13-1
13 HYPERTENSION Pass the Salt, Please . . . . . . . . . . . . . . . . . . . . Level II Julia M. Koehler, PharmD, FCCP James E. Tisdale, PharmD, BCPS, FCCP
INSTRUCTOR’S GUIDE TO CHANGES IN THIS EDITION CASEBOOK Objectives •
Revised slightly to reflect the fact that new JNC hypertension guidelines are not yet available as of the time of writing of this case, but will likely be released around the time that this book is published.
Patient Presentation •
Revisions to patient: 64-year-old (rather than 62 years old), type 2 diabetes mellitus (DM) (rather than type 1 diabetes), and new comorbid condition (gout). Patient is now also taking insulin lispro, carvedilol, fluticasone/salmeterol, naproxen, and allopurinol.
Clinical Pearl •
New clinical pearl added highlighting the fact that the majority of patients with hypertension require two or more antihypertensive medications to achieve blood pressure goal.
INSTRUCTOR’S GUIDE Case Summary •
Revised to include discussion of NSAIDs as possible contributor to lack of blood pr essure control.
CASE SUMMARY A 64-year-old African American man with HTN, COPD, DM type 2, BPH, chronic kidney disease, and gout presents to his new family medicine physician for evaluation and follow-up of his medical problems. His BP is poorly controlled, despite treatment with doxazosin, hydrochlorothiazide/triamterene, and carvedilol. He states he is recovering from a cold, for which he has been taking guaifenesin and pseudoephedrine (Mucinex D®), and it is possible that the use of this medication has contributed to his poorly controlled HTN. In addition, the patient takes naproxen for relief of both headaches and acute gout pain. Because NSAIDs may also exacerbate HTN, consideration of other options for HA and gout pain relief should be explored. The patient admits a lack of adherence to the low-sodium diet recommended by his former primary care physician. Physical examination reveals signs and symptoms consistent with target organ damage. Interventions for this patient should include instruction on lifestyle modification, including appropriate diet and exercise, and drug therapy. Selection of an antihypertensive regimen should include consideration of the degree of this patient’s HTN as well as patient-specific variables, such as ethnicity and comorbid conditions. This case points out the need to treat each patient as an individual and to consider all patient factors when selecting drug therapy.
QUESTIONS Problem Identification 1.a. Create a list of this patient’s drug-related drug-related problems, problems, including any medications that may be contributing to his uncontrolled HTN. •
HTN inadequately treated with current lifestyle modification recommendations and current pharmacotherapy; possibly aggravated by current medication use for cold symptoms, as well as NSAID use for headaches and episodes of acute gout pain. ✓
Mucinex D® contains pseudoephedrine. Because pseudoephedrine has sympathomimetic activity, it has the potential to increase BP or worsen BP control. A metaanalysis analyzing the effects of pseudoephedrine on BP illustrated that pseudoephedrine use contributed to a small (~1 mm Hg) and statistically significant increase in both systolic blood pressure (SBP) and heart rate. While the findings of this meta-analysis suggest that the increases in BP and heart rate observed with pseudoephedrine use may not be clinically significant, the authors did note that shorter duration of pseudoephedrine use, as well as higher doses and immediate-release preparations, was associated with greater increases in BP.1 In any case, consideration could be given to discontinuation of Mucinex D® if no longer indicated in this patient, or possible switch to a preparation that contains only guaifenesin.
✓
Because of their potential to promote sodium retention, NSAIDs, such as naproxen, may also precipitate increases in blood pressure and may compromise the efficacy of blood pressure–lowering medications. Alternatives to NSAIDs for headache relief and relief of pain secondary to acute gouty attacks should be considered for this patient.
Problem Identification •
•
Revised to include NSAIDs as a possible cause of poor BP control. Added discussion on use of β-blockers for hypertension management in patients with COPD.
Therapeutic Alternatives •
Added discussion of therapeutic alternatives for hypertension in a patient with comorbid gout.
Optimal Plan •
Added discussion about appropriateness of a nonselective β-blocker in a hypertensive patient with COPD and lack of compelling indication for a β-blocker in this case.
