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Running head: HYPERTENSION TREATMENT
Hypertension Treatment Integrative Literature Review
Sarah Thomas
State University of New York Polytechnic Institute
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HYPERTENSION TREATMENT
Hypertension Treatment Integrative Literature Review
Hypertension is the most common condition that presents in primary care. About 1 in 3
US adults have high blood pressure (CDC, 2014). Hypertension is defined as a systolic blood
pressure (SBP) greater than 140 mm Hg and/or a diastolic blood pressure (DBP) greater than 90
mm Hg (James, et al., 2014). Hypertension can lead to myocardial infarction, stroke, renal failure
and death if not detected early and treated appropriately (James et al., 2014). It is known as the
“silent killer” because patients with elevated blood pressure are typically asymptomatic with no
warning signs unless target organ damage is involved (Dunphy, Winland Brown, & Thomas,
2011).
Although clinical guidelines exist for the treatment of hypertension, management and
adequate control still present as major clinical challenges for providers and National Health Care
Systems (Tocci, Borghi & Volpe, 2013). According to the National Health and Nutrition
Examination Survey (NHANES), only 53% of adults with hypertension are controlled with
blood pressures of less than 140/90 mm Hg. The goal of treatment in hypertensive patients is to
reduce cardiovascular and renal morbidity and mortality (James et al., 2014).
Purpose Statement
The purpose of this review is to perform an integrative analysis of the most current
literature. The literature review is aimed at finding the current state of science and best practice
guidelines for the treatment of hypertension. The goal is to provide scientific evidence that will
improve quality of care for patients with hypertension by providing direction and insight for
health care providers and institutions.
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HYPERTENSION TREATMENT
Methodology
Relevant articles for the purpose of this literature review were obtained using the State
University of New York Institute of Technology, Cayan Library electronic database.
MedlinePlus, CINAHL Plus with Full Text and PubMed were the primary databases utilized.
Centers for Disease Control, American Heart Association and the National Heart, Lung and
Blood Institute were also utilized for additional searches.
The key terms used to execute this literature review were ‘hypertension’, ‘hypertension
treatment’, ‘antihypertensive agents’, ‘hypertension drug therapy’, ‘blood pressure medications’
and ‘hypertension medications’. The literature search was restricted to research articles that
were published in academic journals and printed in the English language. The search was also
restricted to articles published between the years 2011 and 2015. Literature dated before 2011
was also reviewed for comparison and analysis. The articles were reviewed for relevance, sorted
by subject, and summarized for the purpose of this literature review. 12 quality research articles
that focus on the management and treatment of hypertension were finally chosen and an analysis
of these articles was completed (see Appendix A).
Treatment
There are seven major classes of effective antihypertensive medications and an array of
combinations designed to reduce pill burden and improve compliance to therapy. Still however,
only half of US adults with hypertension are adequately controlled (Cushman, 2012). The main
challenge for providers in managing hypertension is in choosing the most appropriate drug,
whether as initial treatment or add-on therapy (Cushman, 2012). Steps towards greater control of
hypertension are being made however, in large part due to the publication and widespread
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adoption of guidelines produced by the Joint National Committee on the Prevention, Detection,
Evaluation and Treatment of High Blood Pressure (Harman et al., 2013).
Pharmacologic Therapy
Monotherapy. According to Tocci, et al. (2013), the majority of physicians consider
ACE inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) the most useful, effective and
well tolerated options to start antihypertensive monotherapy treatment. Only a small number of
physicians consider the use of beta blockers (BB’s), calcium channel blockers (CCBs) or
diuretics (Tocci et al., 2013). Harman et al. (2013) discuss however that the African American
population demonstrate a reduced blood pressure response to monotherapy with ACEIs, or ARBs
compared with diuretics or calcium channel blockers (CCBs). African American patients using a
thiazide diuretic are more likely to have blood pressure controlled to their therapeutic target than
persons not taking thiazides (Harman et al., 2013).
