Recommendation-Specific Supportive Text 1. Weight loss is a core recommendation and should be achieved through a combination of reduced calorie intake and increased physical activity.S6.2-1 The BP-lowering effect of weight loss in patients with elevated BP is con- sistent with the corresponding effect in patients with established hypertension, with an apparent dose re- sponse relationship of about 1 mm Hg per kilogram of weight loss. Achievement and maintenance of weight loss through behavior change are challengingS6.2-64 S6.2-66 but feasible over prolonged periods of follow-up.S6.2-64 For those who do not meet their weight loss goals with nonpharmacological interventions, pharmacotherapy or minimally invasive and bariatric surgical procedures can Surgical procedures tend to be more effective but are usually reserved for those with more severe and intractable obesity because of the fre- quency of complications.S6.2-69 2. The DASH eating plan is the diet best demonstrated to be effective for lowering BP. Because the DASH diet is high in fruits, vegetables, and low-fat dairy products, it pro- vides a means to enhance intake of potassium, calcium, magnesium, and fiber. In hypertensive and nonhyperten- sive adults, the DASH diet has produced overall reduc- tions in SBP of approximately 11 mm Hg and 3 mm Hg, and the diet was especially effective When combined with weight lossS6.2-6 or a reduction in sodium intake,S6.2-5,S6.2-30 the effect size was substantially increased. Most of the clinical trial Table 15. Best Proven Nonpharmacological Interventions for Prevention and Treatment of Hypertension* Nonpharmacological Intervention Dose Approximate Impact on SBP Hypertension Normotension Reference Weight loss Weight/body fat Best goal is ideal body weight, but aim for at least a 1-kg reduction in body weight for most adults who are overweight. Expect about 1 mm Hg for every 1-kg reduction in body weight. Healthy diet DASH dietary pattern Consume a diet rich in fruits, vegetables, whole grains, and low-fat dairy products, with reduced content of saturated and total fat. Reduced intake of dietary sodium Dietary sodium Optimal goal is <1500 mg/d, but aim for at least a 1000-mg/d reduction in most adults. Enhanced intake of dietary potassium Dietary potassium Aim for 3500 5000 mg/d, preferably by consumption of a diet rich in potassium. Physical activity Aerobic 90 150 min/wk 65% 75% heart rate reserve Dynamic resistance 90 150 min/wk Isometric resistance 4 2 min (hand grip), 1 min rest between exercises, 30% 40% maximum voluntary contraction, 3 sessions/wk Moderation in alcohol intake Alcohol consumption In individuals who drink alcohol, reduce alcohol to: Men: 2 drinks daily Women: 1 drink daily Resources: Your Guide to Lowering Your Blood Pressure With DASH How Do I Make the DASH? Available at: https://www.nhlbi.nih.gov/health/resources/heart/ hbp-dash-how-to. Accessed September 15, 2017.S6.2-72 Top 10 Dash Diet Tips. Available at: http://dashdiet.org/dash_diet_tips.asp. Accessed September 15, 2017.S6.2-73 *Type, dose, and expected impact on BP in adults with a normal BP and with hypertension. In the United States, one standard drink contains roughly 14 g of pure alcohol, which is typically found in 12 oz of regular beer (usually about 5% alcohol), 5 oz of wine (usually about 12% alcohol), and 1.5 oz of distilled spirits (usually about 40% alcohol).S6.2-29 DASH indicates Dietary Approaches to Stop Hypertension; and SBP, systolic blood pressure. Whelton et al 2017 High Blood Pressure Clinical Practice Guideline e37 experience comes from short-term feeding studies,S6.2-7 but lifestyle change with the DASH diet has been suc- cessful in at least 2 trials that used a behavioral inter- vention over a 4-monthS6.2-30 period of follow-up. Websites and books provide advice on imple- mentation of the DASH diet.S6.2-13,S6.2-71 S6.2-74 Counseling by a knowledgeable nutritionist can be helpful. Several other diets, including diets that are low in calories from vegetarian and a Mediterranean dietary pattern,S6.2-49,S6.2-63 have been shown to lower BP. 3. Sodium reduction interventions prevent hypertension and lower BP in adults with hypertension, especially in those with higher levels of BP, blacks, older persons, and others who are particularly susceptible to the effects of sodium on BP.S6.2-8 S6.2-11 Sodium reduction interventions may prevent CVD.S6.2-76,S6.2-77 Lifestyle change (behavior- al) interventions usually reduce sodium intake by about 25% (approximately 1000 mg per day) and result in an average of about a 2 mm Hg to 3 mm Hg reduction in SBP in nonhypertensive individuals, though the reduc- tion can be more than double this in more susceptible individuals, those with hypertension, and those con- currently on the DASH dietS6.2-5 or receiving a weight Sodium reduction in adults with hypertension who are already being treated with BP- lowering medications further reduces SBP by about 3 mm Hg and can facilitate discontinuation of medica- tion, although this requires maintenance of the lifestyle change and warrants careful monitoring.S6.2-12 When combined with weight loss, the reduction in BP is al- most doubled. A reduction in sodium intake may also lower SBP significantly in individuals with resistant hypertension who are taking multiple antihypertensive (see Section 11.1). Reduced dietary sodium has been reported to augment the BP-lowering effects of RAS blocker therapy.S6.2-79 Maintenance of the lifestyle changes necessary to reduce sodium in- take is challenging,S6.2-2 S6.2-4,S6.2-12 but even a small decrement in sodium consumption is likely to be es- pecially in those whose BP is salt sensitive.S6.2-82 In the United States, most dietary sodium comes from addi- tions during food processing or during commercial food preparation at sit-down and fast-food restaurants.S6.2-83,S6.2-84 Person-specific and policy approaches can be used to reduce dietary sodium intake.S6.2-85,S6.2-86 Individuals can take action to reduce their dietary intake of sodium by choice of fresh foods, use of food labels to choose foods that are lower in sodium content, choice of foods with a no added sodium label, judicious use of condiments and sodium-infused foods, use of spices and low-sodium flavorings, careful ordering when eating out, control of food portion size, and avoiding or minimizing use of salt at the table. Dietary counseling by a nutrition- ist with expertise in behavior modification can be help- ful. A reduction in the amount of sodium added during food processing, as well as fast food and restaurant food preparation, has the potential to substantially reduce so- dium intake without the need for a conscious change in 4. Dietary potassium is inversely related to BP and hy- pertension in migrant studies,S6.2-88 cross-sectional and prospective cohort studies.S6.2-92 Likewise, dietary potassiumS6.2-93 S6.2-96 and a high in- take of fruits and vegetables are associated with a lower incidence of stroke.S6.2-97 Potassium interventions have been effective in lowering BP,S6.2-13,S6.2-14,S6.2-16,S6.2-81 especially in adult patients consuming an excess of and in blacks.S6.2-13 The typical BP-lowering effect of a 60-mmol (1380-mg) adminis- tration of potassium chloride has been about 2 mm Hg and 4 to 5 mm Hg in adults with normotension and hypertension, respectively, although the response is up to twice as much in persons consuming a high-sodium diet. A reduction in the sodium/potassium index may be more important than the corresponding changes in either electrolyte alone.S6.2-99 Some but not all studies suggest that the intervention effect may be restricted to adult patients with a low (1500-mg to 2000-mg) daily intake of potassium.S6.2-92,S6.2-100 Most of the intervention experience comes from trials of relatively short duration but the BP-lowering effect of potassium in adult patients consuming a high- sodium diet has been reproduced after an interval of 4.4 In most trials, potassium supplementation was achieved by administration of potassium chloride pills, but the BP response pattern was similar when di- etary modification was used.S6.2-13 Because potassium- rich diets tend to be heart healthy, they are preferred over use of pills for potassium supplementation. The 2015 Dietary