Use of Fixed Dose Combination Antihypertensives for Uncontrolled Hypertension Patients Currently on Monotherapy

• Introduction
  
  
• Impact of HTN in High-Risk Populations
  
  
• Achieving BP Goals with Combination Therapy
  
  
• Improved adherence
  
  
• ACEIs and Diuretics
  
  
• ARBs and Diuretics
  
  
• Beta-blockers and Diuretics
  
  
• CCBs and ACEIs
  
  
• Conclusion
  
  
• Figures
  
  
• References
  
  

References

1. American Heart Association/American Stroke Association. Heart disease and stroke statistics – 2006 update. Available at:http://www.americanheart.org/downloadable/heart/1140534985281Statsupdate06book.pdf. Accessed on February 23, 2006.

2. Materson BJ, Reda DJ, Cushman WC, et al. Single-drug therapy for hypertension in men. A comparison of six antihypertensive agents with placebo. The Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents. N Engl J Med. 1993;328:914-921. Erratum in: N Engl J Med. 1994;330:1689.

3. U.S. Department of Health and Human Services, National Institutes of Health, National Heart, Lung, and Blood Institute, National High Blood Pressure Education Program. JNC-7 express: the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Available at: http://www.nhlbi.nih.gov/guidelines/hypertension/express.pdf. Accessed on February 24, 2006.

4. Douglas JG, Bakris GL, Epstein M, et al; Hypertension in African Americans Working Group of the International Society on Hypertension in Blacks. Management of high blood pressure in African Americans: consensus statement of the Hypertension in African Americans Working Group of the International Society on Hypertension in Blacks. Arch Intern Med. 2003;163:525-541.

5. American Diabetes Association. Standards of medical care in diabetes. Diabetes Care. 2005;28(suppl 1):S4-S36.
6. Bakris GL, Williams M, Dworkin L, et al. Preserving renal function in adults with hypertension and diabetes: a consensus approach. National Kidney Foundation Hypertension and Diabetes Executive Committees Working Group. Am J Kidney Dis. 2000;36:646-661.

7. American Heart Association. High blood pressure statistics. Available at: http://www.americanheart.org/presenter.jhtml?identifier=2139. Accessed on February 24, 2006.

8. Isomaa B, Almgren P, Tuomi T, et al. Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care. 2001;24:683-689.

9. Vasan RS, Beiser A, Seshadri S, et al. Residual lifetime risk for developing hypertension in middle-aged women and men: The Framingham Heart Study. JAMA. 2002;287:1003-1010.

10. Centers for Disease Control and Prevention. National diabetes fact sheet: general information and national estimates on diabetes in the United States, 2002. Available at: http://www.cdc.gov/diabetes/pubs/pdf/ndfs_2003.pdf. Accessed on February 24, 2006.

11. Oparil S, Miller AP. Gender and blood pressure. J Clin Hypertens (Greenwich). 2005;7:300-309.

12. Hyman DJ, Pavlik VN. Self-reported hypertension treatment practices among primary care physicians: blood pressure thresholds, drug choices, and the role of guidelines and evidence-based medicine. Arch Intern Med. 2000;160:2281-2286.

13. Berlowitz DR, Ash AS, Hickey EC, et al. Inadequate management of blood pressure in a hypertensive population. N Engl J Med. 1998;339:1957-1963.

14. Neal B, MacMahon S, Chapman N; Blood Pressure Lowering Treatment Trialists’ Collaboration. 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;356:1955-1964.

15. Stratton IM, Adler AI, Neil HA, et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ. 2000;321:405-412.

16. Hyman DJ, Pavlik VN, Vallbona C. Physician role in lack of awareness and control of hypertension. J Clin Hypertens (Greenwich). 2000;2:324-330.

17. Holmes JS, Shevrin M, Goldman B, Share D. Translating research into practice: are physicians following evidence-based guidelines in the treatment of hypertension? Med Care Res Rev. 2004;61:453-473.

18. Skolnik NS, Beck JD, Clark M. Combination antihypertensive drugs: recommendations for use. Am Fam Physician. 2000;61:3049-3056.

