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. In addition, the selection of medications for use in treating high BP in patients with CVD is guided by their use for other compelling indications (eg, beta blockers after MI, ACE inhibitors for HFrEF), as discussed in specific guidelines for the clinical condition.S9-2 S9-4 The present guideline does not address the recommendations for treatment of hyperten- sion occurring with acute coronary syndromes. Whelton et al 2017 High Blood Pressure Clinical Practice Guideline e49 9.1. Stable Ischemic Heart Disease Recommendations for Treatment of Hypertension in Patients With Stable Ischemic Heart Disease (SIHD) References that support recommendations are summarized in Online Data Supplements 30-32. COR LOE Recommendations I SBP: B-R 1. In adults with SIHD and hypertension, a BP target of less than 130/80 mm Hg is DBP: C-EO I SBP: B-R 2. Adults with SIHD and hypertension (BP 130/80 mm Hg) should be treated with medications (eg, GDMTS9.1-6 beta blockers, ACE inhibitors, or ARBs) for compelling indications (eg, previous MI, stable angina) as first-line therapy, with the addition of other drugs (eg, dihydropyridine CCBs, thiazide diuretics, and/or mineralocorticoid receptor antagonists) as needed to further DBP: C-EO I B-NR 3. In adults with SIHD with angina and persistent uncontrolled hypertension, the addition of dihydropyridine CCBs to GDMTS9.1-6 beta blockers is recommended.S9.1-8,S9.1-11,S9.1-12 IIa B-NR 4. In adults who have had a MI or acute coronary syndrome, it is reasonable to continue GDMT (S9.1-6) beta blockers beyond 3 years as long- term therapy for hypertension.S9.1-13,S9.1-14 IIb C-EO 5. Beta blockers and/or CCBs might be considered to control hypertension in patients with CAD (without HFrEF) who had an MI more than 3 years ago and have angina. Synopsis Hypertension is a major risk factor for ischemic heart disease. Numerous RCTs have demonstrated the benefits of antihy- pertensive drug therapy in reducing the risk of ischemic heart disease. The following recommendations apply only to man- agement of hypertension in patients with SIHD without HF. See Section 9.2 for recommendations for the treatment of patients with SIHD and HF. Figure 5 is an algorithm on management of hypertension in patients with SIHD. Recommendation-Specific Supportive Text 1. In patients with increased cardiovascular risk, reduction of SBP to <130/80 mm Hg has been shown to reduce CVD complications by 25% and all-cause mortality by 2. After 5 years of randomized therapy in high-CVD-risk patients, ramipril produced a 22% reduction in MI, stroke, or CVD compared with placebo.S9.1-10 No added benefit on CVD outcomes was seen when compared with CCBs and diuretics.S9.1-15,S9.1-16 After 4.2 years of randomized therapy in patients with SIHD, perindopril reduced CVD death, MI, or cardiac arrest by 20% com- pared with placebo.S9.1-7 Beta blockers are effective drugs for preventing angina pectoris, improving exercise time until the onset of angina pectoris, reducing exercise-in- duced ischemic ST-segment depression, and preventing Because of their com- pelling indications for treatment of SIHD, these drugs are recommended as a first-line therapy in the treatment of hypertension when it occurs in patients with SIHD. GDMT beta blockers for SIHD that are also effective in lowering BP include carvedilol, metoprolol tartrate, metoprolol succinate, nadolol, bisoprolol, propranolol, and timolol. Atenolol is not as effective as other antihy- pertensive drugs in the treatment of hypertension.S9.1-23 3. Dihydropyridine CCBs are effective antianginal drugs that can lower BP and relieve angina pectoris when added to beta blockers in patients in whom hyperten- sion is present and angina pectoris persists despite beta- GDMT beta blockers for SIHD that are also effective in low- ering BP include carvedilol, metoprolol tartrate, meto- prolol succinate, nadolol, bisoprolol, propranolol, and timolol. 4. In randomized long-term trials, use of beta blockers af- ter MI reduced all-cause mortality by 23%.S9.1-13 Given the established efficacy of beta blockers for treating hy- pertension and SIHD, their use for treatment continuing beyond 3 years after MI is reasonable.S9.1-6,S9.1-25 5. GDMT beta blockers and CCBs are effective antihyper- tensive and antianginal agents. CCBs include dihydro- pyridine and nondihydropyridine agents. CCBs can be Figure 5. Management of hypertension in patients with SIHD. Colors correspond to Class of Recommendation in Table 1. *GDMT beta blockers for BP control or relief of angina include carvedilol, metoprolol tartrate, metoprolol succinate, nadolol, bisoprolol, propranolol, and timolol. Avoid beta blockers with intrinsic sympathomimetic activity. The beta blocker atenolol should not be used because it is less effective than placebo in reducing cardiovascular events. If needed for BP control. ACE indicates angiotensin-converting enzyme; ARB, angiotensin receptor blocker; BP, blood pressure; CCB, calcium channel blocker; GDMT, guideline-directed management and therapy; and SIHD, stable ischemic heart disease. used separately or together with beta blockers beginning 3 years after MI in patients with CAD who have both hypertension and angina. 9.2. Heart Failure Recommendation for Prevention of HF in Adults With Hypertension References that support the recommendation are summarized in Online Data Supplement 33. COR LOE Recommendation I SBP: B-R 1. In adults at increased risk of HF, the optimal BP in those with hypertension should be less DBP: C-EO Synopsis Antecedent hypertension is present in 75% of patients with In the Cardiovascular Health StudyS9.2-5 and the Health, Aging and Body Composition Study,S9.2-6 of 4408 persons (53.1% women, with a mean age of 72.8 years, living in the community, and not receiving antihyper- tensive drugs at baseline) developed HF over 10 years.S9.2-7 Compared with those with an average SBP <120 mm Hg, the adjusted incidence of HF was increased 1.6, 2.2, and 2.6 times in those with average SBPs between 120 and 139 mm Hg, between 140 and 159 mm Hg, and 160 mm Hg, No RCTs are available that compare one BP-lowering agent to another for the management of patients with HF. The following recommendations for treatment of hyperten- sion in HF are based on use of drugs that lower BP and also have compelling indications for management of HF (with HFrEF or HFpEF) as recommended in current ACC/AHA Recommendation-Specific