CPhA Professional Advancement

2005

Learning Series

Caring for Patients with Hypertension

Application of the 2005 Canadian Guidelines
Cynthia A. Jackevicius, BScPhm, MSc, PharmD, BCPS, FCSHP

This program has been approved for 1.5 CEUs by the Canadian Council on Continuing Education in Pharmacy CCCEP #196-1104 This lesson is valid until November 30, 2007

This lesson has been sponsored with an unrestricted educational grant from

EP
Suggested retail price: $15 plus GST for CPhA members, $25 plus GST for non-members. This lesson is available from the CPhA Online Learning Centre, with online marking at www.pharmacists.ca. If online access is not available to you, contact CPhA at 1-800- 917-9489.

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Disclaimer

Lesson description
ypertension is a common condition affecting many Canadians. More deaths world wide are attributable to hyper tension than to other common risk factors such as smoking and high cholesterol. Hypertension is a significant risk factor for coronary artery disease, stroke, congestive heart failure, renal failure, peripheral vascular dis ease, dementia, and atrial fibril lation. Optimal treatment of hypertension reduces the risk of developing target organ damage and adverse clinical outcomes. However, research suggests that many Canadians are unaware that they have hypertension, and of those aware, many are under treated, leaving their blood pres sure uncontrolled. The Canadian Hypertension Education Pro gram (CHEP) has embarked on a process to revise and imple ment evidence-based recommen dations for the management of hypertension on an annual basis in an attempt to improve the management of hypertension in Canada. The latest 2005 guide lines are summarized in the fol lowing lesson. Pharmacists can play a vital role in assisting patients with hypertension. Opportunities for pharmacist participation in the care of patients with hypertension are reviewed. Cases will be used to help apply the information con tained in the lesson.

Learning objectives

e have done our best to produce an accurate, timely, and educational Learn ing Series. However, Medi Resource Inc., the Canadian Pharmacists Association, the authors, the reviewers, and the editors assume no respon sibility for any errors or con sequences arising from the use of information contained within this program. With the constant changes in practice and regional differences, it remains the responsibility of the readers as professionals to interpret and apply this les sons information to their own practices. All rights reserved. For this lesson, in compli ance with sections 10.2 and 10.3 of the Guidelines and Criteria for CCCEP Accreditation, the author, expert reviewers, and MediResource Inc. report that the author previously received an honorarium from the spon sor company for a presenta tion on an unrelated topic. No other real or potential con flict of interest in relation to the sponsor of the CE lesson exists.

pon successful completion of this lesson, the partici pant should be able to: 1. define and classify hyperten sion 2. discuss the complications of hypertension 3. describe effective non-phar macological therapies for hypertension 4. summarize the recommenda tions of the 2005 canadian hypertension guidelines 5. discuss the efficacy, adverse effects and monitoring of antihypertensive agents 6. explain the reasons for poor response to antihypertensive therapy 7. educate patients receiving antihypertensive therapy

Correspondence
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Author
Cynthia Jackevicius, BScPhm, MSc, PharmD, FCSHP Cynthia Jackevicius has provided pharmaceutical care to patients with cardiovascular disease in both the inpatient and outpatient setting of the Heart and Circu lation Program at the University Health Network - Toronto Gen eral Hospital for many years. In addition to her clinical experi ence, she has also been involved with numerous teaching activi ties at the hospital with students and residents, as well as in the Faculty of Pharmacy and the Fac ulty of Medicine at the Univer sity of Toronto. She has lectured widely and written numerous articles on many aspects of treat ment of patients with cardio vascular disease. Cynthia also conducts research at the Insti tute for Clinical Evaluative Sci ences in Toronto where she is an Adjunct Scientist. Current ongoing research focuses on the quality of care of patients with cardiovascular disease and adherence to medications.

Expert reviewers
John Hawboldt, BScPhm, PharmD Dr. Hawboldt is currently an Assistant Professor at the School of Pharmacy at Memorial Uni versity and is cross-appointed to the Health Care Corporation of St. Johns, Department of Phar macy. He provides care to both inpatients on the Infectious Dis eases Consult Service and Gen eral Medicine. Dr. Hawboldt is also affiliated with the Drug Uti lization Committee and the Anti biotic Utilization Committee of the Health Care Corporation and is responsible for drug utiliza tion evaluations (DUEs), formu lary reviews, and more. As a part of his teaching responsibil ities, Dr. Hawboldt teaches to the pharmacotherapy of hyper tension to the final year phar macy students. Dr. Hawboldt is also on the School of Pharmacy Curriculum Committee, which is looking at new and innovative ways to improve the pharmacy curriculum. Dr. Hawboldts interests include effective drug utilization, quality initiatives, and curricu lum development. Current ini tiatives include a study on the effectiveness of surgical prophy laxis guidelines as well as the development of a clinical skills course in the school of phar macy. Chantal Pharand, PharmD, BCPS Dr. Chantal Pharand is associate professor at the Faculty of Pharmacy at the Universit de Montral. After completing a PharmD degree, she pursued a research career by completing two research fellowships in car diovascular pharmacology and in cardiovascular therapeutics. For the past ten years, she has been teaching classes on the pathophysiology and pharmaco therapy of cardiovascular dis eases, including hypertension, to pharmacy students and resi dents. In addition, she has been involved in clinical research, being the principal investigator for a number of cardiovascular research projects, as well as being a clinical pharmacist practicing at the Coronary Care Unit of the Hpital du Sacr-Coeur de Montral. She has published sev eral articles, book chapters, and books in the field of cardiology and has given several presenta tions to local and national meet ings on cardiovascular topics, including hypertension.

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Contents
1. Epidemiology and pathophysiology 2. Identifiable causes of hypertension Table 1. Identifiable causes of secondary hypertension 3. Consequences of hypertension 4. Underdiagnosis and treatment 5. Diagnosis and definition of hypertension Table 2. Recommended technique for measuring blood pressure Table 3. Target organ damage Table 4. Causes of poor response to hypertension therapy 6. Therapy 6.1 Initiation of therapy and goals of therapy 6.2 Benefits of treating hypertension Table 5. Threshold for initiation of treatment and target values 6.3 Combination therapy 6.4 Canadian Hypertension Guidelines 2005 recommendations Table 6. Lifestyle modifications to manage hypertension 6.5 Non-pharmacological therapy 6.6 Drug therapy Table 7. Major cardiovascular risk factors Table 8. Useful dual combinations Table 9. Considerations in the individualization of antihypertensive therapy Table 10. Adverse effects and contraindications of antihypertensive agents 6.7 Drug therapy for individualized antihypertensive therapy 6.8 Non-antihypertensive therapy 7. Key differences between Canadian, American, and European guidelines 8. Monitoring Table 11. Monitoring of antihypertensive agents by class 9. Medication adherence 10. Patient education Table 12. Strategies to improve adherence to therapy 11. Opportunities for pharmacists Table 13. Herbal products and hypertension 12. Web resources Table 14. Hypertension and heart disease websites 13. Summary References Questions

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Case Study

PW

is a 57-year-old artist who presents to your pharmacy to obtain some sublingual nitroglycerin for her angina. She just moved to your small community last month. You find out from the patient that she was just diagnosed with stable angina 3 months ago. She also uses nitroglycerin ointment for her angina. After further discussion with the patient, you find out that she has had mild diabetes for 5 years, well controlled on diet. She has had hypertension for 12 years, initially treated with a water pill for a couple of years but recently controlled by lifestyle measures. While waiting to speak with you, she takes her blood pressure on the store machine and is concerned that the reading was 143/92, much higher than her usual reading on her home machine. She also mentions to you that she takes ibuprofen for her osteoarthritis a few times a week, acetaminophen for headaches since she started the nitroglycerin ointment, and Tums for stomach upset usually once a week for the last couple of years. She states that she is a non-smoker, but her husband smokes like a chimney and she has 12 glasses of wine each week. She takes her medications regularly, but prefers to manage with nondrug or natural therapy if possible.

