Weak for Reviewed, New-replaced a For additional information, please refer to Grading Recommendations. b For additional information, please refer to Recommendation Categorization and Appendix D. A. Screening, Diagnosis, and Monitoring a. Screening Recommendation 1. We recommend screening adults for elevated blood pressure periodically. (Strong for | Not Reviewed, Amended) Discussion A 2007 review of the evidence for the USPSTF describes the rationale for blood pressure screening.[29] Based on their review, the USPSTF concluded that the benefits of blood pressure screening far outweigh any risks. The risk for cardiovascular events and the potential benefit from screening and subsequent treatment of HTN depend on both the degree and duration of blood pressure elevation and the presence of other cardiovascular risk factors, such as age, gender, lipid disorders, smoking, and diabetes. Because the degree and duration of blood pressure elevation are unknown before screening, selective screening to identify individuals who would benefit most from detection and treatment of HTN would need to target individuals with other cardiovascular risk factors. The 2015 update from the USPSTF concluded that, given the strong evidence base for the previous recommendations, the indirect evidence path for HTN screening did not need updating.[30] For patients who are screened, estimates of the potential benefit of treatment can be improved both by carefully measuring the degree of blood pressure elevation and by assessing the contribution of other risk factors to global cardiovascular risk.[31-33] Since increasing age is related to greater incidence of HTN, and because lifetime risk of developing HTN is so high (reaching approximately 90% for octogenarians), it is sensible to screen periodically.[34] Multiple separate guidelines make recommendations for rescreening intervals, but none are evidence based. Although not included in the systematic evidence review conducted as part of this guideline update, and thus not considered in determining the strength of recommendation, a 2015 SR by the USPSTF identified 40 studies addressing rescreening interval and hypertensive incidence in screened normotensive persons (defined as blood pressure <140/90 mm Hg using office blood pressure measurements).[35] There were highly variable estimates of incident HTN ranging from 2.2-4.4% at one- year interval and 2.1-28.4% at five-year intervals. This confirms the recommendation that there is value to screening normotensive adults, but the evidence remains unclear as to what the optimal interval should be. As this is a Not Reviewed, Amended recommendation, the Work Group did not systematically review evidence related to this recommendation. Based on the assessment of the quality of the evidence put forth in the 2014 VA/DoD HTN CPG,[29,31-34] the Work Group s confidence in the quality of the evidence is moderate. The body of evidence had some limitations including different treatment goals/targets and confounders in the analysis. Other considerations regarding this recommendation included the benefits, including improved outcomes in cardiovascular events and mortality, outweighing the potential harm of adverse events (e.g., false positive screening, missed diagnosis), which was small. Patient values and preferences were similar, as blood pressure screening is a routine part of almost all outpatient medical care. Thus, the Work Group decided that a Strong for recommendation was warranted. More research is needed on the best screening method for HTN as well as the best interval between screenings in both the general population and those at-risk for HTN. b. Measurement Techniques Recommendation 2. We suggest using attended or unattended, fully automated office blood pressure measurement (programmed to wait five minutes and record the average of three measurements separated by at least 30 seconds). (Weak for | Reviewed, New-added) 3. When fully automated blood pressure measurement is not available, we suggest measurement of blood pressure using standard technique and a properly calibrated and validated sphygmomanometer. (Weak for | Reviewed, New-replaced) Discussion The diagnosis and management of HTN has been based primarily on measurement of blood pressure in a medical clinic or office. Office measurements were used by most observational studies and all randomized controlled trials (RCTs) defining both the risk of various blood pressure levels and the goal blood pressures that have reduced cardiovascular outcomes or mortality. To obtain the values most representative of the patient s office blood pressure, evidence supports that at least two readings be taken on each of two occasions, at least one day apart. Blood pressure was measured by standard technique in all critical studies that have been used to develop recommendations for both the blood pressure levels at which to begin drug treatment as well as the blood pressure goals of treatment. Therefore, in order to make appropriate decisions in clinical practice, blood pressure should be measured with a properly calibrated and validated sphygmomanometer and with a standard technique similar to what has been used in studies.[36] Older studies used manual blood pressure determinations, such as with a mercury sphygmomanometer, while more recent studies have used fully automated oscillometric sphygmomanometers. A fully automated oscillometric manometer can be set to wait a specified rest time and take an average of several blood pressure readings with one activation. A semi-automated oscillometric device takes a single reading without a rest period after activation. SRs and meta-analyses have reported that blood pressure readings were similar when comparing fully automated oscillometric sphygmomanometer with daytime average ambulatory blood pressure readings, but routine office readings without standard technique averaged 7.0 to 14.5 mm Hg higher than fully automated readings.[37,38] In one SR, SBP readings using research quality manual or oscillometric technique averaged 7 mm Hg higher than fully automated oscillometric technique; however, in the one study included in the SR in which the order was randomized, there was very little difference between these two techniques, suggesting the others may have been biased by regression to the mean.[38] In addition, another SR/meta-analysis concluded that, when fully automated oscillometric readings were obtained, there was not a significant difference in blood pressure levels when an observer was in the room (attended) or the patient was alone in the room (unattended).[39] As a good summary of standard measurement technique used in research studies, the 2019 AHA recommendations for blood pressure measurement include the following key steps about proper seated blood pressure measurement in the office (adapted).[36] Table 2. Key Steps for Proper Blood Pressure Measurements Key Steps Specific Instructions Step 1: Properly prepare the patient 1. Have the patient relax, sitting in a chair with feet flat on floor and back supported. The patient should be seated for 3-5 min without talking or moving around before recording the first blood pressure reading. 2. The patient should avoid caffeine, exercise, and smoking for at least 30 min before measurement. 3. Ensure that the patient has emptied his/her bladder. 4. Neither the patient nor the observer should talk during the rest period or during the measurement. 5. Remove clothing covering the location of cuff placement. 6. Measurements made while the patient is sitting on an examining table do not fulfill these criteria. Step 2: Use proper technique for blood pressure measurements 1. Use an upper-arm cuff blood pressure measurement device that has been validated and ensure that the device is calibrated periodically. 2. Support the patient s arm (e.g., resting on a desk) at heart level; the patient should not be holding his/her arm because isometric exercise will affect the blood pressure levels. 3. Position the middle of the cuff on the patient s upper arm at the level of the right atrium (midpoint of the sternum). 