Supportive Text 1. In adults with hypertension (SBP 130 mm Hg or DBP 80 mm Hg) and a high risk of CVD, a strong body of evidence supports treatment with antihypertensive medications (see Section 8.1.2) and more-intensive rath- er than less-intensive intervention (see Section 8.1.5). In SPRINT, a more intensive intervention that targeted an SBP <120 mm Hg significantly reduced the primary outcome (CVD composite) by about 25%.S9.2-9 The in- cidence of HF, a component of the primary outcome, was also substantially decreased (hazard ratio: 0.62; 95% confidence interval: 0.45 0.84). Meta-analyses of clinical trials have identified a similar beneficial ef- fect of more-intensive BP reduction on the incidence of but the body of information from stud- ies confined to trials that randomly assigned partici- pants to different BP targets is more limited and less In addition, the available trials were effi- cacy studies in which BP measurements were more con- sistent with guideline recommendations than is common in clinical practice, resulting in lower absolute values for SBP. For both of these reasons, the SBP target recom- mended during BP lowering (<130 mm Hg) is higher than that used in SPRINT. 9.2.1. Heart Failure With Reduced Ejection Fraction Recommendations for Treatment of Hypertension in Patients With HFrEF References that support recommendations are summarized in Online Data Supplement 34. COR LOE Recommendations I C-EO 1. Adults with HFrEF and hypertension should be prescribed GDMTS9.2.1-2 titrated to attain a BP of less than 130/80 mm Hg. III: No Benefit B-R 2. Nondihydropyridine CCBs are not recommended in the treatment of hypertension in adults with HFrEF.S9.2.1-1 Synopsis Approximately 50% of patients with HF have HFrEF.S9.2.1-2 S9.2.1-6 Numerous RCTs have shown that treatment of HFrEF with GDMT reduces mortality and HF hospitalizations.S9.2.1-7 Large-scale RCTs have shown that antihypertensive drug therapy reduces the incidence of HF in patients with In ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial), chlorthalidone reduced the risk of HFrEF more than amlo- dipine and doxazosin but similarly to lisinopril.S9.2.1-12,S9.2.1-13 Recommendation-Specific Supportive Text 1. This recommendation is based on guidance in the 2017 ACC/AHA/HFSA guideline focused update on heart (see figure from the HF focused update that is reproduced in Online Data Supplement A). Lifestyle modification, such as weight loss and sodium reduction, may serve as adjunctive measures to help these agents work better. No RCT evidence is available to support the superiority of one BP-lowering medication with compel- ling indications for treatment of HFrEF over another. Medications with compelling indications for HF that may be used as first-line therapy to treat high BP include ACE inhibitors or ARBs, angiotensin receptor neprilysin inhibitors, mineralocorticoid receptor antagonists, diuret- ics, and GDMT beta blockers (carvedilol, metoprolol succinate, or bisoprolol). Clinical trials evaluating goal BP reduction and opti- mal BP-lowering agents in the setting of HFrEF and con- comitant hypertension have not been performed. However, in patients at higher CVD risk, BP lowering is associated with fewer adverse cardiovascular events.S9.2.1-7 GDMT for HFrEF with agents known to lower BP should consider a goal BP reduction consistent with a threshold now associ- ated with improved clinical outcomes but not yet proven by RCTs in an HF population. 2. Nondihydropyridine CCBs (verapamil, diltiazem) have myocardial depressant activity. Several clinical trials have demonstrated either no clinical benefit or even worse outcomes in patients with HF treated with these Therefore, nondihydropyridine CCBs are not recommended in patients with hypertension and HFrEF. Whelton et al 2017 High Blood Pressure Clinical Practice Guideline e51 9.2.2. Heart Failure With Preserved Ejection Fraction Recommendations for Treatment of Hypertension in Patients With HFpEF References that support recommendations are summarized in Online Data Supplements 35 and 36. COR LOE Recommendations I C-EO 1. In adults with HFpEF who present with symptoms of volume overload, diuretics should be prescribed to control hypertension. I C-LD 2. Adults with HFpEF and persistent hypertension after management of volume overload should be prescribed ACE inhibitors or ARBs and beta blockers titrated to attain SBP of less than 130 Synopsis Approximately 50% of patients with HF have The ejection fraction in these studies has varied from >40% to 55%.S9.2.2-2 Patients with HFpEF are usually older women with a history of hypertension. Obesity, CHD, DM, AF, and hyperlipidemia are also highly preva- lent in patients with HFpEF.S9.2.2-2,S9.2.2-11,S9.2.2-12 Hypertension is the most important cause of HFpEF, with a prevalence of 60% to 89% in large RCTs, epidemiological studies, and HF Patients with HFpEF also have an exag- gerated hypertensive response to exercise.S9.2.2-14 Hypertensive acute pulmonary edema is an expression of HFpEF.S9.2.2-15 BP control is important for prevention of HFpEF in patients with hypertension.S9.2.2-2,S9.2.2-16 S9.2.2-19 ALLHAT showed that treatment of hypertension with chlorthalidone reduced the risk of HF compared with amlodipine, doxazosin, and Improved BP control also reduces hospi- talization, CVD events, and mortality.S9.2.2-2,S9.2.2-16 S9.2.2-19 Recommendation-Specific Supportive Text 1. Diuretics are the only drugs used for the treatment of hypertension and HF that can adequately control the fluid retention of HF. Appropriate use of diuretics is also crucial to the success of other drugs used for the treatment of hypertension in the presence of HF. The use of inappropriately low doses of diuretics can result in fluid retention. Conversely, the use of inap- propriately high doses of diuretics can lead to volume contraction, which can increase the risk of hypotension and renal insufficiency. Diuretics should be prescribed to all patients with hypertension and HFpEF who have evidence of, and to most patients with a prior history of, fluid retention. 