Efficacy and Safety of Fixed Combinations of Irbesartan/Hydrochlorothiazide in Older vs Younger Patients With Hypertension Uncontrolled With Monotherapy
William C. Cushman MD
From the University of Tennessee College of Medicine and Veterans Affairs Medical Center, Memphis, TN; 1 Orange County Research Center, Tustin, CA; 2 the University of Maryland School of Medicine, Baltimore, MD; 3 the Department of Medicine, University of Chicago, Chicago, IL; 4 the Association of Black Cardiologists, Atlanta, GA; 5 Morehouse School of Medicine, Atlanta, GA; 6 the University of Arizona, Tucson, AZ; 7 Tri-State Medical Group, Inc, Beaver, PA; 8 and State University of New York Health Science Center at Brooklyn, Brooklyn, NY 9
Search for more papers by this authorJoel M. Neutel MD
From the University of Tennessee College of Medicine and Veterans Affairs Medical Center, Memphis, TN; 1 Orange County Research Center, Tustin, CA; 2 the University of Maryland School of Medicine, Baltimore, MD; 3 the Department of Medicine, University of Chicago, Chicago, IL; 4 the Association of Black Cardiologists, Atlanta, GA; 5 Morehouse School of Medicine, Atlanta, GA; 6 the University of Arizona, Tucson, AZ; 7 Tri-State Medical Group, Inc, Beaver, PA; 8 and State University of New York Health Science Center at Brooklyn, Brooklyn, NY 9
Search for more papers by this authorElijah Saunders MD
From the University of Tennessee College of Medicine and Veterans Affairs Medical Center, Memphis, TN; 1 Orange County Research Center, Tustin, CA; 2 the University of Maryland School of Medicine, Baltimore, MD; 3 the Department of Medicine, University of Chicago, Chicago, IL; 4 the Association of Black Cardiologists, Atlanta, GA; 5 Morehouse School of Medicine, Atlanta, GA; 6 the University of Arizona, Tucson, AZ; 7 Tri-State Medical Group, Inc, Beaver, PA; 8 and State University of New York Health Science Center at Brooklyn, Brooklyn, NY 9
Search for more papers by this authorGeorge L. Bakris MD
From the University of Tennessee College of Medicine and Veterans Affairs Medical Center, Memphis, TN; 1 Orange County Research Center, Tustin, CA; 2 the University of Maryland School of Medicine, Baltimore, MD; 3 the Department of Medicine, University of Chicago, Chicago, IL; 4 the Association of Black Cardiologists, Atlanta, GA; 5 Morehouse School of Medicine, Atlanta, GA; 6 the University of Arizona, Tucson, AZ; 7 Tri-State Medical Group, Inc, Beaver, PA; 8 and State University of New York Health Science Center at Brooklyn, Brooklyn, NY 9
Search for more papers by this authorKeith C. Ferdinand MD
From the University of Tennessee College of Medicine and Veterans Affairs Medical Center, Memphis, TN; 1 Orange County Research Center, Tustin, CA; 2 the University of Maryland School of Medicine, Baltimore, MD; 3 the Department of Medicine, University of Chicago, Chicago, IL; 4 the Association of Black Cardiologists, Atlanta, GA; 5 Morehouse School of Medicine, Atlanta, GA; 6 the University of Arizona, Tucson, AZ; 7 Tri-State Medical Group, Inc, Beaver, PA; 8 and State University of New York Health Science Center at Brooklyn, Brooklyn, NY 9
Search for more papers by this authorElizabeth O. Ofili MD
From the University of Tennessee College of Medicine and Veterans Affairs Medical Center, Memphis, TN; 1 Orange County Research Center, Tustin, CA; 2 the University of Maryland School of Medicine, Baltimore, MD; 3 the Department of Medicine, University of Chicago, Chicago, IL; 4 the Association of Black Cardiologists, Atlanta, GA; 5 Morehouse School of Medicine, Atlanta, GA; 6 the University of Arizona, Tucson, AZ; 7 Tri-State Medical Group, Inc, Beaver, PA; 8 and State University of New York Health Science Center at Brooklyn, Brooklyn, NY 9
Search for more papers by this authorJames R. Sowers MD
From the University of Tennessee College of Medicine and Veterans Affairs Medical Center, Memphis, TN; 1 Orange County Research Center, Tustin, CA; 2 the University of Maryland School of Medicine, Baltimore, MD; 3 the Department of Medicine, University of Chicago, Chicago, IL; 4 the Association of Black Cardiologists, Atlanta, GA; 5 Morehouse School of Medicine, Atlanta, GA; 6 the University of Arizona, Tucson, AZ; 7 Tri-State Medical Group, Inc, Beaver, PA; 8 and State University of New York Health Science Center at Brooklyn, Brooklyn, NY 9
