NATIONAL CLINICAL PRACTICE GUIDELINES Adult Hypertension Clinical Practice Guidelines Reviewed/Approved by the National Guideline Directors: November 2016 Next Review/Approval: November 2018 Developed by the National Hypertension Guideline Development Team Disclaimer This guideline is informational only. It is not intended or designed as a substitute for the reasonable exercise of independent clinical judgment by practitioners, considering each patient s needs on an individual basis. Guideline recommendations apply to populations of patients. Clinical judgment is necessary to design treatment plans for individual patients.
Table of Contents Table of Contents... 2 Adult Hypertension Clinical Practice Guidelines... 3 Purpose... 3 Background... 3 Methods... 3 Recommendations... 4 Topic: Screening and Diagnosis of High Blood Pressure... 4 Topic: Treatment Initiation and Blood Pressure Targets... 4 Appendix A: National Hypertension Guideline Development Team... 6 Appendix B1: Crosswalk of KP Recommendations... 7 Topic: Screening and Diagnosis of High Blood Pressure... 7 Topic: Treatment Initiation and Blood Pressure Targets... 7 Appendix B2: Crosswalk of Recommendation Ratings... 11 Appendix C: Rationale for KP-Modified Recommendation... 14 Topic: Diastolic Blood Pressure Targets... 14 Topic: Systolic Blood Pressure Targets... 15 Topic: Hypertension Treatment in Patients with CKD... 16 Topic: Blood Pressure Targets in the Diabetic Population 60 years... 17 Appendix D: Systematic Review... 18 Topic: Screening and Diagnosis of High Blood Pressure... 18 AGREE II Summary... 18 Key Questions... 18 Inclusion/Exclusion Criteria... 18 USPSTF Analytic Framework... 19 Topic: Treatment Initiation and Blood Pressure Targets... 19 AGREE II Summary... 19 Key Questions... 19 Inclusion/Exclusion Criteria... 19 References... 21 2
Adult Hypertension Clinical Practice Guidelines Purpose This guideline was developed by the KP National Hypertension Guideline Development Team (GDT) (Appendix A) to assist primary care physicians and other health care professionals in the outpatient treatment of hypertension in non-pregnant adults aged 18 and older. Background This guideline is an interim update of the 2016 KP National Clinical Practice Guideline for Hypertension. Recommendations are based on the 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults Report from the Panel Members Appointed to the Eighth Joint National Committee (JNC 8) 1 and the 2015 United States Preventive Services Task Force (USPSTF) recommendations for Screening for High Blood Pressure. 2 Major changes in this interim update are: The addition of the USPSTF 2015 recommendations for screening and diagnosis of high blood pressure. Methods KP National Guideline Program follows a methodology 3 that incorporates well-established scientific frameworks to critically appraise evidence and evaluate external guidelines. In developing these recommendations, the GDT considered the 2014 KP recommendations and the 2015 USPSTF recommendations. The GDT s decisions and justification are outlined in Appendix B1. Recommendations are accompanied by language that clinicians should use to weigh the strength of the recommendation against the individual patient situation. The KP National Guideline methodology, updated most recently in 2016, streamlines ratings to strong, weak, or no recommendation (i.e., when evidence is reviewed but is inadequate to drive a recommendation for or against an intervention). The current KP guidelines evolved from multiple rating systems. Appendix B2 provides a crosswalk to compare language between current KP guidelines, JNC8, and the USPSTF. The GDTs develop guideline recommendations using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria, which considers the balance between desirable and undesirable effects, quality of evidence, patient values and preferences, and resource use. When the GDT changes a previous KP guideline, adapts an external guideline with some modifications, or reviews new evidence to inform its recommendation, the GRADE framework provides transparency into those decisions. Appendix C summarizes GDT deliberations from the GRADE process. KP recommendations that were unchanged and external guidelines that were adopted verbatim are not subject to GRADE assessment. Additional evidence review work that was completed to inform the development of these recommendations can be found in Appendix D. This includes an assessment of the quality of the JNC8 recommendations and the 2015 USPSTF recommendations for KP adoption using the AGREE II 4 tool. 3
