Single-pill triple-combination therapy: An alternative to multiple-drug treatment of hypertension

Postgraduate Medicine

Volumn 123, Issue 6, 2011, Pages 21-31

  Chrysant, Steven G ^a  

^a UNIVERSITY OF OKLAHOMA COLLEGE OF MEDICINE   (United States)

Author keywords

Aliskiren; Amlodipine; Antihypertensive agents; Drug combinations; Hydrochlorothiazide; Hypertension; Olmesartan; Valsartan

Indexed keywords

ALISKIREN PLUS HYDROCHLOROTHIAZIDE; ALISKIREN PLUS VALSARTAN; AMLODIPINE PLUS BENAZEPRIL; AMLODIPINE PLUS OLMESARTAN; AMLODIPINE PLUS TELMISARTAN; ANTIHYPERTENSIVE AGENT; ATENOLOL PLUS CHLORTALIDONE; BENAZEPRIL PLUS HYDROCHLOROTHIAZIDE; BENDROFLUMETHIAZIDE PLUS NADOLOL; BISOPROLOL FUMARATE PLUS HYDROCHLOROTHIAZIDE; CANDESARTAN HEXETIL PLUS HYDROCHLOROTHIAZIDE; CAPTOPRIL PLUS HYDROCHLOROTHIAZIDE; CHLORTALIDONE PLUS CLONIDINE; ENALAPRIL PLUS HYDROCHLOROTHIAZIDE; EPROSARTAN PLUS HYDROCHLOROTHIAZIDE; FOSINOPRIL PLUS HYDROCHLOROTHIAZIDE; HYDRA ZIDE; HYDRALAZINE PLUS HYDROCHLOROTHIAZIDE; HYDROCHLOROTHIAZIDE PLUS IRBESARTAN; HYDROCHLOROTHIAZIDE PLUS LISINOPRIL; HYDROCHLOROTHIAZIDE PLUS LOSARTAN; HYDROCHLOROTHIAZIDE PLUS METHYLDOPA; HYDROCHLOROTHIAZIDE PLUS METOPROLOL; HYDROCHLOROTHIAZIDE PLUS MOEXIPRIL; HYDROCHLOROTHIAZIDE PLUS OLMESARTAN; HYDROCHLOROTHIAZIDE PLUS PROPRANOLOL; HYDROCHLOROTHIAZIDE PLUS QUINAPRIL; HYDROCHLOROTHIAZIDE PLUS SPIRONOLACTONE; HYDROCHLOROTHIAZIDE PLUS TELMISARTAN; HYDROCHLOROTHIAZIDE PLUS TRIAMTERENE; HYDROCHLOROTHIAZIDE PLUS VALSARTAN; MONOPRILO HCT; TIMOLIDE; TRANDOLAPRIL PLUS VERAPAMIL; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ARTICLE; BLOOD PRESSURE REGULATION; CARDIOVASCULAR RISK; CEREBROVASCULAR ACCIDENT; DIZZINESS; DRUG APPROVAL; DRUG EFFICACY; DRUG INDUCED HEADACHE; DRUG SAFETY; DRUG TOLERABILITY; ESSENTIAL HYPERTENSION; EUROPE; HEART INFARCTION; HUMAN; HYPERTENSION; LIFESTYLE MODIFICATION; MONOTHERAPY; MORTALITY; PATIENT COMPLIANCE; PERIPHERAL EDEMA; PILL; PRACTICE GUIDELINE; RENIN ANGIOTENSIN ALDOSTERONE SYSTEM; RISK MANAGEMENT; RISK REDUCTION; TREATMENT RESPONSE;

AMIDES; AMLODIPINE; ANTIHYPERTENSIVE AGENTS; DRUG COMBINATIONS; DRUG DESIGN; FUMARATES; HUMANS; HYDROCHLOROTHIAZIDE; HYPERTENSION; IMIDAZOLES; MEDICATION ADHERENCE; PHYSICIAN'S PRACTICE PATTERNS; PRACTICE GUIDELINES AS TOPIC; TETRAZOLES; VALINE;

EID: 82155171249     PISSN: 00325481     EISSN: 19419260     Source Type: Journal    
DOI: 10.3810/pgm.2011.11.2492     Document Type: Article