Search for more papers by this authorRobert Madder DO
From the University of Tennessee College of Medicine and Veterans Affairs Medical Center, Memphis, TN; 1 Orange County Research Center, Tustin, CA; 2 the University of Maryland School of Medicine, Baltimore, MD; 3 the Department of Medicine, University of Chicago, Chicago, IL; 4 the Association of Black Cardiologists, Atlanta, GA; 5 Morehouse School of Medicine, Atlanta, GA; 6 the University of Arizona, Tucson, AZ; 7 Tri-State Medical Group, Inc, Beaver, PA; 8 and State University of New York Health Science Center at Brooklyn, Brooklyn, NY 9
Search for more papers by this authorMichael A. Weber MD
From the University of Tennessee College of Medicine and Veterans Affairs Medical Center, Memphis, TN; 1 Orange County Research Center, Tustin, CA; 2 the University of Maryland School of Medicine, Baltimore, MD; 3 the Department of Medicine, University of Chicago, Chicago, IL; 4 the Association of Black Cardiologists, Atlanta, GA; 5 Morehouse School of Medicine, Atlanta, GA; 6 the University of Arizona, Tucson, AZ; 7 Tri-State Medical Group, Inc, Beaver, PA; 8 and State University of New York Health Science Center at Brooklyn, Brooklyn, NY 9
Search for more papers by this authorWilliam C. Cushman MD
From the University of Tennessee College of Medicine and Veterans Affairs Medical Center, Memphis, TN; 1 Orange County Research Center, Tustin, CA; 2 the University of Maryland School of Medicine, Baltimore, MD; 3 the Department of Medicine, University of Chicago, Chicago, IL; 4 the Association of Black Cardiologists, Atlanta, GA; 5 Morehouse School of Medicine, Atlanta, GA; 6 the University of Arizona, Tucson, AZ; 7 Tri-State Medical Group, Inc, Beaver, PA; 8 and State University of New York Health Science Center at Brooklyn, Brooklyn, NY 9
Search for more papers by this authorJoel M. Neutel MD
From the University of Tennessee College of Medicine and Veterans Affairs Medical Center, Memphis, TN; 1 Orange County Research Center, Tustin, CA; 2 the University of Maryland School of Medicine, Baltimore, MD; 3 the Department of Medicine, University of Chicago, Chicago, IL; 4 the Association of Black Cardiologists, Atlanta, GA; 5 Morehouse School of Medicine, Atlanta, GA; 6 the University of Arizona, Tucson, AZ; 7 Tri-State Medical Group, Inc, Beaver, PA; 8 and State University of New York Health Science Center at Brooklyn, Brooklyn, NY 9
Search for more papers by this authorElijah Saunders MD
From the University of Tennessee College of Medicine and Veterans Affairs Medical Center, Memphis, TN; 1 Orange County Research Center, Tustin, CA; 2 the University of Maryland School of Medicine, Baltimore, MD; 3 the Department of Medicine, University of Chicago, Chicago, IL; 4 the Association of Black Cardiologists, Atlanta, GA; 5 Morehouse School of Medicine, Atlanta, GA; 6 the University of Arizona, Tucson, AZ; 7 Tri-State Medical Group, Inc, Beaver, PA; 8 and State University of New York Health Science Center at Brooklyn, Brooklyn, NY 9
Search for more papers by this authorGeorge L. Bakris MD
From the University of Tennessee College of Medicine and Veterans Affairs Medical Center, Memphis, TN; 1 Orange County Research Center, Tustin, CA; 2 the University of Maryland School of Medicine, Baltimore, MD; 3 the Department of Medicine, University of Chicago, Chicago, IL; 4 the Association of Black Cardiologists, Atlanta, GA; 5 Morehouse School of Medicine, Atlanta, GA; 6 the University of Arizona, Tucson, AZ; 7 Tri-State Medical Group, Inc, Beaver, PA; 8 and State University of New York Health Science Center at Brooklyn, Brooklyn, NY 9
Search for more papers by this authorKeith C. Ferdinand MD