4. Use the correct cuff size such that the bladder encircles 75%-100% of the arm. 5. Use either the stethoscope diaphragm or bell for auscultatory readings. Step 3: Take the proper measurements needed for diagnosis and treatment of elevated blood pressure/HTN 1. At the first visit, record blood pressure in both arms. Use the arm that gives the higher reading for subsequent readings (if consistently 10-15 mm Hg higher). 2. Separate repeated measurements by at least 30 seconds. 3. For auscultatory determinations, use a palpated estimate of radial pulse obliteration pressure to estimate SBP. Inflate the cuff 20-30 mm Hg above this level for an auscultatory determination of the blood pressure level. Step 4: Properly document accurate blood pressure readings 1. Record SBP and DBP; if using the auscultatory technique, record SBP and DBP as the onset of the first of at least 2 consecutive beats and the last audible sound, respectively. 2. If using the auscultatory technique, record SBP and DBP to the nearest even number; if oscillometric, record reading displayed (or average displayed). 3. Note the time that the most recent blood pressure medication was taken before measurements. Step 5: Average the readings Use an average of 2 readings obtained on 2 occasions to estimate the patient s blood pressure. If fully automated oscillometric technique, manometer should display average of 2-3 readings. Step 6: Provide blood pressure readings to patient Provide the patient with his or her SBP/DBP readings both verbally and in writing. Assist the patient interpret the results. Abbreviations: DBP: diastolic blood pressure; HTN: hypertension; SBP: systolic blood pressure The 2019 AHA guidelines on measurement of blood pressure also provide a table of proper blood pressure cuff sizes.[36] Miscuffing can provide erroneous values. Table 3. Proper Blood Pressure Cuff Sizes Cuff Size Arm Circumference (cm) Bladder Dimension (width x length, cm) Abbreviation: cm: centimeter Although SRs and meta-analyses have reported the mean differences (MD) in intra-arterial compared with cuff blood pressure measurements and arm compared with leg blood pressure measurements, whenever possible, decisions concerning diagnosis and management of HTN should be made with brachial cuff determinations.[40,41] Previous evidence suggested that automated blood pressure monitors are accurate for SBP but not DBP measurement in the presence of atrial fibrillation. A recent SR and meta-analysis provided additional support by concluding that, although some monitors have been shown to be accurate with atrial fibrillation, there is considerable heterogeneity between devices, particularly for DBP measurement; accuracy for devices untested in atrial fibrillation cannot be assumed.[42] Although standard blood pressure measurement technique in the office is critical to making correct decisions about the diagnosis and management of HTN, there is widespread failure to use proper technique in clinical practice settings.[43] The reasons for this include lack of knowledge of proper technique, lack of appreciation of the importance of many aspects of proper technique, and resistance to change, especially taking the extra time needed for quiet during the rest and measurement periods. There also may be resistance to incorporating fully automated blood pressure technique in practice, since it requires time not speaking with the patient and allowing for rest and several measurements (approximately seven to eight minutes on average when accounting for five minutes of rest and time to take measurements). The main concern is the time required for busy clinic staff to incorporate this technique. However, using automated office blood pressure (AOBP) allows staff to attend to other patients or tasks during this time. In the patient focus group carried out as part of this guideline update, patients described the following (see Appendix B): 1. Patients noted that when their blood pressure was measured by machine in the office setting, they experienced pain and uncomfortable pressure. 2. Some of the patients noted that their blood pressure had to be taken twice when in the office setting, as the first reading was rarely accurate. 3. Patients felt the office blood pressure readings were inaccurate; they trusted the devices they use at home more. 4. There were noticeable differences between blood pressure readings when it was taken manually versus with a machine. The Work Group believed these perspectives from patients generally support use of fully automated oscillometric manometers in clinical practice. Although there is some expense to fully automated oscillometric manometers and concern over pain of measurements, the Work Group believed these issues were minor compared with the benefits of reducing observer error and providing more accurate blood pressure data. As Recommendations 2 and 3 are Reviewed, New-added and Reviewed, New-replaced recommendations, respectively, the Work Group systematically reviewed evidence related to these recommendations in the evidence review conducted as part of this guideline update.[37-42] The Work Group s confidence in the quality of the evidence is very low; however, standard blood pressure measurement technique was used in all major observational studies and RCTs which provide evidence for risk of blood pressure levels and goal blood pressure levels shown to reduce cardiovascular outcomes with treatment. Two SRs showed that fully automated blood pressure measurement accuracy is closer to daytime ambulatory blood pressure measurement accuracy but that research quality (i.e., standard ) measurement could also be acceptable.[37,38] Another SR showed that fully automated readings were similar whether staff were present in the room (attended) or the patient was left alone during the rest and measurements (unattended).[39] Other considerations regarding this recommendation included the benefits of accurate blood pressure data outweighing the potential harm of any adverse events or inconvenience, which was small. Patient values and preferences were somewhat varied. Thus, the Work Group decided upon a Weak for for these recommendations. Recommendation 4. We suggest using out-of-office blood pressure monitoring methods (ambulatory 24-hour monitoring or home blood pressure measurements) to inform the diagnosis and management of hypertension. (Weak for |Reviewed, New-replaced) Discussion Out-of-office blood pressure monitoring methods comprise: (a) 24-hour and daytime/awake ambulatory blood pressure monitoring (ABPM) and (b) home blood pressure monitoring (HBPM). The 2014 VA/DoD HTN CPG included recommendations on ABPM and HBPM to assist in the diagnosis of HTN prior to initiation of drug therapy. The current recommendation is based on very low quality evidence from the 2014 VA/DoD HTN CPG literature review,[44-48] which found that ABPM and HBPM are better predictors of cardiovascular events compared with routine (not AOBP) office blood pressure measurements. However, ABPM and HBPM were not used as entry criteria or as treatment goals in cardiovascular outcome clinical trials. Moreover, with accumulating evidence that AOBP may be equivalent to ABPM and HBPM (see Recommendation 2 and the evidence in the next paragraph), the role of ABPM and HBPM may no longer be as important in confirming the diagnosis of HTN using out-of-office blood pressure measurements as was thought to be the case in 2014. Furthermore, because no studies comparing ABPM versus HBPM on clinical outcomes were identified in the present systematic evidence review, two separate recommendations on ABPM and HBPM from the 2014 VA/DoD HTN CPG were combined into a single Weak for recommendation. Evidence from two SRs demonstrated that fully automated office blood pressure measurements were similar to SBP and DBP obtained with day-time/awake ABPM and HBPM. Pappaccogli et al. (2019) showed no significant difference for both SBP (-1.85 mm Hg) and DBP (0.12 mm Hg) in the pooled analysis of 16 studies comparing AOBP with daytime ABPM.