References (81)

1. Roger VL, Go AS, Lloyd-Jones DM, et al; American Heart Association Statistics Committee and Stroke Statistics Committee. Heart Disease and Stroke Statistics-2011 Update: a report from the American Heart Association. Circulation. 2011;123(4):459-463.
2. Yoon SS, Ostchega Y, Louis T. Recent trends in the prevalence of high blood pressure and its treatment and control, 1999-2008 [NCHS data brief, no. 48]. October, 2010. National Center for Health Statistics. http://www.cdc.gov/nchs/data/databriefs/db48.pdf. Accessed July 18, 2011.
3. Egan BM, Zhao Y, Axon RN. US trends in prevalence, awareness, treatment, and control of hypertension, 1988-2008. JAMA. 2010; 303(20):2043-2050.
4. Healthy People Web site. Heart and Stroke. 2010. http://healthypeople. gov/2020/topicsobjectives2020/overview.aspx?topicid=21. Accessed July 18, 2011.
5. Heidenreich PA, Trogdon JG, Khavjou OA, et al; American Heart Association Advocacy Coordinating Committee; Stroke Council; Council on Cardiovascular Radiology and Intervention, et al. Forecasting the future of cardiovascular disease in the United States: a policy statement from the American Heart Association. Circulation. 2011;123(8):933-944.
6. Chobanian AV, Bakris GL, Black HR, et al; Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure. National Heart, Lung, and Blood Institute; National High Blood Pressure Education Program Coordinating Committee. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension. 2003;42(6): 1206-1252.
7. 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): 1755-1762.
8. Major cardiovascular events in hypertensive patients randomized to doxazosin vs chlorthalidone: the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT). ALLHAT Collaborative Research Group. JAMA. 2000;283(15):1967-1975.
9. 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):2022-2031.
10. Staessen JA, Wang JG, Thijs L. Cardiovascular protection and blood pressure reduction: a meta-analysis. Lancet. 2001;358(9290):1305-1315.
11. Staessen JA, Li Y, Thijs L, Wang JG. Blood pressure reduction and cardiovascular prevention: an update including the 2003-2004 secondary prevention trials. Hypertens Res. 2005;28(5):385-407.
12. Turnbull F; Blood Pressure Lowering Treatment Trialists' Collaboration. Effects of different blood-pressure-lowering regimens on major cardiovascular events: results of prospectively-designed overviews of randomised trials. Lancet. 2003;362(9395):1527-1535.
13. Lewington S, Clarke R, Qizilbash N, Peto R, Collins R; Prospective Studies Collaboration. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet. 2002;360(9349):1903-1913.
14. Cushman WC, Ford CE, Cutler JA, et al; ALLHAT Collaborative Research Group. Success and predictors of blood pressure control in diverse North American settings: the antihypertensive and lipidlowering treatment to prevent heart attack trial (ALLHAT). J Clin Hypertens (Greenwich). 2002;4(6):393-404.
15. 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 bendrofl umethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a multicentre randomized controlled trial. Lancet. 2005;366(9489):895-906.
16. Lewis EJ, Hunsicker LG, Clarke 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(12):851-860.
17. Mancia G, Laurent S, Agabiti-Rosei E, et al; European Society of Hypertension. Reappraisal of European guidelines on hypertension management: a European Society of Hypertension Task Force document. J Hypertens. 2009;27(11):2121-2158.
18. Gradman AH. Rationale for triple-combination therapy for management of high blood pressure. J Clin Hypertens (Greenwich). 2010;12(11):869-878.
19. Lithell H, Hansson L, Skoog I, et al; SCOPE Study Group. The Study on Cognition and Prognosis in the Elderly (SCOPE): principal results of a randomized double-blind intervention trial. J Hypertens. 2003;21(5): 875-886.
