Adult Guidelines INTRODUCTION

Background High is a major cause of , Service Task Force (USPSTF), the American Heart Association stroke, and renal disease.1 It is the most common reason for (AHA), and the American Diabetes Association (ADA). The key death and disability-adjusted life years worldwide.1, 2 In the recommendations from each source were carefully reviewed by United States, it leads to more cardiovascular deaths than any the committee, and those recommendations with the strongest other modifiable risk factor.1, 3 Each increase of 20 mm Hg in evidence and those most consistent with best practice care for systolic blood pressure or 10 mm Hg in diastolic blood pressure the Sutter Health population were included. doubles the risk of major cardiovascular and stroke events. 4 Improving blood pressure control significantly reduces the risk Guideline Recommendations of cardiovascular disease and death,5 and is a major priority for This guideline is intended for the care of adults with Sutter Health. hypertension in an ambulatory setting. It is not intended for Clinical Practice Guidelines Benefit pregnant patients, hospitalized patients, children or adolescents. It is intended to help clinicians, educators, case managers and A clinical practice guideline can help improve consistency patients make decisions according to standard clinical practice of best-practice evidence-based care in a health care and to improve the care and management of patients with organization. It allows all members of a care team to screen, hypertension in Sutter Health. However, it should not replace diagnosis, monitor, treat and educate patients using standard individual clinical judgment nor specialty consultation when recommendations consistently across care environments, indicated. All clinical decisions should be made within the specialties, and affiliates. It helps ensure outcome metrics are context of the specific situation for each patient, including consistent with recommended patient care. It helps translate best current health, medications, risk of treatment side effects, quality practice care into electronic health record tools and standards, of life, life expectancy, and patient preference. patient education materials, and staff training resources. And it provides a means to adjust care efficiently and consistently across The guideline is divided into the following major topics: the organization when new evidence emerges. Implementation (click on the topic to jump to that section) of clinical practice guidelines is a key recommendation of I. Screening for Elevated Blood Pressure and national campaigns to improve clinical outcomes of chronic Hypertension conditions. II. Definitions and Diagnoses of Elevated Blood Pressure Guideline Committee Process and Hypertension III. Pattern of Hypertension Diagnosis The following Sutter Health Adult Hypertension Clinical Practice Guideline was written by a 29-person multi-disciplinary IV. In-Office Measurement of Blood Pressure team from across Sutter Health. The team was carefully crafted V. Out-of-Office Measurement of Blood Pressure to represent the wide spectrum of Sutter Health’s clinical VI. Evaluation and Causes of Hypertension community: geography (both Bay and Valley geographic regions), types of providers (cardiologists, family physicians, VII. Lifestyle Treatment for Hypertension internists, advanced practice clinicians, registered nurses, VIII. Medication Treatment Thresholds and Treatment registered dieticians, pharmacists, educators), type of practice Targets (foundation and independent affiliates), type of department IX. Medication Treatment for Hypertension (local office and system office), and type of work (in-person patient care, case management, quality and population health). X. Medication Treatment based on Comorbidities A patient representative was included in the writing team. XI. Resistant and Refractory Hypertension Writing this guideline was a multi-step process. Major sources XII. Preoperative Hypertension Management of standards for hypertension were identified which rely on clinical outcome trials and report the level of evidence for XIII. General Strategies to Improve Hypertension Control their recommendations – such as the United States Preventive XIV. Abbreviations XV. References Table 10: Secondary Causes of Hypertension Table 11: Hypertension Medications Rev. Aug. 2018 Adult Hypertension Guidelines

I. Screening for Elevated Blood Pressure and Hypertension Screen for Elevated Blood Pressure and Hypertension in adults (United States Preventative Task Force [USPSTF] Recommendation Level A)6 • Screening blood pressure (BP) should be measured by health care professionals, such as in an office visit. • Ideally results should be placed in the patient health record. • BP should be measured at every office visit. • USPSTF recommends – Screen at least every year if6 • 40 years old or older or • Increased risk for elevated BP or hypertension including – Overweight or obese adults – Black adults – Screen at least every 3 to 5 years if6 • Less than 40 years old and • No increased risk for elevated BP or hypertension

II. Definitions and Diagnoses of Elevated Blood Pressure and Hypertension • To make the diagnosis of Elevated Blood Pressure (R03.0) or Hypertension (I10) use the mean (average) of 2 to 3 BP measurements1, 6, 7 obtained over 2 to 3 visits1, 7 based on the table below. • Note: Individuals with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in 2 different categories should be designated to the higher BP category

Table 1: Definitions of Elevated Blood Pressure and Hypertension (based on the 2017 ACC/AHA Hypertension Guideline*1)

Category (ICD-10) Systolic Blood Pressure (SBP) Diastolic Blood Pressure (DBP) Normal <120 mm Hg and <80 mm Hg Elevated Blood Pressure (R03.0) 120–129 mm Hg and <80 mm Hg Hypertension Stage 1 (I10) 130–139 mm Hg or 80–89 mm Hg Stage 2 (I10) ≥140 mm Hg or ≥90 mm Hg Hypertensive Urgency (I16.0) ≥180 without evidence of new or worsening and/or ≥ 120 without evidence of new or worsening target organ damage*** target organ damage*** (I16.1)** ≥180 with evidence of new or worsening target and/or ≥ 120 with evidence of new or worsening organ damage*** target organ damage*** * Note: “The 2017 ACC/AHA Hypertension Guideline” is an abbreviation for “The 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/ NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults.” 1 ** According to the 2017 ACC/AHA Hypertension Guideline, “The 1-year death rate associated with hypertensive emergencies is > 79%, and the median survival is 10.4 months if the emergency is left untreated” 1 *** Target organ damage diagnoses include: hypertensive encephalopathy, intracranial hemorrhage, acute ischemic stroke, acute MI, acute left ventricular heart failure with pulmonary edema, unstable angina pectoris, dissecting aortic , acute renal failure, and eclampsia.1 Symptoms or history suspicious for new or worsening target organ damage include: Confusion, loss of consciousness, seizure, acute head trauma, headache, numbness/weakness on one side of the body, change in vision, difficulty speaking, chest pain, trouble breathing, nausea/vomiting, acute severe back pain, dark brown or bloody urine, pregnant (AHA Patient Handout: Hypertension Crisis)1, 8 Rev. Aug. 2018 Adult Hypertension Guidelines | 2 III. Pattern of Hypertension Diagnosis • Normotension – Definition: Normal BP readings both in-office and out-of-office1 • Sustained Hypertension – Definition: Hypertension readings both in-office and out-of-office1 • Masked Hypertension – Definition: Hypertension BP readings out-of-office and normal BP readings in-office1 – Associated with significant increased cardiovascular disease (CVD) and all-cause mortality risk, similar to sustained hypertension and double that of normotensive patients.1 – Prevalence increases with increasing in-office BP readings.1 Prevalence is also higher in chronic kidney disease (CKD) patients (occurs in up to 30% of CKD patients) and is associated with higher risk of CKD progression.1 – Consider screening for masked hypertension in a patient with increased CVD risk, CKD, evidence of target organ damage, or SBP 120-130 mmHg or DBP 75-80 mmHg.1 • White Coat Hypertension – Definition: Hypertension readings in-office and normal BP readings out-of-office 1 – Associated with minimal or only slightly increased CVD and all-cause mortality compared to normotensive patients.1 – Prevalence increases with increasing age, in women versus men, in non-smoking versus current smoking, and when in-office measurement of BP are attended by clinicians 1 – Consider screening for white coat hypertension (called “white coat effect” if on treatment) if SBP 130-160 mmHg, DBP 80-100 mmHg 1, at high risk for white coat hypertension, or treated BP is above target even on three medications (resistant hypertension)1 – The ACC/AHA 2017 Hypertension Guideline states: “The rate of conversion of white coat hypertension to sustained hypertension is 1% to 5% per year, with a higher incidence in patients with elevated BP, older patients, patients with obesity, or black patients.”1

Table 2: Patterns of Hypertension Diagnosis copied from the 2017 ACC/AHA Hypertension Guideline1

Diagnosis Pattern In-office Setting Out-of-office Setting Normotensive No hypertension No hypertension Sustained hypertension Hypertension Hypertension Masked hypertension No hypertension Hypertension White coat hypertension Hypertension No hypertension

Rev. Aug. 2018 Adult Hypertension Guidelines | 3 IV. In-Office Measurement of Blood Pressure • Accurately measuring BP is key to managing the BP correctly.1 • The ideal technique for the in-office measurement of BP is described in detail below.1 Take the actual technique into consideration when interpreting the results. May consider another visit to re-measure the BP depending on circumstances.