[37] The same SR compared AOBP and HPBM using pooled data from seven studies and also found no statistically significant difference in SBP and DBP between the two methods. Similar findings from 19 studies were reported in another SR by Roerecke et al. (2019), which demonstrated a non-significant pooled mean difference in SBP of 0.3 mm Hg (95% CI -1.1 to 1.7 mm Hg) between AOBP and awake ABPM in patients who had an office SBP >130 mm Hg.[38] The Work Group did not find any evidence comparing the predictive value of AOBP versus out-of-office blood pressure on clinical outcomes. Another key reason for the recommendation to preferentially use ABPM and HBPM in the 2014 VA/DoD HTN CPG was the ability of out-of-office blood pressure to assist in the identification of white coat and masked HTN in untreated individuals, as well as uncontrolled white coat and uncontrolled masked HTN in patients receiving antihypertensive medications. The 2014 VA/DoD HTN CPG, 2015 USPSTF,[20] and 2017 AHA/ACC [4] guidelines all recommended ruling out white coat HTN in individuals with newly diagnosed elevated office blood pressure to avoid unnecessary initiation of drug therapy. Since the evidence review and HTN outcome trials in general did not identify or exclude patients with white coat HTN as distinct from other forms of HTN, it is possible that white coat HTN is not a totally benign condition. Accordingly, it is unknown whether patients with white coat HTN benefit or do not benefit from treatment. Therefore, the Work Group concluded there was very low quality evidence supporting the utility of out-of-office blood pressure measurements in confirming diagnosis of HTN prior to the initiation of drug therapy. Nevertheless, ABPM and HBPM are valuable methods in identifying masked HTN, which is diagnosed with elevated out-of-office blood pressure in the setting of normal or controlled office blood pressure. Masked HTN should be suspected in individuals with normal or controlled office blood pressure if they report higher home blood pressure values, in the presence of target organ damage and certain chronic conditions, such as CKD. We did not find any evidence of harm associated with ABPM and HBPM; however, patient training is required for both methods, and there could be some differences in patient preferences due to increased burden of out-of-office blood pressure monitoring. Overall, the equipment used for HBPM is more readily available than for ABPM. Some patients may not be willing to wear a 24-hour ABPM on multiple occasions. As this is a Reviewed, New-replaced recommendation, the Work Group systematically reviewed evidence related to this recommendation in the evidence review conducted as part of this guideline update [37,38] as well as the evidence from the 2014 VA/DoD HTN CPG.[44-48] The Work Group s confidence in the quality of the evidence is very low. The body of evidence had some limitations, such as observational study design, small sample sizes, selection and attrition bias in individual studies, and a lack of consistent reporting of blood pressure measurement methods. New considerations regarding this recommendation included evidence that AOBP provides similar blood pressure values as day-time ambulatory and home blood pressure, and that there are no outcome trials that have used out-of-office blood pressures as either entry criteria or as treatment goals. While we did not identify head-to-head comparison studies between HBPM and ABPM, both approaches seem to be of similar value for making a decision in patients in whom the diagnosis or control of HTN remains uncertain (e.g., when AOBP is not available, when there is significant discrepancy between self-monitored home blood pressure and office blood pressure, and if masked HTN is suspected). HBPM is more readily available than ABPM and requires fewer resources; however, careful patient education on proper blood pressure measurement technique and the frequency and use of validated HBPM are recommended. More research is needed to evaluate the effectiveness of using out-of-office blood pressure to manage HTN and whether treating to ABPM or HBPM guided blood pressure goals would improve cardiovascular morbidity and mortality in hypertensive individuals. c. Monitoring Recommendation 5. Among patients treated for hypertension, we suggest offering home blood pressure self- monitoring with co-interventions for lowering systolic and diastolic blood pressure. (Weak for | Reviewed, New-added) Discussion When compared with usual care, home blood pressure self-monitoring has been shown to improve SBP and DBP control when paired with a co-intervention. Our evidence review found two SRs of RCTs comparing blood pressure self-monitoring or HBPM with usual care.[49,50] One SR of 29 RCTs showed improved blood pressure control compared to usual care (adjusted MD in SBP 2.7 mm Hg).[49] Another SR and meta-analysis comparing blood pressure self-monitoring alone to usual care found that self- monitoring was not associated with lower blood pressure. However, when paired with co-interventions (including tailored medication titration and education or lifestyle counseling) blood pressure self- monitoring was associated with a lower blood pressure (MD in SBP -6.1 mm Hg).[50] Three additional RCTs had results consistent with the SRs, finding self-monitoring more effective than usual care when accompanied by a co-intervention involving medication titration in response to self- monitoring data.[51-53] Studies in which medication adherence was examined revealed no difference in medication adherence between self-monitoring of blood pressure and usual care. Despite general consistency in the evidence supporting home blood pressure monitoring and self- monitoring and ease of implementation, there is some variability in provider and patient preferences regarding this treatment. There was some question among the Work Group members whether a 2-4 mm Hg reduction in blood pressure was clinically significant. Some patient focus group participants expressed a desire for additional education on the use of home blood pressure management and additional interventions that they could institute on their own. However, some patients may not want the extra burden of monitoring their own blood pressure at home. Other considerations include the added cost of a home blood pressure monitor if not provided by the institution, patients in whom HBPM is not feasible, and the additional time patients would have to devote to the co-intervention. An informational video for patients on how to use a home blood pressure monitor is available on the VA/DoD Clinical Practice 10 Home blood pressure monitoring video is available on the VA/DoD Clinical Practice Guidelines page at https://www.healthquality.va.gov/guidelines/cd/htn/index.asp; or directly at https://www.youtube.com/watch?v=IHY5MJc4Z_M&feature=youtu.be. As this is a Reviewed, New-added recommendation, the Work Group systematically reviewed evidence related to this recommendation in the evidence review conducted as part of this guideline update.[49-53] The Work Group s confidence in the quality of the evidence is very low due to the subjective outcome assessment, incomplete outcome data, selective reporting, lack of blinding, and recruitment bias. The body of evidence had some limitations including confounders in the analysis.[49-51,53] Other considerations regarding this recommendation included the benefits of improved blood pressure and increased participation in care, which outweigh the potential harms (none identified). Patient values and preferences were somewhat varied. Thus, the Work Group decided upon a Weak for recommendation. More research is needed on the specific co-intervention paired with HBPM to identify the most effective intervention. B. Treatment Goals and General Approaches to Hypertension Management a. Blood Pressure Goals Recommendation 6. For all patients, including those with type 2 diabetes, we suggest treating to a systolic blood pressure goal of <130 mm Hg. (Weak for | Reviewed, New-added) Discussion Pharmacologic treatment of HTN has been demonstrated to decrease the risk of major adverse cardiovascular events (MACE) such as CHD, stroke, heart failure, and overall mortality in patients with HTN, including patients with both HTN and diabetes.