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

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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


Currently available combination therapies

Fixed-Dose CombinationBrand NameDose Range, Total, mg/da
Angiotensin II Receptor Blocker + Thiazide Diuretic
Azilsartan/chlorthalidoneEdarbyclor40/12.5; 40/25
Candesartan/HCTZAtacand HCT16/12.5; 32/12.5; 32/25
Eprosartan/HCTZTeveten HCT600/12.5; 600/25
Irbesartan/HCTZAvalide150/12.5; 300/25
Losartan/HCTZHyzaar50/12.5; 100/12.5; 100/25
Olmesartan/HCTZBenicar HCT20/12.5; 30/12.5
Telmisartan/HCTZMicardis HCT40/12.5; 80/12.5; 80/25
Valsartan/HCTZDiovan HCT80/12.5; 160/12.5; 160/25; 320/12.5
β-Blocker + Thiazide Diuretic
Atenolol/chlorthalidoneTenoretic50/25; 100/25
Bisoprolol/HCTZZiac2.5/6.25; 5/6.25; 10/6.25
Metoprolol tartrate/HCTZLopressor HCT50/25; 100/25; 100/50
Metoprolol succinate extended/release + HCTZDutoprol25/12.5; 50/12.5; 100/12.5
Nadolol + bendroflumethiazideCorzide40/5; 80/5
Propanolol + HCTZInderide40/25; 80/25
Calcium Channel Blocker + ACEI
Amlodipine/benazeprilLotrel2.5/10; 5/10; 5/20; 5/40; 10/20; 10/40
ACEI + Thiazide Diuretic
Benazepril/HCTZLotensin HCT5/6.25; 10/12.5; 20/12.5; 20/25
Captopril/HCTZCapozide25/15; 25/25; 50/15; 50/25
Enalapril/HCTZVaseretic10/25 (1-2)
Fosinopril/HCTZMonopril HCT10/12.5; 20/12.5
10/12.5; 20/12.5
Moexipril/HCTZUniretic7.5/12.5; 15/12.5; 15/25
Quinapril + HCTZAccuretic10/12.5; 20/12.5; 20/25
ACEI + Calcium Channel Blocker
Trandolapril/verapamilTarka2/180; 2/240; 4/240
Angiotensin II Receptor Blocker + Calcium Channel Blocker
Telmisartan/amlodipineTwynsta40/5; 40/10; 80/5; 80/10
Angiotensin II Receptor Blocker + Calcium Channel Blocker + Thiazide Diuretic
Calcium Channel Blocker + Angiotensin II Receptor Blocker
Amlodipine/olmesartanAzor5/20; 5/40; 10/20; 10/40
Amlodipine/valsartanExforge5/160; 10/160; 5/320; 10/320
Calcium Channel Blocker + Angiotensin II Receptor Blocker + Thiazide Diuretic
Amlodipine/valsartan/HCTZExforge HCT5/160/12.5; 10/160/12.5; 5/160/25; 10/160/25; 10/320/25
Central α-Agonist + Thiazide Diuretic
Aldoril D
250/15; 250/25
500/30; 500/50
Direct Renin Inhibitor + Angiotensin II Receptor Blocker
Aliskiren/valsartanValturna150/160; 300/320
Direct Renin Inhibitor + Calcium Channel Blocker
Aliskiren + amlodipineTekamlo150/5; 150/10; 300/5; 300/10
Direct Renin Inhibitor + Thiazide Diuretic
Aliskiren/HCTZTekturna HCT150/12.5; 150/25; 300/12.5; 300/25
Direct Renin Inhibitor + Calcium Channel Blocker + Thiazide Diuretic
Aliskiren/amlodipine/HCTZAmturnide150/5/12.5; 300/5/12.5; 300/5/25; 300/10/12.5; 300/10/25
Diuretic Combination (K+ Sparing + Thiazide)
Amiloride/HCTZSeveral generics5/50 (1-2)
Spironolactone/HCTZAldactazide25/25 (1/2-1)
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:;; Accessed June 27-28, 2012.

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