Office BP Measurement Technique – Use an automated upper-arm cuff. Calibrate periodically according to manufacturer’s instructions. – The patient should avoid caffeine, exercise, and smoking for 30 minutes or more before the measurement and empty his/her bladder.1 – The patient should sit relaxed in a chair with his/her feet on the floor and the back supported.1, 6, 7 The patient should not sit or lie on an examining table during the measurement.1 – The patient should rest for more than 5 minutes before the measurement.6, 1, 7 The patient and the observer should not talk during the rest period or measurement. 1 – Use the correct cuff size.1, 6, 7 See table below. The cuff should encircles 80% of the arm. 1 Record if an alternate size is required.1 – Place the cuff on upper bare arm. Align the center of the cuff to the midpoint of the sternum.6, 1, 7 The arm should be supported, such as resting on a surface1 – Measure the BP in both arms the first visit. For follow-up visits, use the arm that had the higher reading.1 – Repeat the BP measurement 2 or more times separated by 1 to 2 minutes1 (Especially consider if the first reading is elevated). Use the mean (average) of the readings.6, 1 – USPSTF notes that multiple measurements have a higher positive predictive value than a single measurement6 – Record the time the patient most recently took their BP medication.1 Give the patient the results of their BP measurement.1

• See these handouts to remind staff and patients about the best technique for BP measurement in an office setting. Consider posting these handouts near BP measurement sites. https://targetbp.org/wp-content/uploads/2017/11/Measuring_ Blood_Pressure_In-Office.pdf and https://targetbp.org/wp-content/uploads/2017/12/ Measuring_BP_Positioning_Poster_2.pdf 1 • The technique to measure BP to evaluate for orthostatic is described below (consider in the work-up for dizziness or syncope for example). – First measure the blood pressure and pulse after the patient has been lying supine for > 5 minutes 8 – Then have the patient stand up and re-measure the blood pressure and pulse after 1 minute.9, 1 – A drop in SBP > 20 mmHg or DBP > 10 mmHg is considered abnormal.9, 1, 8 • Consider provide drop-in BP measurement options for patients. Be alert that non- billed BP measurements are not counted in Integrated Healthcare Association (IHA) dashboard metrics.

Rev. Aug. 2018 Adult Hypertension Guidelines | 4 Table 3: Blood Pressure Cuff Size in Adults (based on the 2017 ACC/AHA Hypertension Guideline1)

Arm Circumference Usual Cuff Size 22–26 cm 8.7–10.2 inches Small adult 27–34 cm 10.6–13.4 inches Adult 35–44 cm 13.8–17.3 inches Large adult 45–52 cm 17.7–20.5 inches Adult thigh

V. Out-of-Office Measurement of Blood Pressure • Out-of-office measurement of BP confirms hypertension diagnosis patterns, and is important for hypertension management.6, 1, 7, 10, 11, 12 It includes home BP monitoring (HBPM) and/or ambulatory BP monitoring (ABPM)1 Note the USPSTF recommends obtaining measurements of out-of-office blood pressure for diagnostic confirmation before starting treatment6 • The difference between out-of-office BP readings and in-office BP readings is usually considered clinically significant when office SBPs are 20 mmHg or DBPs are 10 mmHg different than HBPM or ABPM readings 1 • If a patient is diagnosed with White Coat or Masked Hypertension continue to monitor in-office and out-of-office to evaluate for change in category 1

Home Blood Pressure Monitoring (HBPM) • Use an automated, validated, cuff-style upper-arm monitor with stored memory. Buy correct cuff size.1 Note avoid wrist and finger monitors which yield less reliable readings. See these links about recommended and validated home blood pressure monitoring brands.11 Note most brands do pass validation. – http://www.dableducational.org/sphygmomanometers/recommended_cat.html – https://bihsoc.org/bp-monitors/for-home-use • Check for differences between the left and right side when first using cuff.1 In general, use the side with the higher reading. Note some patients might find it easier to use when placing the cuff on the non-dominant arm. • Have the patient bring their home BP cuff to clinic appointments for evaluation1, 11 (Especially when first begin monitoring, if unsure of cuff accuracy, when home readings are variable or inconsistent with office readings, and at least once a year). Compare BP readings taken on both the office cuff and home cuff at the same time. If the difference in readings done simultaneously is greater than 10 mmHg then the home device may not be accurate.11 • Note that BP levels in the office may correspond to somewhat lower BP levels at home. (This difference is less prominent when the BP is closer to normal.) Take this into consideration when setting home BP targets for individual patients.1

Rev. Aug. 2018 Adult Hypertension Guidelines | 5 • Adequately train the patient to do HBPM 1, 11 See these patient handouts and video about how to measure BP at home. Use the technique in the box below – http://www.heart.org/idc/groups/heart-public/@wcm/@hcm/documents/ downloadable/ucm_445846.pdf – https://targetbp.org/tools_downloads/self-measured-blood-pressure-video/ – http://www.heart.org/HEARTORG/Conditions/HighBloodPressure/ KnowYourNumbers/Monitoring-Your-Blood-Pressure-at-Home_UCM_301874_ Article.jsp – https://www.mayoclinic.org/diseases-conditions/high-blood-pressure/in-depth/ high-blood-pressure/art-20047889?pg=2

Home BP Measurement Technique – Avoid smoking, caffeinated beverages, or exercise for 30 minutes before taking BP measurements. Empty bladder.1 – Sit relaxed in a straight back chair with feet flat on the floor and the back supported. Uncross legs. – Place arm on a flat surface like a table. The upper arm should be at heart level. Place the cuff on the bare arm, with the bottom of the cuff just above the bend of the elbow. – Rest quietly for ≥ 5 min before BP measurements. Remain still.1,11 – Take at least 2 BP readings with > 1 minute in between each.1,11 – Record the results.

• Individualize frequency of home BP measurement, such as below. – Check readings in the morning before taking medications and in evening before dinner.1, 11 – Consider checking at least 3 times per week.11 – Especially consider checking the week before an office visit or after changing treatment.1 • Base clinical decisions on the mean (average) of multiple BP readings taken on multiple occasions1, 11 (Note some BP cuffs automatically calculate the mean) Ambulatory Blood Pressure Monitoring (ABPM) • Ambulatory BP monitoring is the best method to diagnose hypertension6 • ABPM is usually measures BP for 24 hours, every 15 to 30 minutes during the day and every 15 minutes to 1 hour during the night 1 • Consider ABPM if home BP readings differ significantly than office based readings to correctly classify diagnosis and inform treatment decisions1 • Note Medicare covers ABPM for patients with the following criteria “ABPM is only covered for those patients with suspected white coat hypertension defined as: office blood pressure >140/90 mm Hg on at least three separate clinic/ office visits with two separate measurements made at each visit; at least two documented blood pressure measurements taken outside the office which are <140/90 mm Hg; and no evidence of end-organ damage.”13 • Refer to the 2017 ACC/AHA 2017 Hypertension Guideline for information about reference values for ABPM1

Rev. Aug. 2018 Adult Hypertension Guidelines | 6 VI. Evaluation and Causes of Hypertension Characteristics consistent with • Gradual increase in BP1 • Lifestyle factors associated with elevated BP (e.g., increased weight, decreased physical activity, high-sodium diet, less healthy eating pattern, excessive alcohol)1 • Family history of hypertension1 • Personal history of pregnancy induced hypertension, pre-eclampsia, and eclampsia Evaluation of patients with hypertension • Tests at diagnosis – Consider fasting glucose, creatinine (Cr) and estimated Glomerular Filtration Rate (eGFR), sodium (Na), potassium (K), calcium (Ca), complete blood count (CBC), lipid panel, thyroid stimulating hormone (TSH), urinalysis, and electrocardiogram (EKG)1 – May also consider A1C, uric acid, urine albumin-to-creatinine ratio, and/or an echocardiogram 1 • Follow-up tests – If patients are on a diuretic, ACE inhibitor or ARB, check the Cr (eGFR), K, and Na at least annually1, 7 and 1-2 weeks after medication changes. (Note may consider the basic metabolic panel (BMP) instead which includes all three tests). – Consider checking BMP annually for all patients with hypertension. Characteristics consistent with possible secondary causes of hypertension (list is copied from the ACC/AHA 2017 Hypertension Guideline) 1 • Drug-resistant or drug-induced hypertension • Abrupt onset of hypertension • Onset of hypertension at <30 year old • Exacerbation of previously controlled hypertension • Disproportionate target organ damage for degree of hypertension • Accelerated/malignant hypertension • Onset of diastolic hypertension in older adults (age ≥65 years old) • Unprovoked or excessive hypokalemia (Note the ACC/AHA 2017 Hypertension Guideline states “A specific remediable cause of hypertension can be identified in 10% of adult hypertension patients.”1) Evaluation of patients with possible secondary causes of hypertension See table in the appendix about secondary causes of hypertension – including information about prevalence, clinical indications, physician exam, screening tests, confirmatory tests, and additional notes.