From the University of Tennessee College of Medicine and Veterans Affairs Medical Center, Memphis, TN; 1 Orange County Research Center, Tustin, CA; 2 the University of Maryland School of Medicine, Baltimore, MD; 3 the Department of Medicine, University of Chicago, Chicago, IL; 4 the Association of Black Cardiologists, Atlanta, GA; 5 Morehouse School of Medicine, Atlanta, GA; 6 the University of Arizona, Tucson, AZ; 7 Tri-State Medical Group, Inc, Beaver, PA; 8 and State University of New York Health Science Center at Brooklyn, Brooklyn, NY 9
Search for more papers by this authorElizabeth O. Ofili MD
From the University of Tennessee College of Medicine and Veterans Affairs Medical Center, Memphis, TN; 1 Orange County Research Center, Tustin, CA; 2 the University of Maryland School of Medicine, Baltimore, MD; 3 the Department of Medicine, University of Chicago, Chicago, IL; 4 the Association of Black Cardiologists, Atlanta, GA; 5 Morehouse School of Medicine, Atlanta, GA; 6 the University of Arizona, Tucson, AZ; 7 Tri-State Medical Group, Inc, Beaver, PA; 8 and State University of New York Health Science Center at Brooklyn, Brooklyn, NY 9
Search for more papers by this authorJames R. Sowers MD
From the University of Tennessee College of Medicine and Veterans Affairs Medical Center, Memphis, TN; 1 Orange County Research Center, Tustin, CA; 2 the University of Maryland School of Medicine, Baltimore, MD; 3 the Department of Medicine, University of Chicago, Chicago, IL; 4 the Association of Black Cardiologists, Atlanta, GA; 5 Morehouse School of Medicine, Atlanta, GA; 6 the University of Arizona, Tucson, AZ; 7 Tri-State Medical Group, Inc, Beaver, PA; 8 and State University of New York Health Science Center at Brooklyn, Brooklyn, NY 9
Search for more papers by this authorRobert Madder DO
From the University of Tennessee College of Medicine and Veterans Affairs Medical Center, Memphis, TN; 1 Orange County Research Center, Tustin, CA; 2 the University of Maryland School of Medicine, Baltimore, MD; 3 the Department of Medicine, University of Chicago, Chicago, IL; 4 the Association of Black Cardiologists, Atlanta, GA; 5 Morehouse School of Medicine, Atlanta, GA; 6 the University of Arizona, Tucson, AZ; 7 Tri-State Medical Group, Inc, Beaver, PA; 8 and State University of New York Health Science Center at Brooklyn, Brooklyn, NY 9
Search for more papers by this authorMichael A. Weber MD
From the University of Tennessee College of Medicine and Veterans Affairs Medical Center, Memphis, TN; 1 Orange County Research Center, Tustin, CA; 2 the University of Maryland School of Medicine, Baltimore, MD; 3 the Department of Medicine, University of Chicago, Chicago, IL; 4 the Association of Black Cardiologists, Atlanta, GA; 5 Morehouse School of Medicine, Atlanta, GA; 6 the University of Arizona, Tucson, AZ; 7 Tri-State Medical Group, Inc, Beaver, PA; 8 and State University of New York Health Science Center at Brooklyn, Brooklyn, NY 9
Search for more papers by this authorAbstract
Subgroup analysis of the Irbesartan/Hydrochlorothiazide Blood Pressure Reductions in Diverse Patient Populations (INCLUSIVE) trial evaluated the efficacy and safety of irbesartan/hydrochlorothiazide (HCTZ) fixed combinations in patients aged 65 years or older with uncontrolled systolic blood pressure (SBP) after ≥4 weeks of antihypertensive monotherapy. The INCLUSIVE trial was a prospective, open-label, single-arm trial carried out in 119 sites. Of 844 patients completing placebo treatment, 212 were aged 65 years or older. Participants received treatment with placebo (4–5 weeks), HCTZ 12.5 mg (2 weeks), irbesartan/HCTZ 150/12.5 mg (8 weeks), and then irbesartan/HCTZ 300/25 mg (8 weeks). From baseline to week 18 (n=184, intent-to-treat population), mean change in SBP was −23.0±13.3 mm Hg (P<.001) and diastolic BP (DBP) was −10.9±7.7 mm Hg (P<.001). Mean SBP/DBP at study end was 134.0±14.7/75.1±8.4 mm Hg, and SBP, DBP, and SBP/DBP goal was achieved in 73%, 96%, and 72% of patients, respectively. Irbesartan/HCTZ combination therapy allowed SBP goal attainment in 73% of patients aged 65 years or older whose hypertension was previously uncontrolled with antihypertensive monotherapy.