Conversely, Giles et al. (2013) state that nebivolol (BB) is an effective first-line
monotherapy in adults aged 18-54 years with stage 1 or 2 hypertension. Although thiazide
diuretics are considered an effective treatment in the older population (55-69 years), they are less
effective with those aged 21-54 years (Giles et al., 2013). According to Giles et al. (2013)
treatment with nebivolol in this population results in significant SBP and DBP reductions in as
early as 2 weeks after initiation and improves overall blood pressure control regardless of sex,
race, ethnicity, stage of hypertension and obesity status. Sendur et al. (2014) also report that
nevibolol is an effective treatment option for monotherapy by significantly lowering blood
pressure and improving endothelial function. Participants seeing results with nevibolol in this
study have mean age of 50.1 (Sendur et al., 2014).
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Combination therapy. According to Bays, Zhu and Schumacher (2013), 75 % of
patients will require combination therapy to adequately control their blood pressure. In fact,
initial use of combination therapy compared with monotherapy may achieve earlier blood
pressure control, improve long-term adherence and reduce cardiovascular risk in many patients
(Bays, et al., 2013). According to Harman et al. (2013), if a patient’s blood pressure is greater
than 20 SBP/10 DBP mm Hg over their target; two medications should be prescribed as initiation
therapy. This is especially true for African Americans who often require more aggressive
treatment (Harman et al., 2013). The literature demonstrates that drug therapy combinations
which include thiazide diuretics provide the greatest blood pressure reduction and control (Bays
et al., 2013; Harman et al., 2013; Toth, 2014). Combinations that include diuretics are also
preferred in patients with high cardiovascular risk due to the benefits of fluid volume reduction
(Bays, et al., 2013).
Bays et al. (2013) reviewed and compared nine randomized, double-blind studies of the
ARB telmisartan and thiazide diuretic hydrochlorothiazide as compared with monotherapies. The
data demonstrates that telmisartan/hydrochlorothiazide significantly lowers blood pressure as
early as 1–4 weeks after therapy initiation and achieves greater goal attainment than with
monotherapies or placebo (Bays, et al., 2013) Similarly, Toth (2014) examines combination drug
therapy including a thiazide diuretic in patients who are at high cardiovascular risk and whose
blood pressure was not adequately controlled despite current drug therapy. The study involves
treatment with the triple-drug combination perindopril (ACEI) 10 mg/indapamide (thiazide
diuretic) 2.5 mg/amlodipine (CCB) 5 or 10 mg (Toth, 2014). Results indicate that reductions in
blood pressure can be noted just 1 month after the switch to perindopril/indapamide/amlodipine
in patients with resistant hypertension that were previously treated unsuccessfully with a wide
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array of antihypertensive agents (Toth, 2014). Participants demonstrated a mean blood pressure
decrease of 28.3 systolic and 13.8 diastolic mmHg and an overall control rate of 72% (Toth,
2014). Likewise, Harman et al. (2013) state that for African American patients, thiazide
diuretics are particularly effective for dual and combination therapy with one or more drugs from
other antihypertensive classes. African Americans represent a high proportion of adults with
hypertension, and there is a recognized need for more aggressive therapy and tailored therapy to
achieve adequate control in this ethnic group (Harman et al., 2013).
Blood Pressure Variability
Variability in blood pressure is associated with increased risk of stroke, coronary heart
disease, and mortality. Using antihypertensive agents to control blood pressure throughout a 24
hour period with minimal variability is of great clinical importance, especially among elderly
patients (Omboni, Malacco, Mallion, Fabrizzi & Volpe, 2013). Cardiovascular events tend to
occur most frequently with fluctuations in blood pressure, especially in the morning (Kario,
Kushiro, Termukai, Ishikawa, Hiramatsu, Kobayashi and Shimada, 2013). Morning SBP is one
of the strongest independent predictors for stroke among clinic, 24-hour, sleep, awake, evening,
and pre-awake blood pressures (Kario et al., 2013).
According to the literature, studies show that ACE inhibitiors are not as effective in
controlling blood pressure variability when compared with other antihypertensive agents
(Omboni, et al., 2013; Muntner, et al., 2014). Omboni et al. (2013) state that olmesartan (ARB)
is an effective antihypertensive in control morning blood pressure rise as compared with ramipril
(ACEI) which failed to provide adequate morning blood pressure control. Similarly, Muntner et
al. (2014) discuss methods in which to limit visit-to-visit variability in SBP (2014). Patients
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taking chlorthalidone (thiazide diuretic) or amlodipine (CCB) had lower variability of blood
pressure when compared with those taking lisinopril (ACEI).