References •
Revised and updated; two new references added.
Copyright © 2011 by The McGraw-H McGraw-Hill ill Companies, Inc. All rights reserved.
C H A P T E R 1 3
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13-2 •
S E C T I O N 2
C a r d i o v a s c u l a r D i s o r d e r s
•
Possible doxazosin-induced orthostasis/dizziness. Possible drug–disease contraindication between carvedilol (a nonselective β-blocker) and COPD. In the absence of a clear indication for carvedilol in this patient, either an alternative, β1-selective β-blocker or another class of antihypertensive agent should be substituted for carvedilol.
•
Nonadherence to lifestyle modification recommendations.
•
Chronic kidney disease with evidence of proteinuria.
1.b. How would you classify this patient’s hypertension, according to current hypertension guidelines? •
JNC 7 guidelines (current hypertension guidelines at the time of writing of this casebook chapter) recommend the following classification system for BP 2:
Category
Systolic BP (mm Hg)
Diastolic BP (mm Hg)
Normal Prehypertension Stage 1 HTN Stage 2 HTN
<120 120–139 140–159 ≥160
<80 80–89 90–99 ≥100
•
•
addition, since DM and chronic kidney disease are considered coronary heart disease risk equivalents, the Framingham risk score is not intended for patients with DM and/or chronic kidney disease; in patients with DM and/or chronic kidney disease, the 10-year risk for heart disease is >20%. Therefore, it is not necessary to calculate the Framingham risk score in this patient.
Based on his BP readings of 162/90 and 164/92 mm Hg, this patient can be classified as having Stage 2 HTN. (When systolic and diastolic BPs fall into different categories, the higher of the two numbers is used to classify the patient’s stage of HTN.) In general, there is a strong correlation between BP and CV morbidity and mortality. According to JNC 7 guidelines, a patient’s risk for developing cardiovascular disease (CVD) doubles with each increment of 20/10 mm Hg above a BP of 115/75 mm Hg. For this reason, JNC 7 guidelines recommend that for patients whose BP falls in the category of Stage 2, more than one BP-lowering medication will be necessary in order to adequately lower BP and reduce the risk of CVD.
•
1.d. What evidence of target organ damage or clinical CVD does this patient have? •
•
•
•
According to JNC 7, the risk factors for CVD are HTN, smoking, obesity (BMI >30 kg/m2), physical inactivity, dyslipidemia, DM, microalbuminuria, kidney disease (estimated glomerular filtration rate <60 mL/min), age (men >55 years or women >65 years), and family history of premature CVD (men <55 years or women <65 years). 2 ( Note: The American Society of Hypertension [ASH] defines a family history of premature CVD as age <50 in men, and age <60 in women. Additional CV risk factors defined by ASH but not specifically defined by JNC 7 include: high heart rate, central obesity [increased abdominal circumference and/or waist-to-hip ratio], psychosocial stressors, and elevated high-sensitivity C-reactive pr otein [hs-CRP].)3 This patient’s CV risk factors, as defined by JNC 7, include: ✓
HTN
✓
Estimated glomerular filtration rate <60 mL/min
✓
Proteinuria
✓
DM
✓
Age (male >55 years)
✓
Physical inactivity
Family history cannot necessarily be included as a known CV risk factor for this patient based on the information given. The Framingham risk score is intended for patients who are at risk for, but who do not yet have, coronary heart disease. In
Copyright © 2011 by The McGraw-Hill Companies, Inc. All rights reserved.
Evidence of target organ damage or clinical CVD: ✓
Eyes: arteriovenous nicking
✓
Kidneys: (+) proteinuria, elevated serum creatinine (SCr)/ chronic kidney disease
✓
Heart: LVH, EF 45%
Desired Outcome 2. List the goals of treatment for this patient (including his goal BP). •
•
1.c. What are the patient’s known CV risk factors, and what is his Framingham risk score? •
Given the patient’s comorbid diagnoses of DM and chronic kidney disease (i.e., “CHD risk equivalents”), aggressive CV risk reduction is warranted.