19. 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;154:1461-1468.

20. Epstein M, Bakris G. Newer approaches to antihypertensive therapy. Use of fixed-dose combination therapy. Arch Intern Med. 1996;156:1969-1978.

21. Gradman AH, Cutler NR, Davis PJ, Robbins JA, Weiss RJ, Wood BC. Combined enalapril and felodipine extended release (ER) for systemic hypertension. Enalapril-Felodipine ER Factorial Study Group. Am J Cardiol. 1997;79:431-435.

22. American Society of Hypertension. Review of clinical hypertension. Available at: http://www.ash-us.org/assets/pub/pdf_files/Review_Final32205.pdf. Accessed on February 27, 2006.

23. 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;288:2981-2997.

24. Black HR, Elliott WJ, Grandits G, et al; CONVINCE Research Group. Principal results of the Controlled Onset Verapamil Investigation of Cardiovascular End Points (CONVINCE) trial. JAMA. 2003;289:2073-2082.

25. Dahlof B, Sever PS, Poulter NR, et al; ASCOT Investigators. 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.

26. Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G. 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;342:145-153. Erratum in: N Engl J Med. 2000;342:1376; N Engl J Med. 2000;342:748.

27. PROGRESS Collaborative Group. Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6,105 individuals with previous stroke or transient ischaemic attack. Lancet. 2001;358:1033-1041. Erratum in: Lancet. 2001;358:1556.

28. Wing LM, Reid CM, Ryan P, et al; Second Australian National Blood Pressure Study Group. A comparison of outcomes with angiotensin-converting--enzyme inhibitors and diuretics for hypertension in the elderly. N Engl J Med. 2003;348:583-592.

29. 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;277:739-745.

30. MacKay JH, Arcuri KE, Goldberg AI, Snapinn SM, Sweet CS. 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;156:278-285.

31. 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;351:1755-1762.

32. Saseen JJ, Carter BL, Brown TE, Elliott WJ, Black HR. Comparison of nifedipine alone and with diltiazem or verapamil in hypertension. Hypertension. 1996;28:109-114.

33. Neutel JM, Saunders E, Bakris GL, et al; INCLUSIVE Investigators. The efficacy and safety of low- and high-dose fixed combinations of irbesartan/hydrochlorothiazide in patients with uncontrolled systolic blood pressure on monotherapy: the INCLUSIVE trial. J Clin Hypertens (Greenwich). 2005;7:578-586.

34. Neutel JM. Metabolic manifestations of low-dose diuretics. Am J Med. 1996;101:71S-82S.

35. Neutel JM, Black HR, Weber MA. Combination therapy with diuretics: an evolution of understanding. Am J Med. 1996;101:61S-70S.

36. Carter BL, Ernst ME, Cohen JD. Hydrochlorothiazide versus chlorthalidone: evidence supporting their interchangeability. Hypertension. 2004;43:4-9.

37. Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial Collaborative Research Group. Diuretic versus alpha-blocker as first-step antihypertensive therapy: final results from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Hypertension. 2003;42:239-246.

38. Messerli FH, Grossman E, Lever AF. Do thiazide diuretics confer specific protection against strokes? Arch Intern Med. 2003;163:2557-2560. Erratum in: Arch Intern Med. 2004;164:446.

39. Psaty BM, Lumley T, Furberg CD. Meta-analysis of health outcomes of chlorthalidone-based vs nonchlorthalidone-based low-dose diuretic therapies. JAMA. 2004;292:43-44.

40. Middlemost SJ, Tager R, Davis J, Sareli P. Effectiveness of enalapril in combination with low-dose hydrochlorothiazide versus enalapril alone for mild to moderate systemic hypertension in black patients. Am J Cardiol. 1994;73:1092-1097.

41. Chrysant SG. Antihypertensive effectiveness of low-dose lisinopril-hydrochlorothiazide combination. A large multicenter study. Lisinopril-Hydrochlorothiazide Group. Arch Intern Med. 1994;154:737-743.

42. Guul SJ, Os I, Jounela AJ. The efficacy and tolerability of enalapril in a formulation with a very low dose of hydrochlorothiazide in hypertensive patients resistent to enalapril monotherapy. Am J Hypertens. 1995;8:727-731.

