Skip to main content
Log in

Desirable Therapeutic Characteristics of an Optimal Antihypertensive Agent

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

Abstract

Hypertension affects 65 million people in the US, and is a major cause of morbidity and mortality, but less than one-third of patients with hypertension are treated to goal blood pressure. Multiple factors have been cited, and include suboptimal adherence to treatment and lifestyle modifications, limited access to healthcare services, and the failure of health professionals to treat hypertension aggressively. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) recommends a goal blood pressure of <140/90mm Hg for most patients and <130/80mm Hg for those with diabetes mellitus or chronic kidney disease. The ‘ideal’ antihypertensive agent would have a number of characteristics: (i) effective in lowering blood pressure to recommended goals; (ii) high efficacy as monotherapy; (iii) rapid onset of effect; (iv) convenient once-daily dose administration to maximise compliance; (v) sustained efficacy over 24 hours; (vi) response increases with higher doses (clear dose-response effect); and (vii) optimum tolerability profile. Although the ideal agent does not yet exist and will vary from patient to patient, drug development and new formulations have provided more options for clinicians and patients and certain drug classes appear to show promise because they possess many beneficial characteristics. Hypertension treatment needs to be tailored to individual patients’ age, race, socioeconomic situation, concomitant conditions and family history. Physicians and other clinical providers have an important role to play in hypertension management, particularly by combining culturally sensitive patient care with aggressive treatment. Regular follow-up that is directed at achieving goal blood pressure, while monitoring the patient for possible drug-related adverse effects, will help ensure and support adherence to treatment regimens. By supporting the integration of lifestyle changes into this plan, the clinician can further influence and have a positive impact on a patient’s overall cardiovascular profile.

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

Access this article

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

Instant access to the full article PDF.

Table I
Table II
Table III
Fig. 1
Table IV
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Sonnenschein E, Brody JA. Effect of population aging on proportionate mortality from heart disease and cancer, US 2000–2050. J Gerontol B Psychol Sci Soc Sci 2005; 60(2): S110–2

    Article  PubMed  Google Scholar 

  2. Lewington S, Clarke R, Qizilbash N, et al. Age-specific relevance of usual blood pressure to vascular mortality: a metaanalysis of individual data for one million adults in 61 prospective studies. Lancet 2002; 360(9349): 1903–13

    Article  PubMed  Google Scholar 

  3. Fields LE, Burt VL, Cutler JA, et al. The burden of adult hypertension in the United States 1999 to 2000: a rising tide. Hypertension 2004; 44(4): 398–404

    Article  PubMed  CAS  Google Scholar 

  4. Chobanian AV, Bakris GL, Black HR, et al. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA 2003; 289(19): 2560–72

    Article  PubMed  CAS  Google Scholar 

  5. Hajjar I, Kotchen TA. Trends in prevalence, awareness, treatment, and control of hypertension in the United States, 1988–2000. JAMA 2003; 290(2): 199–206

    Article  PubMed  Google Scholar 

  6. Berlowitz DR, Ash AS, Hickey EC, et al. Inadequate management of blood pressure in a hypertensive population. N Engl J Med 1998; 339(27): 1957–63

    Article  PubMed  CAS  Google Scholar 

  7. Hosie J, Wiklund I. Managing hypertension in general practice: can we do better? J Hum Hypertens 1995; 9 Suppl. 2: S15–18

    PubMed  Google Scholar 

  8. Hyman DJ, Pavlik VN. Characteristics of patients with uncontrolled hypertension in the United States. N Engl J Med 2001; 345(7): 479–86

    Article  PubMed  CAS  Google Scholar 

  9. European Society of Hypertension-European Society of Cardiology guidelines for the management of arterial hypertension. J Hypertens 2003; 21(6): 1011–53

    Article  Google Scholar 

  10. Stergiou GS, Salgami EV. New European, American and International guidelines for hypertension management: agreement and disagreement. Expert Rev Cardiovasc Ther 2004; 2(3): 359–68

    Article  PubMed  CAS  Google Scholar 

  11. JBS 2. Joint British Societies’ guidelines on prevention of cardiovascular disease in clinical practice. Heart 2005; 91 Suppl. 5: v1–52

    Article  Google Scholar 

  12. Sacks FM, Svetkey LP, Vollmer WM, et al. Effects on blood pressure of reduced dietary sodium and the Dietary Approaches to Stop Hypertension (DASH) diet. DASH-Sodium Collaborative Research Group. N Engl J Med 2001; 344(1): 3–10