2. In a trial of patients with HFpEF and MI, patients ran- domized to propranolol had at 32-month follow-up a 35% reduction in mortality rate.S9.2.2-3 After 21 months of treatment in patients with HFrEF and HFpEF, compared with placebo, those randomized to nebivolol had a 14% reduction in mortality or CVD hospitalization if they had HFrEF and a 19% reduction if they had HFpEF.S9.2.2-4 In patients with HFpEF, the primary outcome (a composite of CVD death or HF hospitalization) was observed in 22% for candesartan and 24% for placebo (11% reduc- tion), but fewer patients receiving candesartan were hos- pitalized for HF.S9.2.2-5 The use of nitrates in the setting of HFpEF is associated with a signal of harm and in most situations should be avoided. For many other common antihypertensive agents, including alpha blockers, beta blockers, and calcium channel blockers, limited data ex- ist to guide the choice of antihypertensive therapy in the setting of HFpEF.S9.2.2-21 Renin-angiotensin-aldosterone system inhibition, however, with ACE inhibitor or ARB and especially MRA would represent the preferred choice. A shared decision-making discussion, with the patient influenced by clinician judgment, should drive the ultimate choice of antihypertensive agents. 9.3. Chronic Kidney Disease Recommendations for Treatment of Hypertension in Patients With CKD References that support recommendations are summarized in Online Data Supplements 37 and 38 and Systematic Review Report. COR LOE Recommendations I SBP: B-RSR 1. Adults with hypertension and CKD should be treated to a BP goal of less than DBP: C-EO IIa B-R 2. In adults with hypertension and CKD (stage 3 or higher or stage 1 or 2 with albuminuria [ 300 mg/d, or 300 mg/g albumin-to-creatinine ratio or the equivalent in the first morning void]), treatment with an ACE inhibitor is reasonable to slow kidney disease IIb C-EO 3. In adults with hypertension and CKD (stage 3 or higher or stage 1 or 2 with albuminuria [ 300 mg/d, or 300 mg/g albumin-to- creatinine ratio in the first morning void]) (S9.3-7,S9.3-8), treatment with an ARB may be reasonable if an ACE inhibitor is not tolerated. 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 and Hypertension is the most common comorbidity affecting patients with CKD. Hypertension has been reported in 67% to 92% of patients with CKD, with increasing preva- lence as kidney function declines.S9.3-14 Hypertension may occur as a result of kidney disease, yet the presence of hyper- tension may also accelerate further kidney injury; therefore, treatment is an important means to prevent further kidney functional decline. This tight interaction has led to exten- sive debate about the optimal BP target for patients with Masked hypertension may occur in up to 30% of patients with CKD and portends higher risk of CKD CKD is an important risk factor for and the coexistence of hypertension and CKD further increases the risk of adverse CVD and cerebrovas- cular events, particularly when proteinuria is present.S9.3-25 Even as the importance of hypertension treatment is widely accepted, data supporting BP targets in CKD are limited, as patients with CKD were historically excluded from clinical trials. Furthermore, CKD is not included in the CVD risk calculations used to determine suitability for most clinical Until publication of the SPRINT results, most guidelines for BP targets in patients with CKD favored treatment to a with consideration of the lower target of <130/80 mm Hg for those with more severe pro- teinuria ( 300 mg albuminuria in 24 hours or the equiva- lent), if tolerated.S9.3-16 S9.3-18 Patients with stage 3 to 4 CKD ) comprised 28% of the SPRINT study population, and in this group inten- sive BP management seemed to provide the same benefits for reduction in the CVD composite primary outcome and all-cause mortality as were seen in the full study cohort. Given that most patients with CKD die from CVD complica- tions, this RCT evidence supports a lower target of <130/80 mm Hg for all patients with CKD (Figure 6). It is appro- priate to acknowledge that many patients with CKD have additional comorbidities and evidence of frailty that caused them to be excluded from past clinical trials. Observational studies of CKD cohorts indicate a higher risk of mortality at lower systolic pressures and a flat relationship of SBP to event risk in elderly patients with CKD,S9.3-29,S9.3-30 which sup- ports concerns that these complex patients may be at greater risk of complications from intensive BP treatment and may fail to achieve benefits from lower BP targets. In contrast, in the prespecified subgroup analysis of the elderly cohort in SPRINT, frail elderly patients did sustain benefit from the lower BP target, which supports a lower goal for all patients, including those with CKD.S9.3-31 In this setting, incremental BP reduction may be appropriate, with careful monitoring of physical and kidney function. An ACE inhibitor (or an ARB, in case of ACE inhibitor intolerance) is a preferred drug for treatment of hyperten- sion if albuminuria ( 300 mg/day or 300 mg/g creatinine by first morning void) is present, although the evidence is (Figure 6). In the course of reducing intra- glomerular pressure and thereby reducing albuminuria, serum creatinine may increase up to 30% because of concur- rent reduction in GFR.S9.3-32 Further GFR decline should be investigated and may be related to other factors, including volume contraction, use of nephrotoxic agents, or renovas- The combination of an ACE inhibitor and an ARB should be avoided because of reported harms dem- onstrated in several large cardiology trialsS9.3-34,S9.3-35 and in 1 diabetic nephropathy trial.S9.3-36 Because of the greater risk of hyperkalemia and hypotension and lack of demonstrated benefit, the combination of an ARB (or ACE inhibitor) and a direct renin inhibitor is also contraindicated during manage- ment of patients with CKD.S9.3-37 Figure 6 is an algorithm on management of hypertension in patients with CKD. Recommendation-Specific Supportive Text 1. We recommend ASCVD risk assessment in all adults with hypertension, including those with CKD. As a matter of convenience, however, it can be assumed that the vast majority of patients with CKD have a 10-year ASCVD risk 10%, placing them in the high risk cat- egory that requires initiation of antihypertensive drug therapy at BP 130/80 mm Hg (see Section 8.1.2, Figure 4 and Table 23 for BP thresholds for initiating antihypertensive drug treatment). In SPRINT, the par- ticipants with CKD who were randomized to intensive antihypertensive therapy (SBP target <120 mm Hg) ap- peared to derive the same beneficial reduction in CVD events and all-cause mortality that was seen in their counterparts without CKD at baseline. Likewise, in- tensive therapy was beneficial even in those 75 years of