Recommendations Topic: Screening and Diagnosis of High Blood Pressure Screen all adults aged 18 for hypertension. (Strong Recommendation) o For adults aged 18-39 years with normal blood pressure (< 130/85 mm Hg) without other risk factors, screen every 3 to 5 years. o For adults aged 40 years and those at increased risk of high blood pressure, screen annually. Persons at increased risk include those who have high-normal blood pressure (130-139 / 85-89 mm Hg), who are overweight or obese, and African Americans. Obtain measurements outside of the clinical setting for diagnostic confirmation before starting treatment. (Strong Recommendation) Topic: Treatment Initiation and Blood Pressure Targets In the general population aged 60 years, initiate pharmacologic treatment to lower blood pressure (BP) at systolic blood pressure (SBP) 150mm Hg or diastolic blood pressure (DBP) 90 mm Hg and treat to a goal SBP < 150 mm Hg and goal DBP < 90 mm Hg. (Strong Recommendation) In the general population aged 60 years, consider not adjusting treatment if pharmacologic treatment for high BP results in lower achieved SBP (e.g.,< 140mmHg) and treatment is well tolerated and without adverse effects on health or quality of life. (Weak Recommendation) In the general population < 60 years, initiate pharmacologic treatment to lower BP at DBP 90mmHg and treat to a goal DBP < 90mmHg. (Strong Recommendation) This is an adapted recommendation. In the general population < 60 years, initiate pharmacologic treatment to lower BP at SBP 140mmHg and treat to a goal SBP < 140mmHg. (Strong recommendation) This is an adapted recommendation. In the population aged 60 years with chronic kidney disease (CKD), consider initiating pharmacologic treatment at SBP 140mmHg or DBP 90 mmhg and treat to goal SBP < 140mmHg and goal DBP < 90mmHg. (Weak Recommendation)** This is an adapted recommendation. **When weighing the risks and benefits of a lower BP goal for people aged 70 years with estimated GFR < 60 ml/min/ 1.73m2, antihypertensive treatment should be individualized, taking into consideration factors such as frailty, comorbidities, albuminuria, and estimation of non-agerelated egfr decline (e.g.,, egfr + (age/2) < 85). In the population aged 60 years with diabetes, initiate pharmacologic treatment to lower BP at SBP 140mmHg or DBP 90mmHg and treat to a goal SBP < 140mmHg and goal DBP < 90mmHg. (Strong Recommendation) This is an adapted recommendation. 4
In the general non-african American population, including those with diabetes, consider initiating antihypertensive treatment to include a thiazide-type diuretic, calcium channel blocker (CCB), angiotensin-converting enzyme inhibitor (ACEI), or angiotensin receptor blocker (ARB). (Weak Recommendation) In the general African American population, including those with diabetes, consider initiating initial antihypertensive treatment to include a thiazide-type diuretic or CCB. (Weak Recommendation) In the population aged 18 years with CKD, consider initial (or add-on) antihypertensive treatment that includes an ACEI or ARB to improve kidney outcomes. This applies to all CKD patients with hypertension regardless of race or diabetes status. (Weak Recommendation) The main objective of hypertension treatment is to attain and maintain goal BP. If goal BP is not reached within a month of treatment, consider increasing the dose of the initial drug or add a second drug from one of the thiazide-type diuretic, CCB, ACEI, or ARB classes. The clinician should consider continued assessment of BP and adjust the treatment regimen until goal BP is reached. If goal BP cannot be reached with 2 drugs, consider adding and titrating a third drug from the indicated classes. Consider avoiding combined use of an ACEI and an ARB. If goal BP cannot be reached using only the drugs in these classes because of contraindications or the need for more than 3 drugs to reach goal BP, antihypertensive drugs from other classes can be considered. Consider referral to a hypertension specialist for patients in whom goal BP cannot be attained using the above strategy or for the management of complicated patients for whom additional clinical consultation is needed. (Weak Recommendation) The complete guideline and supplemental document from the report from the JNC 8 can be accessed below: The report from the Panel Members Appointed to the Eighth Joint National Committee (JNC 8) James PA, Oparil S, Carter BL, et al. 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults: Report From the Panel Members Appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014; 311(5):507-520. Supplemental Document for the report from the Panel Members Appointed to the Eighth Joint National Committee (JNC 8) Appendix to the JNC 8 Guideline The complete list of recommendations from the USPSTF can be accessed below: High Blood Pressure in Adults: Screening Siu AL. Screening for high blood pressure in adults: U.S. Preventive Services Task Force recommendation statement. Ann. Intern. Med. 2015;163(10):778-786. 5