Martinez-Garcia, Capote and Campos-Rodriguez (2014) also examine the management
and reduction of blood pressure variability by using continuous positive airway pressure (CPAP)
to reduce mean 24-hour blood pressure in patients with obstructive sleep apnea (OSA).
According to Martinez-Garcia et al. (2014), OSA is present in 70% of patients with
hypertension. The application of CPAP for 4 of more hours per night shows a significant
reduction in 24-hour mean blood pressure in patients with OSA as compared to those without
CPAP (Martinez-Garcia, et al., 2014).
Alternative Therapy
An important component in the strategy to decrease cardiovascular risk is the
recommendation for patients to adopt lifestyle changes that reduce blood pressure (Briasoulis &
Bakris, 2013). Data shows that lifestyle changes such as reduced salt intake, eating a healthy and
well-balanced diet, weight loss, aerobic exercise, and stress relief are known to reduce
cardiovascular risk (Briasoulis & Bakris, 2013). According to Houston and Sparks (2013),
essential nutritional deficiencies are common in individuals with hypertension, especially the
elderly. Macro and micronutrients are fundamental in the regulation of blood pressure and in
preventing organ damage. Houston and Sparks (2013) present data that support the use of
combination nutraceutical supplements to lower blood pressure. The research demonstrates that
an active daily blend of seven nutrients (vitamin C, grape seed extract, magnesium, vitamin B6,
biotin, vitamin D3, pyridoxine, and taurine) taken by hypertensive patients significantly lowers
both systolic and diastolic blood pressure with an average decrease of 15.9 mm Hg and 11.35
mm Hg respectively (Houston & Sparks, 2013).
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In addition to lifestyle and dietary changes, many additional modalities are being utilized
and evaluated due to their potential ability to lower blood pressure (Briasoulis & Bakris, 2013).
Non-traditional treatments are being used by a growing number of people for the prevention and
treatment of hypertension. According to Park et al. (2014), attempts to avoid potential side
effects of antihypertensive medications and failure of these treatments to control hypertension
are two commonly reported reasons patients use complementary and alternative medicine
(CAM). Qigong is a traditional Oriental medicine used to heal and prevent disease through
movement, meditation, breathing and energy flow (Park et al., 2014). According to Park et al.
(2014), qigong is an effective CAM for patients with both prehypertension and essential
hypertension with an average SBP decrease of 17.03 mm Hg and DBP decrease of 9.98 mm Hg.
Park et al. (2014) also state that no adverse events have been reported for qigong, while patients
report unwanted side effects related to their antihypertensive medications. According to the
American Heart Association, it is reasonable for individuals with blood pressure levels over
120/80 mm Hg to consider alternative therapies as adjuvant methods to help lower blood
pressure (Briasoulis & Bakris, 2013).
Analysis
Similarities and Differences
A trend that is apparent in much of the literature involves treatment options that reduce
variability of blood pressure readings. Omboni et al. (2013) and Martinez-Garcia et al. (2013)
explore both pharmacological and non-pharmacological options for reducing mean 24-hour
blood pressure. Kario et al. (2013) also discuss medications that provide sustained 24-hour blood
pressure lowering effects, while specifically targeting morning systolic blood pressure. Muntner
et al. (2014) focus on hypertensive agents that limit visit-to-visit variability in blood pressure.
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Both Omboni et al. (2013) and Muntner et al. (2014) conclude that ACEIs are not as effective in
controlling blood pressure variability as other antihypertensive agents such as CCBs and ARBs.
Another marked similarity among the literature is the use of thiazide diuretics in
pharmacological combinations that are used for treatment and management of hypertension.
Bays et al. (2013), Harman et al. (2013) and Toth (2014) all report effective treatment of
hypertension in combinations that that include a thiazide diuretic. Bays et al. (2013) and Harman
et al. (2013) present information on dual-therapy with the inclusion of hydrochlorothiazide while
Thoth (2014) focuses on triple combination therapy that includes indapamide.
