MODULE 4: Enhancing Adherence with Antihypertensives: The Role of Fixed-Dose Combinations and Home Blood Pressure Monitoring

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Medical Education Library

MODULE 4: Enhancing Adherence with Antihypertensives: The Role of Fixed-Dose Combinations and Home Blood Pressure Monitoring

August 2012 · Vol. 61, No. 08 Suppl: S23-S26,S35

By

Louis Kuritzky, MD

References

1. Egan BM, Zhao Y, Axon RN. US trends in prevalence, awareness, treatment, and control of hypertension, 1988-2008. JAMA. 2010;303(20):2043-2050.

2. Vrijens B, Vincze G, Kristanto P, Urquhart J, Burnier M. Adherence to prescribed antihypertensive drug treatments: longitudinal study of electronically compiled dosing histories. BMJ. 2008;336(7653):1114-1117.

3. Nelson MR, Reid CM, Ryan P, Willson K, Yelland L. Self-reported adherence with medication and cardiovascular disease outcomes in the Second Australian National Blood Pressure Study (ANBP2). Med J Aust. 2006;185(9):487-489.

4. Muszbek N, Brixner D, Benedict A, Keskinaslan A, Khan ZM. The economic consequences of noncompliance in cardiovascular disease and related conditions: a literature review. Int J Clin Pract. 2008;62(2):338-351.

5. Jamerson K, Bakris GL, Dahlöf B, et al; . ACCOMPLISH Investigators. Exceptional early blood pressure control rates: the ACCOMPLISH trial. Blood Press. 2007;16(2):80-86.

6. Gradman AH, Basile JN, Carter BL, et al. Combination therapy in hypertension. J Am Soc Hypertens. 2010;4(2):90-98.

7. World Health Organization. Adherence to long-term therapies: evidence for action. http://apps.who.int/medicinedocs/en/d/Js4883e/. Published 2003. Accessed March 21, 2012.

8. 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.

9. Osterberg L, Blaschke T. Adherence to medication. N Engl J Med. 2005;353(5):487-497.

10. 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.

11. Kaufman DW, Kelly JP, Rosenberg L, Anderson TE, Mitchell AA. Recent patterns of medication use in the ambulatory adult population of the United States: the Slone survey. JAMA. 2002;287(3):337-344.

12. Sica DA. Rationale for fixed-dose combinations in the treatment of hypertension: the cycle repeats. Drugs. 2002;62(3):443-462.

13. Paulis L, Steckelings UM, Unger T. Key advances in antihypertensive treatment. Nat Rev Cardiol. 2012;9(5):276-285.

14. Wood S. TIPS 2: Full-dose polypill boosts efficacy, with no increased side effects. theHeart.org Web site. http://www.theheart.org/article/1387105.do?utm_campaign=newsletter&utm_medium=email&utm_source=20120419_EN_Heartwire. Published April 19, 2012. Accessed April 20, 2012.

15. Hilleman DE, Ryschon KL, Mohiuddin SM, Wurdeman RL. Fixed-dose combination vs monotherapy in hypertension: a meta-analysis evaluation. J Hum Hyper-tens. 1999;13(7):477-483.

16. 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.

17. 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.

18. Gerbino PP, Shoheiber O. Adherence patterns among patients treated with fixed-dose combination versus separate antihypertensive agents. Am J Health Syst Pharm. 2007;64(12):1279-1283.

19. Brixner DI, Jackson KC, II, 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.

20. Baser O, Andrews LM, Wang L, Xie L. Comparison of real-world adherence, healthcare resource utilization and costs for newly initiated valsartan/amlodi-pine single-pill combination versus angiotensin receptor blocker/calcium channel blocker free-combination therapy. J Med Econ. 2011;14(5):576-583.

21. Simons LA, Ortiz M, Calcino G. Persistence with a single pill versus two pills of amlodipine and atorvastatin: the Australian experience, 2006-2010. Med J Aust. 2011;195(3):134-137.

22. 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.

23. Makaryus AN, Friedman EA. Patients’ understanding of their treatment plans and diagnosis at discharge. Mayo Clin Proc. 2005;80(8):991-994.

24. Harmon G, Lefante J, Krousel-Wood M. Overcoming barriers: the role of providers in improving patient adherence to antihypertensive medications. Curr Opin Cardiol. 2006;21(4):310-315.