Table 1. Identifiable causes of secondary hypertension35

chronic kidney disease primary hyperaldosteronism renovascular disease cushing syndrome pheochromocytoma coarctation of the aorta thyroid or parathyroid disease

3. Consequences of hypertension
Hypertension damages the lining of arteries and accelerates atherosclerosis. Complications of hyper tension include damage to the end organs, includ ing the heart, eyes, kidneys, brain, and large vessels. Hypertension is a major risk factor for cerebrovas cular disease (stroke, transient ischemic attacks), coronary artery disease (myocardial infarction [MI], angina), renal failure, congestive heart failure, peripheral vascular disease, dementia, and atrial fibrillation. When hypertension is combined with other cardiovascular risk factors, the chance for sub sequent cardiovascular morbidity and mortality is increased.3,4 According to the Framingham study, patients with hypertension are at a significantly increased risk of coronary disease, stroke, periph eral artery disease, and cardiac failure.6 In reviewing PWs medical history, you note that she has developed one of the potential complications of hypertension in that she was just recently diag nosed with angina. Therefore, she has known cor onary artery disease and atherosclerosis. No other complications are apparent.

1. Epidemiology and pathophysiology

ypertension, or high blood pressure, is a common medical condition, affecting a large proportion of Canadians. It is estimated to be the leading risk factor associated with death world wide.1 Based on a large population-based survey across Canada, 22% of Canadians between 18 and 70 years, or just over one in five, and 50% of Canadians 65 years and older have hypertension.2 Risk factors for the development of hypertension include age, family history, obesity, sedentary lifestyle, sodium intake, and high dietary fat intake. Ethnic origin also plays a role, in that African-Americans have the highest prevalence of hypertension worldwide. The most common type of hypertension is called pri mary (or essential) hypertension, which is defined as arterial hypertension without a definable cause. Primary hypertension is a multifactorial disorder influenced by both genetic predisposition and envi ronmental factors.3

4. Underdiagnosis and treatment

The Canadian Heart Health Survey found that too many Canadians are not aware of their hyperten sion or, if they are aware, it is not under control. Over 40% of patients were unaware that they had hypertension. Only 16% of those with hypertension in the survey were treated and had their blood pres sure under control. The remainder were aware of their hypertension but either were treated without control (21%) or were untreated and uncontrolled (22%). Undiagnosed, untreated, and uncontrolled hypertension clearly places a significant strain on the healthcare system and reduces population health in Canada.2 Recent data suggest that there have been signifi cant increases in the prescription of major classes of antihypertensive drugs in Canada, including thi azide diuretics, in the three years after the Cana dian Hypertension Education Program began.7 This increased utilization coincides with the release of the

2. Identifiable causes of hypertension

Secondary hypertension occurs when elevated blood pressure is due to a specific cause, such as drugs or certain conditions, including pregnancy. It accounts for approximately 10% of all hypertensive patients.4 Identifiable causes of hypertension are listed in Table 1. This lesson will focus on the management of essential hypertension.

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annual recommendations of the Canadian Hyper tension Society, possibly representing an improve ment in treatment rates of hypertension in Canada. It is vital for all healthcare professionals, including pharmacists, to understand the current limitations with the diagnosis and treatment of hypertension in Canada and to become involved in improving the current situation. A follow-up survey will be con ducted in 2006 to assess the prevalence, treatment, and control rates for hypertension in Canada.

Table 2. Recommended technique for measuring blood pressure8

1. Seat the patient with his/her back supported, arm bare and supported at heart level. 2. Make sure that the patient has not smoked within 1530 minutes or consumed caffeine within one hour before the measurement. 3. Ensure that the bowel and bladder are comfortable. 4. Have the patient rest for 5 minutes before taking the measurement. 5. Use an appropriate-size cuff. 6. Use a mercury manometer or recently calibrated aneroid or a validated electronic device. 7. Measure blood pressure on both arms at the initial visit to determine if there is a difference. 8. Take two measurements separated by one minute on the side where the blood pressure is the highest. Average the results.

5. Diagnosis and definition of hypertension

The Canadian Hypertension Society (CHS) Guide lines suggest a standardized technique for measuring blood pressure, as listed in Table 2.8 Hypertension is defined as a persistent office blood pressure read ing of 140 mmHg or more systolic, or 90 mmHg or more diastolic. Isolated systolic hypertension, which occurs more frequently in the elderly, is diagnosed when the systolic blood pressure (SBP) is greater than 140 mmHg but the diastolic blood pressure (DBP) is less than 90 mmHg. A key message from the 2005 CHS guidelines is that the diagnosis of hypertension can be expedited. It is recommended that hypertension may be diagnosed in the clinic visit as follows according to visit number: Visit 1 2 3 4 5 Diagnose hypertension if findings indicate: Hypertensive urgency/emergency BP 180/110 or target organ damage, diabetes, chronic kidney disease with BP 140/90 SBP 160 or DBP 100 SBP 140 or DBP 90 SBP 140 or DBP 90

Table 3. Target organ damage3,4,8

heart left ventricular hypertrophy angina acute coronary syndromes need for coronary revascularization heart failure brain stroke or transient ischemic attack chronic kidney disease/renal insufficiency peripheral arterial disease intermittent claudication retinopathy induce or aggravate hypertension (Table 4). If the possibility of white coat hypertension exists, 24-hour ambulatory blood pressure monitoring should be conducted.8 If, at the last diagnostic visit, the blood pressure is less than 140/90 mmHg, and the patient has no evidence of risk factors or target organ damage, the patient should be assessed yearly if the blood pres sure is in the high normal range of 130/85 to 139/89 mmHg and at two-year intervals if the last blood pressure is 120/80 to 129/84. These patients frequently go on to develop hypertension.8 While you know that hypertension cannot be diagnosed with one measurement by the machine in your store, PW already has an established diagnosis of hypertension. You know there are many reasons for improper technique related to various blood pressure monitors. You

New to the 2005 CHS guidelines is that hyper tension may also be diagnosed by ambulatory and self/home blood pressure monitoring with values as indicated in Table 5. Note that different algo rithms are noted in the 2005 guidelines for 24-hour ambulatory blood pressure monitoring and self/ home blood pressure monitoring. Hypertensive emergency is defined by very ele vated blood pressure readings with DBP usually higher than 120130 mmHg and the presence of acute or imminent complications for target organs, such as papilledema, cardiac ischemia, or enceph alopathy. Hypertensive urgency is defined by the same blood pressure parameters as hypertensive emergency, but without any evidence of acute target organ damage. See Table 3 for a list of acute and chronic target organ damage. A search should be made for potentially modifiable factors that can

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calm down PW through your discussion and have her repeat her blood pressure after sitting calmly for 5 minutes. The second measurement is 139/92, giving her an average of 141/92. In reviewing PWs history, you notice that she may have potential drug-related causes that may aggravate

her hypertension. She is taking ibuprofen for her arthritis, which may contribute to sodium and water retention. You know that acetaminophen is the first-line therapy for treatment of pain due to osteoarthritis and consider this as you continue to assess her case.