Guidelines for AmericansS6.2-101 encourage a diet rich in potassium and identify the adequate intake level for adult patients as 4700 mg/day.S6.2-102 The World Health Organization recommends a potassium intake of at least 90 mmol (3510 mg) per day from food for adult Good sources of dietary potassium include fruits and vegetables, as well as low-fat dairy products, selected fish and meats, nuts, and soy products. Four to five servings of fruits and vegetables will usually provide 1500 to >3000 mg of potassium. This can be achieved by a diet, such as the DASH diet, that is high in potassium 5. A BP-lowering effect of increased physical activity has been repeatedly demonstrated in clinical trials, espe- cially during dynamic aerobic exercise,S6.2-18,S6.2-20,S6.2-22 but also during dynamic resistance trainingS6.2-18,S6.2-21 and static isometric exercise.S6.2-18,S6.2-19,S6.2-31 The average reductions in SBP with aerobic exercise are approxi- mately 2 to 4 mm Hg and 5 to 8 mm Hg in adult patients with normotension and hypertension, respectively.S6.2-18 Most trials have been of relatively short duration, but increased physical activity has been an intrinsic compo- nent of longer-term weight reduction interventions used to reduce BP and prevent hypertension.S6.2-3,S6.2-4,S6.2-12 BP-lowering effects have been reported with lower- and higher-intensity exercise and with continuous and in- terval exercise training.S6.2-18,S6.2-103 Meta-analyses sug- gest isometric exercise results in substantial lowering of 6. In observational studies, there is a strong, predictable di- rect relationship between alcohol consumption and BP, especially above an intake of 3 standard drinks per day (approximately 36 ounces of regular beer, 15 ounces of wine, or 4.5 ounces of distilled spirits).S6.2-29,S6.2-104,S6.2-105 Meta-analyses of RCTs that have studied the effect of reduced alcohol consumption on BP in adults have iden- tified a significant reduction in SBP and DBP.S6.2-23,S6.2-24 The benefit has seemed to be consistent across trials, but confined to those consuming 3 drinks/day, as well as dose dependent, with those consuming 6 drinks/day at baseline who reduce their alcohol intake by about 50%, experiencing an average reduction in SBP/DBP of ap- Only limited in- formation is available on the effect of alcohol reduction on BP in blacks.S6.2-23,S6.2-106 In contrast to its effect on BP, alcohol seems to have a beneficial effect on several bio- markers for CVD risk, including high-density lipoprotein Observational studies have shown a relatively consistent finding of an inverse relationship between alcohol intake and CHD,S6.2-109,S6.2-110 within a moderate range (approximately 12 14 and 9 standard drinks/week for men and women, respectively). On bal- ance, it seems reasonable for those who are consuming moderate quantities of alcohol ( 2 drinks/day) to con- tinue their moderate consumption of alcohol. 7. Patient Evaluation The patient evaluation is designed to identify target organ damage and possible secondary causes of hypertension and to assist in planning an effective treatment regimen. Historical features are relevant to the evaluation of the patient (Table 16). The pattern of BP measurements and changes over time may differentiate primary from secondary causes of hypertension. A rise in BP associated with weight gain, lifestyle factors (such as a job change requiring travel and meals away from home), reduced frequency or intensity of physical activity, or advancing age in a patient with a strong family history of hypertension would suggest the diagnosis of primary hyper- tension. An evaluation of the patient s dietary habits, physi- cal activity, alcohol consumption, and tobacco use should be performed, with recommendation of the nonpharmacological interventions detailed in Section 6.2 where appropriate. The history should also include inquiry into possible occurrence of symptoms to indicate a secondary cause (Tables 13 and 16). The patient's treatment goals and risk tolerance should also be elicited. This is especially true for older persons, for whom an assessment of multiple chronic conditions, frailty, and prognosis should be performed, including consideration of the time required to see benefit from intervention, which may not be realized for some individuals. The physical examination should include accurate measure- ment of BP (Table 8). Automated oscillometric devices provide an opportunity to obtain repeated measurements without a pro- vider present, thereby minimizing the potential for a white coat effect. Change in BP from seated to standing position should be measured to detect orthostatic hypotension (a decline >20 mm Hg in SBP or >10 mm Hg in DBP after 1 minute is abnor- mal). For adults 30 years of age with elevated brachial BP, a thigh BP measurement is indicated; if the thigh measurement is lower than arm pressures, a diagnosis of coarctation of the aorta should be considered. The physical examination should include assessment of hypertension-related target organ dam- age. Attention should be paid to physical features that suggest secondary hypertension (Table 13). 7.1. Laboratory Tests and Other Diagnostic Procedures Laboratory measurements should be obtained for all patients with a new diagnosis of hypertension to facilitate CVD risk factor profiling, establish a baseline for medication use, and screen for secondary causes of hypertension (Table 17). Optional tests may provide information on target organ damage. Monitoring of serum sodium and potassium levels is helpful during diuretic or RAS blocker titration, as are serum creatinine and urinary albumin as markers of CKD Measurement of thyroid-stimulating hor- mone is a simple test to easily detect hypothyroidism and hyperthyroidism, 2 remediable causes of hypertension. A decision to conduct additional laboratory testing would be appropriate in the context of increased hypertension severity, poor response to standard treatment approaches, a dispropor- tionate severity of target organ damage for the level of BP, or historical or clinical clues that support a secondary cause. 7.2. Cardiovascular Target Organ Damage Pulse-wave velocity, carotid intima-media thickness, and coronary artery calcium score provide noninvasive estimates Table 16. Historical Features Favoring Hypertension Cause Primary Hypertension Secondary Hypertension Gradual increase in BP, with slow rate of rise in BP BP lability, episodic pallor and dizziness (pheochromocytoma) Lifestyle factors that favor higher BP (eg, weight gain, high-sodium diet, decreased physical activity, job change entailing increased travel, excessive consumption of alcohol) Snoring, hypersomnolence (obstructive sleep apnea) Prostatism (chronic kidney disease due to post-renal urinary tract obstruction) Family history of hypertension Muscle cramps, weakness (hypokalemia from primary aldosteronism or secondary aldosteronism due to renovascular disease) Weight loss, palpitations, heat intolerance (hyperthyroidism) Edema, fatigue, frequent urination (kidney disease or failure) History of coarctation repair (residual hypertension associated with coarctation) Central obesity, facial rounding, easy bruisability (Cushing's syndrome) Medication or substance use (eg, alcohol, NSAIDS, cocaine, amphetamines) Absence of family history of hypertension BP indicates blood pressure; and NSAIDs, nonsteroidal anti-inflammatory drugs. Whelton et al 2017 High Blood Pressure Clinical Practice Guideline e39 of vascular target organ injury and atherosclerosis.S7.2-1 High BP readings, especially when obtained several years before a noninvasive measurement, are associated with an increase in subclinical CVD risk.S7.2-2 S7.2-4 Although carotid intima-media thickness values and coronary artery calcium scores are associated with cardiovascular events, inadequate or absent information on the effect of improve- ment in these markers on cardiovascular events prevents their routine use as surrogate markers in the treatment of hypertension. LVH is a secondary manifestation of hypertension and independently predicts future CVD events. LVH is com- monly measured by electrocardiography, echocardiography, Left ventricular (LV) mass is associated with body size (particularly lean body mass), tobacco