•
The goal BP according to JNC 7 guidelines for a patient with diabetes (or kidney disease) is <130/80 mm Hg. This is also the recommended goal BP according to the National Kidney Foundation and the American Diabetes Association and is consistent with the recommendations for a patient with high coronary artery disease risk, according to the 2007 American Heart Association scientific statement on the management of HTN in patients at risk for or with known IHD. 4 The general goal when treating HTN is to prevent or reduce the likelihood of morbidity and/or mortality resulting from uncontrolled high BP (e.g., retinal damage leading to blindness, renal dysfunction or progression of existing kidney disease, stroke, heart failure, acute myocardial infarction). This should be accomplished while attempting to maximize both pharmacotherapeutic and pharmacoeconomic benefits, while minimizing the risk for adverse drug events. Additionally, other modifiable risk factors for coronary artery disease should be treated when present.
Therapeutic Alternatives 3.a. What lifestyle modifications should be encouraged for this patient to achieve and maintain adequate BP reduction? •
In order for this patient to receive maximal benefit from the drug therapy for his HTN, lifestyle modifications should be again encouraged, instituted, and continued indefinitely. Recommended lifestyle modifications should include the following: ✓
Weight reduction: Maintain normal body weight (BMI 18.5–24.9 kg/m2). A 10-kg weight loss may result in an approximate 5–20 mm Hg decrease in SBP.2
✓
Sodium restriction: Not more than 2.4 g of sodium or 6 g of sodium chloride (NaCl) per day. Adequate sodium restriction may yield an estimated 2–8 mm Hg decrease in SBP.
✓
Dietary Approaches to Stop Hypertension (DASH) diet: A diet that is high in calcium, high in potassium, and low in saturated fat.5 The DASH diet is rich in fruits, vegetables, and low-fat dairy products. It has been demonstrated to be particularly effective in producing BP lowering in African American patients.6 The DASH diet may decrease BP by 8–14 mm Hg.
13-3 of alcohol intake: Not more than 1 oz or 30 mL of ethanol per day (e.g., 24 oz of beer, 10 oz of wine, or 3 oz of 80-proof whiskey in men; one drink per day in women and lighter-weight persons).
for the breakdown of bradykinin. (It is believed that accumulation of bradykinin in the lungs is the etiology of ACE inhibitor–associated cough.) Similar to ACE inhibitors, ARBs have also been demonstrated to reduce proteinuria and delay the progression of kidney disease in patients with diabetes. Typically, ARBs are reserved for patients who are intolerant of ACE inhibitors due to cough.
✓ Moderation
✓
Exercise: ≥30 minutes per day most days of the week. Recommended exercise should include regular aerobic activity, such as brisk walking.
✓
Smoking cessation (or encouragement to continue avoiding smoking in this patient case).
✓
3.b. What reasonable pharmacotherapeutic options are available for controlling this patient’s BP, and what comorbidities and individual patient considerations should be taken into account when selecting pharmacologic therapy for his HTN? How might Mr Frank’s HTN medications potentially affect his other medical problems? •
There are several classes of antihypertensive agents that can be considered in the treatment of HTN. Available classes of antihypertensive agents include the following: ✓
✓
Thiazide and thiazidelike diuretics work by blocking sodium reabsorption in the distal tubule. Thiazides have been demonstrated to reduce morbidity and mortality in patients with HTN and are considered the first-line drugs of choice according to JNC 7 guidelines and the findings of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).7 Thiazide diuretics, as well as calcium channel blockers, may have greater BP-lowering effects in African-American patients compared to other classes of antihypertensives. 6