Table 4. Causes of poor response to hypertension therapy35

improper blood pressure measurement volume overload or pseudotolerance excess sodium intake volume retention from kidney disease inadequate diuretic therapy lack of weight reduction drug-induced or other causes inadequate doses inappropriate combinations drug interactions nonsteroidal anti-inflammatory drugs, COX2 inhibitors cocaine, amphetamines, other illicit drugs sympathomimetics (decongestants, anorectics) oral contraceptives adrenal steroids cyclosporine and tacrolimus erythropoietin thyroid hormone excess venlafaxine licorice drugs high in sodium (e.g., Alka-Seltzer) selected over-the-counter dietary supplements and medicines (e.g., ephedra, ma huang) associated conditions obesity excessive alcohol intake sleep apnea chronic pain and/or mental illness patient-related issues unclear instructions for therapy lack of education/understanding of risks inconvenient dosing lack of patient involvement/empowerment adverse effects nonadherence to diet or drugs memory/cognitive deficit identifiable causes of secondary hypertension chronic kidney disease primary hyperaldosteronism renovascular disease cushing syndrome pheochromocytoma coarctation of the aorta thyroid or parathyroid disease

6. Therapy
6.1 Initiation of therapy and goals of therapy
Initiation of pharmacological therapy and treatment targets are dependent on specific patient character istics. Threshold values for initiation of drug ther apy and treatment targets are listed in Table 5. For the majority of patients, the goal is to achieve a blood pressure less than 140/90 mmHg. How ever, the table lists other important target levels dependent on patient factors. Other goals of treat ing hypertension include preventing morbidity and mortality associated with hypertension.9 PW is using nitroglycerin for her angina, which may also have antihypertensive effects. You want to determine whether she meets criteria for drug therapy and is achieving the goal of therapy. Upon reviewing the handy table you have in your Palm, you note that she also has diabetes in addition to mixed diastolic/systolic hypertension. Given this, she should initiate therapy at a blood pressure >130/80 and achieve a target value <130/80 regularly. You note that her current blood pressure is above this value. You also find out that her home blood pressures are above this value, but had all been below 140/90.

6.2 Benefits of treating hypertension

The risk of cardiovascular events and mortality increases as both systolic and diastolic blood pres sures increase.10 The absolute benefit of treatment varies according to the patients baseline risk level. However, the relative benefit, regardless of baseline

Table 5. Threshold for initiation of treatment and target values9

Condition Isolated systolic hypertension Home BP measurement (no diabetes, renal disease, or proteinuria) Diabetes Renal disease Proteinuria >1g/day Initiation Target SBP/DBP SBP/DBP mmHg mmHg <140/90 <140 160

Diastolicsystolic hypertension 140/90

135/85 130/80 130/80 125/75

<135/85 <130/80 <130/80 <125/75

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risk or pretreatment blood pressure, is consistently around 2530% reduction in clinical outcomes.5 A recent meta-analysis suggests that for a chronic reduction in diastolic blood pressure of 56 mmHg, there is a 3540% reduction in stroke and a 814% reduction in coronary heart disease.11 From another meta-analysis in elderly patients, a reduction of 89 mmHg in systolic blood pressure was found to reduce stroke-related events by 50% and cardiovas cular events by 3040%.12

agents to achieve their blood pressure target and a significant proportion required three agents.13 At the end of the five-year follow-up of the ALLHAT study, 63% of patients required at least two antihyper tensive agents to achieve blood pressure control.14 In several studies (AASK, HOT, MDRD, ABCD, UKPDS), patients with diabetes or renal impairment required an average of 3.2 medications to reach target diastolic blood pressure goals.15

6.3 Combination therapy

Many patients will need combination drug therapy to control their blood pressure to the target range. In the HOT study, 68% of patients required at least two

6.4 Canadian Hypertension Guidelines 2005 recommendations

The Canadian Hypertension Society creates revised guidelines each year and publishes the guidelines in the Canadian Journal of Cardiology as well as on

Table 6. Lifestyle modifications to manage hypertension3,9

Modification Weight reduction Recommendation Maintain normal body weight (BMI 18.524.9 kg/m2). Weight loss (5 kg) in those who are overweight (BMI>25). Target waist circumference of <102 cm in men and <88 cm in women. Consume a diet rich in fruits, vegetables, and low-fat dairy products, with a reduced content of saturated and total fat and salt (available at www.nhlbi.nih.gov). Reduce dietary sodium intake to no more than 100 mmol/day (2.4 g sodium or 6 g sodium chloride) in saltsensitive individuals (such as Canadians of African descent, >45 years old, impaired renal function, or diabetes). Engage in regular moderate-intensity aerobic physical activity such as brisk walking (at least 3060 minutes per day, 4 or more days of the week). Limit consumption to no more than 2 drinks per day in most men and no more than 1 drink per day in women and lighter-weight persons. Maximum of 14 drinks per week for men and 9 drinks per week for women. Explore various pharmacological and non-pharmacological strategies and programs to help quit. Maintain smoke-free environments if currently not a smoker. Consume approximately >80 mmol/day of dietary potassium For those salt-sensitive individuals. Requirements may be less in patients with renal disease. Comments Approximate SBP reduction 520 mmHg/10kg (~22lbs) weight loss Approximate SBP reduction 814 mmHg Approximate SBP reduction 28 mmHg

Adopt DASH eating plan

Dietary sodium reduction

Physical activity

Approximate SBP reduction 49 mmHg Approximate SBP reduction 24 mmHg

Moderation of alcohol consumption

Smoking cessation/ smoke-free environment Adequate dietary potassium intake

Stress management

For those in whom stress appears to be an important issue: behaviour modification incorporation of relaxation techniques

BMI: body mass index, DASH: Dietary Approaches to Stop Hypertension, SBP: systolic blood pressure

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their website, www.hypertension.ca. The following treatment recommendations are summarized from the 2005 CHS guidelines, and include important updates related to recently published clinical trials, such as the ALLHAT study.

Table 7. Major cardiovascular risk factors5,9

Related to initiation of antihypertensive drug therapy elevated systolic blood pressure cigarette smoking obesity (BMI 30) physical inactivity dyslipidemia family history of premature heart disease (men <55 years, women <65 years) Related to initiation of preventative statin therapy (Section 6.8) cigarette smoking dyslipidemia (cholesterol/HDL ratio 6) diabetes mellitus male 55 years or older family history of premature heart disease (men <55 years, women <65 years) previous stroke or transient ischemic attack left ventricular hypertrophy ECG abnormalities microalbuminuria or proteinuria peripheral vascular disease
BMI: body mass index: ECG: electrocardiogram: HDL: high-density lipoprotein

6.5 Non-pharmacological therapy

Non-drug therapy is an important cornerstone in the management of hypertension. Non-pharmaco logical therapy, in the form of lifestyle modifica tion, is important as an initial step in some patients to control their blood pressure, and as an adjunct to all patients receiving pharmacological therapy. Current recommendations are summarized in Table 6, including estimated reductions in SBP for some interventions.9 PW notes that she is very good about maintaining lifestyle modifications to control her blood pressure. You review the various aspects with her and discover that she is only physically active 12 times per week since her move to your community. You discuss ways of incorporating more activity into her routine. She also is concerned about the effects of her husbands smoking on her health, and you both decide to ask him to schedule an appointment at the pharmacy to discuss his cardiac risk factors and potential for smoking cessation at a future date.