use, heart rate (inverse), and long-standing DM.S7.2-7 S7.2-9 BP low- ering leads to a reduction in LV mass. In TOMHS (Treatment of Mild Hypertension Study), the long-acting diuretic chlorthalidone was slightly more effective in reducing LVH than were a calcium channel blocker (CCB) (amlodipine), ACE inhibitor (enalapril), alpha-receptor blocker (doxazo- sin), or beta-receptor blocker (acebutolol).S7.2-10 Beta block- ers are inferior to angiotensin receptor blockers (ARBs), angiotensin-converting enzyme (ACE) inhibitors, and CCBs in reducing LVH.S7.2-11 Hypertension adversely impacts other echocardiographic markers of cardiac structure and function, including left atrial size (both diameter and area; left atrial size is also a precursor of AF); diastolic function (many parameters; a precursor of HF with preserved ejection fraction [HFpEF]); cardiac struc- ture; and subclinical markers of LV systolic function, such as myocardial strain assessment with echocardiography and MRI. Assessment of LVH by means of echocardiography or MRI is not universally recommended during evaluation and management of hypertension in adults because there are limited data on the cost and value of these measures for CVD risk reclassification and changes in type or intensity of treatment. Assessment of LVH is most useful in adults who are young ( 18 years of age) or have evidence of sec- ondary hypertension, chronic uncontrolled hypertension, or history of symptoms of HF. Electrocardiographic criteria for LVH correlate weakly with echocardiographic or MRI definitions of LVH and are less strongly related to CVD Imprecision in lead placement accounts, in part, for the poor correlation of electrocardiographic mea- surements with direct imaging results. However, electrocar- diographic LVH has been valuable in predicting CVD risk in some reports.S7.2-16,S7.2-17 Electrocardiography may also be useful in the assessment of comorbidities, such as rhythm disturbances and prior MI. LVH, as assessed by electrocardiography, echocar- diography, or MRI, is an independent predictor of CVD Reduction in LVH can predict a reduction in CVD risk, independent of change in BP.S7.2-20 When used in CVD risk predictor models, echocardiographic LVH has a small but significant independent effect on CVD risk in younger patients. At older ages, LVH measured by electrocardiography or MRI provides no independent con- tribution to prediction of CVD risk.S7.2-21 S7.2-23 Patients can be classified into 4 groups on the basis of the presence or absence of LVH and a determination of whether the LVH has an eccentric (normal relative wall thickness) or concentric 8. Treatment of High BP Clinicians managing adults with high BP should focus on over- all patient health, with a particular emphasis on reducing the risk of future adverse CVD outcomes. All patient risk factors need to be managed in an integrated fashion with a comprehen- sive set of nonpharmacological (see Section 6) and pharmaco- logical strategies. As patient BP and risk of future CVD events increase, BP management should be intensified. 8.1. Pharmacological Treatment 8.1.1. Initiation of Pharmacological BP Treatment in the Context of Overall CVD Risk For any specific difference in BP, the relative risk of CVD is constant across groups that differ in absolute risk of ath- albeit with some evidence of lesser relative risk but greater excess risk in older than in younger adults.S8.1.1-5 S8.1.1-8 Thus, there are more poten- tially preventable CVD events attributable to elevated BP in individuals with higher than with lower risk of CVD and in older than in younger adults. The relative risk reduction for CVD prevention with use of BP-lowering medications is fairly constant for groups that differ in CVD risk across a wide range of estimated absolute riskS8.1.1-9,S8.1.1-10 and across groups defined by sex, age, body mass index, and the pres- ence or absence of DM, AF, and CKD.S8.1.1-5,S8.1.1-11 S8.1.1-21 As a consequence, the absolute CVD risk reduction attributable to BP lowering is greater at greater absolute levels of CVD Put another way, for a given magnitude of BP reduction due to antihy- pertensive medications, fewer individuals at high CVD risk would need to be treated to prevent a CVD event (ie, lower number needed to treat) than those at low CVD risk. Table 17. Basic and Optional Laboratory Tests for Primary Hypertension Basic testing Fasting blood glucose* Complete blood count Lipid profile Serum creatinine with eGFR* Serum sodium, potassium, calcium* Thyroid-stimulating hormone Urinalysis Electrocardiogram Optional testing Echocardiogram Uric acid Urinary albumin to creatinine ratio *May be included in a comprehensive metabolic panel. eGFR indicates estimated glomerular filtration rate. 8.1.2. BP Treatment Threshold and the Use of CVD Risk Estimation to Guide Drug Treatment of Hypertension Recommendations for BP Treatment Threshold and Use of Risk Estimation* to Guide Drug Treatment of Hypertension References that support recommendations are summarized in Online Data Supplement 23. COR LOE Recommendations I SBP: A 1. Use of BP-lowering medications is recommended for secondary prevention of recurrent CVD events in patients with clinical CVD and an average SBP of 130 mm Hg or higher or an average DBP of 80 mm Hg or higher, and for primary prevention in adults with an estimated 10-year atherosclerotic cardiovascular disease (ASCVD) risk of 10% or higher and an average SBP 130 mm Hg or higher or an average DBP 80 mm Hg or DBP: C-EO I C-LD 2. Use of BP-lowering medication is recommended for primary prevention of CVD in adults with no history of CVD and with an estimated 10-year ASCVD risk <10% and an SBP of 140 mm Hg or higher or a DBP of 90 mm Hg or higher.S8.1.2-3,S8.1.2-10 S8.1.2-13 *ACC/AHA Pooled Cohort Equations (http://tools.acc.org/ASCVD-Risk- to estimate 10-year risk of atherosclerotic CVD. ASCVD was defined as a first CHD death, non-fatal MI or fatal or non-fatal stroke. Synopsis Whereas treatment of high BP with BP-lowering medi- cations on the basis of BP level alone is considered cost use of a combination of absolute CVD risk and BP level to guide such treatment is more efficient and cost effective at reducing risk of CVD than is use of BP level Practical approaches have been developed to translate evidence from RCTs into individual patient treat- ment recommendations that are based on absolute net ben- efit for CVD risk,S8.1.2-25 and several national and international guidelines recommend basing use of BP-lowering medica- tions on a combination of absolute risk of CVD and level of BP instead of relying solely on level of BP.S8.1.2-26 S8.1.2-31 Attempts to use absolute risk to guide implementation of pharmacological treatment to prevent CVD have had mixed results, with many reports of improvements in pro- vider prescribing behaviors, patient adherence, and reduc- tions in risk,S8.1.2-32 S8.1.2-38 but with others showing no impact on Use of global CVD risk assess- ment is infrequent in routine clinical practice,S8.1.2-41 S8.1.2-46 which suggests that intensive efforts would be required to achieve universal implementation. The choice of specific risk calculators for estimation of risk and risk threshold has been an important source of variability, ambiguity, and controversy.S8.1.2-47 S8.1.2-54 In addition, implementation of a standard (worldwide) abso- lute CVD risk threshold for initiating use of BP-lowering medications would result in large variations in medication use at a given level of BP across countries.S8.1.2-48,S8.1.2-54,S8.1.2-55 Future research in this area should focus on issues related to implementation of a risk-based approach to CVD prevention, including the use of BP-lowering medications. Although several CVD risk assessment tools are available, on the basis of current knowledge, we recommend use of the ACC/AHA Pooled Cohort Equations (http://tools.acc.org/ ASCVD-Risk-Estimator/) to estimate 10-year risk of athero- sclerotic CVD (ASCVD) to establish the BP threshold for It should be kept in mind that the ACC/AHA Pooled Cohort Equations are validated for US adults ages 40 to 79 years in the absence of concurrent statin For those >79 years old, the 10-year ASCVD risk is generally >10%, and thus the SBP threshold for