Rev. Aug. 2018 Adult Hypertension Guidelines | 7 Table 4: Medications and substances that may affect BP (based on the 2017 ACC/ AHA Hypertension Guideline1)

Medication/Substance Management Strategy Alcohol • Limit alcohol to ≤1 drink daily for women and people over 65 and ≤2 drinks for men 14 • Avoid use depending on clinical situation Amphetamines (e.g., • Avoid or limit use when possible amphetamine, methylphenidate • Consider alternate therapies dexmethylphenidate, dextroamphetamine) Antidepressants: MAOIs, SNRIs, • Avoid or limit use when possible TCAs • Consider alternative agent with lower risk: such as SSRIs • Avoid tyramine containing foods with MAOIs Atypical antipsychotics: • Avoid or limit use when possible (e.g.,clozapine, olanzapine) • Consider agents with lower risk of metabolic side effects: such as aripiprazole, ziprasidone Caffeine • Associated with acute increases in BP in patients with hypertension. • Long-term use not associated with increased BP or CVD • Generally limit caffeine intake to <300 mg per day. • Consider avoiding use in patients with uncontrolled hypertension Decongestants: phenylephrine, • Avoid or limit use when possible pseudoephedrine • Use for shortest duration possible • Avoid in severe or uncontrolled hypertension Herbal supplements: Ma Huang • Avoid use [ephedra], St. John’s wort [with MAO inhibitors, yohimbine]) Immunosuppressants (e.g., • Consider agents which may be associated with less effects on BP cyclosporine) (such as tacrolimus) Oral contraceptives • Consider use low-dose (e.g., 20–30 mcg ethinyl estradiol) or progestin-only form of oral contraceptives. • Avoid use in severe or uncontrolled hypertension • Consider alternative forms of birth control where appropriate Non-steroidal anti-inflammatory • Avoid or limit use when possible drugs (NSAIDs) • Consider alternate therapies Recreational drugs (e.g., • Avoid use “bath salts” [MDPV], cocaine, methamphetamine, etc.) Systemic corticosteroids (e.g., • Avoid or limit use when possible dexamethasone, fludrocortisone, • Consider alternative therapies or modes of administration when methylprednisolone, prednisone, feasible prednisolone) Angiogenesis inhibitor (e.g., • Initiate or intensify antihypertensive therapy if needed bevacizumab) and tyrosine kinase inhibitors (e.g., sunitinib, sorafenif)

Rev. Aug. 2018 Adult Hypertension Guidelines | 8 VII. Lifestyle Treatment for Hypertension • According to the ACC/AHA 2017 Hypertension Guideline “Correcting the dietary aberrations, physical inactivity, and excessive consumption of alcohol that cause high BP is a fundamentally important approach to prevention and management of high BP, either on their own or in combination with pharmacological therapy.”2 • Use Lifestyle interventions outlined in Table 5 – These interventions may be sufficient alone to treat Stage 1 hypertension1 – These interventions are an integral component in the treatment of Stage 2 hypertension1 – Use team-based care to promote lifestyle change1, 10 – Use with effective evidence-based behavioral and motivational strategies 1 Ideas and examples below: • General – Use motivational interviewing techniques – Set goals (SMART goals) which foster self-efficacy – Use shared medical appointments – Encourage involvement of spouse/family – Encourage meaningful social relationships – Link patient to community and social services when needed – Recognize success and encourage reluctant adopters • Nutrition: – Refer to a registered dietician when able – Encourage the plate method – Encourage food tracking such as smart phone apps – Give recipe prescriptions/consider culinary medicine – Teach behavior strategies used in the diabetes prevention program (DPP) (Refer to formal DPP if the patient has prediabetes) • Physical Activity (for additional resources: http://www.exerciseismedicine.org/) – Refer to an exercise professional when able – Routinely assess physical activity as part of standard clinical workflow – Educate to associate physical activity with reduced risk of heart disease, stroke, diabetes and many cancers. – Use Exercise Prescription (actually write it out) • FITT (frequency, intensity, time, type) – Encourage The “talk test” as an estimate of intensity • Moderate intensity – can talk but cannot sing – Encourage pedometer and record keeping (paper/pencil, internet, other, wearable activity monitors) • Increase daily average by 500 steps over baseline each week • Goal: 10,000 steps per day for baseline health

Rev. Aug. 2018 Adult Hypertension Guidelines | 9 Table 5: Lifestyle Treatment (based on the 2017 ACC/AHA Hypertension Guideline) 1, 7, 12, 14,

Lifestyle Treatment— Approx. Effect on Particularly Effective in Hypertension (SBP) Description the Following Situations Additional Notes Heart-healthy Such as: • In combination with weight Other eating patterns that lower BP include: eating pattern DASH (Dietary Approaches to Stop loss and sodium reduction Mediterranean: ↓ 11 mmHg Hypertension): – Emphasize vegetables, fruit, legumes, whole grains, seeds, – Emphasize fruits, vegetables, nuts, and olive oil whole grains, and low- dairy – Include low to moderate amounts of chicken, fish, dairy, eggs products and red wine – Limited saturated and total fat – Limit red meats Vegetarian: – Exclude or limit meat, with or without eggs, dairy and/or fish. Whole food, plant-based – Emphasize minimally-processed foods particularly vegetables, fruits, whole grains, legumes, nuts, seeds, herbs and spices – Exclude or limit animal products (red meat, poultry, fish, eggs, and dairy products) Weight loss • By reduced calorie intake and Patients who are overweight In addition to behavior change, pharmacotherapy and/ or ↓ 5 mmHg or increased physical activity or obese bariatric surgical procedures can be considered ↓ 1 mmHg per each kg weight loss Sodium reduction • Optimal goal is <1500 mg/day • Very high BP • In the USA, most dietary sodium comes from additions during ↓ 5 to 6 mmHg • Aim for at least a 1000 mg/day • Black patients food processing or during commercial food preparation at sit-down and fast-food restaurants. reduction • Older patients • Support cooking/eating at home with fresh whole foods • Even a small decrease in sodium • ACE inhibitor/ARB use consumption is likely to be beneficial. Potassium increase • By dietary potassium (ideal) or by • Black patients • Such as in the DASH diet ↓ 4 to 5 mmHg potassium supplementation • Patients with high-sodium • A reduction in the sodium/potassium index may be more • Aim for 3500–5000 mg/day diet important than the corresponding changes in either NOTE: avoid if contraindicated, • Patients with low-potassium electrolyte alone such as if CKD or taking drugs that diet initially reduce potassium excretion Physical activity • Moderate intensity aerobic Patients with higher baseline • Aerobic at least 30 minutes most, preferably all, days of the ↓ 5 to 8 mmHg exercise (strong evidence) BP will show greater decrease week (> 150 minutes per week) (aerobic) • Resistance and/or static isometric • Accumulating evidence that small bouts of 10 minutes ↓ 4 mmHg exercise (evidence weaker, but throughout day are effective (resistance) emerging) • Dynamic resistance exercise 2-3 days per week • Use a structured exercise program if able Limit alcohol drinks • No more than 2 (men) and 1 Patients who are initially 1 standard drink contains roughly 14 gm of pure alcohol, ↓ 4 mmHg (woman) standard drinks per day. drinking ≥ 3 drinks per day typically found in 12 oz. of regular beer, 5 oz. of wine, and • Note the NIH recommends only 1.5 oz. of distilled spirits 1 standard drink per day for all adults over 65.14 Stress reduction Deep breathing exercises, • Evidence stronger for short term vs. long term benefit techniques yoga, mindfulness-based stress • Possible indirect long-term effect with reduction of other risk reduction, tai chi, transcendental factors (i.e. overeating, alcohol) meditation, practice of gratitude and joy

Rev. Aug. 2018 Adult Hypertension Guidelines | 10 VIII. Medication Treatment Thresholds and Treatment Targets Identify an individual BP Treatment Threshold and Treatment Target for each patient using the figures below1 • Individualize for each patient based on patient characteristics1, 12 • Balance CVD risk reduction benefit against potential risks of treatment1, 12 • Emphasize the use of lifestyle modification in reaching BP targets1, 12 • Evaluate for potential for white coat effect1, 12 • Include patient preference, clinical judgment, and team-based approach in decision making1, 12 • Consider use the http://tools.acc.org/ASCVD-Risk-Estimator/ tool to estimate ASCVD 10-year risk1 (this is the calculator used in the Epic)

Threshold to Begin Treatment Treatment Target (Goal) Begin medication for BP using the CVD Risk Table and Titrate BP medication using the Treatment Risk Table Treatment Risk Table below to individualize the treatment below to individualize the target (goal). Generally consider threshold to either BP ≥ 130/80 or BP ≥ 140/90 BP < 130/80 if able (or alternate BP < 140/90)

Table 6: CVD Risk Table Table 7: Treatment Risk Table

Favor 130/80 if one or Favor 140/90 if most or Favor 130/80 if most Favor 140/90 if one or more characteristics all characteristics or all characteristics more characteristics listed below 1 listed below1 listed below1 listed below1 CVD Diagnosis CVD diagnosis present CVD diagnosis absent Side Effect Risks Low side effect risks High side effect risks of Medcation 10-yr ASCVD Risk ASCVD Risk ≥ 10% ASCVD risk <10% Burden of Less burden More burden Age Age ≥ 65 yo Age < 65 yo Comorbidity (favor SBP 130) Life Expectancy Normal life expectancy Limited life expectancy Comorbidities • Diabetes* None of comorbidities • CKD in this table Risk of Fall Low fall risk High fall risk • Heart Failure Standing SBP SBP >110 mmHg SBP <110 mmHg • Stable Ischemic Heart Disease Ambulatory Ambulatory Not ambulatory • History of stroke • Peripheral Community- Community dwelling Not community Disease dwelling, dwelling Noninstitutionalized