[54] Treatment of SBP to a goal of less than 130 mm Hg may lead to a reduction in cardiovascular events when compared to higher thresholds. The SR and meta-analysis by Ettehad et al. (2016) provides evidence in support of this recommendation.[54] This review included 78 RCTs comparing HTN treatment to placebo and 14 RCTs comparing intensive HTN treatment to standard treatment. The effect of a 10 mm Hg reduction on the relative risk of major cardiovascular events was estimated as a function of different baseline SBPs. Across a broad range of initial SBPs starting at greater than 130 mm Hg, a 10 mm Hg lowering in SBP was associated with improvements in the composite cardiovascular outcome. For people with diabetes, the SR and meta-analysis by Ettehad et al. (2016) showed pharmacologic treatment of HTN was associated with a 12% relative risk reduction for major adverse cardiovascular events (MACE) per 10 mm Hg reduction in SBP.[54] While this relative reduction in MACE is less than that observed in the non-diabetic population, the difference in impact between the diabetic and the non-diabetic population is neither statistically nor clinically significant. However, SRs limited to studies comparing a standard SBP threshold to a more intensive blood pressure threshold in HTN patients have arrived at contradicting conclusions, likely based on differences in inclusion criteria. The SR by Saiz et al. (2018) found no benefit of targeting an SBP threshold of 130 mm Hg when compared to a higher SBP threshold of 150 mm Hg.[55] This mirrors the findings from the SR by Weiss et al. (2017) that looks at studies targeting a lower threshold.[56] In contrast, the SR by Reboussin et al. (2018) found significant reductions in the risk of major cardiovascular events associated with an SBP target of less than 130 mm Hg.[57] The largest individual study to date examining SBP targets, the Systolic Blood Pressure Intervention Trial (SPRINT), included HTN patients age 50 and over and demonstrated a 25% reduction in cardiovascular events in the intensive treatment group targeting an SBP of 120 mm Hg.[58] Only a small proportion of SPRINT participants (those with known CVD) would have been included in the SR by Saiz et al. (2018),[55] which could perhaps explain why Saiz et al. (2018) did not find benefits for reducing SBP below 150 mm Hg. Specifically for HTN patients with diabetes, the SR and meta-analysis by Brunstrom et al. (2017) suggests that benefit of treatment in patients with diabetes may be limited to those with a baseline SBP of >140 mm Hg or to an achieved SBP of 130-140 mm Hg.[59] Overall, the available evidence was primarily for patients with type 2 diabetes with very limited evidence for those with type 1 diabetes. As shown by the SR by Ettehad et al. (2016), the proportional reduction in the rates of cardiovascular outcomes resulting from a 10 mm Hg reduction in blood pressure did not differ among people with prior cardiovascular disease (CVD) events, coronary heart disease (CHD), CHF, or cerebrovascular disease.[54] Two other SRs specifically examined the risk of stroke recurrence among patients receiving more intensive HTN therapy.[60,61] These SRs also suggested a reduction in stroke recurrence based on additional HTN therapy. For many patients, benefits of intensive therapy seem to outweigh harms.[58,62] Yet, targeting an SBP goal of <130 does not mean that it must always be achieved; if older or particularly frail people develop side effects while titrating therapy to achieve this lower threshold, they may wish to have medications tapered back or changed. The patient focus group revealed that some patients do not want to take medications for treatment of HTN. This may limit the ability to achieve lower targets of SBP with intensive treatment, as this often requires multiple medications and may require frequent visits. Despite the conflicting evidence supporting an SBP goal of 130 mm Hg or less, the results from the SR by Ettehad et al. (2016) do demonstrate benefit in lowering SBP for those between 130 and 150 mm Hg.[54] Thus, there is strong evidence from one SR suggesting that lowering SBP by 10 mm Hg among people with an SBP above 130 mm Hg reduces the risk of cardiovascular events.[54] However, there are inconsistencies among other studies comparing a standard threshold with more intensive therapy. The evidence reviewed included very few adults under the age of 60, which, based on the GRADE methodology, resulted in a weaker recommendation. More intensive therapy often requires additional medications, which require further resources and which some people might prefer not to take. These results are in contrast to stronger evidence for the older population of age 60 who have hypertension, with or without diabetes (see Recommendation 7 and Recommendation 8). The research supporting the goal of SBP <130 mm Hg in the general HTN population, with or without diabetes, is less robust than higher thresholds, which, according to our methodology, resulted in a weaker recommendation for this SBP goal. As this is a Reviewed, New-added recommendation, the Work Group systematically reviewed evidence related to this recommendation to treat hypertensive adults, including those with type 2 diabetes, to an SBP goal of less than 130 mm Hg. [54-57,59-61] The Work Group s confidence in the quality of the evidence is moderate. For people with an SBP above 130 mm Hg, a further 10 mm Hg reduction in SBP was associated with improved cardiovascular outcomes. There is some inconsistency in the data, as SRs that only compared a standard threshold to a more intensive threshold reached contradictory conclusions. However, there were different inclusion criteria and methods across the SRs. The benefit of improved cardiovascular outcomes outweighs the potential harm of AEs; however, patients may or may not be accepting of HTN medication therapy.[63] Some patients are concerned over AEs of medication and may indicate that they want to avoid or limit use of medications, when possible. Patients, however, may be more likely to accept medications with SDM and careful titration. Based on the above, the Work Group decided upon a Weak for recommendation. Additional RCTs would be needed to definitively recommend an SBP target of less than 130 mm Hg. Given the results of SPRINT, such a large clinical trial is unlikely to be performed in the U.S. in a general (lower risk) hypertensive population. Ongoing clinical trials from other countries that mirror the SPRINT protocol, or conducted among hypertensive patients excluded from or not robustly represented in SPRINT, could provide additional evidence. In hypertension patients with diabetes, additional data from RCTs may be available in the next few years as two large trials, Blood Pressure Control Target in Diabetes (BPROAD) and Intervention for High-normal or Borderline-elevated Blood Pressure in Adults with Type 2 Diabetes (IPAD) are currently enrolling in China. These trials should provide further evidence for the benefit of specific SBP thresholds and goals in patients with diabetes. Recommendation 7. For patients 60 years and over, we recommend treating to a systolic blood pressure goal of <150 mm Hg with added benefit to lowering systolic blood pressure further for those between 130 mm Hg and 150 mm Hg. (Strong for | Reviewed, Amended) Discussion Among people age 60 and over with moderate to severe HTN, there is evidence that treating to an SBP goal of 150 mm Hg or less reduces cardiovascular morbidity and mortality. This strong recommendation is based on evidence from RCTs that compared a more intensive HTN strategy with placebo or a standard or less intensive strategy. The SR by Weiss et al. (2017) considered adults age 60 and over from 21 RCTs, nine of which specifically included individuals with an SBP of 160 mm Hg or higher.