Age also presents as another similarity among the literature. The majority of research
focuses on older adult populations above the age of 55 years. This could be in large part due to
the fact that hypertension generally presents in the older population and is a very frequent
condition among persons age 65 years and over (Omboni, et al., 2014). Harman et al. (2013),
Kario et al. (2013) and Muntner et al. (2014) all include research findings with a mean age of 60
or above. Omboni et al. (2013) specifically include participants age 60 years and older in their
research. Bays et al. (2013), Martinez-Garcia et al. (2013) and Tocci et al. (2013) present
findings with a mean age of 54 or above. Adversely, Giles et al. (2013) specifically target adults
with hypertension aged 54 and younger. Sendur et al. (2014) also present data for participants
with a mean age of 50.1 years. Both of these studies conclude that nevibolol is an effective
hypertensive medication as monotherapy for this age group. According to Giles et al. (2013) this
population has a different hemodynamic profile of hypertension when compared with those 55
and older, therefore warranting a separate assessment in regards to treatment.
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Conclusion
It is evident from the literature that many different treatment options and medications are
available that are effective in treating and managing hypertension. Options for treatment
however may vary based on the population being treated. Controlling blood pressure to below
target goals proves to be more difficult in certain populations such as the elderly and African
Americans. It is also apparent that younger populations with hypertension may require different
types of therapy based on their differences in cellular and cardiovascular function.
There is an abundance of literature supporting different medication classes and treatments
in the older adult population due to their high incidence of hypertension. Only one study in this
review specifically targets individuals under the age of 55. A second study however presents
similar results with the same medication (nevibolol) on patients with newly diagnosed
hypertension and had a statistically lower mean age (50.1) than the rest of the studies. Therefore,
the logical direction for treatment research at this time would be in the younger adult population.
Obesity, especially childhood obesity, is becoming an epidemic, and it is known that there is a
positive correlation between obesity, high blood pressure and higher risks of cardiovascular
related illness and mortality. According to the reviewed literature, nevibolol (BB) is an effective
first-line treatment for hypertensive patients age 54 and below due to its specific action on
endothelial function, which plays a large part in the typical etiology of hypertension in younger
patients. In looking at the current published guidelines for hypertension however, BBs are not
typically utilized as first line monotherapy treatment. This may be due to the fact that the
research and literature guiding these publications is heavily targeting older adults.
Another conclusion that can be made from the literature analysis is that a growing
number of patients are seeking out alternative therapies to medications. Whether it is due to
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adverse medication affects, financial burden or not being properly controlled on medications,
CAM therapy is becoming a part of many treatment regimens. Patients are going to be requesting
information and asking questions about these treatment modalities and want the opinions of
medical professionals. They are going to wonder if what they read on the internet or saw on
television or what their neighbor has tried will work on them too. It is also the statement of the
American Heart Association that alternative therapies have a legitimate place in the management
of hypertension. In order to provide patients with the most useful and up-to-date information and
recommendations, clinicians need to become more aware of the CAM therapies that are available
and get familiar with those that have been shown effective in managing hypertension. All
treatment avenues should be utilized in the battle to reduce cardiovascular risk, and in an attempt
to increase the percentage of people whose blood pressure is adequately controlled.
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References
Bays, H., Zhu, D. & Schumacher, H. (2014). Single-pill combination of telmisartan and
hydrochlorothiazide: studies and pooled analyses of earlier hypertension treatment. High
Blood Pressure and Cardiovascular Prevention, 21(2), 119-126.
Briasoulis, A. & Bakris, G. (2013). Complementary alternative therapies for hypertension: Is it
worth it? Retrieved from American Heart Association
Centers for Disease Control and Prevention. (2014). High Blood Pressure. Retrieved from
http://www.cdc.gov/bloodpressure/
Cushman, W. (2012). Rethinking the role of thiazide-type diuretics in the management of
hypertension. Journal of Family Practice, 61(8), S15-S18.
Giles, T., Khan, B., Lato, J., Brener, L. Ma, Y. & Lukic, T. (2013). Nebivolol monotherapy in
younger adults (younger than 55 years) with hypertension: A randomized, placebocontrolled trial. Official Journal of the American Society of Hypertension, Inc., 15(9),
687-693
Dunphy, L., Winland Brown, J., Porter, B., & Thomas, D. (2011). Primary Care: The Art and
rd
Science of Advanced Practice Nursing. 3 Edition. Philadelphia: F.A Davis.