20. 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(23):2417-2428.
21. Martin LR, Williams SL, Haskard KB, DiMatteo MR. The challenge of patient adherence. Ther Clin Risk Manag. 2005;1(3):189-199.
22. Kravitz RL, Hays RD, Sherbourne CD, et al. Recall of recommendations and adherence to advice among patients with chronic medical conditions. Arch Intern Med. 1993;153(16):1869-1878.
23. Bibbins-Domingo K, Chertow GM, Coxson PG, et al. Projected effect of dietary salt reductions on future cardiovascular disease. N Engl J Med. 2010;362(7):590-599.
24. Ho PM, Magid DJ, Shetterly SM, et al. Importance of therapy intensification and medication nonadherence for blood pressure control in patients with coronary disease. Arch Intern Med. 2008;168(3):271-276.
25. Veronesi M, Cicero AF, Prandin MG, et al. A prospective evaluation of persistence on antihypertensive treatment with different antihypertensive drugs in clinical practice. Vasc Health Risk Manag. 2007;3(6):999-1005.
26. Yiannakopoulou EC, Papadopulos JS, Cokkinos DV, Mountokalakis TD. Adherence to antihypertensive treatment: a critical factor for blood pressure control. Eur J Cardiovasc Prev Rehabil. 2005;12(3):243-249.
27. van Wijk BL, Klungel OH, Heerdink ER, de Boer A. Rate and determinants of 10-year persistence with antihypertensive drugs. J Hypertens. 2005;23(11):2101-2107.
28. Osterberg L, Blaschke T. Adherence to medication. N Engl J Med. 2005;353(5):487-497.
29. Chapman RH, Benner JS, Petrilla AA, et al. Predictors of adherence with antihypertensive and lipid-lowering therapy. Arch Intern Med. 2005;165(10):1147-1152.
30. Fung V, Huang J, Brand R, Newhouse JP, Hsu J. Hypertension treatment in a Medicare population: adherence and systolic blood pressure control. Clin Ther. 2007;29(5):972-984.
31. Basile J. What's new in hypertension since JNC7 guidelines? J Manag Care Med. 2010;13(3):28-36.
32. Nesbitt SD. Overcoming therapeutic inertia in patients with hypertension. Postgrad Med. 2010;122(1):118-124.
33. Okonofua EC, Simpson KN, Jesri A, Rehman SU, Durkalski VL, Egan BM. Therapeutic inertia is an impediment to achieving the Healthy People 2010 blood pressure control goals. Hypertension. 2006;47(3):345-351.
34. Heisler M, Hogan MM, Hofer TP, Schmittdiel JA, Pladevall M, Kerr EA. When more is not better: treatment intensification among hypertensive patients with poor medication adherence. Circulation. 2008;117(22):2884-2892.
35. 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(15):2281-2286.
36. Spranger CB, Ries AJ, Berge CA, Radford NB, Victor RG. Identifying gaps between guidelines and clinical practice in the evaluation and treatment of patients with hypertension. Am J Med. 2004;117(1):14-18.
37. Ofili EO. Dispelling the myth of "aggressive" antihypertensive therapy. J Clin Hypertens (Greenwich). 2006;8(1 suppl 1):4-11.
38. Rose AJ, Shimada SL, Rothendler JA, et al. The accuracy of clinician perceptions of "usual" blood pressure control. J Gen Intern Med. 2008;23(2):180-183.
39. Cushman WC, Basile J. Achieving blood pressure goals: why aren't we? J Clin Hypertens (Greenwich). 2006;8(12):865-872.
40. The sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Arch Intern Med. 1997;157(21):2413-2446.
41. The 1988 report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. Arch Intern Med. 1988;148(5):1023-1038.
42. The fifth report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC V). Arch Intern Med. 1993;153(2):154-183.
43. Flack JM, Sica DA, Bakris G, et al. Management of high blood pressure in blacks: an update of the International Society on Hypertension in Blacks consensus statement. Hypertension. 2010;56(5):780-800.