anti- hypertensive drug treatment for patients >79 years old is 130 mm Hg. Two recent reviews have highlighted the importance of using predicted CVD risk together with BP to guide antihy- pertensive drug therapy.S8.1.2-22,S8.1.2-23 Figure 4 is an algorithm on BP thresholds and recommen- dations for treatment and follow-up. Recommendation-Specific Supportive Text 1. For the purposes of secondary prevention, clinical CVD is defined as CHD, congestive HF, and stroke. Several meta- analyses of RCTs support the value of using BP-lowering medications, in addition to nonpharmacological treat- ment, in patients with established CVD in the absence of hypertension, defined previously by an SBP 140 mm Hg or a DBP 90 mm Hg.S8.1.2-1,S8.1.2-6,S8.1.2-7,S8.1.2-9 Many RCTs of BP lowering in adults without CVD have used inclusion criteria designed to increase the level of CVD risk in the study populations to increase trial ef- ficiency by facilitating shorter duration and a smaller sample size. As a consequence, few relatively low-risk adults with hypertension have been included in the trials. Trial results provide evidence of CVD prevention from use of BP-lowering medications in adults with an aver- age SBP 130 mm Hg or an average DBP 80 mm Hg and clinical CVD; 5-year risk of CVD (defined as stroke, CHD, HF, or other CVD death) of approximately 6% an estimated 10-year CVD death rate of approximately 4.5%;S8.1.2-4 or an annual rate of major CVD events of approximately 0.9% per year.S8.1.2-7 In the absence of clinical CVD, these risk estimates are roughly equivalent to a 10-year risk of ASCVD exceeding 10% as per the ACC/AHA Pooled Cohort Equations.S8.1.2-56 SPRINT (Systolic Blood Pressure Intervention Trial) provides additional support for the use of BP-lowering medications in patients without CVD at SBP levels 130 mm Hg; however, it is important to note that few SPRINT participants had untreated SBP between 130 mm Hg and 139 mm Hg at baseline. Furthermore, SPRINT used a Framingham 10-year risk of general CVD exceeding 15% to identify increased CVD risk.S8.1.2-8 Although this level of risk is lower than the levels described previously, being roughly equivalent to a 6% to 7% 10-year ASCVD risk per the ACC/AHA Pooled Cohort Equations, most of the participants in SPRINT had a much higher level of CVD risk. This recommendation differs from JNC 7 in its use of CVD risk, rather than diabetes or CKD, to recognize patients, including older adults, with a SBP/ DBP <140/90 mm Hg who are likely to benefit from BP lowering drug therapy in addition to nonpharma- cological antihypertensive treatment. In JNC 7, the BP Whelton et al 2017 High Blood Pressure Clinical Practice Guideline e41 threshold for initiation of antihypertensive drug therapy was 140/90 mm Hg for the general adult population and 130/80 mm Hg for adults with diabetes or CKD. Since the publication of JNC 7 in 2003, we have gained additional experience with risk assessment and new data from randomized trials, observational studies and simu- lation analyses have demonstrated that antihypertensive drug treatment based on overall ASCVD risk assessment combined with BP levels may prevent more CVD events than treatment based on BP levels alone.S8.1.2-15 S8.1.2-24 According to an analysis of NHANES 2011-2014, the new definition results in only a small increase in the per- centage of US adults for whom antihypertensive medica- tion is recommended in conjunction with lifestyle modifi- cation. The previously cited meta-analyses are consistent with the conclusion that lowering of BP results in benefit in higher-risk individuals, regardless of their baseline treated or untreated BP 130/80 mm Hg and irrespective of the specific cause of their elevated risk. These analy- ses indicate that the benefit of treatment outweighs the potential harm at threshold BP 130/80 mm Hg. 2. This recommendation is consistent with prior guidelines, such as JNC 7. In addition, for those for whom nonphar- macological therapy has been ineffective, antihyperten- sive drug treatment should be added in patients with an SBP 140 mm Hg or a DBP 90 mm Hg, even in adults who are at lower risk than those included in RCTs. The rationale for drug treatment in patients with an SBP 140 mm Hg or a DBP 90 mm Hg and an estimated 10-year risk of CVD <10% is based on several lines of evidence. First, the relationship of SBP with risk of CVD is known to be continuous across levels of SBP and similar across groups that differ in level of absolute risk.S8.1.2-10 Second, the relative risk reduction attributable to BP-lowering medication therapy is consistent across the range of ab- solute risk observed in trials,S8.1.2-3,S8.1.2-11,S8.1.2-58 supporting the contention that the relative risk reduction may be simi- lar at lower levels of absolute risk. This is the case even in a meta-analysis of trials in adults without clinical CVD and an average SBP/DBP of 146/84 mm Hg.S8.1.2-5 Finally, modeling studies support the effectiveness and cost- effectiveness of treatment of younger, lower-risk patients Figure 4. Blood pressure (BP) thresholds and recommendations for treatment and follow-up. Colors correspond to Class of Recommendation in Table 1. *Using the ACC/AHA Pooled Cohort Equations.S8.1.2-56,S8.1.2-57 Note that patients with DM or CKD are automatically placed in the high-risk category. For initiation of RAS inhibitor or diuretic therapy, assess blood tests for electrolytes and renal function 2 to 4 weeks after initiating therapy. Consider initiation of pharmacological therapy for stage 2 hypertension with 2 antihypertensive agents of different classes. Patients with stage 2 hypertension and BP 160/100 mm Hg should be promptly treated, carefully monitored, and subject to upward medication dose adjustment as necessary to control BP. Reassessment includes BP measurement, detection of orthostatic hypotension in selected patients (eg, older or with postural symptoms), identification of white coat hypertension or a white coat effect, documentation of adherence, monitoring of the response to therapy, reinforcement of the importance of adherence, reinforcement of the importance of treatment, and assistance with treatment to achieve BP target. ACC indicates American College of Cardiology; AHA, American Heart Association; ASCVD, atherosclerotic cardiovascular disease; BP, blood pressure; CKD, chronic kidney disease; DM, diabetes mellitus; and RAS, renin-angiotensin system. over the course of their life spans.S8.1.2-12,S8.1.2-13 Although the numbers needed to treat with BP-lowering medications to prevent a CVD event in the short term are greater in young- er, lower-risk individuals with hypertension than in older, higher-risk adults with hypertension, the estimated gains in lifeexpectancyattributabletolong-termuseofBP-lowering medications are correspondingly greater in younger, low- er-risk individuals than in older adults with a higher risk of Indirect support is also provided by evi- dence from trials using BP-lowering medications to reduce the risk of developing higher levels of BPS8.1.2-59 S8.1.2-61 and, in one case, to achieve a reduction in LV mass.S8.1.2-62 In the HOPE-3 (Heart Outcomes Prevention Evaluation-3) BP Trial, there was no evidence of short-term benefit during treatment of adults (average age 66 years) with a relatively low risk of CVD (3.8% CVD event rate during 5.6 years of follow-up). However, subgroup analysis suggested benefit in those with an average SBP approximately >140 mm Hg (and a CVD risk of 6.5% during the 5.6 years of follow- We acknowledge the importance of excluding white coat hypertension before initiating pharmacological therapy in hypertensive patients with low ASCVD risk. This may be accomplished (as described in Section 4) by HBPM or ABPM as appropriate. 