age with frailty or the slowest gait speed. There was no difference in the principal kidney outcome ( 50% decline in eGFR or ESRD) between the intensive-and standard-therapy (SBP target <140 mm Hg) groups.S9.3-26 Three other RCTsS9.3-1 S9.3-3 have evaluated the effect Figure 6. Management of hypertension in patients with CKD. Colors correspond to Class of Recommendation in Table 1. *CKD stage 3 or higher or stage 1 or 2 with albuminuria 300 mg/d or 300 mg/g creatinine. ACE indicates angiotensin- converting enzyme; ARB, angiotensin receptor blocker; BP blood pressure; and CKD, chronic kidney disease. Whelton et al 2017 High Blood Pressure Clinical Practice Guideline e53 of differing BP goals of <140/90 mm Hg versus 125 130/75 80 mm Hg on CKD progression in patients with CKD. None of these trials demonstrated a benefit for more intensive BP reduction, although post hoc follow- up analyses favored the lower targets in patients with more severe proteinuria,S9.3-38,S9.3-39 and these trials were underpowered to detect differences in CVD event rates. Recent meta-analyses and systematic reviews that in- cluded patients with CKD from SPRINT support more intensive BP treatmentS9.3-40 S9.3-42 to reduce cardiovas- cular events but do not demonstrate a reduction in the rate of progression of kidney disease (doubling of se- rum creatinine or reaching ESRD). More intensive BP treatment may result in a modest reduction in GFR, which is thought to be primarily due to a hemodynamic effect and may be reversible. Electrolyte abnormali- ties are also more likely during intensive BP treatment. More intensive BP lowering in patients with CKD is also supported by a BP Lowering Treatment Trialists Collaboration meta-analysis of RCTs in patients with 2. Evidence comes from AASK (The African American Study of Kidney Disease and Hypertension), 2 small trials (1 positive, 1 negative), and a meta-analysis.S9.3-3,S9.3-6,S9.3-10,S9.3-11 Albuminuria is quantified by 24-hour urine collection. A 10% to 25% increase in serum creatinine may occur in some patients with CKD as a result of ACE inhibitor therapy. 3. ARBs were shown to be noninferior to ACE inhibitors in clinical trials in the non-CKD population.S9.3-35 to 25% increase in serum creatinine may occur in some patients with CKD as a result of ARB therapy. 9.3.1. Hypertension After Renal Transplantation Recommendations for Treatment of Hypertension After Renal Transplantation References that support recommendations are summarized in Online Data Supplements 39 and 40. COR LOE Recommendations IIa SBP: B-NR 1. After kidney transplantation, it is reasonable to treat patients with hypertension to a BP goal of less than 130/80 mm Hg.S9.3.1-1 DBP: C-EO IIa B-R 2. After kidney transplantation, it is reasonable to treat patients with hypertension with a calcium antagonist on the basis of improved GFR and kidney survival.S9.3.1-2 Synopsis After kidney transplantation, hypertension is common because of preexisting kidney disease, the effects of immunosuppres- sive medications, and the presence of allograft pathology.S9.3.1-3 Transplant recipients frequently harbor multiple CVD risk fac- tors and are at high risk of CVD events. Hypertension may accelerate target organ damage and kidney function decline, particularly when proteinuria is present.S9.3.1-4 S9.3.1-6 Use of calcineurin inhibitor based immunosuppression regimens after transplantation is associated with a high (70% to 90%) prevalence of hypertension.S9.3.1-7 Hypertension is less common when calcineurin inhibitors have been used without corticosteroids in liver transplantation patients,S9.3.1-8 although prevalence rates have not differed in steroid mini- mization trials after kidney transplantation.S9.3.1-9,S9.3.1-10 Reports from long-term belatacept-based immunosuppres- sion studies indicate higher GFR and preservation of kid- ney function. However, hypertension was still present in the majority of patients, although fewer agents were needed to achieve BP goals.S9.3.1-11 Severity of hypertension and inten- sity of treatment may differ somewhat depending on the type of organ transplanted; however, most concepts relevant to kidney transplant recipients will apply to the other solid organ recipients as well. BP targets change over time after transplantation. Initially, it is important to maintain ample organ perfusion with less stringent BP targets (<160/90 mm Hg) to avoid hypoten- sion and risk of graft thrombosis. Beyond the first month, BP should be controlled to prevent target organ damage as in the nontransplantation setting.S9.3.1-12,S9.3.1-13 Hypertension after transplantation is often associated with altered circadian BP rhythm with loss of the normal nocturnal BP fallS9.3.1-14,S9.3.1-15 and, in some, a nocturnal BP rise. These changes may return to normal after a longer period of follow-up.S9.3.1-16 Recommendation-Specific Supportive Text 1. Although treatment targets for hypertension after trans- plantation should probably be similar to those for other patients with CKD, there are no trials in post-transplan- tation patients comparing different BP targets. As kidney transplant recipients generally have a single functioning kidney and CKD, BP targets should be similar to those for the general CKD population. 2. Limited studies have compared drug choice for initial antihypertensive therapy in patients after kidney trans- plantation. On the basis of a Cochrane analysis,S9.3.1-2 most studies favor CCBs to reduce graft loss and main- tain higher GFR, with some evidence suggesting poten- tial harm from ACE inhibitors because of anemia, hyper- kalemia, and lower GFR. In recognition of this concern, RAS inhibitors may be reserved for the subset of patients with hypertension and additional comorbidities that sup- port the need for ACE inhibitor therapy (ie, proteinuria or HF after transplantation). With appropriate potassium and creatinine monitoring, this has been demonstrated to 9.4. Cerebrovascular Disease Stroke is a leading cause of death, disability, and dementia.S9.4-1 Because of its heterogeneous causes and hemodynamic con- sequences, the management of BP in adults with stroke is complex and challenging.S9.4-2 To accommodate the variety of important issues pertaining to BP management in the stroke patient, treatment recommendations require recognition of stroke acuity, stroke type, and therapeutic objectives. Future studies should target more narrowly defined questions, such as optimal BP-reduction