44. Veterans Administration Cooperative Study Group on Antihypertensive Agents. Effects of treatment on morbidity in hypertension. Results in patients with diastolic blood pressures averaging 115 through 129 mm Hg. JAMA. 1967;202(11):1028-1034.
45. Black HR. Triple fixed-dose combination therapy. Back to the past. Hypertension. 2009;54(1):19-22.
46. Oparil S, Melino M, Lee J, Fernandez V, Heyrman R. Triple therapy with olmesartan medoxomil, amlodipine besylate, and hydrochlorothiazide in adult patients with hypertension: the TRINITY multicenter, randomized, double-blind, 12-week, parallel-group study. Clin Ther. 2010;32(7):1252-1269.
47. Chrysant SG, Oparil S, Melino M, Karki S, Lee J, Heyrman R. Efficacy and safety of long-term treatment with the combination of amlodipine besylate and olmesartan medoxomil in patients with hypertension. J Clin Hypertens (Greenwich). 2009;11(9):475-482.
48. Calhoun DA, Crikelair NA, Yen J, Glazer RD. Amlodipine/valsartan/ hydrochlorothiazide triple combination therapy in moderate/severe hypertension: secondary analyses evaluating efficacy and safety. Adv Ther. 2009;26(11):1012-1023.
49. Calhoun DA, Lacourciere Y, Chiang YT, Glazer RD. Triple antihypertensive therapy with amlodipine, valsartan, and hydrochlorothiazide. A randomized clinical trial. Hypertension. 2009;54(1):32-39.
50. Novartis gains FDA approval for Amturnide, a triple-combination pill to treat high blood pressure in patients uncontrolled on two medications. 2010. http://www.pharma.us.novartis.com/assets/pdf/press-releases/FINAL_US_Amturnide_FDA_Approval_Press_Release.pdf. Accessed July 18, 2011.
51. Lacourciere Y, Taddei S, Konis G, Salko T, Fang H, Zhang J. Aliskiren/amlodipine/hydrochlorothiazide combination provides -49.53/ -22.53 mmHg msSBP/msDBP reduction in patients with severe hypertension (baseline msSBP: 180 < _200 mmHg). Abstract P384. Hypertension. 2010;56(5):E134-E135.
52. Lacourciere Y, Taddei S, Konis G, Salko T, Fang H, Zhang J. Aliskiren/ amlodipine/hydrochlorothiazide provides significant blood pressure reductions in patients with very severe hypertension (systolic BP -/>190 mmHg - <200 mmHg. Abstract 383. Hypertension. 2010;56(5):E134.
53. Geiger H, Barranco E, Gorostidi M, et al. Combination therapy with various combinations of aliskiren, valsartan, and hydrochlorothiazide in hypertensive patients not adequately responsive to hydrochlorothiazide alone. J Clin Hypertens (Greenwich). 2009;11(6):324-332.
54. Chrysant SG, Murray AV, Hoppe UC, et al. Long-term safety and efficacy of aliskiren and valsartan combination with or without the addition of HCT in patients with hypertension. Curr Med Res Opin. 2010;26(12):2841-2849.
55. Clinicaltrials.gov. NCT00219102. A clinical study to evaluate safety and efficacy of the combination of aliskiren, valsartan and hydrochlorothiazide in diabetic hypertensive nonresponder patients. http://clinicaltrials.gov/ct2/show/NCT00219102?term=hypertension+AND+aliskiren&rank=55. Accessed July 18, 2011.
56. Clinicaltrials.gov. NCT00994253. Trial to evaluate the effect of Tekturna (aliskiren), angiotensin inhibitors, diuretics, and calcium channel blockers on coronary fl ow reserve in patients with type II diabetes and hypertension. http://clinicaltrials.gov/ct2/show/NCT00994253?term=NCT00994253&rank=1. Accessed July 18, 2011.
57. Clinicaltrials.gov. NCT00542269. Efficacy and safety of aliskiren +/- ramipril when added to amlodipine in hypertensive patients with metabolic syndrome (ALTO). http://clinicaltrials.gov/ct2/show/NCT00542269?term=triple+AND+combination+AND+hypertension+NOT+ocular&rank=6. Accessed July 18, 2011.
58. Clinicaltrials.gov. NCT01198249. Pharmacokinetic drug interactions between single and concomitant administrations of amlodipine, losartan, and hydrochlorothiazide in subjects with (pre)hypertension. http://clinicaltrials.gov/ct2/show/NCT01198249?term=amlodipine+AND+losartan+AND+HCTZ&rank=1. Accessed July 18, 2011.
