Don t let the pressure get to you:

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Balanced information for better care Don t let the pressure get to you: An update on the changing recommendations for treating hypertension

New trial data and guidelines have made hypertension care more complex; the following is an evidence-based synthesis of the new data. Ensure accurate BP measurement: Check pressure twice during the same visit FIGURE 1. An evaluation of nearly 40,000 patients found that measuring BP a second time in the same visit resulted in lower readings. Nearly 50% of patients who had a systolic blood pressure (SBP) of 140-159 mm Hg at the beginning of the visit had an SBP <140 mm Hg in the same visit. 1 Initial SBP, mm Hg Median change in SBP, mm Hg 0-5 -10-15 -20 <140 140-159 160-180 >180 All Median drop in blood pressure was 8 mm Hg, equivalent to the impact of starting one hypertensive medication. Educate staff on techniques for obtaining accurate BP readings. See AlosaHealth.org/Hypertension for office cards regarding accurate BP assessment. Use home BP measurement to diagnose white coat hypertension and monitor response to treatment. Recommend patients record 3 or 4 BP measurements each day. Continuous automated ambulatory BP monitoring is the most accurate predictor of CV events, 2 but it can be difficult and costly to arrange. 2 Changing recommendations for treating hypertension

Lowering BP reduces CV events across a wide range of pressures The benefit is even greater in older patients. 3 FIGURE 2. A meta-analysis of 42 randomized trials involving 144,220 patients shows that CV benefits occur with any BP reduction, and are greater with lower achieved BPs. 4 Reduction to 120-124 vs. Mean achieved SBP 125-129 130-134 135-139 140-144 145-149 150-154 155-159 160 Favors lower blood pressure Hazard Ratio (95% CI) for major CV event or death 0.82 (0.67-0.97) 0.71 (0.60-0.83) 0.68 (0.55-0.85) 0.58 (0.48-0.72) 0.55 (0.42-0.72) 0.46 (0.34-0.63) 0.41 (0.32-0.54) 0.36 (0.26-0.51) Reduction to 130-134 Reduction to 140-144 135-139 140-144 145-149 150-154 155-159 160 145-149 150-154 155-159 160 0.96 (0.83-1.14) 0.83 (0.74-0.94) 0.78 (0.63-0.98) 0.65 (0.51-0.85) 0.58 (0.48-0.72) 0.51 (0.39-0.69) 0.94 (0.74-1.20) 0.79 (0.63-0.99) 0.70 (0.60-0.84) 0.62 (0.48-0.80) 0.1 1.0 2 Hazard ratio The benefit of achieving lower BP outweighs the risk of harm. FIGURE 3. In a population of patients treated to an SBP goal of <130, far more will benefit from prevented CV events or death than will have side effects. 5 Number of patients treated for one patient to be harmed Number needed to treat for one patient to benefit acute kidney injury hypotension syncope electrolyte abnormality 468 603 Higher number is better 1171 1189 major CV event all cause mortality 70 129 Lower number is better 0 400 800 1200 0 400 800 1200 The rate of injurious falls was no higher in patients with an SBP <130 vs. those with a higher SBP. Alosa Health Balanced information for better care 3

Evolving information on the management of high blood pressure: putting it all together FIGURE 4. The 2017 American College of Cardiology and American Heart Association (ACC/AHA) guideline BP categories, a practical guide for when to start treatment, and treatment goals 6 Normal BP SBP <120 and DBP <80 Elevated BP SBP 120-129 and DBP <80 Hypertension stage 1 SBP 130-139 or DBP 80-89 Hypertension stage 2 SBP 140 or DBP 90 Promote good lifestyle habits. Non-drug therapy Non-drug therapy Non-drug therapy Has ASCVD* or 10-year CVD risk 10% AND N Y No drug needed. Follow up periodically and reassess management as needed. Start BP lowering drug and proceed to drug treatment algorithm (See Figure 5). *ASCVD (atherosclerotic cardiovascular disease) includes acute coronary syndrome, myocardial infarction, angina, revascularization, stroke, TIA, or peripheral arterial disease. All patients requiring management should achieve an SBP <130, and a DBP goal <80 in adults less than 60 years of age. For patients whose management requires assessment of 10-year CVD risk, continue to reassess at follow-up visits. Calculate cardiovascular disease risk using the ASCVD risk calculator: www.cvriskcalculator.com OR tools.acc.org/ascvd-risk-estimator-plus 4 Changing recommendations for treating hypertension