* The ADA 2018 Diabetes Standards of Care concurs with the 2017 ACC/AHA Hypertension Guideline for diabetes patients with high CVD risk to consider a treatment goal of 130/80.7 Note, however, that the ADA differs from the AHA/ACC guideline for diabetes patients with low CVD risk, and recommends 140/90 mm Hg as their treatment goal.7 Take this into consideration when individualizing care for these patients. Rev. Aug. 2018 Adult Hypertension Guidelines | 11 IX. Medication Treatment for Hypertension • Use the Medication Treatment Algorithm (Algorithm 1) below to make general decision about hypertension medications based on individualized Treatment Threshold and Treatment Target • Make decisions based on the mean (average) of the multiple BP readings using validated technique. • Encourage patient to check home blood pressure readings after starting or changing medications, and include results in decisions and management.1 • Use the Medication Table in the appendix (Table 11) to inform decisions about specific types of hypertension medications • Use the Comorbidity Table (Table 8) to inform recommendations about specific medications to use in specific situations • Recommend the following strategies to improve medication adherence as copied from the 2017 ACC/AHA Hypertension Guidelines:1 – Dose medication once daily rather than multiple times daily (adherence is highest for once daily dosing)1 – Use combination pills1 – Create an encouraging, blame-free environment1 – Use patient adherence tools and objective methods to measure adherence1 – Encourage copayment benefit design that encourages adherence1 – Link to health insurance and medication assistance programs1 (note per the ACC/AHA 2017 Hypertension Guideline, “Only 1 in 5 patients have sufficiently high medication adherence to achieve benefits in seen in clinical trials”1)

Rev. Aug. 2018 Adult Hypertension Guidelines | 12 Algorithm 1: Medication Treatment Algorithm6, 1, 7 Determine the treatment threshold and treatment target (goal) for the patient. Include lifestyle modification in combination with medications for BP management.

BP ≥ 130/80 or BP ≥ 140/90 based BP above individual on individual Treatment Threshold Treatment Target ≥ 20/10 BP ≥ 180/120 (extremely high BP) (use tables to determine) (use tables to determine)

CKD & Proteinuria† Black Patients† † Evidence of new or worsening target organ damage?† † † †

Start Medication: Start Medication: Start Medication: Start Two Medications • ACE Inhibitor or ARB* ACE inhibitor Thiazide Diuretic** Together: • Thiazide Diuretic** or or ARB* or CCB*** • ACE Inhibitor or ARB* • CCB*** • Thiazide Diuretic** and/or No Yes (or based on • CCB*** comorbidities table† † † ) Note: consider combination pills Hypertension Hypertension Urgency Emergency (Not an emergency) Provide immediate Restart and/or emergency care intensify treatment (ie 911) Follow-up 1 month (no need to If BP still above individual Treatment Target add 2nd and/or 3rd medication: immediately lower BP) ACE inhibitor or ARB*, Thiazide Diuretic**, and/or CCB*** Treat (whichever not yet added and as tolerated) as applicable Follow-up in 3-6 months once BP at target

If BP persists above target despite use of maximum tolerated doses of medications above then consider add Aldosterone Antagonist **** and evaluate according to the Treatment Resistant Hypertension Algorithm.

* Generally use once daily generic ACE inhibitors such as lisinopril or benazopril. If ACE inhibitor intolerant, use an ARB. Do not use ACE inhibitors and ARBs in combination. Do not use ACE inhibitors or ARBs in pregnancy. ** Generally use chlorthalidone (shows evidence of CVD risk reduction) or HCTZ (lower risk of electrolyte abnormalities). Caution if renal insufficiency. Thiazide diuretics are not effective if GFR < 30. *** Generally use a dihydropyridine CCB such as amlodipine.**** Generally use spiranolactone † Proteinuria defined as albumin-to-creatinine ratio ≥ 300 or albumin-to-creatinine ratio ≥ 30 if diabetes † † In black patients, thiazide diuretics and CCBs are more effective as mono-therapy at lowering BP and reducing CVD events than ACE inhibitors or ARBs. However, ACE inhibitors and ARBs are equally as effective when used is combination with CCB or thiazide diuretic in black patients as they are in other groups † † † See comorbidities table to help determine appropriate medication choice based on individual patient characteristics. † † † † Symptoms or history suspicious for evidence of new or worsening target organ damage: confusion, loss of consciousness, seizure, acute head trauma, headache, numbness/weakness on one side of the body, change in vision, difficulty speaking, chest pain, trouble breathing, nausea/vomiting, acute severe back pain, dark brown or bloody urine, pregnant See comorbidities table and medication table for more details Rev. Aug. 2018 Adult Hypertension Guidelines | 13 X. Medication Treatment based on Comorbidities The comorbities table below provides basic recommendations for medications to use in a variety of chronic comorbidities and conditions related to the management of hypertension. Note this table does not provide information on the urgent or emergent management of acute complications of hypertension (such as acute stroke). Also note that this table does not include all comprehensive information about the treatment of these comorbities.

Table 8: Medication Treatment for Chronic Comorbidites and Other Common Conditions Related to Hypertension 1, 8, 7

Comorbidity Treatment Considerations Diabetes • If albumin-to-creatinine ratio < 30, use ACE inhibitor or ARB, thiazide diuretic, or calcum channel blocker (CCB) • If albumin-to-creatinine ratio ≥ 30 use ACE inhibitor or ARB Note: monitor for hyperkalemia if ACE inhibitor or ARB used Chronic Kidney Disease (CKD) • If albumin-to-creatinine ratio ≥ 300, use ACE inhibitor or ARB Note: Monitor for hyperkalemia if ACE inhibitor or ARB used Note: if the patient GFR is < 30 mL/min than consider a loop diuretic instead of a thiazide diuretic. History of Kidney Transplant • Coordinate care with nephrologist or transplant team Heart Failure with reduced Ejection Guideline-Directed Management and Therapy (GDMT) based on the 2017 ACC/AHA/HFSA Fraction (HFrEF) Guideline Focused Update on Heart Failure15 • ACE inhibitor/ARBs • Angiotensin receptor– neprilysin inhibitors • Aldosterone antagonists • Loop diuretics • Guideline-Directed Management and Therapy (GDMT) beta blockers NOTE: Avoid nondihydropyridine CCBs (they are not recommended) Heart Failure with Preserved Ejection • Diuretics if volume overload. Fraction (HFpEF) • Consider aldosterone antagonists Angina • Beta blockers • Dihydropyridine CCBs • Nitrates Post Myocardial Infarction (MI) • Beta blockers • ACE inhibitor or ARB if HFrEF History of Stroke or Transient Ischemic • Choose medications as otherwise clinically indicated for patient Attack (TIA) Atrial Fibrillation (AF) • CCB or beta blocker if needed for rate control Aortic • Start low doses and titrate gradually Chronic Aortic Insufficiency • Do not use agents that slow heart rate (HR) (such as avoid beta blockers) Thoracic Aortic Disease • Beta blockers Migraine prevention • Beta blockers • Non-dihydropyridine CCBs Raynaud phenomenon • Dihydropyridine CCBs Benign prostatic hyperplasia • Alpha-1-adrenergic antagonists Marfans Syndrome • Beta blockers Risk of Pregnancy • Long acting CCBs • Beta blockers (labetalol preferred once pregnant) • Avoid ACE inhibitors and ARBs Rev. Aug. 2018 Adult Hypertension Guidelines | 14 XI. Resistant and Refractory Hypertension Resistant Hypertension – see the algorithm below for the identification, evaluation, and treatment of resistant hypertension • Definition – ≥ 3 hypertension medications (complementary mechanisms of action including appropriate diuretic*) and BP not at goal1 or – ≥ 4 or more medications even if BP at goal1 *appropriate diuretic is thiazide diuretic if GFR > 30 • Risk factors – older age, black race, obesity, CKD, and diabetes1 • Potential causes – “Pseudoresistance”1 • BP measurement error (technique not correct)1 • White coat effect1 (BP at home are at target despite elevated office visit BPs) • Medication nonadherence1 – Lifestyle factors1 – Interfering substances1 – Secondary causes of hypertension1 • Prognosis – The ACC/AHA 2017 Hypertension Guideline notes: “The risk of MI, stroke, end stage renal disease, and death in adults with resistant hypertension may be 2- to 6-fold higher than in hypertensive adults without resistant hypertension”1 Refractory Hypertension • Definition – ≥ 5 antihypertensive medications of different classes (including a long-acting thiazide- type diuretic and mineralocorticoid receptor antagonist) and BP not at goal1 • Prognosis – The ACC/AHA 2017 Hypertension Guideline notes: “The prevalence of refractory hypertension is low, [but] patients with refractory hypertension experience high rates of CVD complications, including left ventricular hypertrophy, heart failure, and stroke.”1

Rev. Aug. 2018 Adult Hypertension Guidelines | 15 Algorithm for the Evaluation and Management of Resistant Hypertension (based on the 2017 ACC/AHA Hypertension Guideline)1

Identify treatment resistance • ≥ 3 hypertension medications at optimal doses (including a diuretic if possible) and BP ≥ 130/80 or • ≥ 4 antihypertensive medications regardless of blood pressure

Exclude Pseudoresistance • Confirm ideal office BP measurement technique • Evaluate home blood pressure and/or ambulatory blood pressure measurements (evaluate for white coat effect) • Assess for non-adherence of medications

Identify contributing lifestyle factors such as: • Eating pattern • Salt and potassium in diet • Physical activity • Alcohol ingestion