6.6 Drug therapy

Most antihypertensive drugs lower blood pressure by about 1015%. Monotherapy is effective in about 3050% of patients, particularly those in the lower range of hypertensive pressures.5 Initiation of drug therapy should be strongly considered for DBP at or above 90 mmHg and either target organ damage, including cardiovascular disease, or presence of independent cardiovascular risk factors. (See Table 7 for list of risk factors.) Drug therapy should also be strongly considered for DBP at or above 80 mmHg in patients with diabetes. Choice of treat ment depends on associated risk factors, presence of target organ damage or complications, and con comitant diseases or conditions.9 6.6.1 Drug therapy for those without compelling indications Lifestyle modification should be used in concert with drug therapy.9 The Canadian Hypertension Society guidelines now suggest that any of the following five drug classes may be used as first-line therapy: thia zide diuretics, angiotensin converting enzyme inhib itors (ACEIs), angiotensin receptor blockers (ARBs), long-acting calcium channel blockers (CCB), or betablockers (BB). Each of these classes has demonstrated a reduction in morbidity and mortality. Recent evi dence with reductions in morbidity and mortality with blood pressure reduction with ARBs, ACEIs,

Table 8. Useful dual combinations9

Column 1 Column 2 beta-blocker ACEI ARB thiazide diuretic LA CCB

Caution should be exercised when using a nondihydropyridine CCB and a beta-blocker For triple therapy, combine 2 agents from column 1 with 1 agent from column 2
ACEI: angiotensin converting enzyme inhibitor; ARB: angiotensin II receptor blocker; CCB: calcium channel blockers; LA: long-acting

and long-acting CCBs has added them to the list of possible first-line agents with these new guidelines.9 Specific caveats about these therapies are listed in Table 9. If there is only a partial response to stan dard dose monotherapy, it is suggested that nonad herence, secondary hypertension, interfering drugs or lifestyle, and the white coat effect be considered. If none of these are present or cannot be eliminated, then dual combination therapy is recommended. Useful dual combinations include one drug from column 1 with any drug from column 2 in Table 8. If dual therapy is not effective, then triple or quadru ple therapy must be considered.9

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Table 9. Considerations in the individualization of antihypertensive therapy9

Initial therapy
Hypertension without compelling indications for other medications Thiazide diuretics, BBs, ACEIs, ARBs, or LA DHP CCBs (amlodipine, felodipine, LA nifedipine)

Second-line therapy
Combinations of first-line drugs

Notes/cautions
Alpha-blockers are not recommended as initial therapy. BB are not recommended as initial therapy in those >60 years. Hypokalemia should be avoided through use of potassium sparing agents in those prescribed diuretics. Use low-dose thiazides (12.525 mg/day). ACEIs are not recommended as initial monotherapy in African-Americans. BBs are not recommended as initial therapy in smokers. Hypokalemia should be avoided in those prescribed diuretics through use of potassium-sparing diuretics. 34 drug combination may be needed for control.

Isolated systolic hypertension without other compelling indications Diabetes mellitus with nephropathy

Thiazide diuretics; also ARBs or LA DHP CCBs ACEIs or ARBs

Combinations of first-line drugs

Addition of one or more of thiazide diuretics, cardioselective BBs, or LA CCBs, or use of ARB/ ACEI combination Combination of first line drugs or addition of cardioselective BBs (acebutolol, atenolol, bisoprolol, metoprolol) and/or LA CCBs LA CCBs

Diabetes mellitus without nephropathy

ACEIs, ARBs or thiazide diuretics

If SCr>150 mol/L, a loop diuretic should be used instead of a thiazide if volume control is needed. Avoid short-acting nifedipine. Caution with combined use of BB and non-DHP-CCB.

Angina

BBs (strongly consider adding ACEIs) BBs and ACEIs

Prior myocardial infarction

If BB cannot be used and HF present: use LA DHP CCB; if no HF, use LA CCB. Combination of additional agents. Hydralazine/ISDN, thiazide or loop diuretics as additive therapy Avoid non-DHP CCBs (diltiazem, verapamil). ARB may be added to an ACEI or other drugs. Blood pressure reduction reduces recurrent events after the acute phase. Both classes control heart rate. Combinations of additional agents (ARBs if ACEIs intolerant) Avoid ACEIs and ARBs if bilateral renal artery stenosis. Loop diuretics more effective than thiazides in presence of renal disease. Avoid hydralazine and minoxidil.

Heart failure

ACEIs, BBs and spironolactone (class III-IV) (ARBs if ACEI intolerant) ACEIs/diuretic combination BB, non-DHP CCB ACEIs (diuretics as additive therapy)

Past stroke or TIA

Atrial fibrillation Renal disease

Left ventricular hypertrophy

ACEIs, ARBs, LA CCBs, thiazide diuretics (BBs for patients under 60 years of age)

ACEIs: angiotensin converting enzyme inhibitors, ARBs: angiotensin II receptor blocker, BBs: beta-blockers, CCBs: calcium channel blockers, DHP: dihydropyridine, HF: heart failure, ISDN: isosorbide dinitrate, LA: long acting, SCr: serum creatinine, TIA: transient ischemic attack

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Table 10. Adverse effects and contraindications of antihypertensive agents3,4

Drug class ACE inhibitors ARBs Alpha blockers Beta-blockers Contraindications Pregnancy, bilateral renal artery stenosis, hyperkalemia Pregnancy, bilateral renal artery stenosis, hyperkalemia Orthostatic hypotension, heart failure, diabetes Asthma, COPD with reactive airways component, heart block, severe Raynauds syndrome Adverse effects Cough, angioedema, hyperkalemia, loss of taste, rash, renal dysfunction Angioedema (rare), hyperkalemia, renal dysfunction Headache, drowsiness, fatigue, postural hypotension, first dose hypotension, nasal stuffiness, erectile dysfunction Bronchospasm, heart failure, impaired peripheral circulation, insomnia, fatigue, bradycardia, elevated triglycerides, impotence, exercise intolerance, hyperglycemia

Calcium channel blockers Centrally acting agents (methyldopa, clonidine) Diuretics

Heart block, systolic dysfunction Headache, flushing, peripheral edema, gingival hyperheart failure (verapamil, diltiazem) plasia (verapamil), constipation (verapamil), erectile dysfunction Depression, liver disease (methyl- Rebound hypertension with discontinuation, sedation, dopa), diabetes dry mouth, bradycardia, erectile dysfunction, sodium and fluid retention, hepatitis (rare) Gout Hypokalemia, hyperuricemia, glucose intolerance (except indapamide), hypercalcemia (thiazides), hyperlipidemia, hyponatremia, impotence (thiazides)

ACE: angiotensin converting enzyme, ARB: angiotensin receptor blocker, COPD: chronic obstructive pulmonary disease

While the choice of treatment may depend on the patients concomitant diseases or conditions, the impact on mortality reduction should also be con sidered. The most recent large comparative trial, the ALLHAT study, confirmed the central role of thia zide diuretics in the first-line therapy of hyperten sion without compelling indications.14,16 This study found no difference in the primary outcome of fatal coronary disease or nonfatal MI between the drugs studied (chlorthalidone, amlodipine, lisinopril, or doxazosin-based regimens). None of the newer drug classes was found to be any more effective than diuretics in this large, well-conducted study. In fact, the chlorthalidone group also had lower rates of stroke and heart failure as compared to the other therapies.14 In addition, the alpha-blocker arm had been stopped early due to an increased incidence of heart failure with this therapy, despite the fact that doxazosin lowered blood pressure to about the same degree as chlorthalidone.17 As a result, alphablockers are currently not accepted as first-line anti hypertensive therapy.3,9 Despite the fact that diuretics and beta-blockers are the oldest of the drugs suggested for first-line therapy, with evidence demonstrating a significant reduction in morbidity and mortality, and are the least expensive, they are not prescribed as fre quently as expected. This is likely due to some mis

conceptions about unacceptably high rates of side effects with diuretics and beta-blockers. Two large studies (SHEP, TOMHS) have found that the effects of diuretics and beta-blockers on serum lipids were transient and small. For most patients, glucose and cholesterol increases are usually clinically insignifi cant. Despite these metabolic changes, studies have still found a significant morbidity and mortality benefit.18,19 In addition, in terms of tolerability of various drug classes, a large US study found that rates of patient withdrawal from several studies due to adverse effects were 1% for hydrochlorothiazide, 2% for atenolol, 5% for captopril, 6% for placebo, and 7% for diltiazem, demonstrating good tolerance for diuretics and beta-blockers.20 Common adverse effects and contraindications to each antihyperten sive drug class are summarized in Table 10. For isolated systolic hypertension, lifestyle mod ification should be used along with drug therapy with a thiazide diuretic. Other appropriate agents include an ARB or a long-acting dihydropyridine CCB. If there is only a partial response to standard dose monotherapy, it is suggested that nonadher ence, secondary hypertension, interfering drugs or lifestyle and the white coat effect be considered. If none of these are present or cannot be eliminated, then dual combination therapy is recommended with one of the other two drug classes not used.9