β -Blockers lower BP by directly blocking adrenergic stimulation of β receptors. They are relatively contraindicated in patients with known obstructive lung disease, because of their potential to cause bronchospasm. If used in patients with obstructive lung disease, β1-selective agents, such as metoprolol, are preferred, and nonselective β-blockers, such as carvedilol or labetalol, should generally be avoided. β-Blockers may also mask the signs and symptoms of hypoglycemia in patients with diabetes. In comparison to ACE inhibitors, β-blockers were demonstrated to be equally effective in controlling BP and reducing the complications of diabetes in the UKPDS trial. 8 When used as monotherapy, β-blockers may produce less BP-lowering effects in African Americans compared to Caucasians. 6 inhibitors inhibit angiotensin-converting enzyme, thereby blocking the conversion of angiotensin I to angiotensin II. ACE inhibitors have been shown to be especially beneficial in lowering CHD risk in high-risk patients with and without diabetes.9,10 According to JNC 7 guidelines, ACE inhibitors are also considered first-line drugs of choice in patients with diabetes, as they have been demonstrated to reduce proteinuria and retard the progression of kidney disease in such patients.2 As with β-blockers, ACE inhibitors, when used as monotherapy, may produce diminished BP-lowering effects in African Americans compared to Caucasians.6 The BP-lowering effects of ACE inhibitors may be augmented, however, with concomitant diuretic use. Compared to Caucasians, African Americans appear to be at increased risk for experiencing ACE inhibitor–induced angioedema and ACE inhibitor–induced cough.6
✓
✓
✓ ACE
II receptor blockers (ARBs) directly antagonize angiotensin II receptors. Although their mechanism is similar to that of ACE inhibitors, ARBs differ in that they spare angiotensin-converting enzyme and, therefore, allow
✓
✓ Angiotensin
✓
Calcium channel blockers impair transport of calcium through voltage-sensitive calcium channels in vascular smooth muscle. Nondihydropyridine calcium channel blockers, such as verapamil and diltiazem, work directly on the myocardium, producing both negative inotropic and negative chronotropic effects. Dihydropyridine calcium channel blockers, such as amlodipine and nifedipine, yield peripheral vasodilatory effects and may produce a secondary increase in heart rate, or “reflex tachycardia.” Although the amount of existing data is small compared to that which exists for ACE inhibitors, nondihydropyridine calcium channel blockers may reduce coronary events, and data from short-term studies illustrate that nondihydropyridines reduce proteinuria in patients with diabetes. 2,11 Although calcium channel blockers may have greater BP-lowering efficacy in African-American patients compared to other classes of antihypertensives, they are typically not preferred as first-line treatments either over thiazide diuretics in patients without compelling comorbid indications or over other treatments such as ACE inhibitors, in patients with HTN, diabetes, and/or high CHD risk.2
α 1-Adrenergic blockers inhibit adrenergic stimulation of peripheral α1 receptors, resulting in reduced peripheral resistance and vasodilation. Although these agents are effective in relieving the symptoms of BPH, they must be used with caution in elderly patients due to the risk of dizziness, orthostatic hypotension, and resultant potential for syncope. When compared to chlorthalidone as a first-line antihypertensive agent, doxazosin use was associated with a higher incidence of congestive heart failure and combined CVD outcomes in the ALLHAT study. 7 The doxazosin arm of the ALLHAT trial was discontinued early, and current guidelines no longer recommend the use of α1-adrenergic blockers as monotherapy in the treatment of HTN. 2 Central-acting α -agonists, such as clonidine, work by directly simulating presynaptic α2-receptors in the brainstem, thereby reducing sympathetic outflow. This class of antihypertensive agents is considered to be equally effective in lowering BP in all ages and races. This class of medications carries an extensive side-effect profile, which includes drowsiness, sedation, fatigue, depression, dry mouth, orthostasis, bradycardia, and rebound HTN. As such, this class of medications is poorly tolerated by many patients and is not recommended by the JNC for first- or second-line consideration in the management of HTN. 2 Direct vasodilators, such as hydralazine and minoxidil, work by directly relaxing arterial smooth muscle and reducing peripheral vascular resistance. Because these drugs may produce profound peripheral vasodilation, they often cause significant side effects, such as peripheral edema and reflex tachycardia, which warrant additional treatment (i.e., they typically must be used in combination with a β-blocker and a loop diuretic). These agents are most commonly reserved for refractory HTN despite modest doses of three or more antihypertensive agents. Peripheral adrenergic neuron antagonists, such as reserpine, deplete norepinephrine from peripheral neurons and
Copyright © 2011 by The McGraw-Hill Companies, Inc. All rights reserved.