timing and target, as well as ideal antihypertensive agent therapeutic class by patient type and event type. 9.4.1. Acute Intracerebral Hemorrhage Recommendations for Management of Hypertension in Patients With Acute Intracerebral Hemorrhage (ICH) References that support recommendations are summarized in Online Data Supplement 41. COR LOE Recommendations IIa C-EO 1. In adults with ICH who present with SBP greater than 220 mm Hg, it is reasonable to use continuous intravenous drug infusion (Table 19) and close BP monitoring to lower SBP. III: Harm A 2. Immediate lowering of SBP (Table 19) to less than 140 mm Hg in adults with spontaneous ICH who present within 6 hours of the acute event and have an SBP between 150 mm Hg and 220 mm Hg is not of benefit to reduce death or severe disability and can be Synopsis Spontaneous, nontraumatic ICH is a significant global cause of morbidity and mortality.S9.4.1-3 Elevated BP is highly prevalent in the setting of acute ICH and is linked to greater hematoma expansion, neurological worsening, and death and dependency after ICH. Figure 7 is an algorithm on management of hypertension in patients with acute ICH. Recommendation-Specific Supportive Text 1. Information about the safety and effectiveness of early intensive BP-lowering treatment is least well established for patients with markedly elevated BP (sustained SBP >220 mm Hg) on presentation, patients with large and severe ICH, or patients requiring surgical decompres- sion. However, given the consistent nature of the data linking high BP with poor clinical outcomesS9.4.1-4 S9.4.1-6 and some suggestive data for treatment in patients with modestly high initial SBP levels,S9.4.1-1,S9.4.1-7 early lowering of SBP in ICH patients with markedly high SBP levels (>220 mm Hg) might be sensible. A second- ary endpoint in 1 RCT and an overview of data from 4 RCTs indicate that intensive BP reduction, versus BP- lowering guideline treatment, is associated with greater functional recovery at 3 months.S9.4.1-1,S9.4.1-7 2. RCT data have suggested that immediate BP lowering (to <140/90 mm Hg) within 6 hours of an acute ICH was feasible and safe,S9.4.1-1,S9.4.1-8,S9.4.1-9 may be linked to greater attenuation of absolute hematoma growth at 24 and might be associated with modestly better functional recovery in survivors.S9.4.1-1,S9.4.1-7 However, a that examined immediate BP lowering within 4.5 hours of an acute ICH found that treatment to achieve a target SBP of 110 to 139 mm Hg did not lead to a lower rate of death or disability than standard reduction to a target of 140 to 179 mm Hg. Moreover, there were significantly more renal adverse events within 7 days af- ter randomization in the intensive-treatment group than in the standard-treatment group.S9.4.1-2 Put together, nei- ther of the 2 key trialsS9.4.1-1,S9.4.1-2 evaluating the effect of lowering SBP in the acute period after spontaneous ICH met their primary outcomes of reducing death and severe disability at 3 months. 9.4.2. Acute Ischemic Stroke Recommendations for Management of Hypertension in Patients With Acute Ischemic Stroke References that support recommendations are summarized in Online Data Supplement 42. COR LOE Recommendations I B-NR 1. Adults with acute ischemic stroke and elevated BP who are eligible for treatment with intravenous tissue plasminogen activator should have their BP slowly lowered to less than 185/110 mm Hg before thrombolytic therapy is initiated.S9.4.2-1,S9.4.2-2 I B-NR 2. In adults with an acute ischemic stroke, BP should be less than 185/110 mm Hg before administration of intravenous tissue plasminogen activator and should be maintained below 180/105 mm Hg for at least the first 24 hours after initiating drug IIa B-NR 3. Starting or restarting antihypertensive therapy during hospitalization in patients with BP greater than 140/90 mm Hg who are neurologically stable is safe and reasonable to improve long-term BP control, unless IIb C-EO 4. In patients with BP of 220/120 mm Hg or higher who did not receive intravenous alteplase or endovascular treatment and have no comorbid conditions requiring acute antihypertensive treatment, the benefit of initiating or reinitiating treatment of hypertension within the first 48 to 72 hours is uncertain. It might be reasonable to lower BP by 15% during the first 24 hours after onset of stroke. Figure 7. Management of hypertension in patients with acute ICH. Colors correspond to Class of Recommendation in Table 1. BP indicates blood pressure; ICH, intracerebral hemorrhage; IV, intravenous; and SBP, systolic blood pressure. Whelton et al 2017 High Blood Pressure Clinical Practice Guideline e55 III: No Benefit A 5. In patients with BP less than 220/120 mm Hg who did not receive intravenous thrombolysis or endovascular treatment and do not have a comorbid condition requiring acute antihypertensive treatment, initiating or reinitiating treatment of hypertension within the first 48 to 72 hours after an acute ischemic stroke is not effective to prevent death or Synopsis Elevated BP is common during acute ischemic stroke (occurring in up to 80% of patients), especially among patients with a history of hypertension.S9.4.2-10 However, BP often decreases spontaneously during the acute phase of ischemic stroke, as soon as 90 minutes after the onset of symptoms. Countervailing theoretical concerns about arterial hypertension during acute ischemic stroke include aiming to enhance cerebral perfusion of the ischemic tissue while minimizing the exacerbation of brain edema and hem- orrhagic transformation of the ischemic tissue.S9.4.2-11,S9.4.2-12 Some studies have shown a U-shaped relationship between the admission BP and favorable clinical outcomes, with an optimal SBP and DBP ranging from 121 to 200 mm Hg and It is conceivable that an optimal arterial BP range exists during acute ischemic stroke on an individual basis, contingent on the ischemic stroke subtype and other patient-specific comorbidities. Early initiation or resumption of antihypertensive treatment after acute ischemic stroke is indicated only in specific situations: 1) patients treated with tissue-type plasminogen and 2) patients with SBP >220 mm Hg or DBP >120 mm Hg. For the latter group, it should be kept in mind that cerebral autoregulation in the ischemic penumbra of the stroke is grossly abnormal and that systemic perfusion pressure is needed for blood flow and oxygen delivery. Rapid reduction of BP, even to lower levels within the hypertensive range, can be detrimental. For all other acute ischemic stroke patients, the advantage of lowering BP early to reduce death and dependency is uncertain,S9.4.2-4 S9.4.2-9 but restarting antihy- pertensive therapy to improve long-term BP control is reason- able after the first 24 hours for patients who have preexisting hypertension and are neurologically stable.S9.4.2-4,S9.4.2-5,S9.4.2-14 Figure 8 is an algorithm on management of hypertension in patients with acute ischemic stroke. Recommendation-Specific Supportive Text 1. These BP cutoffs correspond to study inclusion criteria in pivotal clinical trials of intravenous thrombolysis for acute ischemic stroke.S9.4.2-1 2. In a large observational study of patients with acute ischemic stroke who received intravenous tissue-type plasminogen activator, high BP during the initial 24 hours was linked to greater risk of symptomatic 3. For the goal of antihypertensive therapy, see Section 8.1.5. 