and consequences of hyperuricemia in hypertension, cardiovascular disease, and renal disease. Am J Kidney Dis 1999; 33: 225–34

    Article  PubMed  CAS  Google Scholar 

  64. Hoieggen A, Alderman MH, Kjeldsen SE, et al. The impact of serum uric acid on cardiovascular outcomes in the LIFE study. Kidney Int 2004; 65: 1041–9

    Article  PubMed  CAS  Google Scholar 

  65. Benz JR, Black HR, Graff A, et al. Valsartan and hydrochlorothiazide in patients with essential hypertension: a multiple dose, double-blind, placebo controlled trial comparing combination therapy with monotherapy. J Hum Hypertens 1998; 12: 861–6

    Article  PubMed  CAS  Google Scholar 

  66. McGill JB, Reilly PA. Telmisartan plus hydrochlorothiazide versus telmisartan or hydrochlorothiazide monotherapy in patients with mild to moderate hypertension: a multicenter, randomized, double-blind, placebo-controlled, parallel-group trial. Clin Ther 2001; 23: 833–50

    Article  PubMed  CAS  Google Scholar 

  67. Laurent S. Clinical benefit of very-low-dose perindopril-indapamide combination in hypertension. J Hypertens 2001; 19 Suppl. 4: S9–14

    CAS  Google Scholar 

  68. Mogensen CE, Viberti G, Halimi S, et al. Effect of low-dose perindopril/indapamide on albuminuria in diabetes. Preterax in albuminuria regression: PREMIER. Hypertension 2003; 41: 1063–71

    CAS  Google Scholar 

  69. Dahlöf B, Gosse P, Guéret P, et al. Perindopril/indapamide combination more effective than enalapril in reducing blood pressure and left ventricular mass: the PICXEL study. J Hypertens 2005; 23: 2063–70

    Article  PubMed  Google Scholar 

  70. Patel A, MacMahon S, Chalmers J, et al. Effects of fixed combination of perindopril and indapamide on microvascular outcomes in patients with type 2 diabetes mellitus (the ADVANCE trial): a randomised controlled trial. Lancet 2007; 370: 829–40

    Article  PubMed  CAS  Google Scholar 

  71. Franklin S, Lapuerta P, Cox D, et al. Initial combination therapy with irbesartan/hydrochlorothiazide for hypertension: an analysis of the relationship between baseline blood pressure and the need for combination therapy. J Clin Hypertens 2007; 9 Suppl. 5: 15–22

    Article  CAS  Google Scholar 

  72. Black HR, Levy DG, Crikelair N, et al. Predictive age- and dose-related responses to antihypertensive therapy: pooled analysis of two randomized clinical trials of valsartan alone and combined with hydrochlorothiazide. J Am Soc Hypertens 2008; 2: 476–83

    Article  PubMed  Google Scholar 

  73. Waeber B, Mourad JJ. Targeting systolic blood pressure: the key to controlling combined systolic/diastolic hypertension. Am J Hypertens 2006; 19: 985–6

    Article  PubMed  Google Scholar 

  74. Gojanovic B, Feihl F, Liaudet L, et al. Concomitant calcium entry blockade and inhibition of the renin-angiotensin system: a rational and effective means for treating hypertension. J Renin Angiotens Aldoster Sys 2008; 9: 1–9

    Article  CAS  Google Scholar 

  75. Gradman AH, Weir MR, Bakris GL. Newer combination therapies in the management of hypertension: an update. J Clin Hypertens 2008; 10: 398–405

    Article  Google Scholar 

  76. Jamerson K, Weber MA, Bakris GL, et al. Benazepril plus amlodipine or hydrochlorothiazide for hypertension in high-risk patients. N Engl J Med 2008; 359: 2417–28

    Article  PubMed  CAS  Google Scholar 

  77. Grossman E, Messerli FH. Long-term safety of antihypertensive therapy. Prog Cardiovasc Dis 2006; 49: 16–25

    Article  PubMed  CAS  Google Scholar 

  78. Luscher TF, Cosentino F. The classification of calcium antagonists and their selection in the treatment of hypertension. Drugs 1998; 55: 509–17