Appendix A: National Hypertension Guideline Development Team Lead Team Joseph Young, MD, Clinical Lead, Internal Medicine, KP Northern California Marc Jaffe, MD, Integrated Cardiovascular Health Clinical Lead, Endocrinology, KP Northern California Richard A. Mularski, MD, MSHS, MCR, FCCP, Methodologist, Pulmonary and Critical Care, KP Northwest Helen W. Wu, PhD, Senior Manager, CMI Evidence Services Qiana R. Amos, MPH, Sr. Consultant, CMI Evidence Services Guideline Development Team Debbi Baker, Sr. Mgr., Clinical Pharmacy Services, KP Georgia Gary Besinque, PharmD, Pharmacy, Southern California Neil Blair, MD, Internal Medicine, KP Northwest Jeffrey Brettler, MD, Internal Medicine, KP Southern California Anna Cosyleon, MD, Internal Medicine, KP Colorado John Golden MD, Cardiology, KP Mid-Atlantic States Steven Hong, MD, Cardiology, KP Hawaii Ali Rahimi, MD, Cardiology, KP Georgia Stephanie Schneider, Prevention Specialist, KP Colorado Sheila Stadler, PharmD, Pharmacy, KP Colorado Elham Syed, MD, Internal Medicine, KP Georgia Ross Takara, Sr. Director, Pharmacy, KP Hawaii Christopher Thomas, MD, Nephrology, KP Northwest Kory Vanderschaaf, PharmD, Pharmacy, KP Colorado With Additional Input from: Alain Flores, MD, Family Medicine, Northern California Lo-An Nguyen, MD, Internal Medicine, Mid-Atlantic States Click here for more information on the Kaiser Permanente National Guideline Program Process and Methodology for Systematic Development of Clinical Practice Recommendations 6
Appendix B1: Crosswalk of KP Recommendations 2016 KP Recommendation Source Recommendation(s) and 2014 KP Recommendations * KP GDT Decision Justification Topic: Screening and Diagnosis of High Blood Pressure In adults aged 18 years, screen for high blood pressure. Obtain measurements outside of the clinical setting for diagnostic confirmation before starting treatment. (Strong Recommendation) The USPSTF recommends screening for high blood pressure in adults aged 18 years. The USPSTF recommends obtaining measurements outside of the clinical setting for diagnostic confirmation before starting treatment. (Grade A) Adopt 2015 USPSTF as is Approved by GDT with no additional changes needed. See evidence review (App. D). Topic: Treatment Initiation and Blood Pressure Targets In the general population aged 60 years, initiate pharmacologic treatment to lower blood pressure (BP) at systolic blood pressure (SBP) 150mm Hg or diastolic blood pressure (DBP) 90 mm Hg and treat to a goal SBP < 150 mm Hg and goal DBP < 90 mm Hg. (Strong Recommendation) The KP 2014 guideline recommends: In the general population aged 60 years, initiate pharmacologic treatment to lower blood pressure (BP) at systolic blood pressure (SBP) 150mm Hg or diastolic blood pressure (DBP) 90 mm Hg and treat to a goal SBP < 150 mm Hg and goal DBP < 90 mm Hg. (Strong Recommendation) No changes from 2014 KP guideline Approved by GDT with no additional changes needed. In the general population aged 60 years, consider not adjusting treatment if pharmacologic treatment for high BP results in lower achieved SBP (e.g., < 140 mm Hg) and treatment is well tolerated and without adverse effects on health or quality of life. (Weak Recommendation) The KP 2014 guideline recommends: In the general population aged 60 years, if pharmacologic treatment for high BP results in lower achieved SBP (e.g., < 140 mm Hg) and treatment is well tolerated and without adverse effects on health or quality of life, treatment does not need to be adjusted. (Expert Opinion Grade E) No changes from 2014 KP guideline Approved by GDT with no additional changes needed. * Various recommendation rating and evidence grading systems are used; see Appendix B2 for a crosswalk with KP recommendation ratings. 7
2016 KP Recommendation Source Recommendation(s) and 2014 KP Recommendations * KP GDT Decision Justification In the general population < 60 years, initiate pharmacologic treatment to lower BP at DBP 90mmHg and treat to a goal DBP < 90mmHg. (Strong Recommendation) The KP 2014 guideline recommends: In the general population < 60 years, initiate pharmacologic treatment to lower BP at DBP 90mmHg and treat to a goal DBP < 90mmHg. (For ages 30-59 years, Strong Recommendation Grade A; For ages 18-29 years, Expert Opinion Grade E) Adapted with minor changes See GRADE assessment (App. C) and evidence review (App. D) In the general population < 60 years, initiate pharmacologic treatment to lower BP at SBP 140mmHg and treat to a goal SBP < 140mmHg. (Strong recommendation) The KP 2014 guideline recommends: In the general population <60 years, initiate pharmacologic treatment to lower BP at SBP 140 mm Hg and treat to a goal SBP <140 mm Hg. (Expert Opinion Grade E) Adapted with minor changes See GRADE assessment (App. C) and evidence review (App. D) In the population aged 60 years with chronic kidney disease (CKD), consider initiating pharmacologic treatment at SBP 140mmHg or DBP 90 mmhg and treat to goal SBP <140mmHg and goal DBP <90mmHg. (Weak Recommendation).** **When weighing the risks and benefits of a lower BP goal for people aged 70 years with estimated GFR < 60 ml/min/ 1.73m 2, antihypertensive treatment should be individualized, taking into consideration factors such as frailty, comorbidities, albuminuria, and estimation of nonage related egfr decline (for example egfr + (age/2) < 85). The KP 2014 guideline recommends: In the population aged 18 years with chronic kidney disease (CKD), initiate pharmacologic treatment to lower BP at SBP 140mmHg or DBP 90mmHg and treat to goal SBP < 140mmHg and goal DBP < 90mmHg. (Expert Opinion Grade E) Adapted with minor changes See GRADE assessment (App. C) and evidence review (App. D) In the population aged 60 years with diabetes, initiate pharmacologic treatment to lower BP at SBP 140mmHg or DBP 90mmHg and treat to a goal SBP <140mmHg and goal DBP <90mmHg. (Strong Recommendation) The KP 2014 guideline recommends: In the population aged 18 years with diabetes, initiate pharmacologic treatment to lower BP at SBP 140mmHg or DBP 90mmHg and treat to a goal SBP <140 mm Hg and goal DBP <90 mm Hg. (Expert Opinion Grade E) Adapted with minor changes See GRADE assessment (App. C) and evidence review (App. D) 8