References
- 1 Hajjar I, Kotchen TA. Trends in prevalence, awareness, treatment, and control of hypertension in the United States, 1988–2000. JAMA. 2003; 290: 199–206.
- 2 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: 398–404.
- 3 Franklin SS, Jacobs MJ, Wong ND, et al. Predominance of isolated systolic hypertension among middle-aged and elderly US hypertensives: analysis based on National Health and Nutrition Examination Survey (NHANES) III. Hypertension. 2001; 37: 869–874.
- 4 Neaton JD, Wentworth D, for the Multiple Risk Factor Intervention Trial Research Group. Serum cholesterol, blood pressure, cigarette smoking, and death from coronary heart disease. Overall findings and differences by age for 316,099 white men. Arch Intern Med. 1992; 152: 56–64.
- 5 Klag MJ, Whelton PK, Randall BL, et al. Blood pressure and end-stage renal disease in men. N Engl J Med. 1996; 334: 13–18.
- 6 Kannel WB. Elevated systolic blood pressure as a cardiovascular risk factor. Am J Cardiol. 2000; 85: 251–255.
- 7 Benetos A, Thomas F, Bean K, et al. Prognostic value of systolic and diastolic blood pressure in treated hypertensive men. Arch Intern Med. 2002; 162: 577–581.
- 8 SHEP Cooperative Research Group. Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). JAMA. 1991; 265: 3255–3264.
- 9 MRC Working Party. Medical Research Council trial of treatment of hypertension in older adults: principal results. BMJ. 1992; 304: 405–412.
- 10 MacMahon S, Rodgers A. The effects of blood pressure reduction in older patients: an overview of five randomized controlled trials in elderly hypertensives. Clin Exp Hypertens. 1993; 15: 967–978.
- 11 Staessen JA, Fagard R, Thijs L, et al. Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension. Lancet. 1997; 350: 757–764.
- 12 Gueyffier F, Bulpitt C, Boissel JP, et al. Antihypertensive drugs in very old people: a subgroup meta-analysis of randomised controlled trials. INDANA Group. Lancet. 1999; 353: 793–796.
- 13 Hansson L, Lindholm LH, Ekbom T, et al. Randomised trial of old and new antihypertensive drugs in elderly patients: cardiovascular mortality and morbidity the Swedish Trial in Old Patients with Hypertension-2 study. Lancet. 1999; 354: 1751–1756.
- 14 Staessen JA, Gasowski J, Wang JG, et al. Risks of untreated and treated isolated systolic hypertension in the elderly: meta-analysis of outcome trials. Lancet. 2000; 355: 865–872.
- 15 Asmar R. Benefits of blood pressure reduction in elderly patients. J Hypertens Suppl. 2003; 21(6): S25–S30.
- 16 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: 2560–2572.
- 17 Izzo JL Jr, Levy D, Black HR. Clinical Advisory Statement. Importance of systolic blood pressure in older Americans. Hypertension. 2000; 35: 1021–1024.
- 18 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: 393–404.