Harman, J., Walker E., Charbonneau, V., Akylbekova, E., Nelson, C., Wyatt, S. (2013).
Treatment of hypertension among African Americans: The Jackson heart study. Official
Journal of the American Society of Hypertension Inc., 15(6), 367-374.
Houston, M. & Sparks, W. (2013). Combination nutraceutical supplement lowers blood pressure
in hypertensive individuals. Integrative Medicine, 12(3), 22-29.
James, P.A., Oparil, S., Carter, B.L., Cushman, W.C., Dennison-Himelfarb, C., Handler, J.,
Lackland, D.T., LeFevre, M…Ortiz, E. (2014). 2014 Evidence-based guidelines for the
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management of high blood pressure in adults. Report from the panel members appointed
to the eighth joint national committee (JNC 8). Journal of the American Medical
Association, 311(5), 507-520.
Kario, K., Saito, I., Teramukai, S., Ishikawa, Y., Hiramatsu, K., Kobayashi, F & Shimada, K.
(2013). Effect of the angiotensin II receptor antagonist olmesartan on morning home
blood pressure in hypertension: HONEST study at 16 weeks. Journal of Human
Hypertension, 27(12), 721-728.
Martinez-Garcia, M., Capote, F. & Campos-Rodriguez, F. (2014). In patients with obstructive
sleep apnea and resistant hypertension, CPAP reduced 24-hour blood pressure. Journal of
the American Medical Association, 310, 2407-15.
Muntner, P., Levitan, E., Lynch, A., Simpson, L., Whittle, J., Davis, B…Oparil, S. (2014) Effect
of chlorthalidone, amlodipine, and lisinopril on visit-to-visit variability of blood pressure:
Results from the antihypertensive and lipid-lowering treatment to prevent heart attack
trial. The Journal of Clinical Hypertension, 16(5), 323-330.
Omboni, S., Malacco, E., Mallion, J., Fabrizzi, P. & Volpe, M. (2014). Olmesartan vs ramipril in
elderly hypertensive patients: review of data from two published randomized, doubleblind studies. High Blood Pressure and Cardiovascular Prevention, 21, 1-19.
Park, J., Hong, S., Lee, M., Park, T., Kang, K., Jung, H., Shin, K. & Liu, Y. (2014). Randomized,
controlled trial of Qigong for treatment of prehypertension and mild essential
hypertension. Alternative Therapies, 20 (4), 21.
Sandur, M., Guven, G., Yorgun, H., Ates, A., Canpolat, U., Sunman, H., Karaham, S., Kaya, B &
Aytemir, K. (2014). Effect of antihypertensive therapy on endothelial markers in newly
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diagnosed stage 1 hypertension: a randomized single-centre study. Anadolu Kardiyol
Derg, 14, 363-369.
Tocci, G., Borghi, C. & Volpe, M. (2012). Clinical management of patients with hypertension
and high cardiovascular risk. High Blood Pressure and Cardiovascular Prevention 21,
107-117.
Toth, K. (2014). Antihypertensive efficacy of triple combination perindopril/indapamide plus
amlodipine in high-risk hypertensives: Results of the PIANIST study. American Journal
Cardiovascular Drugs, 14, 137-145.
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Appendix A
Studies
Focus
Subjects
Population
Age
Method
Findings
Bays, et al.
(2013)
Telmisartan + HCTZ
combo for earlier HTN
management
N = 5.358
From 9
studies
Adult patients with
hypertension and failed
monotherapy
Mean 54 y
Randomized, doubleblind studies
BP targets safely, and more rapidly
achieved with combo of T/H as initial
therapy and after failed monotherapy
when
compared with either monotherapy
Giles et al.
(2013)
Nevibolol
monotherapy in adults
< 55 years
N = 414
nebivolol
N= 207
placebo
Adult patients with BP
> 140/90 age 18-54
Men 55.5%
Mean 45.3 y
Phase IV, multicenter,
randomized, doubleblind, placebocontrolled, parallelgroup trial
Nebivolol treatment resulted in significant
DBP and SBP reductions (observed as
early as 2 weeks after treatment initiation)
and improvement in BP control among
adult patients mean age: 45.3 yea
Harman, et al.
