Review and Update on Treatments for Hypertension

NOVEMBER 01, 2003
Lori C. Brown, PharmD

    Blood pressure is the force against which the heart must pump in order to perfuse the body with blood. Systolic and diastolic pressures are measured. Systolic pressure is the pressure in the blood vessels when the heart contracts and pumps blood. Diastolic pressure is the pressure in the vascular system when the heart is filling. Hypertension is defined as systolic blood pressure >140 mm Hg or diastolic blood pressure >90 mm Hg.

    Hypertension affects about 1 in 4 adult Americans.1 The disease usually occurs in people over the age of 35. Its highest prevalence is in middle-aged and elderly people, in African Americans, and in people who are overweight.2 This common but dangerous disease directly increases the risk of myocardial infarction (MI), congestive heart failure (CHF), stroke, renal failure, atherosclerosis, and dementia.

    Although high blood pressure usually does not have symptoms or make people feel bad, it is important to educate patients on the complications and effects of uncontrolled hypertension. Hypertension leads to an overworked heart and blood vessels, which tire over time, and serious complications may arise. When hypertension is well managed, however, cardiovascular morbidity and mortality decline, and the risk of stroke, coronary artery disease, and congestive heart failure decreases. Unfortunately, US data show that only 54% of hypertensive patients are treated, and only 28% are treated adequately.1

Classification of Hypertension

    The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) provides the following classes of hypertension.

  • Prehypertension: defined as systolic blood pressure of 120 to 139 mm Hg or diastolic blood pressure of 80 to 89 mm Hg. Prehypertensive patients should be educated about and encouraged to adopt healthy lifestyle changes in order to minimize their cardiovascular disease risk.

  • Stage 1 hypertension: defined as systolic blood pressure of 140 to 159 mm Hg or diastolic blood pressure of 90 to 99 mm Hg

  • Stage 2 hypertension: defined as systolic blood pressure >160 mm Hg or diastolic blood pressure >100 mm Hg (Table 1)3

When to Treat

    The goal of hypertensive therapy, whether drug or nondrug, is to prevent cardiovascular disease and death. Each patient?s therapy should be based on his or her untreated blood pressure level and the presence of cardiovascular risk. Nondrug therapy (lifestyle modification) is indicated for all patients with hypertension. Nondrug therapy can be used alone for 6 months for patients who have risk factors and up to 12 months for patients without risk factors. If lifestyle modifications fail to bring blood pressure to goal levels, drug therapy can be added. Drug therapy is indicated as the first line of therapy, however, if a patient has diabetes or cardiovascular, renal, cardiac, cerebrovascular, or retinal disease.

How to Treat

Nondrug Therapies for Hypertension

    Weight reduction, sodium restriction, smoking cessation, and increased physical activity are some of the lifestyle modifications that can help patients achieve their blood pressure goals and reduce cardiovascular disease risk. For example, sodium causes fluid retention, which can exacerbate hypertension. Restricting the daily intake of sodium to <2 g has been shown to reduce both systolic and diastolic blood pressures.4 It is important to educate patients with hypertension about the significant effect a healthy lifestyle can have (Table 2).3 Because hypertension is most often not accompanied by symptoms, patients should monitor their blood pressure regularly. Monitoring devices include manual-inflation cuffs with sphygmomanometer or digital display and automatic-inflation cuffs with digital display with or without memory. Patients should be encouraged to keep a log of their blood pressure readings, since blood pressure does have variations throughout the day.

Drug Therapies

    Diuretics. Diuretics are effective antihypertensive agents because they decrease plasma volume, thereby reducing the pressure against which the heart has to pump. Additionally, they have been shown to reduce morbidity and mortality associated with hypertension. 5 The JNC 7 guidelines recommend diuretics as first-line therapy for hypertension. 3 There are 4 general classes of diuretics: loop, thiazide (or thiazidelike), potassium-sparing, and osmotic. Loop diuretics, such as furosemide, increase sodium excretion, resulting in high urine output, and they are most commonly used for edema. Thiazide and thiazide-like diuretics, such as hydrochlorothiazide, cause increased sodium and chloride excretion and are used most often to treat hypertension. Potassium-sparing diuretics, such as triamterene, are the least potent of all diuretics and often are used in conjunction with other classes of diuretics to minimize potassium loss. Osmotic diuretics are the least commonly used of all diuretics and are not used to treat hypertension.