- 19 Materson BJ, Reda DJ, Cushman WC, et al. Results of combination anti-hypertensive therapy after failure of each of the components. J Hum Hypertens. 1995; 9: 791–796.
- 20 Chaudhry SI, Krumholz HM, Foody JM. Systolic hypertension in older persons. JAMA. 2004; 292: 1074–1080.
- 21 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.
- 22 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: 324–332.
- 23 Taylor AA. Combination drug treatment of hypertension: have we come full circle? Curr Cardiol Rep. 2004; 6: 421–426.
- 24 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.
- 25 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.
- 26 Pool JL, Guthrie RM, Littlejohn TW III, et al. Dose-related antihypertensive effects of irbesartan in patients with mild-to-moderate hypertension. Am J Hypertens. 1998; 11: 462–470.
- 27 Rosenstock J, Rossi L, Lin CS, et al. The effects of irbesartan added to hydrochlorothiazide for the treatment of hypertension in patients non-responsive to hydrochlorothiazide alone. J Clin Pharm Ther. 1998; 23: 433–440.
- 28 Coca A, Calvo C, Sobrino J, et al. Once-daily fixed-combination irbesartan 300 mg/hydrochlorothiazide 25 mg and circadian blood pressure profile in patients with essential hypertension. Clin Ther. 2003; 25: 2849–2864.
- 29 Howe P, Phillips P, Saini R, et al. The antihypertensive efficacy of the combination of irbesartan and hydrochlorothiazide assessed by 24-hour ambulatory blood pressure monitoring. Clin Exp Hypertens. 1999; 21: 1373–1396.
- 30 Raskin P, Guthrie R, Flack J, et al. The long-term antihypertensive activity and tolerability of irbesartan with hydrochlorothiazide. J Hum Hypertens. 1999; 13: 683–687.
- 31 Welsh L, Ferro A. Drug treatment of essential hypertension: the case for initial combination therapy. Int J Clin Pract. 2004; 58: 956–963.
- 32 Marino MR, Vachharajani NN. Pharmacokinetics of irbesartan are not altered in special populations. J Cardiovasc Pharmacol. 2002; 40: 112–122.
- 33 Lacourcière Y. A multicenter, randomized, double-blind study of the antihypertensive efficacy and tolerability of irbesartan in patients aged > or = 65 years with mild to moderate hypertension. Clin Ther. 2000; 22: 1213–1224.
- 34 Neutel JM, Saunders E, Bakris GL, et al. The efficacy and safety of low- and high-dose fixed combinations of irbesartan/HCTZ in patients with uncontrolled systolic blood pressure on monotherapy: the INCLUSIVE trial. J Clin Hypertens (Greenwich). 2005; 7: 578–586.
- 35 O'Brien E, Mee F, Atkins N, et al. Evaluation of three devices for self-measurement of blood pressure according to the revised British Hypertension Society Protocol: the Omron HEM-705CP, Philips HP5332, and Nissei DS-175. Blood Press Monit. 1996; 1: 55–61.
- 36 Douglas JG, Bakris GL, Epstein M, et al. 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.
- 37 National Kidney Foundation. K/DOQI clinical practice guidelines on hypertension and antihypertensive agents in chronic kidney disease. Am J Kidney Dis. 2004; 43(5 suppl 1): S1–S290.
- 38 American Diabetes Association. Standards of medical care in diabetes–2006. Diabetes Care. 2006; 29(suppl 1): S4–S42.
- 39 Fleiss JL. Statistical Methods for Rates and Proportions. 2nd ed. New York, NY: John Wiley & Sons; 1981.
- 40 Bristol-Myers Squibb Sanofi-Synthelabo Partnership. Avalide United States prescribing information. http://www.avalide.com/. Accessed January 27, 2006.
- 41 Hansson L. ‘Why don't you do as I tell you?’ Compliance and antihypertensive regimens. Int J Clin Pract. 2002; 56: 191–196.
- 42 Waeber B, Burnier M, Brunner HR. Compliance with antihypertensive therapy. Clin Exp Hypertens. 1999; 21: 973–985.
- 43 Sica DA. Rationale for fixed-dose combinations in the treatment of hypertension: the cycle repeats. Drugs. 2002; 62: 443–462.