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6.7 Drug therapy for individualized antihypertensive therapy

Table 9 lists the first-line and second-line therapy suggestions for medications in patients with specific conditions that affect drug choice. It is important to recognize that patients may have multiple con comitant conditions that must be taken into account when choosing antihypertensive drug therapy. In addition, the benefits of treating smokers with betablockers remain uncertain in the absence of specific indications like angina or post-MI. Therefore, betablockers are not routinely recommended in smok ers without these indications. For patients with Raynauds syndrome or severe peripheral arterial disease, vasodilator drugs (CCBs, ACEIs, ARBs, alpha-blockers) are first-line therapy, while betablockers should not be used.9 In assessing PWs need for individualized therapy, you need to take into account her diabetes and angina diagnoses. You ask whether her doctor has checked her kidney function recently. She tells you that he did, and said her kidneys were fine now but would need to be checked each year. In determining potential drug therapy for her, you note that first-line therapy for hypertensive patients with diabetes without nephropathy is a thiazide diuretic, an ACEI, or an ARB. You also know that most patients with diabetes will require at least 2 medications to control their blood pressure. Also, first-line therapy for patients with angina is beta-blockers, with a strong consideration for adding an ACEI. Upon checking her pulse, you find her heart rate to be 82 bpm, and determine that she may benefit from the heart-rate-lowering effects of the beta-blocker (target heart rate ~70 bpm for angina) in addition to the ACEI effects for protecting her kidneys from diabetic nephropathy. These agents can be used instead of her topical nitroglycerin.

for all hypertensive patients above 50 years old whose blood pressure is controlled. c) ACEI should be used for all patients with estab lished atherosclerotic disease.5 These recommendations are based on data from recent studies. The ASCOT-LLA study with atorvas tatin found a significant reduction in fatal and non fatal MI with atorvastatin 10 mg/day.21 The Heart Protection Study (HPS) found a significant reduc tion in all-cause mortality associated with the use of simvastatin 40 mg/day, with the results similar in patients with hypertension. This was over and above other therapies known to be cardioprotective, such as, ASA, ACEI, and beta-blockers.22 In the HOT trial, which included a low-dose ASA (75 mg/day) arm, patients given ASA had a significant reduction in major cardiovascular events, particularly fewer MIs.13 The benefits were primarily seen in patients with lower blood pressures; therefore, the blood pressure should be controlled prior to initiation of ASA. In the HOPE trial with ramipril, in patients at high risk for cardiovascular disease, ramipriltreated patients had less MI, stroke and cardiovas cular death. This effect appeared to be independent of blood-pressure-lowering effects and was seen over and above the benefits of other cardioprotec tive agents given, such as ASA, statins, and betablockers.23 In reviewing the recommendations for non-antihypertensive therapy, you find that since she has existing atherosclerosis (angina), she qualifies for statin therapy. She also qualifies for low-dose aspirin therapy based on 1) being above 50 years and having hypertension and 2) primary cardiovascular prevention for chronic stable angina. She also meets the criteria for ACEI therapy based on the HOPE trial. You plan to discuss your findings with her and her doctor to create a plan for her and schedule an appointment for her with her doctor.

6.8 Non-antihypertensive therapy

An important new message from the 2004 update of the guidelines is the headline selected for 2004: Blood pressure control is only one compo nent (albeit a very important component) of the overall vascular protection strategy of the hyper tensive patient. The guidelines recommend deter mining the patients global cardiovascular risk in order to assess the need for other preventive ther apies. Based on this mandate, the following addi tional recommendations have been added to this years guidelines: a) Statins should be considered for all hyperten sives at higher risk (3 or more cardiovascular risk factors) for atherosclerotic complications or with existing atherosclerotic disease (see Table 7 column 2). b) Low-dose ASA should be strongly considered

7. Key differences between Canadian, American, and European guidelines

Two key differences exist between the Canadian and the American (JNC 7) guidelines for hyperten sion. The JNC 7 has introduced the new classifica tion of prehypertension for those with SBP 120139 mmHg or DBP 8089 mmHg in order to identify individuals at high risk for developing hypertension so that lifestyle modifications may be implemented. Based on the ALLHAT study, complimenting prior evidence, JNC 7 places a stronger emphasis on thia zide diuretics as the first-line agent for treatment of hypertension, either alone or in combination with other therapies.3,24,25 Differences also exist in the

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European guidelines, which include a complex clas sification system for stages of hypertension, as well as a detailed determination of risk assessment based on the Framingham criteria. This system provides for a somewhat less aggressive approach compared to the Canadian and American guidelines. Like the Canadian guidelines, the European guidelines defer drug choice for first-line agents to the healthcare providers judgment of the patients specific charac teristics.26

to gradually step-down therapy in certain patients, especially if lifestyle modifications are maintained.9 Specific adverse effects and laboratory param eters that are recommended to be monitored are drug-specific and are summarized in Table 11. In order to measure the effectiveness of therapy, the following should be monitored: blood pressure measurements target organ damage heart, kidney, eye, brain adherence drug interactions

8. Monitoring
Most antihypertensive drugs lower blood pressure by about 1015%.5 The time to respond to therapy ranges from 2 to 8 weeks. If a patients blood pressure is not at target, monthly visits should be scheduled until control is achieved for 2 consecu tive months. If the patient has symptoms, severe hypertension, intolerance to therapy, or target organ damage, then more frequent visits may be needed in order to meet the goals of therapy more quickly. For patients whose blood pressure readings have been below target for 2 consecutive monthly visits, follow-up is appropriate at 36 month intervals. If hypertension has been controlled for over one year in uncomplicated patients, it may be possible

In order to measure toxicity to therapy, adverse effects and drug interactions should be assessed on a regular basis. For those patients who will be conducting home measurement of blood pressure, several issues need to be addressed. Patients need to have a device that has the appropriate cuff size for their arm and has met the standards of the Association for the Advancement of Medication Instrumentation (AAMI) and/or the British Hypertension Society (BHS) and/or International Protocol (IP). Although approved devices may be difficult to find, the CHS now has a logo to indicate ones approved to meet their standards in Canada. Pharmacists may wish to

Table 11. Monitoring of antihypertensive agents by class3,4

Drug class ACE inhibitors ARBs Alpha-blockers Beta-blockers Pharmacist/patientmonitoring parameters First-dose hypotension, lightheadedness, dizziness, cough, blood pressure, adherence First-dose hypotension, lightheadedness, dizziness, blood pressure, adherence Postural hypotension (especially with first dose), dizziness, blood pressure, adherence Heart rate, blood pressure, energy level, exercise tolerance, dizziness, lightheadedness, sexual dysfunction, symptoms of heart failure, adherence Heart rate (verapamil, diltiazem), peripheral edema, headache (especially with DHPs), symptoms of heart failure, blood pressure, adherence Sedation, dry mouth, heart rate, symptoms of fluid retention, blood pressure, adherence Lightheadedness, dizziness, fluid status, urine output, weight, blood pressure, adherence Signs of heart failure, blood glucose Signs of heart failure Additional physician monitoring parameters Renal function, electrolytes Renal function, electrolytes

Calcium channel blockers Centrally acting agents (methyldopa, clonidine) Diuretics

Liver enzymes (methyldopa), signs of fluid retention Renal function, electrolytes, blood glucose

ACE: angiotensin converting enzyme; ARB: angiotensin receptor blocker; DHP: dihydropyridine

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review the devices they carry to attempt to supply devices of the highest quality. Patients need to be trained in measuring their blood pressure and inter preting their readings. Any blood pressure over 136/83 should be considered elevated (analogous to an office measurement above 140/90).8 There should be regular verifications of the accuracy of the device and the patients measuring techniques with their physician. Self-measurement has been shown to improve patient adherence, especially in patients with known nonadherence and in patients with diabetes, and is an important tool in this regard.27,28 Self-measurement is also useful in patients who are thought to have white coat hyper tension. Since PW measures her blood pressure at home, you review her technique with her and suggest she verify the accuracy of her device. You encourage her to continue measuring her blood pressure, but with the lower target of <130/80 as the goal due to her diabetes (even lower is likely even better and more analogous to an office measurement of 130/80).