    CAS  Google Scholar 

  13. Carlberg B, Samuelsson O, Lindholm LH. Atenolol in hypertension: is it a wise choice? Lancet 2004; 364(9446): 1684–9

    Article  PubMed  CAS  Google Scholar 

  14. Lindholm LH, Carlberg B, Samuelsson O. Should beta blockers remain first choice in the treatment of primary hypertension? A meta-analysis. Lancet 2005; 366(9496): 1545–53

    Article  PubMed  CAS  Google Scholar 

  15. Beevers DG. The end of beta blockers for uncomplicated hypertension? Lancet 2005; 366(9496): 1510–2

    Article  PubMed  Google Scholar 

  16. 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(9311): 995–1003

    Article  PubMed  CAS  Google Scholar 

  17. 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 (Greenwich) 2002; 4(6): 393–404

    Article  Google Scholar 

  18. Hansson L, Zanchetti A, Carruthers SG, et al. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. HOT Study Group. Lancet 1998; 351(9118): 1755–62

    CAS  Google Scholar 

  19. Israili ZH, Hall WD. Cough and angioneurotic edema associated with angiotensin-converting enzyme inhibitor therapy: a review of the literature and pathophysiology. Ann Intern Med 1992; 117(3): 234–42

    PubMed  CAS  Google Scholar 

  20. Kostis JB, Kim HJ, Rusnak J, et al. Incidence and characteristics of angioedema associated with enalapril. Arch Intern Med 2005; 165(14): 1637–42

    Article  PubMed  CAS  Google Scholar 

  21. Brown NJ, Ray WA, Snowden M, et al. Black Americans have an increased rate of angiotensin converting enzyme inhibitor-associated angioedema. Clin Pharmacol Ther 1996; 60(1): 8–13

    Article  PubMed  CAS  Google Scholar 

  22. Burkhart DG, Brown NJ, Griffin MR, et al. Angiotensin converting enzyme inhibitor-associated angioedema: higher risk in blacks than whites. Pharmacoepidemiol Drug Saf 1996; 5(3): 149–54

    Article  PubMed  CAS  Google Scholar 

  23. Haider AW, Larson MG, Franklin SS, et al. Systolic blood pressure, diastolic blood pressure, and pulse pressure as predictors of risk for congestive heart failure in the Framingham Heart Study. Ann Intern Med 2003; 138(1): 10–6

    PubMed  Google Scholar 

  24. Borghi C, Dormi A, L’Italien G, et al. The relationship between systolic blood pressure and cardiovascular risk: results of the Brisighella Heart Study. J Clin Hypertens (Greenwich) 2003; 5(1): 47–52

    Article  Google Scholar 

  25. Lloyd-Jones DM, Evans JC, Larson MG, et al. Differential control of systolic and diastolic blood pressure: factors associated with lack of blood pressure control in the community. Hypertension 2000; 36(4): 594–9

    Article  PubMed  CAS  Google Scholar 

  26. Odama U, Bakris G. Target organ damage in hypertension. J Clin Hypertens (Greenwich) 2000; 2(5): 312–8

    Google Scholar 

  27. Fahey T, Schroeder K, Ebrahim S. Interventions used to improve control of blood pressure in patients with hypertension. Cochrane Database Syst Rev 2005; (1): CD005182

  28. Therapeutic control of blood pressure in the Hypertension Detection and Follow-up Program. Hypertension Detection and Follow-up Program Cooperative Group. Prev Med 1979; 8(1): 2–13

    Article  Google Scholar 

  29. Julius S, Kjeldsen SE, Brunner H, et al. VALUE trial: long-term blood pressure trends in 13,449 patients with hypertension and high cardiovascular risk. Am J Hypertens 2003; 16(7): 544–8

    Article  PubMed  Google Scholar 

  30. Neal B, MacMahon S, Chapman N. Effects of ACE inhibitors, calcium antagonists, and other blood-pressure-lowering drugs: results of prospectively designed overviews of randomised trials. Blood Pressure Lowering Treatment Trialists’ Collaboration. Lancet 2000; 356(9246): 1955–64

    CAS  Google Scholar 

  31. Turnbull F. Effects of different blood-pressure-lowering regimens on major cardiovascular events: results of prospectively-designed overviews of randomised trials. Lancet 2003; 362(9395): 1527–35

    Article  PubMed  CAS  Google Scholar 

  32. Cheung BM, Cheung GT, Lauder IJ, et al. Meta-analysis of large outcome trials of angiotensin receptor blockers in hypertension. J Hum Hypertens 2006; 20(1): 37–43