8.1.3. Follow-Up After Initial BP Evaluation Recommendations for Follow-Up After Initial BP Evaluation References that support recommendations are summarized in Online Data Supplement 24. COR LOE Recommendations I B-R 1. Adults with an elevated BP or stage 1 hypertension who have an estimated 10- year ASCVD risk less than 10% should be managed with nonpharmacological therapy and have a repeat BP evaluation within 3 to I B-R 2. Adults with stage 1 hypertension who have an estimated 10-year ASCVD risk of 10% or higher should be managed initially with a combination of nonpharmacological and antihypertensive drug therapy and have a repeat BP evaluation in 1 month.S8.1.3-1,S8.1.3-2 I B-R 3. Adults with stage 2 hypertension should be evaluated by or referred to a primary care provider within 1 month of the initial diagnosis, have a combination of nonpharmacological and antihypertensive drug therapy (with 2 agents of different classes) initiated, and have a repeat BP I B-R 4. For adults with a very high average BP (eg, SBP 180 mm Hg or DBP 110 mm Hg), evaluation followed by prompt antihypertensive drug treatment is recommended.S8.1.3-1,S8.1.3-2 IIa C-EO 5. For adults with a normal BP, repeat evaluation every year is reasonable. Synopsis An important component of BP management in hypertensive patients is follow-up. Different periods of time for follow-up are recommended depending on the stage of hypertension, the presence or absence of target organ damage, treatment with antihypertensive medications, and the level of BP control. Recommendations for follow-up are summarized in Figure 4. Recommendation-Specific Supportive Text 1. Nonpharmacological therapy (see Section 6.2) is the preferred therapy for adults with elevated BP and an appropriate first-line therapy for adults with stage 1 hy- pertension who have an estimated 10-year ASCVD risk of <10%. Adherence to and impact of nonpharmacologi- cal therapy should be assessed within 3 to 6 months. 2. Nonpharmacological therapy can help reduce BP in pa- tients with stage 1 hypertension with an estimated 10- yearASCVD risk of 10% and should be used in addition to pharmacological therapy as first-line therapy in such patients (see Section 6.2). 3. Prompt evaluation and treatment of patients with stage 2 hypertension with a combination of drug and non- pharmacological therapy are important because of the elevated risk of CVD events in this subgroup, especially those with multiple ASCVD risk factors or target organ 4. Prompt management of very high BP is important to re- duce the risk of target organ damage (see Section 11.2). The rapidity of the treatment needed is dependent on the patient s clinical presentation (presence of new or wors- ening target organ damage) and presence or absence of CVD complications, but treatment should be initiated within at least 1 week. 5. Given that the lifetime risk of hypertension exceeds 80% in US adults,S8.1.3-3 it is likely that individuals with a normal BP will develop elevated BP in the future. BP may change over time because of changes in BP-related lifestyle fac- tors, such as degree of sedentary lifestyle, dietary sodium intake, body weight, and alcohol intake. Less commonly, secondary causes of hypertension can occur over time and lead to an increase in BP. Periodic BP screening can iden- tify individuals who develop elevated BP over time. More frequent BP screening may be particularly important for individuals with elevated ASCVD risk. 8.1.4. General Principles of Drug Therapy Recommendation for General Principle of Drug Therapy References that support recommendations are summarized in Online Data Supplement 25. COR LOE Recommendation III: Harm A 1. Simultaneous use of an ACE inhibitor, ARB, and/or renin inhibitor is potentially harmful and is not recommended to treat adults with Synopsis Pharmacological agents, in addition to lifestyle modification (see Section 6.2), provide the primary basis for treatment of high BP. A large number of clinical trials have demonstrated that antihypertensive pharmacotherapy not only lowers BP but reduces the risk of CVD, cerebrovascular events, and Whelton et al 2017 High Blood Pressure Clinical Practice Guideline e43 Numerous classes of antihypertensive agents are available to treat high BP (Table 18). Agents that have been shown to reduce clinical events should be used preferentially. Therefore, the pri- mary agents used in the treatment of hypertension include thia- zide diuretics, ACE inhibitors, ARBs, and CCBsS8.1.4-8 S8.1.4-11 (see Section 8.1.6). Although many other drugs and drug classes are available, either confirmation that these agents decrease clinical outcomes to an extent similar to that of the primary agents is lack- ing, or safety and tolerability may relegate their role to use as sec- ondary agents. In particular, there is inadequate evidence to support the initial use of beta blockers for hypertension in the absence of specific cardiovascular comorbidities (see Section 9). When the initial drug treatment of high BP is being consid- ered, several different strategies may be contemplated. Many patients can be started on a single agent, but consideration should be given to starting with 2 drugs of different classes for those with stage 2 hypertension (see Section 8.1.6.1). In addition, other patient-specific factors, such as age, concur- rent medications, drug adherence, drug interactions, the over- all treatment regimen, out-of-pocket costs, and comorbidities, should be considered. From a societal perspective, total costs must be taken into account. Shared decision making, with the patient influenced by clinician judgment, should drive the ulti- mate choice of antihypertensive agent(s). Many patients started on a single agent will subsequently require 2 drugs from different pharmacological classes to reach their BP goals.S8.1.4-12,S8.1.4-13,S8.1.4-14 Knowledge of the pharmacological mechanisms of action of each agent is important. Drug regimens with complementary activity, where a second antihypertensive agent is used to block com- pensatory responses to the initial agent or affect a different pressor mechanism, can result in additive lowering of BP. For example, thiazide diuretics may stimulate the renin-angio- tensin-aldosterone system. By adding an ACE inhibitor or ARB to the thiazide, an additive BP-lowering effect may be Use of combination therapy may also improve adherence. Several 2- and 3-fixed-dose drug combinations of antihypertensive drug therapy are available, with complemen- tary mechanisms of action among the components (Online Data Supplement D). However, it should be noted that many triple-dose combinations may contain a lower-than-optimal dose of thiazide diuretic. Table 18 is a summary of oral antihypertensive drugs. Recommendation-Specific Supportive Text 1. Drug combinations that have similar mechanisms of ac- tion or clinical effects should be avoided. For example, 2 drugs from the same class should not be administered together (eg, 2 different beta blockers, ACE inhibitors, or nondihydropyridine CCBs). Likewise, 2 drugs from classes that target the same BP control system are less effective and potentially harmful when used together (eg, ACE inhibitors, ARBs). Exceptions to this rule in- clude concomitant use of a thiazide diuretic, K-sparing diuretic, and/or loop diuretic in various combinations. Also, dihydropyridine and nondihydropyridine CCBs can be combined. High-quality RCT data demonstrate that simultaneous administration of RAS blockers (ie, ACE inhibitor with ARB; ACE inhibitor or ARB with renin inhibitor aliskiren) increases cardiovascular and renal 8.1.5. BP Goal for Patients With Hypertension Recommendations for BP Goal for Patients With Hypertension References that support recommendations are summarized in Online Data Supplement 26 and Systematic Review Report. COR LOE Recommendations I SBP: B-RSR 1. For adults with confirmed hypertension and known CVD or 10-year ASCVD event risk of 10% or higher (see Section 8.1.2), a BP target of less than 130/80 mm Hg is DBP: C-EO IIb SBP: B-NR 2. For adults with confirmed hypertension, without additional markers of increased CVD risk, a BP target of less than 130/80 mm Hg may be reasonable.S8.1.5-6 S8.1.5-9 DBP: C-EO SR indicates systematic review. Synopsis Refer to the Systematic Review 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 for the complete systematic evidence review for additional data Several trials have tested whether more intensive BP control improves major CVD outcomes. Meta- analyses and systematic reviews of these trials provide strong support for the more intensive approach, but the data are less clear in identification of a specific optimal BP target.S8.1.5-1 Recent trials that address optimal BP targets include