    Article  PubMed  CAS  Google Scholar 

  79. Grossman E, Messerli FH. Effect of calcium antagonists on plasma norepinephrine levels, heart rate, and blood pressure. Am J Cardiol 1997; 80: 1453–8

    Article  PubMed  CAS  Google Scholar 

  80. Bang LM, Chapman TM, Goa KL. Lercanidipine: a review of its efficacy in the management of hypertension. Drugs 2003; 63: 2449–72

    Article  PubMed  CAS  Google Scholar 

  81. Kuschnir E, Acuna E, Sevilla D, et al. Treatment of patients with essential hypertension: amlodipine 5 mg/benazepril 20 mg compared with amlodipine 5 mg, benazepril 20mg, and placebo. Clin Ther 1996; 18: 1213–24

    Article  PubMed  CAS  Google Scholar 

  82. Karlberg BE, Andrup M, Oden A. Efficacy and safety of a new long-acting drug combination, trandolapril/verapamil as compared to monotherapy in primary hypertension. Blood Press 2000; 9: 140–5

    Article  PubMed  CAS  Google Scholar 

  83. Messerli FH, Oparil S, Feng Z. Comparison of efficacy and side effects of combination therapy of angiotensinconverting enzyme inhibitor (benazepril) with calcium antagonist (either nifedipine or amlodipine) versus high-dose calcium antagonist monotherapy for systemic hypertension. Am J Cardiol 2000; 86: 1182–7

    Article  PubMed  CAS  Google Scholar 

  84. Pool J, Kaihlanen P, Lewis G, et al. Once-daily treatment of patients with hypertension: a placebo-controlled study of amlodipine and benazepril vs amlodipine or benazepril alone. J Hum Hypertens 2001; 15: 495–8

    Article  PubMed  CAS  Google Scholar 

  85. Jamerson KA, Nwose O, Jean-Louis L, et al. Initial angiotensin-converting enzyme inhibitor/calcium channel blocker combination therapy achieves superior blood pressure control compared with calcium channel blocker monotherapy in patients with stage 2 hypertension. Am J Hypertens 2004; 17: 495–501

    Article  PubMed  CAS  Google Scholar 

  86. Philipp T, Smith TR, Glazer R, et al. Two multicenter, 8-week, randomized, double-blind, placebo-controlled, parallel-group studies evaluating the efficacy and tolerability of amlodipine and valsartan in combination and as monotherapy in adult patients with mild to moderate essential hypertension. Clin Ther 2007; 29: 563–80

    Article  PubMed  CAS  Google Scholar 

  87. Luft FC, Aronoff GR, Sloan RS, et al. Calcium channel blockade with nitrendipine: effects on sodium home-ostasis, the renin-angiotensin system, and the sympathetic nervous system in humans. Hypertension 1985; 7: 438–42

    PubMed  CAS  Google Scholar 

  88. Gennari C, Nami R, Pavese G, et al. Calcium-channel blockade (nitrendipine) in combination with ACE inhibition (captopril) in the treatment of mild to moderate hypertension. Cardiovasc Drug Ther 1989; 3 Suppl. 1: 319–25

    Article  Google Scholar 

  89. Messerli FH. Vasodilatory edema: a common side effect of antihypertensive therapy. Curr Cardiol Reports 2002; 4: 479–82

    Article  Google Scholar 

  90. Weir MR, Rosenberger C, Fink JC. Pilot study to evaluate a water displacement technique to compare effects of diuretics and ACE inhibitors to alleviate lower extremity edema due to dihydropyridine calcium antagonists. Am J Hypertens 2001; 14: 963–8

    Article  PubMed  CAS  Google Scholar 

  91. Fogari R, Zoppi A, Derosa G, et al. Effect of valsartan addition to amlodipine on ankle oedema and subcutaneous tissue pressure in hypertensive patients. J Hum Hypertens 2007; 21: 220–4

    PubMed  CAS  Google Scholar 

  92. Bakris G, Molitch M, Hewkin A, et al. Differences in glucose tolerance between fixed-dose antihypertensive drug combinations in people with metabolic syndrome. Diabetes Care 2006; 29: 2592–7

    Article  PubMed  CAS  Google Scholar 

  93. Cooper-Dehoff R, Cohen JD, Bakris GL, et al. Predictors of development of diabetes mellitus in patients with coronary artery disease taking antihypertensive medications (findings from the INternational VErapamil SR-Trandolapril STudy [INVEST]). Am J Cardiol 2006; 98: 890–4