Evaluate for interfering substances such as: • NSAIDs • Sympathomimetic (amphetamines, decongestants, etc) • Oral contraceptives • Corticosteroids • Caffeine • Herbal supplements (Ma Huang, ephedra etc) • Antidepressants (TCA, SNRIs, MAOIs) or antipsychotics

Screen for secondary causes of hypertension such as: • Primary aldosteronism (elevated aldosterone/renin ratio) • CKD (eGFR <60 mL/min/1.73 m2) • Renal artery stenosis (young, female, known atherosclerotic disease, worsening kidney function) • Pheochromocytoma (episodic hypertension, palpitations, diaphoresis, headache) • Obstructive sleep apnea (snoring, witnessed apnea, excessive daytime sleepiness)

Optimize medication treatment such as: • Maximize diuretic therapy (or switch HCTZ to chlorthalidone) • Add an aldosterone antagonist • Use a loop diuretics in patients with CKD and/or patients receiving potent vasodilators (e.g., minoxidil) • Add other agents with different mechanisms of actions (refer to medication table)

Refer to specialist • Refer to appropriate specialist for known or suspected secondary cause(s) of hypertension • Consider referring to hypertension specialist if BP remains uncontrolled after 6 months of treatment

Rev. Aug. 2018 Adult Hypertension Guidelines | 16 XII. Preoperative Hypertension Management (note: intraoperative management of hypertenion not included in this guideline) • General – Continue hypertension therapy when undergoing planned elective major surgery1 expect for recommendations below – Consider delay elective major surgery if BP > 180/1101 • Specific medications recommendations – ACE inhibitor and ARBs • Consider holding ACE inhibitor and ARBs therapy the morning of major surgery1 – Beta Blockers • Continue beta blockers in patients who are on them chronically when undergoing major surgery1 • Do not abruptly discontinue beta blockers perioperatively (it is potentially harmful)1 • Do not start beta blockers on the day of surgery in patients who have not been on beta blockers.1 – Central Alpha Agonists • Do not abruptly discontinue clonidine perioperatively (it is potentially harmful)1

XIII. General Strategies to Improve Hypertension Control • Encourage and provide support for lifestyle change as an integral part of treatment for elevated blood pressure and both stage 1 and stage 2 hypertension.1, 10 • Use team-based care1, 10 which achieves more BP lowering than usual care alone1 – Include physicians, advanced practice clinicians, nurses, pharmacists, registered dietitians, social workers, coaches1, 10 – Integrate community health workers on clinical teams1, 10 – Provide health literate educational materials on nutrition, exercise, alcohol moderation, medication management and smoking cessation.10 • Per the ACC/AHA 2017 Hypertension Guideline create a “clear, detailed, and current evidence-based plan of care that ensures the achievement of treatment and self- management goals, encourages effective management of comorbid conditions, prompts timely follow-up with the healthcare team and adheres to CVD GDMT.”1 • Provide system level support and quality improvement strategies including – Clinical decision support based on treatment algorithms1, 10 – Electronic health records (EHR)1, 10 – Registries (to identify undiagnosed patients and improve hypertension control rates)1, 10 – Technology-based remote monitoring1 – Self-management support tools and education materials1, 10 – Focus on health literacy when communicating with patients1 – Monitoring of performance1 – Telehealth strategies1 – Incentives to providers and health system financing strategies to achieve BP control1

Rev. Aug. 2018 Adult Hypertension Guidelines | 17 ABBREVIATIONS:

ABPM Ambulatory blood pressure HBPM Home blood pressure monitoring monitoring

ACC American College of HCTZ Hydrochlorothiazide Cardiologists HFpEF Heart Failure with preserved ACE Angiotensin Converting Ejection Fraction inhibitors Enzyme inhibitors HFrEF Heart Failure with reduced AHA American Heart Association Ejection Fraction

ARBs Angiotensin Receptor Blockers HR Heart rate

ASCVD Atherosclerotic Cardiovascular ICD-10 International Statistical Disease Classification of Diseases and Related Health Problems, BID Twice daily 10th revision

BMP Basic Metabolic Panel IHA Integrated Healthcare Association BP Blood Pressure K Potassium BPH Benign prostatic hypertrophy LFTs Liver function tests Ca Calcium MAOIs Monoamine oxidase inhibitors CAD Coronary artery disease MI Myocardial Infarction CBC Complete blood count Na Sodium CDC Center for Disease Control and Prevention NSAIDs Nonsteroidal Anti- inflammatory Drugs CNS Central nervous system SBP Systolic blood pressure Cr Creatinine SLE Systemic lupus erythematosus CVD Cardiovascular disease SMART Goals Specific, measurable, DASH Dietary Approaches to achievable, results-focused, Stop Hypertension and time- bound goals

DBP Diastolic blood pressure SNRIs Serotonin and norepinephrine reuptake inhibitors DPP Diabetes prevention program SSRIs Selective serotonin reuptake eGFR estimated Glomerular inhibitors Filtration Rate TCAs Tricyclic antidepressants EKG Electrocardiogram TIA Transient Ischemic Attack FITT Frequency, intensity, time, type TID Three times daily

GDMT Guideline-Directed Management USPSTF United States Preventative and Therapy Task Force GFR Glomerular Filtration Rate

Rev. Aug. 2018 Adult Hypertension Guidelines | 18 REFERENCES:

1. Whelton, Paul K. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults. 2017, Hypertension, pp. 1-192. 2. Lim, S S. A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. 9859, 2012, Lancet, Vol. 380, pp. 2224-60. 3. Danaei, Goodarz. The preventable causes of death in the United States: comparative risk assessment of dietary, lifestyle, and metabolic risk factors. 2009, PLoS Med, Vol. 6. 4. American College of Cardiology American Heart Association Task Force on Clinical Practice Guidelines. Detailed Summary From the 2017 Guideline for the Prevention, Detection, Evaluation and Management of High Blood Pressure in Adults. [Online] 2017. [Cited: May 27, 2018.] https://healthmetrics.heart.org/wp-content/ uploads/2017/11/Detailed-Summary.pdf. 5. Ettehad, D. Blood pressure lowering for prevention of cardiovascular disease and death: a systematic review and meta-analysis. 387, 2016, Lancet, Vol. 5, pp. 957-67. 6. United States Preventive Services Task Force. Screening for High Blood Pressure in Adults: U.S. Preventive Services. 10, 2015, Annals of Internal Medicine, Vol. 163, pp. 778-788. 7. American Diabetes Association. Standards of Medical Care in Diabetes – 2018. Supplement 1, 2018, Diabetes Care, Vol. 41. 8. UpToDate. [Online] UpToDate, Inc., May 17, 2018. https://www.uptodate.com/contents/table-of-contents. 9. Juraschek, Stephen P. Comparison of Early versus Late . 2017, JAMA, Vol. 177, pp. 1316-1323. 10. Centers for Disease Control and Prevention. Best Practices for Cardiovascular Disease Prevention Programs: A Guide to Effective Health Care System Interventions and Community Programs Linked to Clinical Services. Atlanta, GA: Centers for Disease Control a. 2017. 11. American Medical Association; The Johns Hopkins University. Self-Measured Blood Pressure Monitoring Programs: Engaging Patients in Self-Management. s.l. : American Medical Association and The Johns Hopkins University., 2015. 12. Qaseem, Amir. Pharmacologic Treatment of Hypertension in Adults Aged 60 Years or Older to Higher Versus Lower Blood Pressure Targets: A Clinical Practice Guideline From the American College of Physicians and the American Academy of Family Physician. 2017, Annals of Internal Medicine, Vol. 166, pp. 430-439. 13. Centers for Medicare & Medicaid Services. National Coverage Determination (NCD) for Ambulatory Blood Pressure Monitoring (20.19). [Online] Centers for Medicare & Medicaid Services. [Cited: July 1, 2018.] 14. National Institutes of Health (NIH). National Institute on Alcohol Abuse and Alcoholism. Drinking Guidelines for Older Adults. [Online] [Cited: June 13, 2018.] https://www.thelancet.com/journals/lancet/article/PIIS0140- 6736(18)30134-X/fulltext. 15. Yancy, Clyde W. 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure. [Online] 2017. [Cited: May 20, 2018.] http://circ.ahajournals.org/content/circulationaha/ early/2017/04/26/CIR.0000000000000509.full.pdf. 16. Lexicomp Online. [Online] Wolters Kluwer Clinical Drug Information, Inc. [Cited: July 1, 2018.] http://online.lexi. com/lco/action/home.