SPRINT and ACCORD (Action to Control Cardiovascular Risk in Diabetes), with targets for more inten- sive (SBP <120 mm Hg) and standard (SBP <140 mm Hg) and SPS-3, with a more intensive target These trials yielded mixed results in achieving their primary endpoints. SPRINT was stopped early, after a median follow-up of 3.26 years, when more intensive treatment resulted in a significant reduction in the primary outcome (a CVD composite) and in all-cause mortality rate. In ACCORD, more intensive BP treatment failed to demonstrate a significant reduction in the primary outcome (a CVD com- posite). However, the incidence of stroke, a component of the primary outcome, was significantly reduced. The standard gly- cemia subgroup did show significant benefit in ACCORD, and a meta-analysis of the only 2 trials (ACCORD and SPRINT) testing an SBP goal of <120 mm Hg showed significant reduc- tion in CVD events.S8.1.5-17 SPS-3 failed to demonstrate benefit for the primary endpoint of recurrent stoke (P=0.08) but found a significant reduction in a subgroup with hemorrhagic stroke. Pooling of the experience from 19 trials (excluding SPRINT) that randomly assigned participants to different BP treatment targets identified a significant reduction in CVD events, MI, and stroke in those assigned to a lower (average achieved SBP/DBP was 133/76 mm Hg) versus a higher BP treatment Similar patterns of benefit were reported in 3 other meta-analyses of trials in which participants were randomly Table 18. Oral Antihypertensive Drugs Class Drug Usual Dose, Range (mg/d)* Daily Frequency Comments Primary agents Thiazide or thiazide- type diuretics Chlorthalidone 12.5 25 1 Chlorthalidone is preferred on the basis of prolonged half-life and proven trial reduction of CVD. Monitor for hyponatremia and hypokalemia, uric acid and calcium levels. Use with caution in patients with history of acute gout unless patient is on uric acid lowering therapy. ACE inhibitors Benazepril 10 40 1 or 2 Do not use in combination with ARBs or direct renin inhibitor. There is an increased risk of hyperkalemia, especially in patients with CKD or in those on K+ supplements or K+ -sparing drugs. There is a risk of acute renal failure in patients with severe bilateral renal artery stenosis. Do not use if patient has history of angioedema with ACE inhibitors. Avoid in pregnancy. ARBs Azilsartan 40 80 1 Do not use in combination with ACE inhibitors or direct renin inhibitor. There is an increased risk of hyperkalemia in CKD or in those on K+ supplements or K+ -sparing drugs. There is a risk of acute renal failure in patients with severe bilateral renal artery stenosis. Do not use if patient has 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 is discontinued. Avoid in pregnancy. CCB dihydropyridines Amlodipine 2.5 10 1 Avoid use in patients with HFrEF; amlodipine or felodipine may be used if required. They are associated with dose-related pedal edema, which is more common in women than men. CCB nondihydropyridines Diltiazem ER 120 360 1 Avoid routine use with beta blockers because of increased risk of bradycardia and heart block. Do not use in patients with HFrEF. There are drug interactions with diltiazem and verapamil (CYP3A4 major substrate and moderate inhibitor). Verapamil-delayed onset ER evening) Secondary agents Diuretics loop Bumetanide 0.5 2 2 These are preferred diuretics in patients with symptomatic HF. They are preferred over thiazides in patients with moderate-to-severe CKD (eg, GFR <30 mL/min). Diuretics potassium sparing Amiloride 5 10 1 or 2 These are monotherapy agents and minimally effective antihypertensive agents. Combination therapy of potassium-sparing diuretic with a thiazide can be considered in patients with hypokalemia on thiazide monotherapy. Avoid in patients with significant CKD (eg, GFR <45 mL/min). (Continued) Whelton et al 2017 High Blood Pressure Clinical Practice Guideline e45 Diuretics aldosterone antagonists Eplerenone 50 100 1 or 2 These are preferred agents in primary aldosteronism and resistant hypertension. Spironolactone is associated with greater risk of gynecomastia and impotence as compared with eplerenone. This is common add-on therapy in resistant hypertension. Avoid use with K+ supplements, other K+ -sparing diuretics, or significant renal dysfunction. Eplerenone often requires twice-daily dosing for adequate BP lowering. Beta blockers cardioselective Atenolol 25 100 2 Beta blockers are not recommended as first-line agents unless the patient has IHD or HF. These are preferred in patients with bronchospastic airway disease requiring a beta blocker. Bisoprolol and metoprolol succinate are preferred in patients with HFrEF. Avoid abrupt cessation. Beta blockers cardioselective and vasodilatory Nebivolol 5 40 1 Nebivolol induces nitric oxide induced vasodilation. Avoid abrupt cessation. Beta blockers noncardioselective Nadolol 40 120 1 Avoid in patients with reactive airways disease. Avoid abrupt cessation. Beta blockers intrinsic sympathomimetic activity Acebutolol 200 800 2 Generally avoid, especially in patients with IHD or HF. Avoid abrupt cessation. Beta blockers combined alpha- and beta-receptor Carvedilol 12.5 50 2 Carvedilol is preferred in patients with HFrEF. Avoid abrupt cessation. Direct renin inhibitor Aliskiren 150 300 1 Do not use in combination with ACE inhibitors or ARBs. Aliskiren is very long acting. There is an increased risk of hyperkalemia in CKD or in those on K+ supplements or K+ -sparing drugs. Aliskiren may cause acute renal failure in patients with severe bilateral renal artery stenosis. Avoid in pregnancy. Alpha-1 blockers Doxazosin 1 16 1 These are associated with orthostatic hypotension, especially in older adults. They may be considered as second-line agent in patients with concomitant BPH. - agonist and other centrally acting drugs Clonidine oral 0.1 0.8 2 These are generally reserved as last-line because of significant CNS adverse effects, especially in older adults. Avoid abrupt discontinuation of clonidine, which may induce hypertensive crisis; clonidine must be tapered to avoid rebound hypertension. Clonidine patch 0.1 0.3 1 weekly Direct vasodilators Hydralazine 100 200 2 or 3 These are associated with sodium and water retention and reflex tachycardia; use with a diuretic and beta blocker. Hydralazine is associated with drug-induced lupus-like syndrome at higher doses. Minoxidil is associated with hirsutism and requires a loop diuretic. Minoxidil can induce pericardial effusion. *Dosages may vary from those listed in the FDA-approved labeling (available at https://dailymed.nlm.nih.gov/dailymed/) From Chobanian et al JNC 7.S8.1.4-15 ACE indicates angiotensin-converting enzyme; ARB, angiotensin receptor blocker; BP, blood pressure; BPH, benign prostatic hyperplasia; CCB, calcium channel blocker; CKD, chronic kidney disease; CNS, central nervous system; CVD, cardiovascular disease; ER, extended release; GFR, glomerular filtration rate; HF, heart failure; HFrEF, heart failure with reduced ejection fraction; IHD, ischemic heart disease; IR, immediate release; LA, long-acting; and SR, sustained release. Table 18. Continued Class Drug Usual Dose, Range (mg/d)* Daily Frequency Comments assigned to different BP targetsS8.1.5-3 S8.1.5-5 and in larger meta- analyses that additionally included trials that compared dif- ferent intensities of treatment.S8.1.5-12 Data from the most demonstrate a linear association between mean achieved SBP and risk of CVD mortality with the lowest risk at 120 to 124 mm Hg. The totality of the available information pro- vides evidence that a lower BP target is generally better than a higher BP target and that some patients will benefit from an SBP treatment goal <120 mm Hg, especially those at high risk The specific inclusion and exclusion criteria of any RCT may limit extrapolation to a more general population with hypertension. In addition, all of the relevant trials have been efficacy studies in which BP measurements were more consistent with guideline recommendations than is common in clinical practice, resulting in lower absolute values for SBP. For both of these reasons, the SBP target recommended dur- ing BP lowering (<130 mm Hg) is higher than that which was used in SPRINT. Recommendation-Specific