    Article  PubMed  CAS  Google Scholar 

  33. Staessen JA, Li Y, Thijs L, et al. Blood pressure reduction and cardiovascular prevention: an update including the 2003–2004 secondary prevention trials. Hypertens Res 2005; 28(5): 385–407

    Article  PubMed  Google Scholar 

  34. Psaty BM, Lumley T, Furberg CD, et al. Health outcomes associated with various antihypertensive therapies used as first-line agents: a network meta-analysis. JAMA 2003; 289(19): 2534–44

    Article  PubMed  CAS  Google Scholar 

  35. Singer GM, Izhar M, Black HR. Goal-oriented hypertension management: translating clinical trials to practice. Hypertension 2002; 40(4): 464–9

    Article  PubMed  CAS  Google Scholar 

  36. Black HR, Elliott WJ, Neaton JD, et al. Baseline characteristics and early blood pressure control in the CONVINCE trial. Hypertension 2001; 37(1): 12–8

    Article  PubMed  CAS  Google Scholar 

  37. Oparil S, Silfani TN, Walker JF. Role of angiotensin receptor blockers as monotherapy in reaching blood pressure goals. Am J Hypertens 2005; 18: 287–94

    Article  PubMed  CAS  Google Scholar 

  38. Smith DH, Dubiel R, Jones M. Use of 24-hour ambulatory blood pressure monitoring to assess antihypertensive efficacy: a comparison of olmesartan medoxomil, losartan potassium, valsartan, and irbesartan. Am J Cardiovasc Drugs 2005; 5(1): 41–50

    Article  PubMed  CAS  Google Scholar 

  39. Neutel JM, Smith DH, Silfani TN, et al. Effects of a structured treatment algorithm on blood pressure goal rates in both stage 1 and stage 2 hypertension. J Hum Hypertens 2006; 20(4): 255–62

    Article  PubMed  CAS  Google Scholar 

  40. Romain TM, Patel RP, Heaberlin AM, et al. Assessment of factors influencing blood pressure control in a managed care population. Pharmacotherapy 2003; 23(8): 1060–70

    Article  PubMed  Google Scholar 

  41. 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 (9 Suppl.): 2–6

    PubMed  CAS  Google Scholar 

  42. Schroeder K, Fahey T, Ebrahim S. How can we improve adherence to blood pressure-lowering medication in ambulatory care? Systematic review of randomized controlled trials. Arch Intern Med 2004; 164(7): 722–32

    Article  PubMed  Google Scholar 

  43. Bardage C, Isacson DG. Self-reported side-effects of antihypertensive drugs: an epidemiological study on prevalence and impact on health-state utility. Blood Press 2000; 9(6): 328–34

    Article  PubMed  CAS  Google Scholar 

  44. Ambrosioni E, Leonetti G, Pessina AC, et al. Patterns of hypertension management in Italy: results of a pharmacoepidemiological survey on antihypertensive therapy. Scientific Committee of the Italian Pharmacoepidemiological Survey on Antihypertensive Therapy. J Hypertens 2000; 18(11): 1691–9

    CAS  Google Scholar 

  45. Ram CV. Antihypertensive drugs: an overview. Am J Cardiovasc Drugs 2002; 2(2): 77–89

    Article  PubMed  CAS  Google Scholar 

  46. Spencer C, Lip G. Antihypertensive drugs. Pharmaceutical J 1999; 263(7061): 351–4

    Google Scholar 

  47. Weir MR, Flack JM, Applegate WB. Tolerability, safety, and quality of life and hypertensive therapy: the case for low-dose diuretics. Am J Med 1996; 101(3A): 83–92S

    Article  Google Scholar 

  48. Greenberg A. Diuretic complications. Am J Med Sci 2000; 319(1): 10–24

    Article  PubMed  CAS  Google Scholar 

  49. Weber MA. The role of the new beta-blockers in treating cardiovascular disease. Am J Hypertens 2005; 18 (12 Pt 2): 169–76S

    Article  Google Scholar 

  50. Glanz M, Garber AJ, Mancia G, et al. Meta-analysis of studies using selective alpha1-blockers in patients with hypertension and type 2 diabetes. Int J Clin Pract 2001; 55(10): 694–701

    PubMed  CAS  Google Scholar 

  51. Clark JA, Zimmerman HJ, Tanner LA. Labetalol hepatotoxicity. Ann Intern Med 1990; 113(3): 210–3

    PubMed  CAS  Google Scholar 

  52. van Zwieten PA. Centrally acting imidazoline I1-receptor agonists: do they have a place in the management of hypertension? Am J Cardiovasc Drugs 2001; 1(5): 321–6