Lifestyle interventions are the foundation of any BP lowering regimen Non-drug approaches such as a low sodium, heart healthy, or DASH diet; aerobic exercise as tolerated; and weight loss are key components of any treatment plan. All four major anti-hypertensive drug classes are equally good choices for patients requiring drug therapy: thiazide diuretics, angiotensin converting enzyme inhibitors (ACEIs) / angiotensin receptor blockers (ARBs), or calcium channel blockers (CCBs). 7 Achieving the BP goal is more important than the path there. FIGURE 5. Algorithm for initiating and intensifying drug treatment in eligible patients Is the SBP >20 mm Hg above goal? N Y Initiate a single agent,* either a: thiazide, long acting ACEI / ARB, or CCB. Two agents will likely be necessary (e.g., ACEI + CCB). Monitor response to treatment, assess adherence, and screen for side effects. If not at BP goal, up-titrate a single medication or add another agent. * For African Americans, initiate a thiazide or CCB. Combining an ACEI and an ARB confers no additional benefit and may increase adverse events. For older patients, start one medication and intensify therapy at the first follow-up visit. While beta-blockers are indicated to prevent CV outcomes in patients with ASCVD, they are no longer first-line drugs for the management of hypertension because they are less effective than other drug classes in preventing stroke. 7 Alosa Health Balanced information for better care 5

Costs FIGURE 6. Price of a 30-day supply of drugs commonly used to treat hypertension ACEIs benazapril 7.5 mg enalapril 10 mg fosinopril 15 mg lisinopril 10 mg moexipril 15 mg perindopril 4 mg quinapril 15 mg ramipril 2.5 mg trandolopril 2 mg $10 $10 $16 $4 $19 $21 $14 $11 $10 ARBs azilsartan (Edarbi) 40 mg candesartan 8 mg eprosartan 600 mg irbesartan 150 mg losartan 50 mg olmesartan 20 mg telmisartan 40 mg valsartan 80 mg $34 $45 $12 $7 $13 $21 $12 $184 CCBs amlodipine 5 mg felodipine ER 5 mg nifedipine ER 30 mg $6 $15 $16 Diuretics clorthalidone 25 mg hydrochlorothiazide (HCTZ) 25 mg indapamide 2.5 mg $16 $10 $4 Direct renin inhibitor aliskiren (Tekturna) 150 mg $187 ACEIs + CCBs benazepril 10 mg/amlodipine 5 mg $16 benazepril 10 mg/amlodipine 5 mg (Lotrel) $275 ACEIs + diuretics benazepril 10 mg/hctz 12.5 mg $23 enalapril 10 mg/hctz 25 mg $10 fosinopril 10 mg/hctz 12.5 mg $24 lisinopril 10 mg/hctz 12.5 mg $4 moexipril 15 mg/hctz 25 mg $19 quinapril 20 mg/hctz 25 mg $17 ARBs + CCBs olmesartan 20 mg/amlodipine 5 mg olmesartan 20 mg/amlodipine 5 mg (Azor) telmisartan 40 mg/amlodipine 5 mg telmisartan 40 mg/amlodipine 5 mg (Twynsta) valsartan 160 mg/amlodipine 5 mg valsartan 160 mg/amlodipine 5 mg (Exforge) $30 $23 $57 $222 $268 $258 ARBs + diuretics azilsartan 40 mg/chlorthalidone 25 mg (Edarbyclor) candesartan 16 mg/hctz 12.5 mg irbesartan 150 mg/hctz 12.5 mg losartan 50 mg/hctz 12.5 mg losartan 50 mg/hctz 12.5 mg (Hyzaar) olmesartan 20 mg/hctz 12.5 mg olmesartan 20 mg/hctz 12.5 mg (Benicar HCT) telmisartan 40 mg/hctz 12.5 mg telmisartan 40 mg/hctz 12.5 mg (Micardis HCT) valsartan 80 mg/hctz 12.5 mg valsartan 80 mg/hctz 12.5 mg (Diovan HCT) $14 $8 $14 $11 $48 $49 $131 $188 $216 $207 $279 ARB / CCB / diuretic olmesartan 20 mg/amlodipine 5 mg/hctz 12.5 mg olmesartan 20 mg/amlodipine 5 mg/hctz 12.5 mg (Tribenzor) valsartan 160 mg/amlodipine 5 mg/hctz 25 mg valsartan 160 mg/amlodipine 5 mg/hctz 25 mg (Exforge HCT) $41 $57 $268 $367 Prices from goodrx.com, April 2018. Listed doses are based on Defined Daily Doses by the World Health Organization, and should not be used for dosing in all patients. All prices shown are for generic products unless otherwise noted. These prices are a guide; patient costs may be subject to copays, rebates, and other incentives. 6 Changing recommendations for treating hypertension $0 $100 $200 $300 $400