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27. Calhoun DA, Jones D, Textor S, et al. Resistant hypertension: diagnosis, evaluation, and treatment: A scientific statement from the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research. Hypertension. 2008;51(6):1403-1419.

28. Pickering TG, White WB. American Society of Hypertension Writing Group. When and how to use self (home) and ambulatory blood pressure monitoring. J Am Soc Hypertens. 2008;2(3):119-124.

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32. Ogedegbe G, Schoenthaler A. A systematic review of the effects of home blood pressure monitoring on medication adherence. J Clin Hypertens (Greenwich). 2006;8(3):174-180.

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Table of Contents

MODULE 1: Historical Review of Evidence-Based Treatment of Hypertension

MODULE 2: Rethinking the Role of Thiazide-Type Diuretics in the Management of Hypertension: Which Diuretic Is Best?

MODULE 3: Using Thiazide-Type Diuretics in African Americans with Hypertension

MODULE 4: Enhancing Adherence with Antihypertensives: The Role of Fixed-Dose Combinations and Home Blood Pressure Monitoring

Post-Tests and Evaluations

DISCLOSURE

Dr Kuritzky is a paid consultant to Takeda Pharmaceuticals International, Inc.

Although an estimated 1 out of 3 people in the United States has been diagnosed with hypertension, data from the 2007-2008 National Health and Nutrition Examination Survey found that just 72% are currently being treated and, of those, just half have their blood pressure (BP) controlled with lifestyle changes and/or medication.¹

The failure of so many people with hypertension to obtain BP control, despite the availability of numerous effective medications, is partially due to a lack of adherence to recommended treatments (eg, taking medication, following a diet, and executing lifestyle changes). Adherence is a significant problem in hypertension and evidence shows that just half of patients who initiate drug therapy are persistent with treatment after 1 year.²

Although few studies link nonadherence with long-term outcomes, 1 study found that patients who “forgot” to take their antihypertensive medication were nearly one-third more likely to experience a cardiovascular event or death (hazard ratio [HR], 1.28; 95% confidence interval [CI], 1.04-1.57).³ Adherence is important not only for the health of the patient, but also to provide overall cost savings from the reductions of hospitalizations for complications from an untreated disease.⁴

Barriers to adherence

A significant contributor to nonadherence is treatment complexity, which manifests in hypertension as pill burden. Up to 75% of patients will require more than 1 medication to control their BP; those with resistant hypertension will require 4 or more.^5,6 These medications must often be taken at different times of the day, with varying frequency.^6-9

Reducing the number of daily doses has been consistently found to enhance adherence, and should be considered routinely as a first-line strategy. Complex strategies (eg, group visits, designated office staff to assist hypertensive patients, pharmacist consultation and comanagement, exercise counseling, dietary counseling, multidisciplinary hypertension team care, specific interviewing techniques such as motivational interviewing) are promising, but individual clinicians may not have the resources to take advantage of such labor-intensive intervention. Further, when multimodal intervention is employed, it is often difficult to discern which component(s) of the intervention were most impactful, unless multifactorial study design is employed, which it rarely is. We await further randomized controlled trials in this regard.

A study of approximately 85,000 members of a large managed care organization found that the greater the number of antihypertensive medications prescribed, the lower the rate of patient adherence. Just 63% of those receiving 3-drug regimens and 55% of those receiving 4-drug regimens were completely adherent.¹⁰

In addition, many patients with hypertension, particularly older patients, have comorbid conditions (eg, dyslipidemia or diabetes) that also require treatment, leading to increased treatment complexity and pill burden.^11,12

One option for reducing pill burden is the use of fixed-dose therapies ( TABLE ). Since 2000, many new fixed-dose combinations, including at least 3 triple therapies, have entered the market.¹³ In addition, a so-called “poly-pill” that combines aspirin, 3 antihypertensives, and a statin is under investigation and demonstrating good results in reducing BP and cholesterol levels.¹⁴