C H A P T E R 1 3
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13-4 inhibit release of norepinephrine in response to sympathetic stimulation. Much like central-acting α2-agonists, this class of drugs is associated with significant side effects, such as orthostasis, GI disturbances, bradycardia, drowsiness, depression, and nightmares, which limit the utility of these agents for most patients.
S E C T I O N 2
C a r d i o v a s c u l a r D i s o r d e r s
✓
The direct renin inhibitor aliskiren was approved by the FDA in 2007. This newer class represents the first new type of antihypertensive available for the treatment of HTN in more than a decade. Aliskiren is indicated either alone or in combination with other antihypertensives, such as thiazide diuretics or ARBs. It is administered once daily for the treatment of HTN. Because of the cost of this agent and the limited data available in treating patients with HTN and other comorbidities, it is not currently recommended as a first-line antihypertensive agent.
Comorbidities that must be specifically taken into account when selecting pharmacologic antihypertensive therapy for this patient include: •
✓
✓
•
ACE inhibitors are typically the drugs of choice in patients with diabetes, as they have been demonstrated to reduce proteinuria and delay progression of kidney disease. ARBs have also been demonstrated to have renal protective effects, particularly in patients with type 2 diabetes and in those with advanced kidney disease. There is no indication in this patient to select an ARB over an ACE inhibitor at this time, particularly since it is also important to note the demonstrated benefit of CV risk reduction with ACE inhibitors.
β-Blockers have also been shown to control BP and reduce the complications of diabetes. 8 Caution should be used when selecting a β-blocker for a patient with diabetes, as β-blockers may mask signs and symptoms of hypoglycemia and may contribute to glucose intolerance. This is not an absolute contraindication, however. Thiazides are recommended as first-line antihypertensives in patients with or without diabetes for control of HTN and reduction of morbidity and mortality. 7 It is important to note, however, that in high doses, thiazides may increase blood glucose and cause other metabolic derangements.
Chronic obstructive pulmonary disease: ✓
β-Blockers are relatively contraindicated in patients with moderate to severe obstructive lung disease. Consideration must therefore be given to the severity of the disease, risk versus potential benefit, and relative β-receptor selectivity.
✓
ACE inhibitors are not contraindicated in patients with obstructive lung disease. It is important to note, however, that these drugs may cause cough in 10–20% of patients, and this is an important monitoring parameter in patients with obstructive lung disease.
✓
Thiazide diuretics are considered to be ineffective when CrCl is <30 mL/min. Although this patient’s estimated CrCl is not below 30 mL/min currently, continuous monitoring of the progression of this patient’s kidney disease is important and could affect the potential efficacy of a thiazide diuretic in the future.
✓
Potassium-sparing diuretics should be used with caution in patients with mild kidney disease and should be avoided in patients with significant kidney disease.
Gout: ✓
•
✓
•
α1-Blockers are drugs of choice for symptomatic relief. These agents should not be used as monotherapy in the treatment of HTN, however, based on the findings of the ALLHAT study.12 Both ACE inhibitors and ARBs have been shown to reduce the incidence and severity of proteinuria and delay the progression of kidney disease in patients with diabetes.
Copyright © 2011 by The McGraw-Hill Companies, Inc. All rights reserved.
ACE inhibitors have been shown to reduce LV mass, as have most classes of antihypertensive agents, with the exception of direct vasodilators.
African-American race (not a comorbidity but an important consideration): ✓
β-Blockers and ACE inhibitors are generally thought to be less effective when used as monotherapy for BP lowering in this population of patients. The BP-lowering effect of ACE inhibitors can be enhanced with the addition of a diuretic.
✓
Diuretics and calcium channel blockers are considered to have greater BP-lowering effects than most other antihypertensive classes in African-American patients.