Key messages Make sure the BP measurement is taken accurately, and more than once during a visit. Behavioral interventions, especially reducing sodium intake, form the foundation of BP management. Set 130/80 mm Hg as the BP goal for most patients, based on a synthesis of recent data and guidelines. Achieving the BP goal is more important than the choice of drug within the recommended classes. Reinforce a reduced salt diet and lifestyle modifications throughout treatment. Regularly assess response to treatment: screen for side effects, ask about adherence, and intensify treatment as needed to achieve a patient s BP goal. Visit AlosaHealth.org/Hypertension for more information and resources about BP and its management for clinicians and patients. References: (1) Einstadter D, Bolen SD, Misak JE, Bar-Shain DS, Cebul RD. Association of Repeated Measurements With Blood Pressure Control in Primary Care. JAMA Intern Med. 2018. (2) Banegas JR, Ruilope LM, de la Sierra A, et al. Relationship between Clinic and Ambulatory Blood-Pressure Measurements and Mortality. N Engl J Med. 2018;378(16):1509-1520. (3) Williamson JD, Supiano MA, Applegate WB, et al. Intensive vs Standard Blood Pressure Control and Cardiovascular Disease Outcomes in Adults Aged 75 Years: A Randomized Clinical Trial. JAMA. 2016;315(24):2673-2682. (4) Bundy JD, Li C, Stuchlik P, et al. Systolic Blood Pressure Reduction and Risk of Cardiovascular Disease and Mortality: A Systematic Review and Network Meta-analysis. JAMA Cardiol. 2017;2(7):775-781. (5) Bundy JD, Mills KT, Chen J, Li C, Greenland P, He J. Estimating the Association of the 2017 and 2014 Hypertension Guidelines With Cardiovascular Events and Deaths in US Adults: An Analysis of National Data. JAMA Cardiol. 2018. (6) Whelton PK, Carey RM, Aronow WS, et al. 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: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2018;71(19):e127-e248. (7) Law MR, Morris JK, Wald NJ. Use of blood pressure lowering drugs in the prevention of cardiovascular disease: meta-analysis of 147 randomised trials in the context of expectations from prospective epidemiological studies. BMJ. 2009;338:b1665. Alosa Health Balanced information for better care 7

About this publication These are general recommendations only; specific clinical decisions should be made by the treating physician based on an individual patient s clinical condition. More detailed information on this topic is provided in a longer evidence document at AlosaHealth.org. The Independent Drug Information Service (IDIS) is supported by the PACE Program of the Department of Aging of the Commonwealth of Pennsylvania. This material is provided by Alosa Health, a nonprofit organization which is not affiliated with any pharmaceutical company. IDIS is a program of Alosa Health. This material was produced by Jing Luo, M.D., M.P.H., Instructor in Medicine; Michael A. Fischer, M.D., M.S., Associate Professor of Medicine (principal editor); Niteesh K. Choudhry, M.D., Ph.D., Professor of Medicine; Jerry Avorn, M.D., Professor of Medicine; Dae Kim, M.D., M.P.H., Sc.D., Assistant Professor of Medicine; Gregory Curfman, M.D., Assistant Professor of Medicine; all at Harvard Medical School, and Ellen Dancel, PharmD, M.P.H., Director of Clinical Materials Development at Alosa Health. Drs. Avorn, Choudhry, Fischer, and Luo are physicians at the Brigham and Women s Hospital, and Dr. Kim practices at the Beth Israel Deaconess Medical Center, both in Boston. None of the authors accepts any personal compensation from any drug company. Medical writer: Jenny Cai Copyright 2018 by Alosa Health. All rights reserved.

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