Supportive Text 1. Meta-analysis and systematic review of trials that com- pare more intensive BP reduction to standard BP reduc- tion report that more intense BP lowering significantly reduces the risk of stroke, coronary events, major cardio- vascular events, and cardiovascular mortality.S8.1.5-1 In a stratified analysis of these data, achieving an additional 10 mm Hg reduction in SBP reduced CVD risk when compared with an average SBP of 158/82 to 143/76 mm Hg, 144/85 to 137/81 mm Hg, and 134/79 to 125/76 mm Hg. Patients with DM and CKD were included in (Specific man- agement details are in Section 9.3 for CKD and Section 9.6 for DM.) 2. The treatment of patients with hypertension without ele- vated risk has been systematically understudied because lower-risk groups would require prolonged follow-up to have a sufficient number of clinical events to provide useful information. Although there is clinical trial evi- dence that both drug and nondrug therapy will interrupt the progressive course of hypertension,S8.1.5-6 there is no trial evidence that this treatment decreases CVD mor- bidity and mortality. The clinical trial evidence is stron- gest for a target BP of 140/90 mm Hg in this population. However, observational studies suggest that these indi- viduals often have a high lifetime risk and would benefit from BP control earlier in life.S8.1.5-19,S8.1.5-20 8.1.6. Choice of Initial Medication Recommendation for Choice of Initial Medication References that support the recommendation are summarized in Online Data Supplement 27 and Systematic Review Report. COR LOE Recommendation I ASR 1. For initiation of antihypertensive drug therapy, first-line agents include thiazide diuretics, CCBs, and ACE inhibitors or SR indicates systematic review. Synopsis The overwhelming majority of persons with BP sufficiently elevated to warrant pharmacological therapy may be best treated initially with 2 agents (see Section 8.1.6.1). When ini- tiation of pharmacological therapy with a single medication is appropriate, primary consideration should be given to comor- bid conditions (eg, HF, CKD) for which specific classes of BP-lowering medication are indicated (see Section 9).S8.1.6-1 In the largest head-to-head comparison of first-step drug therapy the thiazide-type diuretic chlorthalidone was superior to the CCB amlodipine and the ACE inhibitor lisinopril in preventing HF, a BP-related outcome of increas- ing importance in the growing population of older persons with Additionally, ACE inhibitors were less effective than thiazide diuretics and CCBs in lowering BP and in prevention of stroke. For black patients, ACE inhibitors were also notably less effective than CCBs in preventing HFS8.1.6-8 and in the prevention of strokeS8.1.6-9 (see Section 10.1).ARBs may be better tolerated than ACE inhibitors in black patients, with less cough and angioedema, but according to the limited available experience they offer no proven advantage over ACE inhibitors in preventing stroke or CVD in this population, making thiazide diuretics (especially chlorthalidone) or CCBs the best initial choice for single-drug therapy. For stroke, in the general popula- tion, beta blockers were less effective than CCBs (36% lower risk) and thiazide diuretics (30% lower risk). CCBs have been shown to be as effective as diuretics for reducing all CVD events other than HF, and CCBs are a good alternative choice for initial therapy when thiazide diuretics are not tolerated. Alpha block- ers are not used as first-line therapy for hypertension because they are less effective for prevention of CVD than other first-step agents, such as thiazide diuretics.S8.1.6-3,S8.1.6-10 Recommendation-Specific Supportive Text 1. The overall goal of treatment should be reduction in BP, in the context of underlying CVD risk. Five drug classes have been shown, in high-quality RCTs, to prevent CVD as compared with placebo (diuretics, ACE inhibitors, ARBs, CCBs, and beta blockers).S8.1.6-11,S8.1.6-12 In head-to-head comparisons of first-step therapy, different drug classes have been reported to provide somewhat divergent capac- ity to prevent specific CVD events. Interpretation of meta- analyses comparing agents from different drug classes is challenging because the relevant RCTs were conducted in different time periods, during which concurrent antihyper- tensive therapy was less or more common, and the efficacy of agents from certain drug classes may have changed. In recognition of this, someS8.1.6-2 but not allS8.1.6-11,S8.1.6-12 meta- analyses, as well as the largest individual RCT that com- pared first-step agents,S8.1.6-3 have suggested that diuretics, especially the long-acting thiazide-type agent chlortha- lidone, may provide an optimal choice for first-step drug therapy of hypertension. In contrast, some meta-analyses have suggested that beta blockers may be less effective, especially for stroke prevention in older adults, but inter- pretation is hampered by inclusion of RCTs that used beta blockers that are now considered to be inferior for preven- tion of CVD.S8.1.6-13,S8.1.6-14 In a systematic review and net- work meta-analysis conducted for the present guideline, beta blockers were significantly less effective than diuretics Whelton et al 2017 High Blood Pressure Clinical Practice Guideline e47 for prevention of stroke and cardiovascular events.S8.1.6-1 Diuretics were also significantly better than CCBs for pre- vention of HF. There were some other nonsignificant differ- ences between diuretics,ACE inhibitors,ARBs, and CCBs, but the general pattern was for similarity in effect. As in- dicated in Section 8.1.6.1, most adults with hypertension require >1 drug to control their BP. As recommended in Section 10.1, for black adults with hypertension (without HF or CKD), initial antihypertensive treatment should in- clude a thiazide diuretic or CCB. 8.1.6.1. Choice of Initial Monotherapy Versus Initial Combination Drug Therapy Recommendations for Choice of Initial Monotherapy Versus Initial Combination Drug Therapy* COR LOE Recommendations I C-EO 1. Initiation of antihypertensive drug therapy with 2 first-line agents of different classes, either as separate agents or in a fixed-dose combination, is recommended in adults with stage 2 hypertension and an average BP more than 20/10 mm Hg above their BP target. IIa C-EO 2. Initiation of antihypertensive drug therapy with a single antihypertensive drug is reasonable in adults with stage 1 hypertension and BP goal <130/80 mm Hg with dosage titration and sequential addition of other agents to achieve the BP target. *Fixed-dose combination antihypertensive medications are listed in Online Data Supplement D. Synopsis Systematic review of the evidence comparing the initiation of antihypertensive treatment with monotherapy and sequential (stepped-care) titration of additional agents versus initiation of treatment with combination therapy (including fixed- dose combinations) did not identify any RCTs meeting the systematic review questions posed in the PICOTS format (P=population, I=intervention, C=comparator, O=outcome, T=timing, S=setting). However, in both ACCORD and SPRINT, 2-drug therapy was recommended for most partici- pants in the intensive- but not standard-therapy groups. Recommendation-Specific Supportive Text 1. Because most patients with hypertension require multiple agents for control of their BP and those with higher BPs are at greater risk, more rapid titration of antihyperten- sive medications began to be recommended in patients with BP >20/10 mm Hg above their target, beginning with the JNC 7 report.S8.1.6.1-1 In these patients, initiation of antihypertensive therapy with 2 agents is recommend- ed. Evidence favoring this approach comes mostly from studies using fixed-dose combination products show- ing greater BP lowering with fixed-dose combination agents than with single agents, as well as better adher- ence to therapy.S8.1.6.1-2,S8.1.6.1-3 The safety and efficacy of this strategy have been demonstrated in adults to reduce BPs to <140/90 mm Hg though not compared with other In general, this approach is rea- sonable in older adults, those at high CVD risk, or those who have a history of hypotension or drug-associated side effects. However, caution is advised in initiating antihypertensive pharmacotherapy with 2 drugs in older patients because hypotension or orthostatic hypotension may develop in some patients; BP should be carefully monitored. 