Rev. Aug. 2018 Adult Hypertension Guidelines | 19 APPENDIX:

Table 10: Secondary Causes of Hypertension (copied from the ACC/AHA 2017 Hypertension Guideline) 1

Common Causes

Additional Notes/ Cause Prevalence Clinical Indications Physical Exam Screening Test Confirmatory Tests Renal 1%-2% Urinary tract infections; obstruction, Abdominal mass Renal ultrasound Tests to evaluate parenchymal hematuria; urinary frequency and (polycystic kidney cause of renal disease nocturia; analgesic abuse; family history disease); skin pallor disease of polycystic kidney disease; elevated serum creatinine; abnormal urinalysis Renovascular 5%-34%* Resistant hypertension; hypertension Abdominal systolic- Renal Duplex Doppler Bilateral selective disease of abrupt onset or worsening or diastolic bruit; ultrasound; MRA; renal intra-arterial increasingly difficult to control; flash bruits over other abdominal CT angiography pulmonary edema (atherosclerotic); (carotid early-onset hypertension, especially in – atherosclerotic women (fibromuscular hyperplasia) or ), femoral Primary 8%-20%† Resistant hypertension; hypertension Arrhythmias (with Plasma aldosterone/renin Oral sodium loading aldosteronism with hypokalemia (spontaneous hypokalemia); ratio under standardized test (with 24-h or diuretic induced); hypertension especially atrial conditions (correction urine aldosterone) and muscle cramps or weakness; fibrillation of hypokalemia and or IV saline infusion hypertension and incidentally discovered withdrawal of aldosterone test with plasma adrenal mass; hypertension and antagonists for 4-6 wk) aldosterone at 4 h of obstructive sleep apnea; hypertension infusion Adrenal CT and family history of early-onset scan, adrenal hypertension or stroke sampling. Obstructive 25%-50% Resistant hypertension; snoring; fitful Obesity, Mallampati Berlin Questionnaire; Polysomnography sleep apnea‡ sleep; breathing pauses during sleep; class III-IV; loss of Epworth Sleepiness daytime sleepiness normal nocturnal Score; overnight BP fall oximetry Drug or 2%-4% Sodium-containing antacids; caffeine; Fine tremor, , Urinary drug screen Response to alcohol nicotine (smoking); alcohol; NSAIDs; sweating (cocaine, (illicit drugs) withdrawal of induced oral contraceptives; cyclosporine ephedrine, MAO suspected agent or tacrolimus; sympathomimetics inhibitors); acute (decongestants, anorectics); cocaine, abdominal pain amphetamines and other illicit drugs; (cocaine) neuropsychiatric agents; erythropoiesis- stimulating agents; clonidine withdrawal; herbal agents (Ma Huang, ephedra)

*Depending on the clinical situation (hypertension alone, 5%; hypertension starting dialysis, 22%; hypertension and peripheral , 28%; hypertension in the elderly with congestive heart failure, 34%). †8% in general population with hypertension; up to 20% in patients with resistant hypertension. ‡Although obstructive sleep apnea is listed as a cause of , RCTs on the effects of continuous positive airway pressure on lowering BP in patients with hypertension have produced mixed results (see Section 5.4.4 for details). §For a list of frequently used drugs causing hypertension and accompanying evidence, see Table 14. BP indicates blood pressure; CT, computed tomography; DOC, 11-deoxycorticosterone; IGF-1, insulin-like growth factor-1; IV, intravenous; MAO, monamine oxidase; MRI, magnetic resonance imaging; MRA, magnetic resonance arteriography; NSAIDs, nonsteroidal anti-inflammatory drugs; OH, hydroxylase; and RCT, randomized clinical trial.

Rev. Aug. 2018 Adult Hypertension Guidelines | 20 Uncommon Causes

Additional Notes/ Cause Prevalence Clinical Indications Physical Exam Screening Test Confirmatory Tests Pheochromocytoma/ 0.1%-0.6% Resistant hypertension; Skin stigmata of 24-h urinary CT or MRI scan of paraganglioma paroxysmal hypertension or neurofibromatosis fractionated abdomen/pelvis crisis superimposed on sustained (café-au-lait spots; metanephrine s or hypertension; “spells,” BP lability, neurofibromas); plasma metanephrine headache, sweating, palpitations, Orthostatic hypotension s under standard pallor; positive family history conditions (supine of pheochromocytoma/ position with indwelling paraganglioma; adrenal IV cannula) incidentaloma Cushing’s syndrome <0.1% Rapid weight gain, especially Central obesity, Overnight 1 mg 24-h urinary free with central distribution; proximal “moon” face, dorsal dexamethaso ne cortisol excretion muscle weakness; depression; and supraclavicular suppression test (preferably multiple); hyperglycemia fat pads, wide (1 cm) midnight salivary violaceous striae, cortisol hirsutism Hypothyroidism <1% Dry skin; cold intolerance; Delayed ankle reflex; Thyroid-stimulating None constipation; hoarseness; weight periorbital puffiness; hormone; free thyroxine gain coarse skin; cold skin; slow movement; goiter Hyperthyroidism <1% Warm, moist skin; heat Lid lag; fine tremor Thyroid-stimulating Radioactive iodine intolerance; nervousness; of the outstretched hormone; free thyroxine uptake and scan tremulousness; insomnia; weight hands; warm, moist loss; diarrhea; proximal muscle skin weakness Aortic coarctation 0.1% Young patient with hypertension BP higher in upper Echocardiogram Thoracic and (undiagnosed or (<30 y of age) extremities than in abdominal CT repaired) lower extremities; angiogram or MRA absent femoral pulses; continuous murmur over patient’s back, chest, or abdominal bruit; left thoracotomy scar (postoperative) Primary Rare Hypercalcemia Usually none Serum calcium Serum parathyroid hyperparathyroidism hormone Congenital adrenal Rare Hypertension and hypokalemia; Signs of virilization Hypertension 11-beta-OH: elevated hyperplasia virilization

Rev. Aug. 2018 Adult Hypertension Guidelines | 21 Table 11: Hypertension Medications1, 4, 8, 16

• This table is a summary of the most common classes and brands of hypertension medications including key considerations in terms of class, name, generic status, dose and titration, general notes, monitoring, dose adjustments, black box warnings if relevant, contraindications, and cautions/adverse reactions/side effects. • This table is not meant to be a comprehensive inclusion of all information about each medication. In particular drug drug interactions are not included in this table. • Information for this table was obtained from the Lexicomp16 UpToDate,8 and the 2017 ACC/AHA Hypertension Guidelines.1, 4 Please refer to the references, each medicaiton’s package insert, and electronic health record prescribing details and alerts for full information.

ACE Inhibitors Commonly Used Others Generic Name (Brand Name) Initial Dose Generic Name (Brand Name) Initial Dose Lisinopril (Prinivil, Zestril) 10-40 mg daily Captopril (Capoten) 12.5-50 mg, BID-TID Benazepril (Lotensin) 10-40 mg total, daily or BID Quinapril (Accupril) 10-40 mg total, daily or BID Enalapril (Vasotec) 5-40 mg total, daily or BID Fosinopril (Monopril) 10-40 mg daily Ramipril (Altace) 2.5-10 mg total, daily or BID

Notes General Notes: • Decreased efficacy as monotherapy in black patients • Consider hold before surgery • Do not use in combination with ARB or direct renin inhibitor Monitoring: K, Cr (at baseline, after starting or adjusting dose and annually) Consider stop ACE inhibitor if persistent hyperkalemia or Cr increases > 30% Dosage Adjustment: Consider renal dosing Black Box Warning: Fetal injury and death. Discontinue as soon as possible when pregnancy detected Contraindications: • Angioedema • Use with aliskiren in patients with diabetes • Co-administration within 36 hours of neprilysin inhibitor (e.g., sacubitril) Cautions/Adverse Reactions/Side Effects: Cough (occurs in 5-20% and is an indication for trial of alternate class like ARB), dizziness, angioedema (risk increased in black patients), anemia (especially if CKD), hyperkalemia, diarrhea

Rev. Aug. 2018 Adult Hypertension Guidelines | 22 Angiotensin II Receptor Blocker (ARB) Commonly Used Others Generic Name (Brand Name) Initial Dose Generic Name (Brand Name) Initial Dose Losartan (Cozaar) 25-100 mg total, daily or BID Candesartan (Atacand) 8-32 mg total, daily Valsartan (Diovan) 80-320 mg daily Eprosartan (Teveten) 400-800 mg total, Olmesartan (Benicar) 20-40 mg daily *brand not available* daily or BID Irbesartan (Avapro) 150-300 mg daily Telmisartan (Micardis) 20-80 mg daily Azilsartan (Edarbi) *brand only* 40-80 mg daily

Notes General Notes: • Decreased efficacy as monotherapy in black patients • Do not use if history of angioedema with ARBs; patients with a history of angioedema with an ACE inhibitor can receive an ARB beginning 6 weeks after ACE inhibitor discontinued 1 Monitoring: • K, Cr (baseline, after starting or adjusting dose and monitor annually) • Consider stop ARB if persistent hyperkalemia or increase in Cr > 30% Dosage Adjustment: • No renal adjustment • Use with caution in severe renal impairment • Consider dose adjustment in hepatic impairment Black Box Warning: Fetal injury and death. Discontinue as soon as possible when pregnancy detected Contraindications: Concomitant use with aliskiren in patients with diabetes Cautions/Adverse Reactions/Side Effects: Severe renal impairment, hyperkalemia, , dizziness, dyspepsia, angioedema (risk increased in black patients), diarrhea, abdominal pain, nausea, URI, congestion, cough (less common than in ACE inhibitors), enteropathy (may be severe) (olmesartan)

Rev. Aug. 2018 Adult Hypertension Guidelines | 23 Thiazide Diuretics Commonly Used Others Generic Name (Brand Name) Initial Dose Generic Name (Brand Name) Initial Dose Hydrochlorothiazide (HCTZ) 12.5-50 mg daily Indapamide (Lozol) 1.25-2.5 mg daily Chlorthalidone (Hygroton) 12.5-25 mg daily