    Beta-Blockers. Like diuretics, betablockers reduce morbidity and mortality associated with hypertension.5 Betablockers reduce the workload of the heart by acting on the sympathetic nervous system. Beta-receptor activation results in increased heart rate and increased force of the heartbeat. Betablockers inhibit this reaction, thereby easing cardiac stress by slowing down the heart rate and decreasing the heart muscle?s contractile force. For these reasons, beta-blockers are used to reduce blood pressure in patients who have had an MI or who have CHF.

    The 2 types of beta-receptors are beta-1 and beta-2 receptors. Beta-1 receptors are found primarily in the heart, and beta-2 receptors are found in the lungs and blood vessels. Beta-1 selective beta-blockers are preferred over nonselective agents for the treatment of hypertension and other cardiac conditions. Nonselective betablockers antagonize both beta-1 and beta-2 receptors and therefore produce noncardiac effects, such as bronchoconstriction and vasoconstriction. Nonselective agents should be avoided in patients with respiratory disease such as asthma or chronic obstructive pulmonary disease. Beta-blocker therapy should be initiated at low doses and titrated upward slowly, so as to minimize the risk of slowing the heart rate down too quickly.

    Angiotensin-Converting Enzyme (ACE) Inhibitors. ACE inhibitors inhibit the breakdown of bradykinin, thereby inhibiting the conversion of angiotensin I to angiotensin II. Angiotensin II is a vasoconstrictor that raises blood pressure, so ACE inhibitors work by vasodilation, without causing reflex tachycardia. ACE inhibitors are the preferred antihypertensive therapy for patients with diabetes because they protect the kidneys from the disease?s harmful effects. The most common side effect of ACE inhibitor therapy is a dry cough, which is a result of bradykinin degradation. ACE inhibitors also can increase serum potassium. A rare but very serious side effect of ACE inhibitors is angioedema, which is characterized by swollen lips and tongue.

    Angiotensin II Receptor Blockers (ARBs). These drugs block the effects of angiotensin II without affecting bradykinin, and therefore they often are used in patients who cannot tolerate ACE inhibitor therapy due to cough. Like ACE inhibitors, ARBs have been shown to protect renal function in patients with type 2 diabetes and nephropathy. ARBs, however, generally are more expensive than ACE inhibitors.6

    Calcium-Channel Blockers. These agents prevent the flow of calcium into the heart muscle cells and blood vessels, resulting in reduced work for the heart and vasodilation. Calcium-channel blockers are the preferred antihypertensive therapy for patients with coronary artery disease (angina) or arrhythmias. Edema and constipation are the 2 most common potential side effects with calciumchannel blocker therapy.

    Alpha-Blockers. These blockers are often used in patients who have hypertension and benign prostatic hyperplasia (BPH) because these medications reduce blood pressure and relieve BPH symptoms. They are, however, associated with more drowsiness and lethargy than other antihypertensive classes.

Putting It All Together: JNC 7 Guidelines

    The JNC 7 Clinical Guidelines were released May 14, 2003. According to these guidelines, most patients should receive a low-dose thiazide diuretic as first-line therapy for hypertension. Usually, more than 1 therapy is needed to bring the patient to his or her goal blood pressure. Second and even third or fourth agents from other classes can be added, depending on patient-specific factors (ethnicity, comorbidities, cost considerations, etc).3

    Antihypertensive medications are effective in helping patients achieve their blood pressure goals. Because hypertension is most often a symptomless disease, antihypertensive therapy has the potential to make patients feel worse than the condition being treated did. Many patients with hypertension discontinue their medications due to a lack of understanding about the disease and its complications, a lack of symptoms, the cost of therapy, or the complexity of the medication regimen.3 Pharmacists and other health care providers should counsel patients about the great importance of adhering to antihypertensive regimens, including nondrug and drug therapies.

    For a list of references, send a stamped, self-addressed envelope to: References Department, Attn. D. Ryan, Pharmacy Times, 241 Forsgate Drive, Jamesburg, NJ 08831; or send an e-mail request to:


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