TABLE

Currently available combination therapies

Fixed-Dose Combination	Brand Name	Dose Range, Total, mg/d^a
Angiotensin II Receptor Blocker + Thiazide Diuretic
Azilsartan/chlorthalidone	Edarbyclor	40/12.5; 40/25
Candesartan/HCTZ	Atacand HCT	16/12.5; 32/12.5; 32/25
Eprosartan/HCTZ	Teveten HCT	600/12.5; 600/25
Irbesartan/HCTZ	Avalide	150/12.5; 300/25
Losartan/HCTZ	Hyzaar	50/12.5; 100/12.5; 100/25
Olmesartan/HCTZ	Benicar HCT	20/12.5; 30/12.5
Telmisartan/HCTZ	Micardis HCT	40/12.5; 80/12.5; 80/25
Valsartan/HCTZ	Diovan HCT	80/12.5; 160/12.5; 160/25; 320/12.5
β-Blocker + Thiazide Diuretic
Atenolol/chlorthalidone	Tenoretic	50/25; 100/25
Bisoprolol/HCTZ	Ziac	2.5/6.25; 5/6.25; 10/6.25
Metoprolol tartrate/HCTZ	Lopressor HCT	50/25; 100/25; 100/50
Metoprolol succinate extended/release + HCTZ	Dutoprol	25/12.5; 50/12.5; 100/12.5
Nadolol + bendroflumethiazide	Corzide	40/5; 80/5
Propanolol + HCTZ	Inderide	40/25; 80/25
Calcium Channel Blocker + ACEI
Amlodipine/benazepril	Lotrel	2.5/10; 5/10; 5/20; 5/40; 10/20; 10/40
ACEI + Thiazide Diuretic
Benazepril/HCTZ	Lotensin HCT	5/6.25; 10/12.5; 20/12.5; 20/25
Captopril/HCTZ	Capozide	25/15; 25/25; 50/15; 50/25
Enalapril/HCTZ	Vaseretic	10/25 (1-2)
Fosinopril/HCTZ	Monopril HCT	10/12.5; 20/12.5
Lisinopril/HCTZ	Prinzide Zestoretic	10/12.5; 20/12.5 20/25
Moexipril/HCTZ	Uniretic	7.5/12.5; 15/12.5; 15/25
Quinapril + HCTZ	Accuretic	10/12.5; 20/12.5; 20/25
ACEI + Calcium Channel Blocker
Trandolapril/verapamil	Tarka	2/180; 2/240; 4/240
Enalapril/felodipine	Lexxel	5/5
Angiotensin II Receptor Blocker + Calcium Channel Blocker
Telmisartan/amlodipine	Twynsta	40/5; 40/10; 80/5; 80/10
Angiotensin II Receptor Blocker + Calcium Channel Blocker + Thiazide Diuretic
Olmesartan/amlodipine/HCTZ	Tribenzor	40/10/25
Calcium Channel Blocker + Angiotensin II Receptor Blocker
Amlodipine/olmesartan	Azor	5/20; 5/40; 10/20; 10/40
Amlodipine/valsartan	Exforge	5/160; 10/160; 5/320; 10/320
Calcium Channel Blocker + Angiotensin II Receptor Blocker + Thiazide Diuretic
Amlodipine/valsartan/HCTZ	Exforge HCT	5/160/12.5; 10/160/12.5; 5/160/25; 10/160/25; 10/320/25
Central α-Agonist + Thiazide Diuretic
Methyldopa/HCTZ	Aldoril Aldoril D	250/15; 250/25 500/30; 500/50
Direct Renin Inhibitor + Angiotensin II Receptor Blocker
Aliskiren/valsartan	Valturna	150/160; 300/320
Direct Renin Inhibitor + Calcium Channel Blocker
Aliskiren + amlodipine	Tekamlo	150/5; 150/10; 300/5; 300/10
Direct Renin Inhibitor + Thiazide Diuretic
Aliskiren/HCTZ	Tekturna HCT	150/12.5; 150/25; 300/12.5; 300/25
Direct Renin Inhibitor + Calcium Channel Blocker + Thiazide Diuretic
Aliskiren/amlodipine/HCTZ	Amturnide	150/5/12.5; 300/5/12.5; 300/5/25; 300/10/12.5; 300/10/25
Diuretic Combination (K+ Sparing + Thiazide)
Amiloride/HCTZ	Several generics	5/50 (1-2)
Spironolactone/HCTZ	Aldactazide	25/25 (1/2-1)
Triamterene/HCTZ	Dyazide Maxide	37.5/25 (1/2-1) 37.5/25; 75/50
ACEI, angiotensin-converting enzyme inhibitor; HCTZ, hydrochlorothiazide. ^aAll 1 dose/d unless otherwise noted. Source: Available at: http://www.RxList.com; http://www.Drugs.com; http://www.empr.com/combination-treatments-for-hypertension-chart/article/191718/. Accessed June 27-28, 2012.