43. Townsend RR, Holland OB. Combination of converting enzyme inhibitor with diuretic for the treatment of hypertension. Arch Intern Med. 1990;150:1175-1183.

44. Lewis EJ, Hunsicker LG, Bain RP, Rohde RD. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. The Collaborative Study Group. N Engl J Med. 1993;329:1456-1462. Erratum in: N Engl J Med. 1993;330:152.

45. Brenner BM, Cooper ME, de Zeeuw D, et al; RENAAL Study Investigators. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med. 2001;345:861-869.

46. Lewis EJ, Hunsicker LG, Clark WR, et al; Collaborative Study Group. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med. 2001;345:851-860.

47. Elliott WJ. Therapeutic trials comparing angiotensin converting enzyme inhibitors and angiotensin II receptor blockers. Curr Hypertens Rep. 2000;2:402-411.

48. Sica DA. Combination angiotensin-converting enzyme inhibitor and angiotensin receptor blocker therapy: its role in clinical practice. J Clin Hypertens (Greenwich). 2003;5:414-420.

49. Sandoval et al. Efficacy and safety of combinations of irbesartan/HCTZ: a subgroup analysis of Hispanic/Latino patients with uncontrolled SBP on monotherapy. American Society of Hypertension Annual Meeting. Poster: Clinical Trials (8:30 AM – 9:30 AM). May 16, 2005

50. Sowers RJ et al. The efficacy and safety of irbesartan/HCTZ 150/12.5 mg and irbesartan/HCTZ 300/25 mg in patients with metabolic syndrome and hypertension uncontrolled on monotherapy. American Diabetes Association Annual Meeting. Poster. 2005.

51. Saunders E et al. The irbesartan/hydrochlorothiazide (HCTZ) blood pressure reductions in diverse patient populations (INCLUSIVE) trial: efficacy and safety in a subgroup of African American patients. NMA or ISHIB?

52. Madder R, Cushman W, and the INCUSIVE Investigators. Efficacy and safety of fixed dose combinations of irbesartan/HCTZ in patients aged > 65 uncontrolled with SBP on monotherapy in the INCLUSIVE trial.

53. A randomized trial of propranolol in patients with acute myocardial infarction. I. Mortality results. JAMA. 1982;247:1707-1714.

54. Dargie HJ. Effect of carvedilol on outcome after myocardial infarction in patients with left-ventricular dysfunction: the CAPRICORN randomized trial. Lancet. 2001;357:1385-1390.

55. Yusuf S, Peto R, Lewis J, Collins R, Sleight P. Beta blockade during and after myocardial infarction: an overview of the randomized trials. Prog Cardiovasc Dis. 1985;27:335-371.

56. Pepine CJ, Handberg EM, Cooper-DeHoff RM, et al; INVEST Investigators. 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;290:2805-2816.

57. Hansson L, Himmelmann A. Calcium antagonists in antihypertensive combination therapy. J Cardiovasc Pharmacol. 1991;18(suppl 10):S76-S80.

58. 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 Drugs Ther. 1989;3(suppl 1):319-325.

59. Bakris GL, Gaxiola E, Messerli FH, et al; INVEST Investigators. Clinical outcomes in the diabetes cohort of the INternational VErapamil SR-Trandolapril study. Hypertension. 2004;44:637-642.

60. Abstracts from the 2003 Scientific Sessions of the American Heart Association. November 9-12, 2003, Orlando, Florida, USA. Circulation. 2003;108(17 suppl):IV1-787.

61. Sever PS, Dahlof B, Poulter NR, et al. Rationale, design, methods and baseline demography of participants of the Anglo-Scandinavian Cardiac Outcomes Trial. ASCOT Investigators. J Hypertens. 2001;19:1139-1147.

62. Ruggenenti P, Fassi A, Ilieva AP, et al; Bergamo Nephrologic Diabetes Complications Trial (BENEDICT) Investigators. Preventing microalbuminuria in type 2 diabetes. N Engl J Med. 2004;351:1941-1951.

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