Optimal Plan 4.a. Recommend specific lifestyle modifications for this patient. •
Nonpharmacologic therapy for this patient should include the following: ✓
Weight reduction. The patient’s current weight is 95 kg, and his BMI is 27 kg/m 2. The patient’s IBW = 82.2 kg. Weight reduction by caloric restriction has been shown to reduce BP, even if IBW is not achieved. A goal for the patient should be to achieve and maintain a BMI of 18.5–24.9 kg/m2.
✓
Sodium restriction. The patient has been nonadherent to his prescribed low-sodium diet. Ideally, he should be restricted to not more than 2.4 g of sodium (6 g NaCl) per day. The patient should be instructed not to add salt to his food. He should also be advised to seek out foods that are low in sodium and/or consult with a dietician to assist w ith implementing a low-sodium diet.
✓
DASH diet . The patient should be given information about and encouraged to try this diet, which is low in sodium, high in calcium and potassium, and low in both saturated and total fat. This diet has been shown to be particularly effective in African American hypertensives and may reduce BP better than both weight loss and sodium restriction alone in these patients. of alcohol intake. The patient should be encouraged to limit his alcohol intake to not more than 1 oz of ethanol, 24 oz of beer, 10 oz of wine, or 3 oz of 80-proof whiskey per day.
✓ Moderation
Chronic kidney disease: ✓
In high doses (e.g., ≥50 mg of hydrochlorothiazide), thiazide diuretics may increase serum uric acid concentrations and cause other “metabolic derangements,” such as alterations in blood glucose and serum lipid concentrations.
Left ventricular hypertrophy:
Benign prostatic hyperplasia: ✓
•
ACE inhibitors have been shown to delay the progression of kidney disease in nondiabetic nephropathy.13
DM: ✓
•
•
✓
✓
Exercise. The patient should be encouraged to participate in 30–45 minutes of aerobic activity most days of the week. Although this can help lower his BP and reduce his overall
13-5 CV risk, this level of activity may not be feasible for this patient, as he may be limited by the severity of his COPD. ✓
Continued smoking avoidance. This patient who was a longtime smoker successfully quit smoking 3 years ago. The patient should be congratulated for his successfully having quit smoking, and he should be encouraged to continue to refrain from smoking and to minimize his exposure to second-hand smoke whenever possible. Smoking cessation results in overall CV risk reduction and may continue to positively affect the rate of decline in the patient’s FEV 1 due to his COPD. If not currently enrolled in a pulmonary rehabilitation program, the patient should receive a referral and be given encouragement to participate in the program in order to improve his functional capacity.
potential for hyperkalemia when combined with an ACE inhibitor, particularly in view of the fact that the patient has CKD. •
•
4.b. Outline a specific and appropriate pharmacotherapeutic regimen for this patient’s uncontrolled HTN, including drug(s), dose(s), dosage form(s), and schedule(s). •
•
•
•
•
Drug therapy for HTN must be individualized based on the patient’s age, race, known pathophysiologic variables, and comorbid conditions. Treatment regimens should be designed not only to achieve desired BP goals (<130/80 mm Hg for this patient), but also to reduce morbidity and mortality associated with HTN. Consideration should be given to either discontinuing the guaifenesin/pseudoephedrine preparation altogether (especially if no longer needed for the treatment of specific cold symptoms in this patient) or switching the product to a preparation that contains guaifenesin without pseudoephedrine. Because this patient has Stage 2 HTN and his current BP is more than 20/10 mm Hg above his goal BP, and because he has both DM and chronic kidney disease, a minimum of two antihypertensive medications are indicated for adequate BP lowering.2,14 Because this patient has diabetes, chronic kidney disease with proteinuria, LVH, and is considered to be at high risk for experiencing a CHD-related event, an ACE inhibitor should be added to the patient’s current antihypertensive regimen. A longacting agent that can be given once daily, such as lisinopril 5 mg po once daily or ramipril 2.5 mg po once daily, should be initiated in this patient and titrated upwards as tolerated in order to achieve the desired BP goal. While ACE inhibitors can cause cough as an adverse effect, the fact that this patient complains of a cough prior to the initiation of ACE inhibitor therapy is not a reason to withhold ACE inhibitors. In addition, the fact that this patient has CKD with a SCr concentration of 2.2mg/dL is also not a reason to withhold therapy with ACE inhibitors; ACE inhibitors have been shown to prevent the progression of kidney disease in patients with SCr concentration 1.5–3.0 mg/dL.13 Hydrochlorothiazide should be continued in this patient, because it is considered an appropriate first-line antihypertensive according to JNC 7 guidelines and, when given in combination with an ACE inhibitor, the two drugs may work synergistically to lower BP in this African-American patient. The dose of hydrochlorothiazide should not be increased, due to the potential for higher doses to cause elevations in blood glucose and other metabolic derangements, including possible elevations in serum uric acid concentration, in this patient with diabetes and gout. ✓