Table 12. Strategies to improve adherence to therapy33,34

Assess adherence at each visit. Discuss with patients their beliefs and motivations. Engage patients into desire for management of their health issues. Use active listening skills to hear patients point of view. Address patients concerns about therapy. Provide patients with tools to help them to remember to take their medications. Help simplify medication regimens (e.g. less frequent dosage, combination products). Tailor pill-taking to fit the patients daily habits. Provide information about the benefits of blood pressure control. Provide realistic estimates of the likelihood of adverse effects. Provide oral and written information about hypertension and medications. Consider the use of home blood pressure monitoring to help patients be engaged in their care. Educate and involve the patients family about their disease and treatment regimens. Involve family and friends in lifestyle and medication adherence. Ensure the regimen is affordable. Use technology to track patients who do not refill prescriptions in a timely manner. Use telephone follow-up to ensure patients are continuing with the management plan. awareness of target and above-target blood pres sure values awareness of their own blood pressure values the asymptomatic nature of blood pressure the serious consequences of uncontrolled hyper tension the need for extended follow-up and chronic treatment the role of medication in controlling blood pres sure, not curing hypertension the benefits of medications in preventing adverse clinical outcomes adverse effects of medications and their manage ment combining drug and non-drug therapies in achieving blood pressure control

9. Medication adherence
Major efforts need to be put into place so that patients can improve their adherence to therapy and achieve their target blood pressure levels.29 From studies conducted assessing adherence, we know that only about 50% of patients continue their anti hypertensive therapy on a continuous long-term basis.30,31 One study has found that patients who discontinue their therapy are at a five times higher risk of having a stroke.32 Lack of adherence may be intentional or unintentional. Some ways of help ing patients with adherence problems are listed in Table 12. The most effective strategy is multifaceted, combining several of the listed strategies involving education, behavioural modification, and support systems.33,34

10. Patient education

Recent survey results suggest that there needs to be improved public awareness of the consequences of hypertension. In this survey, two-thirds of patients who were aware of their hypertension diagnosis thought that their blood pressure was their own pri mary responsibility. However, two-thirds of these patients stated that high blood pressure was not a serious concern.35 Given that this attitude conflicts with the known risks of target organ damage with elevated blood pressure, patient education is critical for accepting and meeting goals of therapy. Some important topics for patient education on hypertension management include:

11. Opportunities for pharmacists

Pharmacists are well positioned to educate Canadi ans about hypertension, to monitor their response in the community setting, to encourage long-term adherence to drug and non-drug therapy, and to

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refer patients to physicians for management deci sions.36 Talking to the patient about the benefits of hypertensive therapy is at least as important as dis cussing adverse effects. When patients understand the potential benefits of drug treatment for hyper tension, they may be more inclined to adhere to therapy. In the discussion of adverse effects, phar macists should discuss with patients how to avoid or manage these effects as they arise in order to help patients continue their therapy if possible.37 Several studies in the United States have demon strated that pharmacists working in hypertension clinics or in collaboration with physicians in family practice are able to improve the care of hyperten sion patients. When pharmacists are involved, blood pressure control and the quality of prescribing are improved compared to control groups receiving usual care. As well, several studies have shown that community-based pharmacists can improve blood pressure control when they focus on patient management.3840 A recent pilot study of 100 hyper tensive patients from Quebec has shown that phar macists in the community setting in Canada can also affect antihypertensive therapy.41 The major inter vention in this study was education and counseling by the pharmacist, rather than comprehensive phar maceutical care. Perhaps even greater impact would be seen in a setting where more detailed and thor ough interventions were possible. Nonpharmacological measures require a great deal of attention by health professionals if they are to be successful. They require behavioural change and continuous reinforcement. Assisting patients with how they can incorporate these modifications into their lifestyle can help them achieve these goals. For example, suggestions about how to incorporate physical activity into daily activities are something the pharmacist can discuss with the patient. Phys ical activity will also help with weight reduction. Weight loss does not need to be dramatic to help with hypertension control. Even a 4.57 kg (~1015 lb) weight loss can have a measurable effect on blood pressure. Pharmacists can also discuss smok ing cessation with patients, exploring the use of prescription and non-prescription cessation aids as well as smoking cessation support groups. Very important to the success of modifying antihyper tensive drug regimens is to develop a rapport with local physicians and act as a resource to help their patients meet their blood pressure targets. Other roles pharmacists can have include:

Table 13. Herbal products and hypertension4244

May worsen hypertension or lessen effect of therapy bayberry blue cohosh capsicum coltfoot country mallow ephedra (ma huang) European mandrake gentian ginseng goldenseal licorice mistletoe Scotchbroom flower yohimbine Claims of some antihypertensive effects (some supporting clinical data) garlic hawthorn individual consultation meetings with patients blood pressure monitoring monitoring overall response to therapy encouraging patient self-monitoring/adherence to therapy hypertension clinic days medication review sessions identification of drug-related causes of hyperten sion simplifying dosing regimens creating patient medication schedules assessment of herbal products in relation to hypertension (see Table 13) home visits rentals of 24-hour blood pressure ambulatory monitors.

Upon questioning, PW states that she takes echinacea for colds as needed in the winter months and ginseng for a general pick-me-up remedy. You discuss with her that ginseng may be contributing to worsening of her blood pressure control and ask her to develop other ways to increase her energy. Increasing her exercise schedule as previously discussed may help her in this regard. You explain to her that even natural remedies and herbal medications can have both beneficial and adverse side effects.

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12. Web resources

Listed in Table 14 is a sample of some websites related to hypertension that may be useful for fur ther information for patients or health profession als.

Table 14. Hypertension and heart disease websites

www.hypertension.ca www.canadianbpcoalition.org www.heartandstroke.ca www.bloodpressure.com www.ccs.ca www.hypertension.qc.ca www.americanheart.org www.ash-us.org www.heartcenteronline.com www.nhlbi.nih.gov/health/public/heart www.mayohealth.org www.mco.edu/org/whl www.phac-aspc.gc.ca/ccdpc-cpcmc/hhk-tcs/ english/03_highpressure/03_high_reduce.htm

13. Summary
Hypertension is a common condition affecting one in every five Canadians. Hypertension is a signifi cant risk factor for coronary artery disease, stroke, congestive heart failure, renal failure, peripheral vas cular disease, dementia, and atrial fibrillation. Many Canadians are unaware that they have hypertension and, of those aware, many are undertreated, leav ing their blood pressure uncontrolled. The Cana dian Hypertension Education Program (CHEP) is attempting to improve the management of hyper tension in Canada by annually revising and imple menting evidence-based recommendations for the management of hypertension. The 2005 guidelines include recommendations for individualization of therapy for specific patients. Pharmacists can become familiar with the current recommendations and play a vital role in assisting patients with many aspects of hypertension management.