(2013)
Treatment of
hypertension in African
Americans
N = 5,302
3393women
1909 men
African American
Adults with
hypertension living in
Jackson, Mississippi
60 + or - 11
Large scale medical
study, community
centered
Houston &
Sparks (2013)
Nutraceutical
supplements to lower
BP
N = 22
intervention
group
N= 20
control
n/a
randomized, doubleblind, placebo
controlled clinical
trial
Kario, et al.
(2013)
Effect of olmesartan on
morning home BP’s
Average 64.8 +
or – 11.9 years
Prospective
observational study
with 2 year f/u
MartinezGarcia, et al.
(2013)
Reduction of 24 hr BP
in pts with OSA with
CPAP
18-75 y
Mean 56
Randomized multicenter trial
Muntner, et al.
(2014)
Which
antihypertensive agents
limit visit-to-visit
variability in BP
Mean 66.8 y
Multi-center
randomized control
trial ALLHAT
chlorthalidone and amlodipine were
associated with lower VVV of BP when
compared with lisinopril
Omboni, et al.
(2013)
Olmesartan vs
Ramipril in elderly pts
with HTN
N = 1426
Adult Patients with
diagnosed
hypertension
23 females
19 males
olmesartan-naive
patients with essential
htn and no history of
recent acute
cardiovascular events
Pts with OSA and
primary resistant HTN
uncontrolled despite
the use of 3 or more
medications
Pts with HTN at 623
clinical sites across the
United States,Canada,
Puerto Rico, and the
US Virgin Islands
Elderly patients with
mild-moderate
essential HTN
most commonly used medication
diuretics, taken by 65% of treated
persons. African Americans more difficult
to control and may need use of different
med classes
significant reduction of SBP over 4-week
period with treatment using standardized
blend of seven nutrients. Larger groups
#’s and longer treatment periods
recommended
both clinic and morning home BP in all,
DM and CKD patients improved with 16week olmesartan-based treatment. Results
showed a sustained 24-hour BP-lowering
effect of olmesartan.
Continuous positive airway pressure
reduced mean 24-hr BP in pts with OSA
and resistant HTN
65-89 y
Randomized, doubleblind studies
Park, et al.
(2014)
effect of
qigong on
prehypertension and
mild hypertension
Olmesartan or
nebivolol on BP and
endothelial function
markers
N = 40
19 qigong
21 control
SBP between 120 and
159 mm Hg and/or
DBP between 80 and
99 mm Hg.
Newly diagnosed
Patients with Stage 1
essential HTN
50 males
19 - 65 y
Randomized, control
trial
Olmesartan superior to Ramipril in
providing sustained and more
homogeneous BP control throughout 24-h
period. It is effective first line option
qigong effective intervention in reducing
BP in prehypertension and mild
hypertension
Mean 52 + or – 9
years
Mean Nevibolol
= 50.1
Olmesartan=54.9
Mean 54.2 years
Randomized open
label study
Both olmesartan and nebivolol caused
similar responses in BP and flow
mediated vasodilatation and endothelial
function improved
Observational, crosssectional survey
Over 18 years
Multi-center,
prospective,
observational, noninterventional, 4
month open-label
clinical study
RAS blocking agentsare preferred choice
by the majority both for starting and for
up-titrating
combination therapies, (RAS
blocking agents plus either diuretics or
calcium-channel blockers, has reported to
be the most effective option for sustained
control and also high levels of adherence
Mean BP decreased and mean HR
decreased. BP targets reached by 72% of
patients, 85.7% of patients with grade 1
HTN 69.5% for grade 2 HTN in patients
who failed to meet goals prior
Sendur et al.
(2014)
Tocci, et al.
(2013)
physicians’ attitudes
and preferences
for daily management
of hypertension
Toth, K. (2014)
Efficacy of triple
combination
Perindopril/Indapamide
plus amlodipine in high
pts with difficult to
control HTN
N=21,341
50.5%
women
N = 194
65% men
N=33,357
55% male
N = 85
N=557
physicians
478 male
N=4,731
2,350
female
Physicians. 261
specialized and 296
general practitioners
Pts with high CV over
18 years of age
withnHTN not
properly controlled
despite therapy
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