[56] Improved cardiovascular outcomes were seen among those given more intensive therapy targeting an SBP less than 150 mm Hg. Among people 60 years and over, there was also evidence of further benefit in lowering systolic blood pressure to levels between 130 and 150 mm Hg.[56] The SR by Ettehad et al. (2016) included 78 studies comparing HTN treatment to placebo and 14 studies comparing intensive HTN therapy to standard treatment. Across a broad range of initial baseline SBPs greater than 130 mm Hg, a 10 mm Hg lowering in SBP was associated with improvements in the composite cardiovascular outcome.[54] Thus, there is likely benefit to further reductions of SBP for those patients with a baseline SBP between 130 and 150 mm Hg. The SR by Ettehad et al. (2016) demonstrated benefit from a 10 mm Hg reduction in SBP but did not evaluate a specific target or threshold.[54] Different SRs have come to different conclusions in recommending a specific target for SBP less than 150 mm Hg with conclusions that are highly sensitive to inclusion criteria of studies in the SRs. The SR by Saiz et al. (2018) considered six RCTs in hypertensive patients with a history of CVD (MI, angina, stroke, and/or peripheral vascular occlusive disease), targeting a blood pressure less than or equal to 135/85 mm Hg when compared to standard therapy and found no benefit for the more intensive approach.[55] This mirrors the findings from the SR by Weiss et al. (2017) that looked at studies targeting a lower threshold.[56] In contrast, the SR by Reboussin et al. (2018) found significant reductions in the risk of major cardiovascular events associated with an SBP target of less than 130 mm Hg.[57] The largest individual study to date examining SBP targets, the Systolic Blood Pressure Intervention Trial (SPRINT), included HTN patients age 50 and over and demonstrated a 25% reduction in cardiovascular events in the intensive treatment group targeting an SBP of 120 mm Hg.[58] Only a small proportion of SPRINT participants (those with known CVD) would have been included in the SR by Saiz et al. (2018),[55] which could perhaps explain why Saiz et al. (2018) did not find benefits for reducing SBP below 150 mm Hg. Treating to a lower SBP goal of <130 mm Hg for older adults is also supported by evidence, but the research support this lower goal is weaker than the evidence for treating to a SBP goal of <150 mm Hg in patients 60 years and older. Thus, the current recommendation is specific to HTN in patients age 60 and over, which is supported by the large number of clinical trials that mostly included older people. Based on the SR by Weiss et al. (2017), there is strong and consistent evidence supporting lowering SBP to a target of 150 mm Hg.[56] Benefits clearly outweigh harms and burdens associated with this therapy. There is less consistency in the evidence supporting additional blood pressure reductions for patients with an SBP between 130 and 150 mm Hg. This more intensive or aggressive approach often requires additional medications which, in turn, require further resources and which some people might not prefer. Benefits of intensive therapy seem to outweigh harms.[58,62] Attempts at lowering systolic blood pressure further for those between 130 mm Hg and 150 mm Hg in order to achieve lower threshold goals is not always feasible; if older or particularly frail people develop side effects while titrating therapy to achieve lower blood pressures, they may wish to have medications tapered back or changed. As this is a Reviewed, Amended recommendation, the Work Group systematically reviewed evidence identified in the evidence review conducted as part of this guideline update.[54-58] For people with an SBP between 130 and 150 mm Hg, there is high confidence in the quality of evidence that additional reductions in blood pressure are beneficial. This is supported by the SR by Ettehad et al. (2016) which found that a 10 mm Hg reduction in SBP was associated with improved cardiovascular outcomes [54] and by the findings of the SR by Reboussin et al. (2018).[57] There is some inconsistency in the data, as not all SRs support further lowering of SBP across all patient groups. The benefit of improved cardiovascular outcomes outweighs the potential harm of adverse events, and patients are generally accepting of HTN therapy. Some patients, though, are concerned about the AEs of medication and may indicate that they want to avoid or limit use of medications, when possible. Recommendation 8. For patients 60 years and over with type 2 diabetes, we recommend treating to a systolic blood pressure goal of <140 mm Hg with added benefit to lowering systolic blood pressure further for those between 130 mm Hg and 140 mm Hg. (Strong for | Reviewed, Amended) Discussion As previously stated, pharmacologic treatment of HTN has been demonstrated to decrease the risk of major adverse cardiovascular events (MACE) such as CHD, stroke, heart failure, and overall mortality in patients with HTN, including patients with both HTN and diabetes.[54] Based on the SR and meta-analysis by Ettehad et al. (2016), pharmacologic treatment of HTN is associated with a 12% relative risk reduction for MACE in patients with diabetes per 10 mm Hg reduction in SBP.[54] This review demonstrated broad reduction in MACE regardless of baseline blood pressure down to an SBP of <130 mm Hg. Brunstr m et al. (2017) performed an SR of SRs with the purpose of determining the optimal blood pressure level and choice of antihypertensive agent in people with diabetes.[59] This study included 11 SRs (three SRs stratified according to baseline SBP, four SRs stratified by attained SBP, and eight SRs addressed choice of antihypertensive agent) and did not report the duration of follow-up for included studies. In these reviews, the mean age for patients was around 60 years. Evidence from Brunstr m et al. (2017) favored intensive blood pressure lowering in a general diabetic population when baseline SBP was >140 mm Hg. Achieving an SBP in the range of 130 to 140 mm Hg was associated with reduced CV events. A lower target of <130 mm Hg or treatment when the baseline SBP was <140 mm Hg was not, however, associated with statistically significantly improved cardiovascular outcomes or mortality. This led to conclusions that achieving an SBP in the range of 130-140 mm Hg is associated with reduced cardiovascular events. There was some evidence for a reduced risk of stroke when patients were treated with antihypertensive therapy when the baseline SBP was <140 mm Hg, though benefits on other cardiovascular outcomes were not seen. Furthermore, there was a non-significant trend towards increased cardiovascular mortality in this group.[59] The SR performed by Ettehad el al. (2016) [54] focused on the general population with HTN but did have a subgroup analysis for patients with diabetes, which provided evidence for the recommendation suggesting treating to the lower target SBP of <130 mm Hg for patients with type 2 diabetes. This is in contrast to the SR by Brunstr m et al. (2017) [59] which provides strong evidence for the older population with type 2 diabetes, including patients with a history of CVD, for a target SBP of 130- 140 mm Hg. The 2014 VA/DoD HTN CPG recommended treatment to an SBP of <150 mm Hg in patients 60 years and over with type 2 diabetes, primarily based on the results of general HTN studies which had sub- populations with diabetes [64,65] and the HTN arm of the UK Prospective Diabetes Study Group.[66] In the 2014 VA/DoD HTN CPG, there was an additional suggestion to treat to an SBP of <140 mm Hg for those patients who tolerate pharmacologic antihypertensive treatment based on evidence from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) and Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) trials;[67,68] however, this evidence was only moderate, which led to the Weak for recommendation in 2014. The SR by Brunstr m et al. (2017) strengthened the evidence providing support for the amended Strong for recommendation to treat to target SBP of <140 mm Hg and to consider additional blood pressure lowering when the SBP is between The patient focus group revealed that some patients do not want to take medications for treatment of HTN. This may limit the ability to achieve target SBP. As this is a Reviewed, Amended recommendation, the Work Group systematically reviewed evidence related to this recommendation identified in the evidence review conducted as part of this guideline update,[54,59] as well as considered evidence from the 2014 VA/DoD HTN CPG.