2. The stepped-care approach defined by the initiation of an- tihypertensive drug therapy with a single agent followed by the sequential titration of the dose and addition of oth- er agents has been the recommended treatment strategy since the first report of the National High Blood Pressure This approach is also reason- able in older adults or those at risk or who have a history of hypotension or drug-associated side effects. This strat- egy has been used successfully in nearly all hypertension treatment trials but has not been formally tested against other antihypertensive drug treatment strategies for effec- tiveness in achieving BP control or in preventing adverse outcomes. 8.2. Achieving BP Control in Individual Patients Recommendations for lifestyle modifications and drug selec- tion are specified in Sections 6.2, 8.1.4, and 8.1.6. Initial drug selections should be based on trial evidence of treatment effi- cacy, combined with recognition of compelling indications for use of an agent from a specific drug class, as well as the indi- vidual patient s lifestyle preferences and traits. For a subset of the initial drug therapy will be well tolerated and effective in achieving the desired level of BP, with only the need for subsequent monitoring (see Section 8.3 for an appropriate follow-up schedule). For others, the initial drug will not be tolerated or will not be effective, requiring either a change in medication or addition of another medi- cation, followed by BP monitoring.S8.2-2 of patients will require additional treatment adjustments. In a minority of this group, achievement of goal BP can be challenging. In patients who do not respond to or do not tolerate treat- ment with 2 to 3 medications or medication combinations, additional trials of treatment tend to be ineffective or poorly tolerated. Some patients may become disillusioned and lost to follow-up, whereas others will identify an alternative health- care provider, including nontraditional healers, or will try popular home remedies. Working with this more demanding subset requires provider expertise, patience, and a mecha- nism to respond efficiently and sensitively to concerns as they arise. In this setting, team-based care (see Section 12) may be effective, encouraging coupling of nonpharmacological and pharmacological treatments, while improving access to and communication with care providers. In the setting of medication intolerance, consider allowing a defined period of time to evaluate the effects of lifestyle mod- ification in patients with a relatively low CVD risk (10-year risk of ASCVD <10%, based on the ASCVD Risk Estimator [http://tools.acc.org/ASCVD-Risk-Estimator]), with sched- uled follow-up visits for assessment of BP levels, including a review of HBPM data, and an appraisal of lifestyle change goal achievements. For patients with a higher level of CVD risk or with significant elevations in BP (SBP or DBP >20 or >10 mm Hg above target, respectively), medication is usually started even while the patient is pursuing lifestyle change (see Section 8.1.2). Consideration of patient comorbidities, lifestyle, and pref- erences may suggest better tolerance or greater effect from one class of medication versus other classes. For example, if hyponatremia is present, it would be important to avoid or stop thiazide diuretic therapy. In this case, a loop diuretic should be used if a diuretic is required. If hypokalemia is present, primary or secondary aldosteronism should be excluded, after which one should consider a potassium-sparing agent, such as spironolactone, eplerenone, triamterene, or amiloride. In addition, reducing dietary sodium intake will diminish urinary potassium losses. If the patient has chronic cough or a history of ACE inhibitor induced cough or develops a cough or bron- chial responsiveness while on an ACE inhibitor, one should use an ARB in place of an ACE inhibitor. For patients with bronchospastic lung disease, a beta-1-selective blocker (eg, bisoprolol, metoprolol) should be considered if beta-blocker therapy is required. A patient who is already adherent to life- style change recommendations, including diligent reduction in sodium intake, may show a greater response to a RAS blocker. Prior patient experience should be considered, as in the case of cough associated with prior use of an ACE inhibitor, which is likely to reoccur if an agent from the same class is prescribed. 8.3. Follow-Up of BP During Antihypertensive Drug Therapy Appropriate follow-up and monitoring enable assessment of adherence (see Section 12.1) and response to therapy, help identify adverse responses to therapy and target organ damage, and allow assessment of progress toward treatment goals. High- quality RCTs have successfully and safely developed strategies for follow-up, monitoring, and reassessment from which rec- ommendations can be made (Figure 4).S8.2-1,S8.2-2 A systematic approach to out-of-office BP assessment is an essential part of follow-up and monitoring of BP, to assess response to therapy; check for evidence of white coat hypertension, white coat effect, masked hypertension, or masked uncontrolled hyperten- sion; and help achieve BP targets (see Sections 4 and 12). 8.3.1. Follow-Up After Initiating Antihypertensive Drug Therapy Recommendation for Follow-Up After Initiating Antihypertensive Drug Therapy References that support the recommendation are summarized in Online Data Supplement 28. COR LOE Recommendation I B-R 1. Adults initiating a new or adjusted drug regimen for hypertension should have a follow-up evaluation of adherence and response to treatment at monthly intervals until control is Recommendation-Specific Supportive Text 1. Components of the follow-up evaluation should include assessment of BP control, as well as evaluation for orthostatic hypotension, adverse effects from medication therapy, adherence to medication and lifestyle therapy, need for adjustment of medication dosage, laboratory testing (including electrolyte and renal function status), and other assessments of target organ damage.S8.3.1-1 S8.3.1-3 8.3.2. Monitoring Strategies to Improve Control of BP in Patients on Drug Therapy for High BP Recommendation for Monitoring Strategies to Improve Control of BP in Patients on Drug Therapy for High BP References that support the recommendation are summarized in Online Data Supplement 29. COR LOE Recommendation I A 1. Follow-up and monitoring after initiation of drug therapy for hypertension control should include systematic strategies to help improve BP, including use of HBPM, team-based care, and telehealth Recommendation-Specific Supportive Text 1. Systematic approaches to follow-up have been shown to improve hypertension control and can be adapted and incorporated into clinical practices according to local needs and resource availability (see Section 8.3.1 for time intervals for treatment follow-up and monitoring and Sections 12.2 and 12.3.2 on systematic strategies to improve BP control). 9. Hypertension in Patients With Comorbidities Certain comorbidities may affect clinical decision-making in hypertension. These include ischemic heart disease, HF with reduced ejection fraction (HFrEF), HFpEF, CKD (includ- ing renal transplantation), cerebrovascular disease, AF, PAD, DM, and metabolic syndrome.S9-1 As noted in Section 8.1.2, this guideline generally recommends use of BP-lowering medications for secondary prevention of CVD in patients with clinical CVD (CHD, HF, and stroke) and an average BP 130/80 mm Hg and for primary prevention of CVD in adults with an estimated 10-year ASCVD risk of 10% and an average SBP 130 mm Hg or an average DBP 80 mm Hg. Although we recommend use of theACC/AHA Pooled Cohort Equations (http://tools.acc.org/ASCVD-Risk-Estimator/) to estimate 10-year risk of ASCVD to establish the BP threshold for treatment, the vast majority of adults with a co-morbidity are likely to have a 10-year risk of ASCVD that exceeds 10%. In some instances, clinical trial confirmation of treatment in patients with comorbidities is limited to a target BP of 140/90 mm Hg. 