Running head: THIAZIDE DIURETICS VERSUS ANGIOTENSIN RECEPTOR 1

Thiazide Diuretics Versus Angiotensin Receptor Blockers in the Treatment of

Hypertension

Maegan Bell

Auburn University

Hypertension, or high blood pressure, plagues millions of Americans each year. It also

contributes to a variety of other cardiovascular incidents, including strokes and heart attacks,

which can greatly increase a patients risk of morbidity and mortality. The Joint National

Committee on Hypertension (JNC) released its eighth report (JNC 8) in 2013, highlighting the

criteria for diagnosing and treating hypertension. The JNC 8 classifies hypertension for adults

under 60 as systolic BP 140 and diastolic BP 90 mm Hg (Mahvan & Mlodinow, 2014, p.

575). Many times high blood pressure itself does not cause symptoms until

the damage to the end organ is severe enough to produce physical

symptoms, giving it the nick name, the silent killer (Staggs, 2009, p. 16).

Staggs (2009) goes on to explain, essentially only four primary mechanisms

are responsible to maintain the overall balance of blood pressure in the body;

these include the sympathetic/parasympathetic nervous system, the

baroreceptors, the renal system and antidiuretic hormone (p. 16). However,

the pathogenesis of essential hypertension is multifactorial and highly

complex (Madhur, 2014). There are multiple medication classes used alone

or in combination for the treatment of hypertension, which include, diuretics,

angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor

blockers (ARBs), beta-blockers, and calcium channel blockers. In addition to

lifestyle modifications, drug therapy can be useful and often necessary in the
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treatment of hypertension.

Diuretics are the first-line therapy in the treatment for hypertension

in the primary care setting (Woo & Wynn, 2012, p. 369). They can be used

either alone or in combination with other antihypertensive drugs. Diuretics

can be broken down into classes, including thiazide diuretics, loop diuretics

and potassium-sparing diuretics. Thiazide diuretics, such as

hydrochlorothiazide, act on the distal renal tubule to inhibit sodium

reabsorption (Woo & Wynn, 2012, p. 369). This lowers blood pressure

systemically by limiting the sodium reabsorption by the kidneys, allowing the

body to excrete more sodium and water, and limiting pressure on the

arteries.

Angiotensin receptor blockers are normally used for those patients

unable to tolerate ACE inhibitors. In this drug class, decreased blood pressure

is achieved by reducing the effects of Angiotensin, including induced

vasoconstriction, sodium retention, and aldosterone release (Madhur, 2014).

ARBs completely block the effects of Angiotensin II by blocking the

Angiotensin receptor themselves (Staggs, 2009, p. 18). According to Black,

Bailey, Zappe, and Samuel (2009), Valsartan is a valuable member of the

cardiorenal treatment armamentarium, with robust clinical trial evidence

demonstrating its ability to lower blood pressure and improve

cardiovascular health (p. 2410).

Hydrochlorothiazide, a diuretic, and valsartan, an ARB, are both used

for the treatment of hypertension in children and adults, although, valsartan

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should not be used in children under the age of six. Hydrochlorothiazide is a

Pregnancy Category B and safe to use during pregnancy, while valsartan is a

Pregnancy Category D and should be avoided. Advantages of diuretics, like

hydrochlorothiazide, are their ease of administration and low cost to the

patient (Staggs, 2009, p. 17). Disadvantages to hydrochlorothiazide include

electrolyte abnormalities, such as hypokalemia (Woo & Wynne, 2012).

Hydrochlorothiazide is also available in multiple combination forms, with

other antihypertensive medications, to aid in treatment options. The main

advantages of ARBs are the reduced incidence of cough and angio-edema

(Black, Bailey, Zappe, & Samuel, 2009, p. 2408). Although ARBs are

expensive, they are the drug of choice for patients who are young and white

and for patient with diabetes, HF, or MI, for whom they are most effective

and have the lowest incidence of adverse reactions (Woo & Wynn, 2012, p.

309). The major draw back to Valsartan is its danger to pregnant women.