[64-68] The Work Group determined the confidence in the quality of the evidence was high in support of intensive treatment of HTN in a general population of patients with diabetes. The benefits of treatment clearly outweigh the harms, though we do note that there is variance in acceptance of intensive treatment from providers and patients and many patients may not be willing to take multiple medications to achieve target SBP levels. The evidence included in the SR conducted as part of this guideline update is primarily from patients with diabetes type 2 who are already on pharmacologic antihypertensive treatment. These patients typically are middle-aged or elderly (but under the age of 80 years). There is little evidence for pharmacologic treatment to a target SBP in patients with type 1 diabetes, adults under the age of 50, or the very old (over 80 years). Future research on any of these subgroups may provide additional evidence regarding appropriate blood pressure goals. Recommendation 9. For patients 30 years and over, we recommend treating to a diastolic blood pressure goal of <90 mm Hg. (Strong for | Reviewed, Amended) Discussion This recommendation is supported by strong clinical trial evidence demonstrating the benefits of treating HTN to a DBP goal of less than 90 mm Hg and was carried forward from the 2014 VA/DoD HTN CPG. Landmark studies, such as the Veterans Administration Cooperative Study Group on Antihypertensive Agents, the Hypertension Detection and Follow-up Program (HDFP), and the Medical Research Council (MRC) trial of treatment of mild HTN, all demonstrated substantial benefits in terms of reduced cardiovascular events by treating to a target DBP of less than 90 mm Hg.[69-73] Eligibility for these studies differed slightly, but all included patients 30 years of age or older. Based on the SR and meta-analysis by Saiz et al. (2018), lower target DBP goals showed no treatment benefit in mortality or cardiovascular This recommendation may or may not apply to patients aged 18 to 29 as clinical trials did not include patients younger than 30. However, it is unlikely that clinical trials will address HTN treatment and optimal DBP targets in younger adults given the low prevalence of primary HTN in younger adults. The Work Group believes that younger adults with elevated DBP may also benefit from treatment. The patient focus group revealed that some patients are resistant to taking medications, and lower targets generally require more medications and more clinical follow-up. Therefore, patients should find this recommendation acceptable. However, providers may note this recommendation differs from other recent HTN guidelines; therefore, our guidance may be confusing. The Work Group feels it is important to highlight for providers that there are no new RCTs providing evidence to lower the DBP target to less than 90 mm Hg (e.g., 80 mm Hg), and recommendations for a lower DBP target in other HTN guidelines are based on expert opinion. Both of these should give providers reassurance in this recommendation when considering treatment. The Work Group, however, did not believe it likely that there would be harm for DBPs treated to lower levels, especially when treating SBP to the appropriate goal.[74] As this is a Reviewed, Amended recommendation, the Work Group systematically reviewed evidence related to this recommendation in the evidence review conducted as part of this guideline update,[55] as well as considered evidence from the 2014 VA/DoD HTN CPG.[69-73] The Work Group s confidence in the quality of the evidence is moderate. Other considerations regarding this recommendation included the lack of data in patients under 30 years, thus the specified age range. Patient values and preferences should be compatible with keeping the higher DBP target. Thus, the Work Group decided upon a Strong for recommendation. b. General Approaches to Hypertension Management Recommendation 10. We recommend offering pharmacist-led medication management as an option for patients with hypertension. (Strong for | Reviewed, New-replaced) Discussion Pharmacist-led interventions have been effective in improving critical outcomes in hypertensive patients. Interventions which have been evaluated include medication initiation, titration and monitoring, blood pressure measurement, reminder systems, patient education regarding both medications and long-term consequences of HTN, and physician feedback. Two SRs with large effect sizes provided much of the basis for this recommendation.[75,76] In the SR of seven RCTs by Greer et al. (2016), pharmacist-led care significantly increased the proportion of patients achieving goal blood pressure of 140/90 mm Hg versus usual care over a median period of 39 weeks (risk ratio 1.45, 95% CI 1.24-1.70). Care was provided by the pharmacist either in person, remotely, or a combination of the two, and some of the included studies granted prescriptive authority.[75] The SR by Santschi et al. (2014) included 39 RCTs and compared pharmacist-led care to usual or collaborative care in over 14,000 patients with HTN. Compared with usual care, pharmacist-led interventions resulted in significantly greater improvements in both SBP (-8.5 mm Hg) and DBP (-4.6 mm Hg) over the mean follow-up period of eight months.[76] Four additional RCTs in the evidence base also evaluated blood pressure reduction via various pharmacist interventions and practice sites.[77-80] The study by Victor et al. (2019) reported a marked reduction in blood pressure when pharmacists provided care in barbershops catering to African American men. Significant and sustained reductions in mean SBP of approximately 20 mm Hg and mean DBP approaching 19 mm Hg were seen after 12 months in over 300 hypertensive patients versus control.[80] The lack of blinding is a limitation to this study. The study by Cheema et al. (2018), using community pharmacists who provided education and lifestyle and adherence advice, reported significant differences versus baseline for reductions in both SBP and DBP.[78] Interventions are not required to be face-to-face to show benefit. The SR by Santschi et al. (2014) included a trial of home blood pressure telemonitoring and pharmacist management intervention in which the interventions stopped after 12 months.[76] In the long-term follow-up of this study, benefits were seen beyond the 12 month intervention period, as Margolis et al. (2018) found that there were significantly greater reductions in SBP in the intervention group than in the usual care group at 6, 12, and 18 months (reductions of 10.7, 9.7, and 6.6 mm Hg, respectively). However, the results were not significant when evaluated at 53 months.[79] In contrast, no differences in blood pressure were noted in a small study that compared pharmacists with an education control.[77] However, results may have been influenced by study limitations related to low patient enrollment. Statistically significant improvements in both medication adherence and medication use with pharmacist-led interventions were reported in the SR by Greer et al. (2016).[75] The barbershop study by Victor et al. (2018) showed an increase in the number of blood pressure medications per participant.[80] Improved adherence in favor of a pharmacist-led intervention was shown in one study conducted in Pakistan in which the intervention involved education.[81] There was also some evidence of improved medication use (in terms of either the numbers of antihypertensive medications used or adherence) in the referenced studies. The Work Group determined that, in addition to providing education, there was a significant role for pharmacists in actively titrating antihypertensive drugs and managing AEs. This conclusion was based on findings from two SRs of RCTs in which pharmacists performed these higher level interventions.