4. Extreme arterial hypertension is detrimental because it can lead to encephalopathy, cardiac compromise, and Recommendations for Management of Hypertension in Patients With Acute Ischemic Stroke (Continued) COR LOE Recommendations Figure 8. Management of hypertension in patients with acute ischemic stroke. Colors correspond to Class of Recommendation in Table 1. BP indicates blood pressure; DBP, diastolic blood pressure; IV, intravenous; and SBP, systolic blood pressure. renal damage. However, hypotension, especially when too rapidly achieved, is potentially harmful because it abruptly reduces perfusion to multiple organs, including the brain. as well as systematic re- views and meta-analyses,S9.4.2-6 S9.4.2-8 indicate that antihy- pertensive agents reduce BP during the acute phase of an ischemic stroke but do not confer benefit with regard to short- and long-term dependency and mortality rate. One RCT did not demonstrate a benefit of continuing pre- stroke antihypertensive drugs during the first few days after an acute stroke, but it was substantially underpow- ered to answer the question.S9.4.2-4 9.4.3. Secondary Stroke Prevention Recommendations for Treatment of Hypertension for Secondary Stroke Prevention References that support recommendations are summarized in Online Data Supplements 43 and 44. COR LOE Recommendations I A 1. Adults with previously treated hypertension who experience a stroke or transient ischemic attack (TIA) should be restarted on antihypertensive treatment after the first few days of the index event to reduce the risk of recurrent stroke and other vascular I A 2. For adults who experience a stroke or TIA, treatment with a thiazide diuretic, ACE inhibitor, or ARB, or combination treatment consisting of a thiazide diuretic plus ACE inhibitor, is I B-R 3. Adults not previously treated for hypertension who experience a stroke or TIA and have an established BP of 140/90 mm Hg or higher should be prescribed antihypertensive treatment a few days after the index event to reduce the risk of recurrent stroke and other vascular I B-NR 4. For adults who experience a stroke or TIA, selection of specific drugs should be individualized on the basis of patient comorbidities and agent pharmacological IIb B-R 5. For adults who experience a stroke or TIA, a BP goal of less than 130/80 mm Hg may be IIb B-R 6. For adults with a lacunar stroke, a target SBP goal of less than 130 mm Hg may be IIb C-LD 7. In adults previously untreated for hypertension who experience an ischemic stroke or TIA and have a SBP less than 140 mm Hg and a DBP less than 90 mm Hg, the usefulness of initiating antihypertensive treatment is not well established.S9.4.3-9 Synopsis Each year in the United States, >750000 adult patients experi- ence a stroke, of which up to 25% are recurrent strokes.S9.4.3-10 For an individual who experiences an initial stroke or TIA, the annual risk of a subsequent or secondary stroke is approxi- and the case mortality rate is 41% after a recurrent stroke versus 22% after an initial stroke.S9.4.3-12 Among patients with a recent stroke or TIA, the prevalence of premor- bid hypertension is approximately 70%.S9.4.3-13 Risk of recurrent stroke is heightened by presence of elevated BP, and guideline- recommended antihypertensive drug treatment to lower BP has been linked to a reduction in 1-year recurrent stroke risk.S9.4.3-14 RCT meta-analyses show an approximately 30% decrease in recurrent stroke risk with BP-lowering therapies.S9.4.3-1 S9.4.3-3 An issue frequently raised by clinicians is whether the presence of clinically asymptomatic cerebral infarction incidentally noted on brain imaging (computed tomography or MRI scan) in patients without a history of or symptoms of a stroke or TIA warrants implementation of secondary stroke prevention measures. Clinically asymptomatic vascular brain injury is increasingly being considered as an entry point for secondary stroke preven- tion therapies, because these apparently silent brain infarctions are associated with typical stroke risk factors, accumulatively lead to subtle neurological impairments, and bolster risk of future symptomatic stroke events.S9.4.3-15 Although the evidence for using antihypertensive treatment to prevent recurrent stroke in stroke patients with elevated BP is compelling,S9.4.3-1 S9.4.3-3 questions remain about when precisely after an index stroke to initiate it, what specific agent(s) to use (if any), which therapeu- tic targets to aim for, and whether the treatment approach should vary by index stroke mechanism and baseline level of BP.S9.4.3-16 Figure 9 is an algorithm on management of hypertension in patients with a previous history of stroke (secondary stroke prevention). Recommendation-Specific Supportive Text 1. Two overviews of RCTs published through 2009 showed that antihypertensive medications lowered the risk of recurrent vascular events in patients with stroke or 2. Specific agents that have shown benefit in either dedi- cated RCTs or systematic reviews of RCT data include diuretics, ACE inhibitors, and ARBs. 3. Support for this recommendation is based on data from 2 dedicated RCTs, as well as a systematic review and meta-analysis, among patients with a history of stroke or 4. Reduction in BP appears to be more important than the choice of specific agents used to achieve this goal. Thus, if diuretic and ACE inhibitor or ARB treatment do not achieve BP target, other agents, such as CCB and/or mineralocorticoid receptor antagonist, may be added. 