    Article  PubMed  Google Scholar 

  53. Eisenberg MJ, Brox A, Bestawros AN. Calcium channel blockers: an update. Am J Med 2004; 116(1): 35–43

    Article  PubMed  CAS  Google Scholar 

  54. McInnes GT. Clinical potential: angiotensin converting enzyme inhibitor or angiotensin II antagonist? J Hypertens Suppl 2001; 19(1): S61–7

    PubMed  CAS  Google Scholar 

  55. Mazzolai L, Burnier M. Comparative safety and tolerability of angiotensin II receptor antagonists. Drug Saf 1999; 21(1): 23–33

    Article  PubMed  CAS  Google Scholar 

  56. Lenfant C, Roccella EJ. A call to action for more aggressive treatment of hypertension. J Hypertens Suppl 1999; 17(1): S3–7

    PubMed  CAS  Google Scholar 

  57. 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(9426): 2022–31

    Article  PubMed  CAS  Google Scholar 

  58. Weber MA, Julius S, Kjeldsen SE, et al. Blood pressure dependent and independent effects of antihypertensive treatment on clinical events in the VALUE trial. Lancet 2004; 363(9426): 2049–51

    Article  PubMed  CAS  Google Scholar 

  59. Staessen JA, Thijisq L, Fagard R, et al. Effects of immediate versus delayed antihypertensive therapy on outcome in the Systolic Hypertension in Europe trial. J Hypertens 2004; 22(4): 847–57

    Article  PubMed  CAS  Google Scholar 

  60. Maillard MP, Wurzner G, Nussberger J, et al. Comparative angiotensin II receptor blockade in healthy volunteers: the importance of dosing. Clin Pharmacol Ther 2002; 71(1): 68–76

    Article  PubMed  CAS  Google Scholar 

  61. Andrejak M, Genes N, Vaur L, et al. Electronic pill-boxes in the evaluation of antihypertensive treatment compliance: comparison of once daily versus twice daily regimen. Am J Hypertens 2000; 13(2): 184–90

    Article  PubMed  CAS  Google Scholar 

  62. Wetzels GE, Nelemans P, Schouten JS, et al. Facts and fiction of poor compliance as a cause of inadequate blood pressure control: a systematic review. J Hypertens 2004; 22(10): 1849–55

    Article  PubMed  CAS  Google Scholar 

  63. Leenen FH, Wilson TW, Bolli P, et al. Patterns of compliance with once versus twice daily antihypertensive drug therapy in primary care: a randomized clinical trial using electronic monitoring. Can J Cardiol 1997; 13(10): 914–20

    PubMed  CAS  Google Scholar 

  64. Marentette MA, Gerth WC, Billings DK, et al. Antihypertensive persistence and drug class. Can J Cardiol 2002; 18(6): 649–56

    PubMed  CAS  Google Scholar 

  65. Muller JE, Tofler GH, Stone PH. Circadian variation and triggers of onset of acute cardiovascular disease. Circulation 1989; 79(4): 733–43

    Article  PubMed  CAS  Google Scholar 

  66. Marler JR, Price TR, Clark GL, et al. Morning increase in onset of ischemic stroke. Stroke 1989; 20(4): 473–6

    Article  PubMed  CAS  Google Scholar 

  67. White WB. Circadian variation of blood pressure: clinical relevance and implications for cardiovascular chronotherapeutics. Blood Press Monit 1997; 2(1): 47–51

    PubMed  Google Scholar 

  68. White WB. Cardiovascular risk and therapeutic intervention for the early morning surge in blood pressure and heart rate. Blood Press Monit 2001; 6(2): 63–72

    Article  PubMed  CAS  Google Scholar 

  69. Ross SD, Akhras KS, Zhang S, et al. Discontinuation of antihypertensive drugs due to adverse events: a systematic review and meta-analysis. Pharmacotherapy 2001; 21(8): 940–53

    Article  PubMed  CAS  Google Scholar 

  70. ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. 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(23): 2981–97

    Google Scholar 

  71. Wizner B, Gryglewska B, Gasowski J, et al. Normal blood pressure values as perceived by normotensive and hypertensive subjects. J Hum Hypertens 2003; 17(2): 87–91

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

Support for the preparation of this manuscript was provided by Daiichi Sankyo, Inc. Thank you to Catherine Rees for her editorial assistance. The author has no conflicts of interest relevant to the contents of this article.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Lisa Mustone Alexander.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Alexander, L.M. Desirable Therapeutic Characteristics of an Optimal Antihypertensive Agent. Drugs 66, 1239–1252 (2006). https://doi.org/10.2165/00003495-200666090-00006

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003495-200666090-00006

Keywords

Navigation