Notes General Notes: • Per the 2017 AHA/ACC hypertension guideline “chlorthalidone is preferred on the basis of prolonged half-life and proven trial reduction of CVD”1 • Chlorthalidone has higher rate of electrolyte abnormality than HCTZ • Thiazide diuretic used more commonly for hypertension treatment. Loop diuretic used more commonly for diuresis. • Thiazide diuretic not effective if GFR < 30. If so consider loop diuretic. • Electrolyte disturbances are less common if used in combination with a potassium sparing medication such as aldosterone antagonist, triamterene, or amiloride • Avoid or stop thiazide diuretic if hyponatremia present Monitoring: Na, K, Cr (check baseline, after starting or adjusting dose and monitor annually) Dosage Adjustment: • Consider start HCTZ at 25 mg for effective dose • Consider renal dosing Contraindications: • Sulfonamide-derived drug allergy • Anuria Cautions/Adverse Reactions/Side Effects: Hypotension, electrolyte disturbances (hypokalemia, hyponatremia, hyperuricemia, hypomagnesium, hypocalemia), hyperlipidemia, nephrotoxicity, polyuria, photosensitivity, hypersensitivity reactions, rash, muscle cramps, elevated blood sugars, sexual dysfunction, sleep disturbance, gout, systemic lupus erythematosus (SLE) exacerbation

Loop Diuretics Commonly Used Others Generic Name (Brand Name) Initial Dose Generic Name (Brand Name) Initial Dose Furosemide (Lasix) 20-80 mg total, BID Bumetanide (Bumex) 0.5-4 mg total, BID

Notes General Notes: • These are preferred diuretics in patients with symptomatic HF. • They are preferred over thiazides in patients with moderate-to-severe CKD (e.g., GFR <30 mL/min). • May need to consider potassium supplementation when patient is taking loop diuretics. Monitoring: Na, K, Cr (check baseline, after starting or adjusting dose and monitor annually) Dosage Adjustment: Consider renal dosing Black Box Warning: Fluid/electrolyte loss. Careful medical supervision and patient-specific dosing required. Contraindications: • Anuria • Hepatic coma (bumetanide) • Patients in severe electrolyte depletion (bumetanide) Cautions/Adverse Reactions/Side Effects: Hypotension, electrolyte disturbances (hypokalemia, hyponatremia, hyperuricemia, hypomagnesium, hypercalemia, hypochloremia [bumetanide]), hyperlipidemia, nephrotoxicity (e.g., azotemia), polyuria, photosensitivity, hypersensitivity reactions, rash, muscle cramps, elevated blood sugars, gout, ototoxicity, SLE exacerbation, low likelihood of sulfonamide allergy cross-reactivity, caution in patients with cirrhosis, diabetes, or benign prostatic hypertrophy (BPH) Rev. Aug. 2018 Adult Hypertension Guidelines | 24 Dihydropyridine CCBs Commonly Used Others Generic Name (Brand Name) Initial Dose Generic Name (Brand Name) Initial Dose Amlodipine (Norvasc) 2.5-10 mg daily Nifedipine ER, (Adalat CC, 60-120 mg daily Felodipine (Plendil) 5-10 mg daily Afeditab CR, Procardia XL)

Notes General Notes: • Dihyropyridine CCB more commonly used for the treatment of hypertension than non-dihyropyridine CCB • Use long acting dihyropyridine CCB. Avoid short-acting dihydropyridine CCBs due to possible increased MI risk Monitoring: HR Dosage Adjustment: • No renal adjustment • Consider dose adjustment in hepatic impairment and elderly Contraindications: None Cautions/Adverse Reactions/Side Effects: Peripheral edema within 2 to 3 weeks of initiation (more common than in nondhydropyridine CCBs, ACE inhibitor or ARB use helps mitigate this side effect more than diuretics), dose-related pedal edema (more common in women than men), fatigue, symptomatic hypotension, flushing, reflex tachycardia/angina/MI, syncope, headache, dyspepsia(amlodipine), gum changes (felodipine)

Non-dihydropyridine CCBs Commonly Used Others Generic Name (Brand Name) Initial Dose Generic Name (Brand Name) Initial Dose Diltiazem ER (Cardizem CD, 120-480 mg daily Verapamil LA (Calan SR, 120-480 mg total, daily or BID Cardizem LA, Tiazac XT, Cartia Isoptin SR) XT, Dilt-XR)

Notes General Notes: • Non-dihydropyridines CCBs diminish cardiac contractility and slow cardiac conduction • Non-dihydropyridines CCBs are used less frequently in HTN treatment then dihydropyridines CCBs • Drug interactions with diltiazem and verapamil (CYP3A4 major substrate and moderate inhibitor) • Avoid use in patient with HFrEF Monitoring: HR, Cr, Liver function tests (LFTs) Dosage Adjustment: No renal adjustment Contraindications: • Sick sinus syndrome or second- or third-degree atrioventricular block (except in patients with functioning artificial pacemaker) • Hypotension (SBP < 90 mmHg) • Acute MI and pulmonary congestion Cautions/Adverse Reactions/Side Effects: • Constipation, edema, headache, dizziness, gingival hyperplasia, rash, dyspepsia, bradycardia, tinnitus, impotence, elevated LFTs • Avoid routine use with beta blockers due to increased risk of bradycardia and heart block

Rev. Aug. 2018 Adult Hypertension Guidelines | 25 Beta Blockers Commonly Used Others Generic Name (Brand Name) Initial Dose Generic Name (Brand Name) Initial Dose Metoprolol succinate ER (Toprol XL) 50-200 mg total, daily or BID Atenolol (Tenormin) 25-100 mg daily Metoprolol tartrate (Lopressor) 100-400 mg total, BID or TID Nebivolol (Bystolic) 5-40 mg daily Carvedilol (Coreg) 6.25-50 mg total, BID Labetalol (Trandate) 200-800 mg total BID Carvedilol ER (Coreg CR) 20-80 mg daily Propranolol IR *brand not available* 160-480 mg total BID Propranolol LA (Inderal LA, 80-320 mg daily Inderal XL) Bisoprolol (Zebeta) 2.5-10 mg daily *brand not available*

Notes General Notes: • Beta-Blockers are not recommended as first-line agents for hypertension unless the patient has ischemic heart disease or heart failure • Atenolol is not as effective as other antihypertensive drugs in the treatment of hypertension and is less effective than placebo in reducing cardiovascular events1 • Guideline-Directed Management and Therapy (GDMT) beta blockers for stable ischemic heart disease that are also effective in lowering BP include carvedilol, metoprolol tartrate, metoprolol succinate, nadolol, bisoprolol, propranolol, and timolol.1 • Guideline-Directed Management and Therapy (GDMT) beta blockers for HFrEF include carvedilol, metoprolol succinate, or bisoprolol1 • Do not withdraw beta blockers abruptly Monitoring: Renal (Cr), HR (for bradycardia) Dosage Adjustment: • To discontinue taper dose over 1-2 weeks • Consider renal dosing • Metoprolol succinate may be cut in half, do not crush/chew Black Box Warning: Abruptly discontinuation can exacerbate angina pectoris and MI. Particularly in patients with ischemic heart disease, reduce dosage over 1-2 weeks and monitor (metoprolol, propranolol) Abrupt discontinuation in patients with coronary artery disease (CAD) may result in possible severe angina, MI, and ventricular arrhythmias (atenolol) Contraindications: • Sinus bradycardia, sinus node dysfunction, second- or third-degree heart block, cardiogenic shock, cardiac failure • Severe peripheral arterial circulatory disease (metoprolol) • Bronchial asthma, bronchospastic disease, severe hepatic impairment (carvediliol, nebivolol, labetalol) • Premature infants with corrected age <5 weeks; infants weighing <2 kg; heart rate <80 bpm; blood pressure <50/30 mm Hg; pheochromocytoma; history of bronchospasm (propranolol) Cautions/Adverse Reactions/Side Effects: Dizziness, bradycardia, fatigue, insomnia, lethargy, confusion, depression, dyspnea, headache, nightmares, constipation, diarrhea, nausea, sexual dysfunction/impotence, syncopye (carvedilol), peripheral edema (nebivolol), masked signs of hypoglycemia

Rev. Aug. 2018 Adult Hypertension Guidelines | 26 Aldosterone Receptor Antagonists Commonly Used Others Generic Name (Brand Name) Initial Dose Generic Name (Brand Name) Initial Dose Spironolactone (Aldactone) 25-100 mg total, daily or BID Eplerenone (Inspra) 50-100 mg total, daily or BID