5. An overview of RCTs showed that larger reductions in SBP tended to be associated with greater reduction in risk of recurrent stroke. However, a separate overview of RCTs in patients who experienced a stroke noted that achieving an SBP level <130 mm Hg was not associ- ated with a lower stroke risk, and several observational Whelton et al 2017 High Blood Pressure Clinical Practice Guideline e57 studies did not show benefit with achieved SBP levels 6. Patients with a lacunar stroke treated to an SBP target of <130 mm Hg versus 130 to 140 mm Hg may be less likely to experience a future ICH. 7. No published RCTs have specifically addressed this question, but a post hoc analysis of an RCT suggests that the effectiveness of antihypertensive treatment for sec- ondary stroke prevention diminishes as initial baseline 9.5. Peripheral Artery Disease Recommendation for Treatment of Hypertension in Patients With PAD References that support the recommendation are summarized in Online Data Supplement 45. COR LOE Recommendation I B-NR 1. Adults with hypertension and PAD should be treated similarly to patients with hypertension without PAD.S9.5-1 S9.5-4 Synopsis Patients with PAD are at increased risk of CVD and stroke. Hypertension is a major risk factor for PAD, so these patients are commonly enrolled in trials of antihypertensive drug therapy. However, patients with PAD typically comprise a small fraction of participants, so in the few trials that report results in patients with PAD, subgroup analyses are generally underpowered. Recommendation-Specific Supportive Text 1. There is no major difference in the relative risk re- duction in CVD from BP-lowering therapy between patients with hypertension and PAD and patients There is also no evidence that any one class of antihypertensive medication or strategy In the INVEST (International Verapamil-Trandolapril) study, the beta blocker at- enolol (with or without hydrochlorothiazide) was compared with the CCB verapamil (with or with- out perindopril). The study showed no significant difference in CVD outcomes between the 2 drug regimens in patients with and without PAD.S9.5-3 No trials have reported the effects of a higher ver- sus a lower BP goal in patients with PAD. In the 1 trial (ALLHAT) that reported the effects of different classes of BP medications on PAD as an outcome, there was no significant difference by medication Figure 9. Management of hypertension in patients with a previous history of stroke (secondary stroke prevention). Colors correspond to Class of Recommendation in Table 1. DBP indicates diastolic blood pressure; SBP, systolic blood pressure; and TIA, transient ischemic attack. 9.6. Diabetes Mellitus Recommendations for Treatment of Hypertension in Patients With DM References that support recommendations are summarized in Online Data Supplements 46 and 47 and Systematic Review Report. COR LOE Recommendations I SBP: B-RSR 1. In adults with DM and hypertension, antihypertensive drug treatment should be initiated at a BP of 130/80 mm Hg or higher with a treatment goal of less than 130/80 DBP: C-EO I ASR 2. In adults with DM and hypertension, all first- line classes of antihypertensive agents (ie, diuretics, ACE inhibitors, ARBs, and CCBs) are useful and effective.S9.6-1,S9.6-9,S9.6-10 IIb B-NR 3. In adults with DM and hypertension, ACE inhibitors or ARBs may be considered in the presence of albuminuria.S9.6-11,S9.6-12 SR indicates systematic review. Synopsis 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 system- atic evidence review for additional data and analyses.S9.6-13 The prevalence of hypertension among adults with DM is approxi- mately 80%, and hypertension is at least twice as common in persons with type 2 DM than in age-matched individuals with- The coexistence of hypertension and DM markedly increases the risk of developing CVD damage, result- ing in a higher incidence of CHD, HF, PAD, stroke, and CVD and may increase risk of microvascular disease, such as nephropathy or retinopathy.S9.6-16,S9.6-18 There is limited quality evidence to determine a precise BP target in adults with DM. No RCTs have explicitly 1) docu- mented whether treatment to an SBP goal <140 mm Hg versus a higher goal improves clinical outcomes in adults with hyper- tension and DM or 2) directly evaluated clinical outcomes associated with SBP <130 mm Hg.S9.6-2 However, 2 high-qual- ity systematic reviews of RCTs support an SBP target of <140 There is little or no available RCT evidence supporting a specific DBP threshold for initiation of pharmacological ther- apy. Several RCTs, including the HOT (Hypertension Optimal Treatment) trial, UKPDS (United Kingdom Prospective Diabetes Study), and ABCD (Appropriate Blood Pressure Control in Diabetes) trial,S9.6-19 S9.6-22 are often cited to support a lower DBP target (eg, 85 or 80 mm Hg) for adults with hypertension and DM. However, these trials were conducted when the diagnostic criteria for DM were more conservative than they are currently (2 fasting glucose levels >140 mg/dL as opposed to 126 mm/dL today). Recommendation-Specific Supportive Text 1. We recommend ASCVD risk assessment in all adults with hypertension, including adults with DM. As a matter of convenience, however, it can be assumed that the vast majority of adults with DM have a 10- year ASCVD risk 10%, placing them in the high risk category that requires initiation of antihypertensive drug therapy at BP 130/80 mm Hg (see Section 8.1.2, Figure 4 and Table 23 for BP thresholds for initiating an- tihypertensive drug treatment). The ACCORD trial,S9.6-5 which compared CVD outcomes in adults with DM and hypertension who were randomized to an SBP target of <140 mm Hg (standard therapy) or <120 mm Hg (intensive therapy), did not document a significant re- duction in the primary outcome (CVD composite) with the lower BP goal, but the trial was underpowered to detect a statistically significant difference between the 2 treatment arms. The ACCORD trial demonstrated a small reduction in absolute risk (1.1%) for stroke, but there were few such events. More adverse events (2% increase in absolute risk) were identified in the lower BP group, especially self-reported hypotension and a reduction in estimated GFR, but these did not result in an excess of stroke or ESRD. The ACCORD trial was a factorial study; secondary analysis demonstrat- ed a significant outcome benefit in the intensive BP/ standard glycemic group,S9.6-3 but benefit in the