Consideration should be given to changing the triamterene/hydrochlorothiazide combination that the patient is currently taking to hydrochlorothiazide only, due to the
•
Doxazosin may be continued in this patient for control of his symptoms of BPH. If continued, consideration should be given to changing the dosing schedule to QHS dosing to reduce possible doxazosin-induced orthostasis/dizziness. As an alternative, the doxazosin could be changed to tamsulosin, but it should be noted that this medication, which is specific for α receptors in the prostate, will not have an impact on BP lowering. There is no reason to select or recommend an ARB over an ACE inhibitor at this time. ARBs are more expensive than ACE inhibitors and, although they have been shown to reduce proteinuria and delay the progression of kidney disease, data regarding their impact on CV risk reduction are lacking. Thus, an ARB should only be prescribed if the patient develops intolerance to the ACE inhibitor, such as ACE inhibitor–induced cough. Carvedilol should be discontinued in this patient . Nonselective β-blockers should generally be avoided in this patient with moderate obstructive lung disease, especially since there is no compelling indication to select a β-blocker for the patient at this time. If a β-blocker is chosen, preference should be given to a β1-selective agent, such as metoprolol.
Outcome Evaluation 5. Based on your recommendations, what parameters should be monitored after initiating this regimen and throughout the treatment course? At what time intervals should these parameters be monitored? •
•
•
Monitor adherence to and accomplishment of lifestyle modifications, including dietary adjustments, exercise, and weight reduction. Because of the close interrelationship of lifestyle modifications with HTN and CV risk, these interventions should be reinforced at each visit throughout the course of treatment. JNC 7 guidelines recommend that BP be monitored at least monthly until it is controlled. More frequent monitoring should be considered in patients with Stage 2 HTN. In this patient, the BP should be rechecked in 2–4 weeks. 2 General laboratory monitoring for this patient should include chemistries (specifically serum sodium, potassium, creatinine, and glucose), uric acid, and a fasting lipid profile. Recheck a follow-up chemistry in 2–4 weeks, and if laboratory results are normal, rechecking follow-up chemistry once every 6 months is reasonable. ✓
•
Monitor serum potassium and BUN/SCr closely (e.g., ideally, approximately 1 week after initiating ACE inhibitor therapy). If SCr increases significantly (i.e., by >30%), discontinue the ACE inhibitor and evaluate the patient for renal artery stenosis.
Monitor for the occurrence of significant adverse effects of drug therapy. If an ACE inhibitor and thiazide diuretic combination was chosen, these adverse effects would include, but not be limited to, orthostasis, headache, dizziness, lightheadedness, sexual dysfunction, glucose intolerance, potassium imbalance, worsening kidney function, and dry cough. If the patient develops a bothersome dry cough, consider switching to an ARB. After initiating an ACE inhibitor in this patient, also monitor closely for the occurrence of angioedema, which occurs most commonly in the African-American patient population (estimated at 5–6% of patients). If an gioedema occurs, discontinue
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13-6 the ACE inhibitor immediately and consider whether or not a switch to an ARB would be safe for this patient. (In a recent meta-analysis, the risk of developing any subsequent angioedema with ARB use following ACE inhibitor–induced angioedema was reported as 2–17%.15) As an alternative, a nondihydropyridine calcium channel blocker, such as verapamil or diltiazem, could be considered for renal protective effect if the patient could not take either an ACE inhibitor or an ARB. ( Note: In light of this patient’s already reduced left ventricular ejection fraction [45%], close monitoring for signs of worsening cardiac function and possible development of systolic heart failure is warranted. In the event that this patient does eventually develop systolic dysfunction, a nondihydropyridine calcium channel blocker would then be contraindicated.) Amlodipine and felodipine are safe for use in patients with heart failure, but there are few data regarding their efficacy for renal protection.