59. Gradman AH, Basile JN, Carter BL, Bakris GL. Combination therapy in hypertension. J Am Soc Hypertens. 2010;4(1):42-50.
60. Chrysant SG. Using fixed-dose combination therapies to achieve blood pressure goals. Clin Drug Investig. 2008;28(11):713-734.
61. Elijovich F, Laffer C. A role for single-pill triple therapy in hypertension. Ther Adv Cardiovasc Dis. 2009;3(3):231-240.
62. Saseen JJ, Carter BL. Hypertension. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 6th ed. New York, NY: McGraw-Hill, 2005:185-217.
63. Sica DA. Thiazide-type diuretics: ongoing considerations on mechanism of action. J Clin Hypertens (Greenwich). 2004;6(11):661-664.
64. Wald DS, Law M, Morris JK, Bestwick JP, Wald NJ. Combination therapy versus monotherapy in reducing blood pressure: meta-analysis on 11,000 participants from 42 trials. Am J Med. 2009;122(3):290-300.
65. Feldman RD, Zou GY, Vandervoort MK, Wong CJ, Nelson SA, Feagan BG. A simplified approach to the treatment of uncomplicated hypertension: a cluster randomized, controlled trial. Hypertension. 2009;53(4):646-653.
66. Law MR, Morris JK, Wald NJ. Use of blood pressure lowering drugs in the prevention of cardiovascular disease: meta-analysis of 147 randomised trials in the context of expectations from prospective epidemiological studies. BMJ. 2009;338:b1665.
67. Chrysant SG. Proactive compared with passive adverse event recognition: calcium channel blocker-associated edema. J Clin Hypertens (Greenwich). 2008;10(9):716-722.
68. 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(3):220-224.
69. Staessen JA, Thijs L, Fagard R, et al; Systolic Hypertension in Europe (Syst-Eur) Trial Investigators. Effects of immediate versus delayed antihypertensive therapy on outcome in the Systolic Hypertension in Europe Trial. J Hypertens. 2004;22(4):847-857.
70. 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):2049-2051.
71. Weir MR, Zappe D, Orloski LA, Sowers JR. How early should blood pressure control be achieved for optimal cardiovascular outcomes? J Hum Hypertens. 2011;25(4):211-217.
72. Brixner DI, Jackson KC, Sheng X, Nelson RE, Keskinaslan A. Assessment of adherence, persistence, and costs among valsartan and hydrochlorothiazide retrospective cohorts in free- and fixed-dose combinations. Curr Med Res Opin. 2008;24(9):2597-2607.
73. Gupta AK, Arshad S, Poulter NR. Compliance, safety, and effectiveness of fixed-dose combinations of antihypertensive agents: a meta-analysis. Hypertension. 2010;55(2):399-407.
74. Yang W, Chang J, Kahler KH, et al. Evaluation of compliance and health care utilization in patients treated with single pill vs free combination antihypertensives. Curr Med Res Opin. 2010;26(9):2065-2076.
75. Bangalore S, Kamalakkannan G, Parkar S, Messerli FH. Fixed-dose combinations improve medication compliance: a meta-analysis. Am J Med. 2007;120(8):713-719.
76. Dragomir A, Côté R, Roy L, et al. Impact of adherence to antihypertensive agents on clinical outcomes and hospitalization costs. Med Care. 2010;48(5):418-425.
77. Setaro JF, Black HR. Refractory hypertension. N Engl J Med. 1992; 327(8):543-547.
78. Kearney PM, Whelton M, Reynolds K, Muntner P, Whelton PK, He J. Global burden of hypertension: analysis of worldwide data. Lancet. 2005;365(9455):217-223.
79. Boyle JP, Thompson TJ, Gregg EW, Barker LE, Williamson DF. Projection of the year 2050 burden of diabetes in the US adult population: dynamic modeling of incidence, mortality, and prediabetes prevalence. Popul Health Metr. 2010;8(1):29.
80. Centers for Disease Control and Prevention. U.S. Obesity Trends. 2010. http://www.cdc.gov/obesity/data/trends.html. Accessed July 18, 2011.
81. Calhoun DA. Use of single-pill combination therapy in the evolving paradigm of hypertension management. Expert Opin Pharmacother. 2009;10(12):1869-1874.