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References
1. Ezzati M, Lopez AD, Rodgers A, Vander Hoorn S, Murray CJ. Comparative Risk Assessment Collabora tive Group. Selected major risk factors and global and regional burden of disease. Lancet 2002;360:134760. 2. Joffres MR, Ghadirian P, Fodor JG, Petrasovits A, Chockalingam A, Hamet P. Awareness, treatment and control of hypertension in Canada. Amer J Hypertens 1997;10:10971102. 3. Chobanian AV, Bakris GL, Black HR, et al. Seventh report of the Joint National Committee on Preven tion, Detection, Evaluation, and Treatment of High Blood Pressure: JNC 7 Complete Report. Hyperten sion 2003;42:120652. 4. DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey ML, editors. Pharmacotherapy: A pathophysi ologic approach. 5th ed. Toronto: McGraw-Hill, 2002. 5. Khan NA, McAlister FA, Campbell NRC, Feldman RD, Rabkin S, Mahon J, et al for the Canadian Hyper tension Education Program. The 2004 Canadian rec ommendations for the management of hypertension: Part II Therapy. Can J Cardiol 2004;20:4154. 6. Kannel WB. Blood pressure as a cardiovascular risk factor: prevention and treatment. J Amer Med Assoc 1996;275:15716. 7. Campbell NRC, McAlister R, Brant R, et al, for the Canadian Hypertension Education Process and Eval uation Committee. Temporal trends in antihyperten sive drug prescriptions in Canada before and after introduction of the Canadian Hypertension Education Program. J Hypertens 2003;21:15917. 8. www.hypertension.ca/recommendations_2005/ CHEP_2005_Diagnosis.ppt. Accessed February 18, 2005. 9. www.hypertension.ca/recommendations_2005/ CHEP_2005_Treatment.ppt. Accessed February 18, 2005. 10. Neaton JD, Wentworth D. Serum cholesterol, blood pressure, cigarette smoking, and death from coro nary heart disease. Overall findings and differences by age for 316,099 white men. Multiple Risk Factor Intervention Trial Research Group. Arch Intern Med 1992;152:5664. 11. MacMahon S, Peto R, Cutler J, Collins R, Sorlie P, Neaton J, et al. Blood pressure, stroke and cor onary heart disease. Part 1, prolonged differenced in blood pressure: Prospective observational studies corrected for the regression dilution bias. Lancet 1990;335:76574. 12. Psaty BM, Smith NL, Siscovick DS, Koepsell TD, Weiss NS, Heckbert SR, et al. Health outcomes associ ated with antihypertensive therapies used as first-line agents: a systematic review and meta-analysis. J Amer Med Assoc 1997;277:73945. 13. Hansson L, Zanchetti A, Carruthers SG, Dahlof B, Elmfeldt D, Julius S, et al, for the HOT Study Group.

Effects of intensive blood-pressure lowering and lowdose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomized trial. Lancet 1998;351:175562. 14. The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major out comes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or cal cium channel blocker or diuretic. The Antihyper tensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). J Amer Med Assoc 2002;288:298197. 15. Bakris GL, Williams M, Dworkin L, Elliot WJ, Epstein M, Toto R, et al. Preserving renal function in adults with hypertension and diabetes: a consensus approach. National Kidney Foundation Hypertension and Dia betes Executive Committees Working Group. Am J Kidney Dis 2000;36:64661. 16. Appel LJ. The verdict from ALLHAT thiazide diuret ics are the preferred initial therapy for hypertension. J Amer Med Assoc 2002;288:303941. 17. The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major cardio vascular events in hypertensive patients randomized to doxazosin vs chlorthalidone. The Antihyper tensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). J Amer Med Assoc 2000;283:196775. 18. Neaton JD, Grimm RH, Prineas RJ, et al for the Treat ment of Mild Hypertension Study Research Group. Treatment of Mild Hypertension Study: final results. J Amer Med Assoc 1993;270:71324. 19. Frost PH, Davis BR, Burlando AJ, et al for the Sys tolic Hypertension in the Elderly Program Cooper ative Research Group. Serum lipids and incidence of coronary heart disease findings from the Systolic Hypertension in the Elderly Program (SHEP). Circu lation 1996;94:23818. 20. Materson BJ, Reda DJ, Cushman WC, et al. Singledrug therapy for hypertension in men: a comparison of six antihypertensive agents with placebo. N Engl J Med 1993;328:91421. 21. Sever PS, Dahlof B, Poulter NR, et al, for the ASCOT Investigators. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentra tions, in the Angelo-Scandinavian Cardiac outcomes Trial Lipid Lowering Arm (ASCOT-LLA): multicen tre randomized trial. Lancet 2003;361:114958. 22. Heart Protection Study Collaborative Group. MRC/ BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomized placebo-controlled trial. Lancet 2002;360:722. 23. The Heart Outcomes Prevention Evaluation Study Investigators. Effects of an angiotensin-convertingenzyme inhibitor, ramipril, on cardiovascular events

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in high-risk patients. N Engl J Med 2000;342:14553. 24. Franco V, Oparil S, Carretero OA. Hypertensive Ther apy: Part I. Circulation 2004;109:29538. 25. Franco V, Oparil S, Carretero OA. Hypertensive Ther apy: Part II. Circulation 2004;109:30818. 26. Mancia G, Rosei A, DeBaker G, et al. 2003 European Society of Hypertension European Society of Car diology guidelines for the management of arterial hypertension. J Hypertens 2003;21:101153. 27. OBrien E, Pickering T, Asmar R, et al. Working Group on Blood Pressure Monitoring of the European Soci ety of Hypertension International Protocol for valida tion of blood pressure measuring devices in adults. Blood Press Monit 2002;7:317. 28. Lopez LM, Taylor JR. Home blood pressure mon itoring: point-of-care testing. Ann Pharmacother 2004;38:86873. 29. Houston Miller N, Hill M, Kottke T, et al. The mul tilevel compliance challenge: recommendations for a call to action. Circulation 1997;95:108590. 30. Caro JJ, Speckman J. Existing treatment strategies: Does noncompliance make a difference? J Hypertens 1998 (Suppl);16:S314. 31. Marentette M, Gerth W, Billings D, Zarnke K. Antihy pertensive persistence and drug class. Can J Cardiol 2002;18:64956. 32. Thrift AG, McNeill JJ, Forbes A, et al. Three impor tant subgroups of hypertensive persons at greater risk of intracerebral hemorrhage. Hypertension 1998;31:12239. 33. Willey C. Behavior-changing methods for improving adherence to medication. Curr Hypertens Rep 1999;1:47781. 34. McDonnell HP, Garg A, Haynes RB. Interventions to enhance patients adherence to medication prescrip tions. J Amer Med Assoc 2002;288:286879. 35. Petrella R. Survey on awareness of hypertension. Per spectives in Cardiology 2002 March. 36. ASHP therapeutic position statement on optimizing treatment of hypertension. Amer J Health-Syst Pharm 2000;57:16273. 37. Myers M. Compliance in hypertension: why dont patients take their pills? Can Med Assoc J 1999;160:645. 38. Carter BL, Barnette DJ, Chrischilles E, Mazzotti GJ, Asali ZJ. Evaluation of hypertensive patients after care provided by community pharmacists in a rural set ting. Pharmacotherapy 1997;17:127485. 39. Carter BL, Zillich AJ. Pharmaceutical care services for patients with hypertension. Pharmacotherapy 2003;37:13357. 40. Carter BL, Zillich AJ, Elliott WJ. How pharmacists can assist physicians with controlling blood pressure. J Clin Hypertens 2003;5:317. 41. Chabot I, Moisan J, Gregoire JP, Milot A. Pharmacist intervention program for control of hypertension. Ann Pharmacother 2003;37:118693.

42. Mansoor GA. Herbs and alternative therapies in the hypertension clinic. Amer J Hypertens 2001;14:9715. 43. Ruck B, Shih RD, Marcus SM. Hypertensive crisis from herbal treatment of impotence. Amer J Emerg Med 1999;17:3178. 44. Fetrow CW, Avila JR. Professionals Handbook of Complementary and Alternative Medicines. Spring house: Springhouse Corp., 1999.

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Questions
According to CCCEP guidelines, participants have two attempts to achieve a score of 70% on the post-test questions. Successful participants will receive a certificate documenting their completion of the course. While not required to do so, participants are encouraged to use the feedback form to provide comments and suggestions about the course.