Valsartan is also available in combination form, for example, with the diuretic

hydrochlorothiazide. Both diuretics and ARBs have multiple other uses than

treating hypertension, with valsartan used for the treatment of migraines

and diabetic neuropathy, and hydrochlorothiazide for edema associated with

heart failure.

JNC 8 guidelines were published in December 2013, almost a decade

after its predecessor JNC 7. These guidelines are simpler than those of JNC

7, with more evidence-based recommendations and less reliance of expert

opinion (Mahvan & Mlodinow, 2014, p. 574). The JNC 8 answers questions regarding when
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to initiate treatment, what kind of treatment is best for individual patients, as well as the best

drug choices. It also provides a helpful algorithm in the form of an easy to understand and

interpret flowchart.

In many patients, monotherapy has not been shown to effectively

reduce blood pressure and adding another drug to the treatment regimen

will often result in additive or synergistic effects (Black et al., 2009, p.

2398). Although JNC 8 stresses the importance of lowering blood pressure

through lifestyle modifications, primarily diet and exercise, it additionally

advocates for a 2-agent combination as a first line therapy for pressure

that exceeds 160/ 100 (Mahvan & Mlodinow, 2014, p.581). Drug selection should be

based on patient factors such as, blood pressure, age, weight, income, race, and gender.

Therefore, in accordance with the JNC8 recommendations, if monotherapy using

hydrochlorothiazide or valsartan is ineffective when combined with lifestyle modifications, then

combination therapy may be beneficial. Black et al. (2009) highlight in their article that for

patients whos BP is not controlled with a diuretic, combination therapy with an ARB/diuretic is

a more effective strategy (p. 2398). The combination drug of valsartan and hydrochlorothiazide

currently available in the United States is Diovan HCT.

Patient education regarding ARBs focuses on administration of the drug, adverse

reactions to expect and appropriate responses to each, and concomitant lifestyle management

(Woo & Wynne, 2012, p. 316). ARBs should be taken as prescribed, with or without food.

Hypotension is the most common side effect, and can be reduced by changing positions slowly

and carefully. Lifestyle changes include cardiac diet, smoking cessation, decreased alcohol

intake, weight loss if applicable, and moderate daily exercise. Diuretics should also be taken as
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prescribed, with evening doses no later in the day than 4 p.m. to decrease the chance of the

patient having to get up to the bathroom at night with diuresis (Woo & Wynne, 2012, p. 377). As

with ARBs, hypotensive responses are common. Diuretics can also cause electrolyte imbalances,

and lab work may need to be monitored, with special diets implemented during therapy. Lifestyle

management is the same as with ARBs. In addition, Black et al. (2009), found that the safety

and tolerability profile of valsartan/HCTZ is similar to, or better than, what would be expected

from each component given as monotherapy (pp. 2408-2409).

JNC 8 provides essential instructions for primary care providers, including nurse

practitioners, to utilize in the care of patients suffering from hypertension. Both

hydrochlorothiazide and valsartan are first-line therapies for the treatment of hypertension, and

should be chosen based on individual patient needs and considerations. Neither drug is

necessarily superior to the other when used alone in treatment. Each patient is different.

Although, evidence shows, if neither drug produces the desired result, a combination of the two

may be more successful in lowering resistant blood pressure.

References

Black, H.R., Bailey, J., Zappe, D., & Samuel, R. (2009). Valsartan: more than a decade of

experience. Drugs, 69(17), 2393-2414. doi:10.2165/11319460-000000000-00000

Madhur, M.S. (2014). Hypertension. Retrieved from Medscape website:

http://emedicine.medscape.com/article/241381-overview

Mahvan, T. D., & Mlodinow, S. G. (2014). JNC 8: What's covered, what's not, and what else to

consider. Journal Of Family Practice, 63(10), 574-584.

Woo, T. & Wynne, A. (2011). Pharmacotherapeutics for Nurse Practitioner Prescribers. (3rd ed.).

Philadelphia: F.A. Davis.

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