inten- sive BP/intensive glycemic control group was no bet- ter than in the intensive BP/standard glycemic control group, which suggests a floor benefit beyond which the combined intensive interventions were ineffective.S9.6-5 An ACCORD secondary analysis suggested that an SBP <120 mm Hg is superior to standard BP control in A meta-analysis of 73 913 patients with DM reported that an SBP <130 mm Hg reduced stroke by 39%. However, there was no significant risk reduction for MI.S9.6-23 Two meta-analyses addressing target BP in adults with DM restricted the analysis to RCTs that randomized patients to different BP levels.S9.6-4,S9.6-7 Target BP of 133/76 mm Hg provided significant benefit compared with that of 140/81 mm Hg for major cardiovascular events, MI, stroke, albu- minuria, and retinopathy progression.S9.6-4 Several meta- analyses of RCTs included all trials with a difference in but 2 restricted their analyses to trials in which participants were randomized to different BP target SPRINT demonstrated cardiovascular benefit from inten- sive treatment of BP to a goal of <120 mm Hg as compared with <140 mm Hg but did not include patients with DM. However, the results of ACCORD and SPRINT were generally In addition, a SPRINT substudy demonstrated that patients with prediabetes derived a benefit similar to that of patients with normoglycemia.S9.6-8 Previous trials have shown similar quantitative benefits from lowering BP in persons with and without DM.S9.6-9 2. BP control is more difficult to achieve in patients with DM than in those without DM, necessitating use of combination therapy in the majority of patients.S9.6-27 All major antihypertensive drug classes (ie, ACE inhibitors, ARBs, CCBs, and diuretics) are useful in the treatment of hypertension in DM.S9.6-1,S9.6-9 However, in ALLHAT, doxazosin was clearly inferior to chlorthalidone, which Whelton et al 2017 High Blood Pressure Clinical Practice Guideline e59 also reduced some events more than amlodipine or 3. ACE inhibitors and ARBs have the best efficacy among the drug classes on urinary albumin excretionS9.6-12 (see Section 9.3). Therefore, an ACE inhibitor or ARB may be considered as part of the combination. A meta- analysis of RCTs of primary prevention of albumin- uria in patients with DM demonstrated a significant reduction in progression of moderately to severely in- creased albuminuria with the use of ACE inhibitors or 9.7. Metabolic Syndrome Metabolic syndrome is a state of metabolic dysregulation characterized by visceral fat accumulation, insulin resis- tance, hyperinsulinemia, and hyperlipidemia, as well as pre- disposition to type 2 DM, hypertension, and atherosclerotic According to data from the NHANES III and the prevalence of metabolic syndrome in the United States was 34.2% in 2006 and has likely increased substantially since that time. The metabolic syndrome is linked to several other disorders, including non- alcoholic steatohepatitis, polycystic ovary syndrome, certain cancers, CKD, Alzheimer s disease, Cushing s syndrome, lipodystrophy, and hyperalimentation.S9.7-5,S9.7-6 Lifestyle modification, with an emphasis on improv- ing insulin sensitivity by means of dietary modification, weight reduction, and exercise, is the foundation of treat- ment of the metabolic syndrome. The optimal antihyper- tensive drug therapy for patients with hypertension in the setting of the metabolic syndrome has not been clearly Although caution exists with regard to the use of thiazide diuretics in this population because of their abil- ity to increase insulin resistance, dyslipidemia, and hyper- uricemia and to accelerate conversion to overt DM, no data are currently available demonstrating deterioration in car- diovascular or renal outcomes in patients treated with these Indeed, as shown in follow-up of ALLHAT, chlorthalidone use was associated with only a small increase in fasting glucose levels (1.5 4.0 mg/dL), and this increase did not translate into increased CVD risk at a later date.S9.7-7 In addition, in post hoc analysis of the nearly two thirds of participants in ALLHAT that met criteria for the meta- bolic syndrome, chlorthalidone was unsurpassed in reducing CVD and renal outcomes compared with lisinopril, amlo- dipine, or doxazosin.S9.7-9,S9.7-11 Similarly, high-dose ARB therapy reduces arterial stiffness in patients with hyperten- sion with the metabolic syndrome, but no outcomes data are available from patients in which this form of treatment was Use of traditional beta blockers may lead to dys- lipidemia or deterioration of glucose tolerance, and ability to lose weight.S9.7-2 In several large clinical trials, the risk of developing DM as a result of traditional beta-blocker therapy However, the newer vasodilating beta blockers (eg, labetalol, carvedilol, nebivolol) have shown neutral or favorable effects on metabolic profiles compared with the traditional beta blockers.S9.7-13 Trials using vasodila- tor beta blockers have not been performed to demonstrate effects on CVD outcomes. 9.8. Atrial Fibrillation Recommendation for Treatment of Hypertension in Patients With AF References that support the recommendation are summarized in Online Data Supplement 48. COR LOE Recommendation IIa B-R 1. Treatment of hypertension with an ARB can be useful for prevention of recurrence Synopsis AF and hypertension are common and often coexistent con- ditions, both of which increase in frequency with age. AF occurs in 3% to 4% of the population >65 years of age.S9.8-3 Hypertension is present in >80% of patients with AF and is by far the most common comorbid condition, regardless of AF is associated with systemic thromboembolism, as recognized in the CHADS2 and CHA2DS2-VASc scoring systems for stroke risk.S9.8-5 It is also associated with gradual worsening of ventricular function, the subsequent development of HF, and increased mortality. Hypertension has long been recognized as a risk factor for AF because it is associated with LVH, decreased diastolic function with impaired LV filling, rising left atrial pressures with left atrial hypertrophy and enlargement, increased atrial fibrosis, and slowing of intra-atrial and interatrial electrical conduction velocities. Such a distortion of atrial anatomy and physiology increases the incidence of AF.S9.8-6 Left atrial pres- sure also increases with ischemic or valvular heart disease and myopathies that are often associated with systemic hyperten- sion, potentially leading to AF. 