    Article  PubMed  CAS  Google Scholar 

  94. Abernethy DR, Schwartz JB. Calcium-antagonist drugs. N Engl J Med 1999; 341: 1447–57

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  96. Poldermans D, Glazes R, Kargiannis S, et al. Tolerability and blood pressure-lowering efficacy of the combination of amlodipine plus valsartan compared with lisinopril plus hydrochlorothiazide in adult patients with stage 2 hypertension. Clin Ther 2007; 29: 279–89

    Article  PubMed  CAS  Google Scholar 

  97. Rudd P. Clinicians and patients with hypertension: unsettled issues about compliance. Am Heart J 1995; 130: 572–89

    Article  PubMed  CAS  Google Scholar 

  98. Waeber B, Brunner HR, Metry JM. Compliance with antihypertensive treatment: implications for practice. Blood Press 1997; 6: 326–31

    Article  PubMed  CAS  Google Scholar 

  99. Maronde RF, Chan LS, Larsen FJ, et al. Underutilization of antihypertensive drugs and associated hospitalization. Med Care 1989; 27: 1159–66

    Article  PubMed  CAS  Google Scholar 

  100. McCombs JS, Nichol MB, Newman CM, et al. The costs of interrupting antihypertensive drug therapy in a Medicaid population. Med Care 1994; 32: 214–26

    Article  PubMed  CAS  Google Scholar 

  101. Monane M, Bohn RL, Gurwitz JH, et al. The effects of initial drug choice and comorbidity on antihypertensive therapy compliance: results from a population-based study in the elderly. Am J Hypertens 1997; 10: 697–704

    Article  PubMed  CAS  Google Scholar 

  102. Dezii CM. A retrospective study of persistence with single-pill combination therapy vs concurrent two-pill therapy in patients with hypertension. Manag Care 2000; 9 Suppl.: 2–6

    PubMed  CAS  Google Scholar 

  103. Taylor AA, Shoheiber O. Adherence to antihypertensive therapy with fixed-dose amlodipine besylate/benazepril HCl versus comparable component-based therapy. Congest Heart Fail 2003; 9: 324–32

    Article  PubMed  CAS  Google Scholar 

  104. Giles TD, Berk BC, Black HR, et al. Expanding the definition and classification of hypertension. J Clin Hypertens 2005; 7: 505–12

    Article  Google Scholar 

  105. Basile J, Houston M, Ferrario C. Incremental risk-factor reduction improves overall cardiovascular benefit: is it time to abandon the silos? J Clin Hypertens 2006; 8: 686–8

    Article  Google Scholar 

Download references

Acknowledgements

No sources of funding were used to assist in the preparation of this review and the authors declare that they are alone responsible for the content. Dr Waeber has received honoraria from Novartis, Servier, Abbott, Sanofi-aventis, AstraZeneca, Daiichi Sankyo and Menarini. Dr Ruilope received honoraria from Novartis, Bayer, Sanofi-aventis, Bristol-Myers Squibb, GlaxoSmithKline, Merck, Servier, Menarini, AstraZeneca, Takeda and Daiichi-Sankyo, and research grants from Novartis, Bayer, Sanofi-aventis and Daiichi-Sankyo. Dr Feihl has no conflicts of interest that are directly relevant to the content of this review.

Author information

Authors and Affiliations

  1. Division of Clinical Pathophysiology, Centre Hospitalier Universitaire Vaudois et Université de Lausanne, MP 14/204, CH-1011, Lausanne, Switzerland

    Bernard Waeber & François Feihl

  2. Hypertension Unit, Hospital 12 de Octubre, Madrid, Spain

    Luis M. Ruilope

Authors
  1. Bernard Waeber
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. François Feihl
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Luis M. Ruilope
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bernard Waeber.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Waeber, B., Feihl, F. & Ruilope, L.M. Fixed-Dose Combinations as Initial Therapy for Hypertension. Drugs 69, 1761–1776 (2009). https://doi.org/10.2165/11316710-000000000-00000

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/11316710-000000000-00000

Keywords

Search

Navigation