The following scenario applies to questions 15: JR is a 57-year-old male with hypertension, osteoarthritis, and asthma. He was diagnosed with hypertension approximately 5 years ago. JR takes hydrochlorothiazide 25 mg daily for his high blood pressure and acetaminophen prn for his osteoarthritis. His most recent blood pressure reading was 156/94. JR is a heavy smoker. 1. What is JRs maximum target blood pressure? a. 120/80 b. 130/85 c. 139/89 d. 125/85 2. When combined with hypertension, which of the following increases JRs risk of subsequent cardio vascular disease? a. asthma b. smoking c. osteoarthritis d. duration of JRs hypertension 3. What changes to JRs lifestyle should be recom mended in order to decrease his blood pressure? a. smoking cessation b. drinking 3 alcoholic beverages per day c. taking a magnesium supplement d. none of the above 4. The consequences of long-term uncontrolled hypertension include: a. stroke or transient ischemic attacks b. kidney disease c. retinopathy d. all of the above 5. Which of the following agents should JR avoid? a. ramipril b. valsartan c. nadolol d. amlodipine

The following scenario applies to questions 616: AT is a 62-year-old woman. She has been on metoprolol 50 mg twice daily for over 10 years to treat her hypertension. Her current blood pressure is 145/90. AT is also taking metformin 500 mg three times daily for diabetes. Her diabetes is not well-controlled, and as a result, she has developed nephropathy (albuminuria 500 mg/day). 6. What changes should be made to ATs hyperten sion therapy? a. No changes need to be made. b. Discontinue metoprolol and start an ACE inhibitor. c. Increase the dose of metoprolol. d. Discontinue metoprolol and start a low-dose thiazide diuretic. 7. What is the goal blood pressure for AT? a. <130/80 b. <140/90 c. <125/75 d. <135/80 8. Which of the following medications should be avoided in hypertensive patients with diabetes? a. sympathomimetics b. alpha-blockers c. central-acting alpha agonists d. all of the above 9. Which statement is not true about hypertension? a. There is a hereditary component to the risk of becoming hypertensive. b. About 10% of patients suffering from hyper tension have a specific underlying pathology as a cause. c. Essential hypertension refers to high blood pressure, for which no definable cause can be found. d. African-Americans are less likely to develop hypertension in their lifetime than are Cauca sians. 10. AT develops a complication while on ACE inhib itor therapy. For which situation might angiotensin II receptor blockers (ARBs) be beneficial? a. when a patient develops renal insufficiency with ACE inhibitors b. when a patient develops hyperkalemia with ACE inhibitors c. where cough has caused a patient with con comitant CHF to discontinue their ACE inhib itor d. where hypertension is accompanied by reno vascular disease

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11. Which medications have been shown through clinical trials to reduce the risk of mortality in patients with hypertension? a. ACE inhibitors, ARBs, beta-blockers, calcium channel blockers, and diuretics b. alpha blockers, beta-blockers, diuretics c. angiotensin receptor blockers, ACE inhibitors, alpha blockers d. angiotensin receptor blockers, ACE inhibitors, central acting agents 12. For elderly hypertensive patients (with isolated systolic hypertension), which statement is true? a. Beta-blockers should be used first line. b. Low-dose thiazide diuretics should be used as first-line therapy. c. Alpha-blockers, as initial monotherapy, are the drugs of choice in this patient group. d. Loop diuretics such as furosemide should be used first line. 13. Which statement about hypertension is false? a. Many hypertensive patients do not adhere to their blood pressure medication. b. Patients with uncontrolled hypertension are urged to continue a sedentary lifestyle until their blood pressure is brought under control. c. In overweight patients, a 5 kg weight loss may reduce blood pressure. d. There is an association between sodium intake and blood pressure levels. 14. ACE inhibitors are indicated as first-line agents for hypertension in all the following situations except: a. systolic dysfunction congestive heart failure b. diabetes mellitus with proteinuria c. atrial fibrillation d. recent myocardial infarction 15. Which agent is least likely to cause exacerbations of high blood pressure? a. pseudoephedrine b. niacin c. venlafaxine d. ginseng 16. Which statement is false? a. Indapamide may cause glucose intolerance. b. High doses of diuretics should be avoided in patients with gout. c. Thiazide diuretics can be used in patients with osteoporosis because they cause calcium retention. d. Patients with hyperlipidemia can be treated with diuretics.

The following scenario applies to questions 1724: AB, a 38-year-old female, comes to the pharmacy to get a refill of her simvastatin, which she uses for hyperlipidemia. While waiting for her prescription, she decides to take her blood pressure using the in-store electronic blood pressure machine. She is shocked when she discovers that her blood pressure is 157/94. She states that she has never had high blood pressure before. 17. Which statement(s) is/are true? a. Only a mercury sphygmomanometer with a stethoscope should be used to measure blood pressure. b. Hypertension is diagnosed after at least five assessments over a six-month period. c. BT should take another blood pressure read ing after one minute and average the 2 read ings. d. B and C 18. AB returns to your pharmacy 4 months later with a prescription for enalapril 2.5 mg daily to treat hypertension. What nonpharmacological treatment(s) can be recommended? a. weight reduction if AB is overweight b. moderate exercise 4 or more times a week c. limiting alcohol intake to a maximum of 9 drinks per week d. all of the above 19. Which of the following hypertension medica tions should not be used as first-line therapy in AB? a. beta-blockers b. long-acting calcium channel blocker c. angiotensin receptor blockers d. alpha-blockers 20. Which of following counseling tips for AB is incorrect? a. AB will reach target blood pressure in 2 to 3 days after starting drug therapy. b. Most medications for hypertension will decrease systolic blood pressure by a maxi mum of approximately 15 mmHg. c. Lifestyle modification, in conjunction with drug therapy, will help AB reach her target blood pressure. d. AB should have her blood pressure measured regularly.

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21. After 6 months of therapy, AB has still not reached her target blood pressure. The enalapril is well tolerated. Which of the following could be rec ommended to improve ABs blood pressure con trol? a. increasing the dose of enalapril b. adding a diuretic c. substituting enalapril with methyldopa d. A or B 22. Beta-blockers are first-line agents in the treat ment of hypertension except in the following con comitant condition(s): a. Raynauds phenomenon b. 2nd or 3rd degree heart block c. isolated systolic hypertension d. all of the above 23. Which of the following should be monitored in patients taking beta-blockers? a. blood pressure b. heart rate c. energy level d. all of the above 24. Which of the following statements is true? a. In the early stage of the disease, hypertension is associated with many symptoms. b. The majority of patients with hypertension have well-controlled blood pressure. c. If a patient has two different blood pressures in each arm, the higher blood pressure is used. d. Electronic blood pressure devices do not require periodic calibration and validation. 25. A patient comes into the pharmacy with a list of herbal medications that she is taking. She was recently diagnosed with hypertension. Which of the following herbal preparations have some clinical data supporting an antihypertensive effect? a. garlic b. ma huang c. licorice d. blue cohosh

26. Verapamil and diltiazem are indicated as firstline therapy in hypertensive patients with concomi tant: a. atrial fibrillation b. stable angina c. myocardial infarction d. systolic dysfunction (CHF) 27. The goal(s) of hypertension therapy is/are: a. to eliminate symptoms b. to reduce blood pressure to below 120/80 in all patients c. to reduce mortality and morbidity d. all of the above 28. Which of the following may cause an inadequate response to hypertension therapy? a. nonadherence b. drug interactions c. renal disease d. all of the above 29. Strategies for improving adherence include all of the following except: a. home blood pressure monitoring b. reminder systems (e.g., dosettes, calendars) c. simplifying regimens d. using self-will alone without other tools 30. Potential roles for pharmacists in improving out comes in patients with hypertension include: a. working with the patient and the physician to optimize the treatment plan b. working with the patient to optimize adher ence c. conducting medication review consultation sessions with patients d. all of the above. To earn CEUs associated with this CE program, you must complete the online post-test available through the CPhA 2005 Home Study Program CD-ROM.

Hypertension
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