S E C T I O N 2
C a r d i o v a s c u l a r D i s o r d e r s
ACE inhibitor (e.g., lisinopril, ramipril): •
•
•
•
•
Patient Education
Antihypertensive agents in general: •
•
•
•
•
Because these drugs lower your blood pressure, you may feel dizzy or lightheaded when going from lying down or sitting to a standing position. Use caution and rise slowly from these positions until you know how your body reacts. As your body gets accustomed to these new medicines and your lower blood pressure, this effect may diminish. If dizziness is extreme or continues beyond a few days, inform your health care provider. These medications can affect different body systems in addition to lowering your blood pressure; they may affect your heart rate and some of your blood tests. It is extremely important to keep all scheduled appointments with your health care providers to properly monitor your progress.
Thiazide diuretic (e.g., chlorthalidone or hydrochlorothiazide): •
•
•
•
•
•
•
These medicines do not cure high blood pressure. You will probably need to continue taking these medications on a longterm basis to keep your blood pressure controlled. Take these medications exactly as prescribed, do not skip doses, and if you do miss a dose, do not “double up” by taking two doses at once.
This medication is used to lower your blood pressure. One of the ways this medicine lowers blood pressure is to cause you to lose extra fluid through increased urination. Because of this, you will want to take this medication early in the day, to avoid having to get up at night to go to the bathroom. You may take this medication with food, milk, or on an empty stomach. Thiazide diuretics can make you sensitive to sunlight. Be sure to apply a sunscreen with a sun protection factor (SPF) of at least 15 before any extended exposure to sunlight. Thiazide diuretics may cause you to lose potassium. Your physician will monitor your potassium balance carefully. If you experience cramping in your feet or lower extremities, this may be a sign that your potassium has dropped. If this occurs, notify your physician.
Copyright © 2011 by The McGraw-Hill Companies, Inc. All rights reserved.
This medication works together with your diuretic, allowing you to use lower doses of both medications and decrease the chance of side effects from either drug. This type of medicine can sometimes cause a chronic dry cough. If this occurs, please contact your heath care provider. This is not dangerous, but it can be bothersome. If you experience any swelling in your face, lips, or tongue, or have breathing problems, immediately stop taking this medication and go to the emergency department for immediate medical attention. If you experience a significant decrease in urinary frequency while taking this medication, be sure to contact your provider.
Doxazosin: •
6. Based on your recommendations, provide appropriate education to this patient.
This medicine lowers BP by relaxing your blood vessels.
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This medicine treats the symptoms of BPH, or an enlarged prostate. It may also treat your high blood pressure. This medicine may make you dizzy or drowsy. Avoid driving, using machines, or doing anything else that could be dangerous if you are not alert. Because you report symptoms of dizziness currently after taking this medicine in the morning, begin taking this medication at night, before you go to bed. If you continue to experience symptoms of dizziness or lightheadedness, or if you experience fainting, notify your physician. Notify your physician if you begin to experience pain on urination, changes in how much or how often you urinate, or red or dark brown urine.
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13-7 8. UKPDS 39. Efficacy of atenolol and captopril in reducing risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 39. UK Prospective Diabetes Study Group. BMJ 1998;317:713–720. 9. Heart Outcomes Prevention Evaluation Study Investigators. Effects of an angiotensin-converting enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med 2000;342:145–153. 10. Heart Outcomes Prevention Evaluation Study Investigators. Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and the MICRO-HOPE substudy. Lancet 2000;355:253–259. 11. American Diabetes Association. Treatment of hypertension in adults with diabetes. Diabetes Care 2002;25:S71–S73. 12. The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major cardiovascular events in hypertensive patients
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