[75,76] Ensuring pharmacists are appropriately qualified to provide these services is also important. The study conducted by Cheema et al. (2018) utilized community pharmacists.[78] However, in both the VA and DoD, this recommendation is intended for pharmacists in the clinic setting, and not dispensing pharmacists. Some variation was noted in patient values and preferences. The patient focus group did not discuss pharmacist-led interventions; however, in the evidence base, patients enjoyed the flexibility and ease of access to pharmacists and appreciated the improved access to care.[75,80] The benefits of pharmacist- led care outweighed the harms due to the low number of adverse events reported with the interventions in the barbershop trial.[80] The SR by Greer et al. (2016) had only limited information regarding patient satisfaction or drug-related problems.[75] This strong recommendation will have implications for resource use, as utilization of pharmacist-led interventions for the treatment of HTN could have significant system implications. As this is a Reviewed, New-replaced recommendation, the Work Group systematically reviewed evidence related to blood pressure management using pharmacist-led care either through in-person interactions, via telehealth, or a combination of the two, and that specifically discussed studies related to pharmacist- led interventions.[75-81] The evidence reviewed included two SRs and five RCTs. The confidence in the quality of evidence was moderate. The recommendation focuses on clinical pharmacists, in contrast to the recommendation in the 2014 VA/DoD HTN CPG, which grouped nurses, pharmacists, and social workers together and centered on adherence in addition to blood pressure control. Although there were variations in the quality of the evidence for the five RCTs, the moderate quality SRs by Greer et al. (2016) and Santschi et al. (2014) with the large effect sizes and the evidence for improved adherence led to the overall confidence in the quality of evidence to be assessed as moderate. Other factors considered by the Work Group for this recommendation included the improved outcomes of blood pressure reduction and blood pressure goal attainment, which outweighed the small risk of adverse events. There was some variation in patient values and preferences. Overall, the strength of the evidence and substantial effect sizes within the two SRs contributed to the Strong for recommendation.[75,76] Recommendation 11. We suggest offering nurse-led interventions as an option for patients treated for hypertension. (Weak for | Reviewed, New-replaced) Discussion Nurse-led interventions for the management of HTN encompass a wide variety of treatment approaches including cardiovascular risk assessment, education, counseling on lifestyle modification, goal setting, action planning, and the initiation and titration of antihypertensive medications using established protocols. When compared with usual care, nurse-led interventions have been found to reduce SBP and DBP, improve adherence to medication therapy, and improve quality of life metrics in patients with HTN.[82-88] All studies reviewed by the Work Group contained multiple components of nurse-led intervention, some paired with other co-interventions. Our evidence review found one SR, by Parappilly et al. (2018), that compared nurse-led interventions to usual care.[88] It was based on 16 RCTS and enrolled a total of 3,568 participants diagnosed with a previous stroke or transient ischemic attack. The researchers observed no statistically significant difference in SBP and DBP changes between nurse-led interventions and usual care. However, the authors indicated that one RCT was found to be an outlier. After removing this study from the meta-analysis, the models demonstrated a statistically significant effect on reducing SBP and DBP in favor of nurse-led interventions when compared to usual care. The authors reported a mean difference in SBP reduction of 2.84 mm Hg and a MD in DBP reduction of 2 mm Hg, favoring nurse-led intervention. All studies included in the SR contained multiple nurse-led components including education, lifestyle changes, providing feedback, appointment scheduling, and medication review and compliance.[88] The Work Group identified two additional RCTs that had results consistent with the SR by Parappilly et al. (2018) (i.e., favoring the nurse- led intervention group).[82,84] One found a reduction in DBP similar to the SR by Parappilly et al. (2018) (i.e., favoring the nurse-led intervention).[82] Three additional RCTs reported more frequent hypertension control or achieving a blood pressure goal of <140/90 mm Hg in the nurse-led intervention group when compared to the usual care control group.[83,85,87] No significant harms were found with nurse-led interventions in studies that reported on the outcome. Medication adherence is a critical component in chronic disease management for HTN. The SR by Parappilly et al. (2018) reported a statistically significant difference between nurse-led intervention and usual care in the change in medication adherence at follow-up.[88] Our evidence review found one RCT reporting a statistically significant difference in medication adherence in favor of nurse-led intervention.[87] Another RCT, by Zhu et al. (2018), found no statistically significant difference between nurse-led intervention and usual care in the change in medication adherence at follow-up.[82] Two additional RCTs found no statistically significant difference between nurse-led intervention and usual care when coupled with co-interventions such as electronic health record (EHR) tools and mobile health technologies.[83,85] These two RCTs had small sample sizes and may have been underpowered to detect the true intervention effect. Two RCTs found a statistically significant change in quality of life metrics favoring the nurse-led intervention group versus usual care.[82,87] However, a third RCT, by Persell et al. (2018), found no quality of life impact when using EHR tools alone or EHR tools plus nurse-led education with usual care or when interventions were compared with one another.[83] Despite general consistency in the evidence supporting the notion that nurse-led interventions inform the management of HTN, there is some variability in provider and patient preferences. The patient focus group revealed that some patients did not feel that their providers offered the full range of management strategies available and prioritized pharmacologic interventions. This highlights an opportunity to utilize nurse-led interventions for lifestyle modification. Additionally, the patient focus group found that patients would like to be offered verbal education as well as educational materials, such as pamphlets. Some patients reported that they did not receive information on the sequelae of high blood pressure and that their providers did not consider individual patient characteristics that could impact their high blood pressure and management strategies. A common theme highlighted in the patient focus group was the desire for ongoing communication and education from providers to patients. This is a potential area in which nurse-led intervention can fill current gaps in care. In general, nurse-led intervention is well received by patients and most providers. Patients often appreciate nurse-led intervention due to increased accessibility to care and time efficiency. As this is a Reviewed, New-replaced recommendation, the Work Group systematically reviewed evidence related to this recommendation identified in the evidence review conducted as part of this guideline update.[82-88] The Work Group s confidence in the quality of the evidence is very low for all included studies due to the lack of objectivity of outcome assessment, incomplete outcome data, selective reporting, small sample size, lack of blinding, and recruitment bias. The body of evidence had some limitations including confounders in the analysis.