Notes General Notes: • Preferred agents in primary aldosteronism and resistant hypertension1 • Greater risk of gynecomastia and impotence with spironolactone compared with eplerenone. • Avoid use with K+ supplements, high K diet, other K+-sparing diuretics or significant renal dysfunction • Avoid sprinolactone use in 1st trimester of pregnancy. Other agents are preferred for hypertension during pregnancy Monitoring: • K, Cr (baseline, after starting or adjusting dose and monitor regularly) • Uric acid • Glucose (spironolactone) Dosage Adjustment: • Adjust dose in renal insufficiency, elderly and heart failure. • Instruct patient to hold dose during episode of diarrhea or dehydration or if loop diuretic therapy is interrupted Contraindications: • Addison’s disease, • Use with eplerenone (spironolactone) • Initiaition with K > 5.5, Creatinine Clearance (CrCl) ≤ 30, • Concurrent use of strong CPY3A4 inhibitors • Patients with hypertention and type 2 diabetes with microalbuminuria • Cr > 2.0 in males or > 1.8 in females • CrCl < 50 • Use with potassium supplements or potassium-sparing diuretics (eplerenone) Cautions/Adverse Reactions/Side Effects: Hyperkalemia, electrolyte abnormalities, dizziness, fatigue, somnolence, sexual dysfunction, rash, diarrhea, cough, flu like syndrome, amenorrhea, gynecomastia, gout, glucose levels, • Caution in hepatic impairment, Monitor K closely in renal insufficiency • Risk of hyperkalemia increases with worsening renal function, ACE inhibitor, ARB, NSAIDS, potassium supplements or potassium-sparing diuretics

Rev. Aug. 2018 Adult Hypertension Guidelines | 27 Alpha 1 Blocker Commonly Used Generic Name (Brand Name) Initial Dose Doxazosin (Cardura) 1-8 mg daily (Max 16 mg/day) Terazosin (Hytrin) 1-20 mg total, daily or BID (Max 20 mg/day) Prazosin (Minipress) 2-20 mg total, BID or TID (Max 20 mg/day)

Notes General Notes: • May consider as second-line agent in patients with concomitant benign prostatic hyperplasia (BPH) • May cause significant orthostatic hypotension • Rule out prostatic carcinoma before beginning therapy for BPH (many symptoms of BPH and prostate cancer are similar) Monitoring: BP (monitor for orthostatic hypotension) Dosage Adjustment: None Contraindications: None Cautions/Adverse Reactions/Side Effects: Dizziness, headache, muscle weakness, peripheral edema, fatigue, somnolence, nausea, congestion, dyspnea, diarrhea, polyuria, orthostatic hypotension, floppy iris syndrome (cataract surgery), priapism, central nervous system (CNS) effects (increased risk of at higher doses) • Use with caution in hepatic impairment • Use with caution if recent MI, HF, or angina as may exacerbate underlying myocardial dysfunction

Rev. Aug. 2018 Adult Hypertension Guidelines | 28 Vasodilators Commonly Used Others Generic Name (Brand Name) Initial Dose Generic Name (Brand Name) Initial Dose Hydralazine (Apresoline) 50-200 mg total, BID to QID Minoxidil (Loniten) 5-100 mg total, daily to TID

Notes General Notes: • Used for the treatment of HFrEF class III-IV in black patients • Needs to be used with diuretic and beta blocker to prevent tachycardia and increased myocardial workload • Use loop diuretic with minoxidil to prevent hirsutism Black Box Warning (Minoxidil): • Cardiac effects. Pericarditis and pericardial effusion that may progress to tamponade. Increased oxygen demand and exacerbate angina pectoris • Appropriate Use. Max doses of a diuretic and two other antihypertensive medications should be used before this drug is ever added. Give with a diuretic to minimize fluid gain and a beta blocker (if no contraindications) to prevent tachycardia and increased myocardial workload. Patients with malignant hypertension and on guanethidine should be hospitalized to ensure blood pressure is reducing and to prevent rapid reduction in blood pressure. Monitoring: • BP • Weight • Creatinine • Electrolytes Dosage Adjustment: • Consider reducing dose in several renal impairment for minoxidil • If GFR < 10 mL/min give every 8-16 hours for hydralazline Contraindications: Hydralazine use is contraindicated in patients with coronary artery disease and mitral valve rheumatic heart disease Cautions/Adverse Reactions/Side Effects: Lupus-like syndrome, peripheral neuritis, Fluid/sodium retention. Postural hypotension, Headache, tachycardia, diarrhea, lack of appetite, nausea, Hirsutism (Minoxidil), Blood dyscrasias (hydralazine), pericardial effusion (minoxidil). • Use with caution in patients 65 years and older due to its potential to exacerbate episodes of syncope (Beers criteria)

Rev. Aug. 2018 Adult Hypertension Guidelines | 29 Direct Renin Inhibitors Commonly Used Generic Name (Brand Name) Initial Dose Aliskiren (Tekturna) *brand only* 150-300 mg daily

Notes General Notes: • Consider use renin-angiotensin system inhibition in patients who cannot tolerate ACE inhibitors or ARBs • Generally do not use with an ACE inhibitor or ARB • Avoid administration with high fat meal due to lower absorption • Decreased efficacy as monotherapy in black patients Monitoring: K, Cr (baseline, after starting or adjusting dose and monitor annually) Dosage Adjustment: None Black Box Warning (Minoxidil): Fetal injury and death. Discontinue as soon as possible when pregnancy detected. Contraindications: Do not use with ACE inhibitor/ARB in patients with diabetes and children < 2 years old. Cautions/Adverse Reactions/Side Effects: Hypersensitivity (including anaphylaxis and angioedema), Diarrhea, hyperkalemia, hypotension. • Use with caution in renal impairment.

Central Alpha Agonist Commonly Used Others Generic Name (Brand Name) Initial Dose Generic Name (Brand Name) Initial Dose Clonidine Oral (Catapress) 0.1-0.8 mg BID Guanfacine (Tenex) 0.5-2 mg daily at bedtime Clonidine Transdermal 0.1-0.3 mg weekly (Catapres-TTS) Methyldopa (Aldomet) 50-1000 mg total, BID

Notes General Notes: • Generally reserved as last-line due to significant central nervous system adverse effects, especially in older adults due to high risk of CNS adverse effects and risk of bradycardia and orthostatic hypotension • Methyldopa preferred agent during pregnancy for hypertension control Monitoring: • BP, HR, Mental status, Cr (baseline) • CBC and LFTs (methyldopa) Dosage Adjustment: • Use with caution in renal failure • Adjust dosing if eGFR < 50 (methyldopa) • Titrate slowly, based on monitoring of bradycardia, sedation, and hypotension • Do not discontinue clonidine abruptly. Taper dose over 2-4 days to avoid rebound hypertension (clonidine) Contraindications: • Avoid in active liver disease and concurrent use of MAOI (methyldopa) Cautions/Adverse Reactions/Side Effects: Bradycardia, CNS depression, drowsiness, headache, fatigue, dizziness, hypotension, sedation, insomnia, constipation, sexual dysfunction, skin reactions (transdermal clonidine), hematologic effects (methyldopa) • Identified in the Beers Criteria as a potentially inappropriate medication in patients 65 years and older • Use with caution in patients with severe coronary insufficiency, including recent MI and conduction disturbances, including sinus node dysfunction, cerebral vascular disease

Rev. Aug. 2018 Adult Hypertension Guidelines | 30 Table 12: Combination Hypertension Medications

Combination Medications (mg) ACE inhibitors + diuretics Benazepril + hydrochlorothiazide 5/6.25, 10/12.5, 20/12.5, 20/25 Captopril + hydrochlorothiazide 25/15, 25/25, 50/15, 50/25 Enalapril + hydrochlorothiazide 5/12.5, 10/25 Lisinopril + hydrochlorothiazide 10/12.5, 20/12.5, 20/25 Quinapril + hydrochlorothiazide 10/12.5. 20/12.5. 20/25 Fosinopril + hydrochlorothiazide 10/12.5. 20/12.5 ARB + diuretics Candesartan + hydrochlorothiazide 16/12.5, 32/12.5, 32/25 Irbesartan + hydrochlorothiazide 150/12.5, 300/12.5 Losartan + hydrochlorothiazide 50/12.5, 100/12.5, 100/25 Telmisartan + hydrochlorothiazide 40/12.5, 80/12.5, 80/25 Valsartan + hydrochlorothiazide 80/12.5, 160/12.5, 160/25, 320/12.5, 320/25 Azilsartan + chlorthalidone *brand only* 40/12.5, 40/25 Olmesartan + hydrochlorothiazide 20/12.5, 40/12.5, 40/25 ARB + CCB Amlodipine + telmisartan 40/5, 40/10, 80/5, 80/10 Amlodipine + valsartan 5/160, 5/320, 10/160, 10/320 Amlodipine + olmesartan 5/20, 5/40, 10/20, 10/40 CCB + ARB + diuretic Amlodipine + valsartan + 5/160/12.5, 5/160/25,10/160/12.5, 10/160/25 ARB + CCB + diuretic hydrochlorothiazide Olmesartan + amolodipine + 20/5/12.5, 40/5/12.5,40/5/25, 40/10/12.5, 40/10/25 hydrochlorothiside Aldosterone Antagonists + diuretic Triamtrene/hydrochlorothiazide 37.5/25, 50/25, 75/50 Beta Blocker + Diuretics Atenolol + chlorthalidone 50/25, 100/25 Metoprolol + hydrochlorthiazide 50/25, 100/25, 100/50 Direct Renin Inhibitors + diuretic Aliskiren/hydrochlorthiazide (Tekturna HCT) 150/12.5, 150/25, 300/12.5, 300/25

Rev. Aug. 2018 Adult Hypertension Guidelines | 31