[82-88] Other considerations regarding this recommendation included the benefits of improved blood pressure and medication adherence outweighing the potential harms (none identified). Patient values and preferences were somewhat varied. Thus, the Work Group decided upon a Weak for recommendation. More research is needed to evaluate the effectiveness of nurse-led intervention to manage HTN in specific subgroups (e.g., age, ethnicity, comorbidities). Additionally, more research is needed to evaluate the effectiveness of nurse-led intervention, such as evaluating initiation and titration of antihypertensive medications using established protocols. Recommendation 12. We suggest offering registered dietitian-led nutrition interventions as an option for patients with hypertension who are or are not on medication. (Weak for | Reviewed, New-replaced) Discussion Registered dietitian-led nutrition interventions, such as education about low sodium diets, weight loss, and increasing consumption of fresh fruits and vegetables, have been found to result in modest but statistically significant lowering of SBP and DBP in treated and untreated hypertensive individuals.[89] The current recommendation is based on low quality evidence from an SR by Reigel et al. (2018), which included 4,491 patients across 13 studies, in which nutrition-based interventions resulted in lower SBP (MD -2.82 mm Hg) and lower DBP (MD -1.37 mm Hg), as compared with the usual care.[89] However, when studies were grouped based on whether the nutrition intervention was delivered by a registered dietitian versus other practitioners, significant reductions in SBP (MD -3.5 mm Hg) and DBP (MD -1.37 mm Hg) were only seen in the registered dietitian-led nutrition intervention group. In addition, blood pressure reductions were more pronounced with interventions longer than six months. No significant harms were found with nutrition interventions. Focus group participants highlighted that patients and caregivers strongly valued dietary interventions to lower blood pressure. Although not systematically reviewed in this guideline update, it is generally accepted that comprehensive dietitian-led intervention can positively impact other aspects of cardiovascular health, such as blood lipid and glucose levels, weight loss, and alcohol cessation. However, there may be barriers in obtaining healthy food choices for some patients. Service Members frequently do not get a choice regarding where they are going, what they are doing, or where they will eat in a deployed/training environment. Food sources may vary (e.g., Meals Ready to Eat (MREs), items received in care packages, training area or forward operating base (FOB)/central operating base (COB) dining facilities). Depending on what area of responsibility the Service Member is deployed to/training in, these rations may be high in sodium and fat. These nutritional factors may impact HTN management and necessitate counseling related to diet. As this is a Reviewed, New-replaced recommendation, the Work Group systematically reviewed the relevant evidence identified in the evidence review conducted as part of this guideline update.[89] The Work Group s confidence in the quality of the evidence is low. The body of evidence showed overall modest effect size, although statistically significant, and had some limitations including small size, inadequate allocation concealment and blinding, and inclusion of dietary approach as a part of multidisciplinary intervention in some individual studies. Other considerations regarding this recommendation included patients preferences. The potential benefit of nutritional intervention to improve global cardiovascular health outweighs potential adverse events and burden, which were not found. Thus, the Work Group decided upon a Weak for recommendation. More research is needed to evaluate intensity and duration of dietitian-led interventions to improve blood pressure control and effectiveness of registered dietitian-led nutritional intervention to manage HTN in specific subgroups (e.g., different ages, ethnicities). Recommendation 13. We suggest technology-based interventions (e.g., e-counseling, electronic transmission of data, telemonitoring, mobile applications) for improving control of hypertension. (Weak for | Reviewed, New-replaced) Discussion Several key words are defined to better understand this recommendation and its impact. Telehealth refers to data communicated between the patient and provider in ways other than face-to-face interactions. This is accomplished through a variety of methods to include use of computers, mobile devices, or mobile applications. In contrast, telemonitoring is the use of information and communication technologies to monitor and transmit items related to patient health status between geographically separated individuals, which permits home monitoring of patients to include nursing or residential care homes using external electronic devices. Methods may include e-counseling, real-time consults, electronic transmission of data and interventions, mobile interventions, and/or interactive digital interventions. Additionally, mHealth is defined as mobile health. The World Health Organization defines it as the use of mobile applications and wireless technology to support the achievement of health goals.[90] In the development of this recommendation, the Work Group considered whether concurrent treatment impacted outcomes. The Work Group considered whether the intervention of interest was provided instead of, or in addition to, usual care (in-person visits). Some of the possible interventions may include mobile applications, telehealth monitoring, telehealth visits with primary care or a subspecialty. The impact of the intervention of interest and any concurrent treatment on the following outcomes was considered: reduction in blood pressure, change in blood pressure from baseline, achievement of lower blood pressure goals and adherence to therapy, and percentage of patients taking medication. In examining instead of or in addition to usual care (in-person visits) , two RCTs, Liu et al. (2018) [91] and Nolan et al. (2018),[92] compared an e-counseling intervention with usual care or control. Liu et al. observed a not statistically significant difference in SBP change between user-driven e-counseling and control, while a statistically significant change was noted with expert-driven e-counseling.[91] Nolan et al. (2018) reported a not statistically significant difference between e-counseling plus usual care for SBP and DBP at four months.[92] Two SRs compared mobile applications or mobile health technology with usual care or control. Alessa et al. (2018) indicated that applications had either a positive or statistically significant positive effect on SBP and DBP as compared to usual care or control.[93] Four of the 12 RCTS in Xiong et al. (2018) reported a statistically significant change in either SBP or DBP in favor of mHealth interventions as compared to usual care.[94] Marquez Contreras et al. (2018) reported a statistically significant difference in SBP change in favor of the mobile application as compared to usual care.[95] Twelve of 21 RCTs in Xiong et al. 2018) reported a significant improvement in medication adherence in the intervention group compared to controls.[94] In looking at telehealth monitoring, one SR by McLean et al. (2016) included seven RCTs comparing interactive digital interventions with usual care. McLean et al. (2016) observed statistically significant changes in SBP and DBP in favor of interactive digital interventions compared to usual care.[96] This recommendation looked at a variety of topics that include web-based interventions and telemonitoring. Two SRs [97,98] and two RCTs [99,100] compared telehealth visits with usual care or control. Chen et al. (2019) and Beishuizen et al. (2016) reported statistically significant differences in favor of web-based interventions for changes in SBP and DBP.