2016 KP Recommendation Source Recommendation(s) and 2014 KP Recommendations * KP GDT Decision Justification In the general non-african American population, including those with diabetes, consider initiating antihypertensive treatment to include a thiazide-type diuretic, calcium channel blocker (CCB), angiotensin-converting enzyme inhibitor (ACEI), or angiotensin receptor blocker (ARB). (Weak Recommendation) The KP 2014 guideline recommends: In the general nonblack population, including those with diabetes, initial antihypertensive treatment should include a thiazide-type diuretic, calcium channel blocker (CCB), angiotensinconverting enzyme inhibitor (ACEI), or angiotensin receptor blocker (ARB). (Moderate Recommendation Grade B) No changes from 2014 KP guideline Approved by GDT with no additional changes needed. In the general African American population, including those with diabetes, consider initiating initial antihypertensive treatment to include a thiazide-type diuretic or CCB. (Weak Recommendation) The KP 2014 guideline recommends: In the general black population, including those with diabetes, initial antihypertensive treatment should include a thiazide-type diuretic or CCB. (For general black population: Moderate Recommendation Grade B; for black patients with diabetes: Weak Recommendation Grade C) No changes from 2014 KP guideline Approved by GDT with no additional changes needed. In the population aged 18 years with CKD, consider initial (or add-on) antihypertensive treatment that includes an ACEI or ARB to improve kidney outcomes. This applies to all CKD patients with hypertension regardless of race or diabetes status. (Weak Recommendation) The KP 2014 guideline recommends: In the population aged 18 years with CKD, initial (or add-on) antihypertensive treatment should include an ACEI or ARB to improve kidney outcomes. This applies to all CKD patients with hypertension regardless of race or diabetes status. (Moderate Recommendation Grade B) No changes from 2014 KP guideline Approved by GDT with no additional changes needed. The main objective of hypertension treatment is to attain and maintain goal BP. If goal BP is not reached within a month of treatment, consider increasing the dose of the initial drug or add a second drug from one of the thiazidetype diuretic, CCB, ACEI, or ARB classes. The clinician The KP 2014 guideline recommends: The main objective of hypertension treatment is to attain and maintain goal BP. If goal BP is not reached within a month of treatment, increase the dose of the initial drug or add a second drug from one of the classes in recommendation6 (thiazide-type No changes from 2014 KP guideline Approved by GDT with no additional changes needed. 9
2016 KP Recommendation Source Recommendation(s) and 2014 KP Recommendations * KP GDT Decision Justification should consider continued assessment of BP and adjust the treatment regimen until goal BP is reached. If goal BP cannot be reached with 2 drugs, consider adding and titrating a third drug from the indicated classes. Consider avoiding combined use of an ACEI and an ARB. If goal BP cannot be reached using only the drugs in these classes because of contraindications or the need for more than 3 drugs to reach goal BP, antihypertensive drugs from other classes can be considered. Consider referral to a hypertension specialist for patients in whom goal BP cannot be attained using the above strategy or for the management of complicated patients for whom additional clinical consultation is needed. (Weak Recommendation) diuretic, CCB, ACEI, or ARB). The clinician should continue to assess BP and adjust the treatment regimen until goal BP is reached. If goal BP cannot be reached with 2 drugs, add and titrate a third drug from the list provided. Do not use an ACEI and an ARB together in the same patient. If goal BP cannot be reached using only the drugs in recommendation 6 because of a contraindication or the need to use more than 3 drugs to reach goal BP, antihypertensive drugs from other classes can be used. Referral to a hypertension specialist may be indicated for patients in whom goal BP cannot be attained using the above strategy or for the management of complicated patients for whom additional clinical consultation is needed. (Expert Opinion Grade E) 10
Appendix B2: Crosswalk of Recommendation Ratings JNC 8 1 Grading System USPSTF 2 Grading System Kaiser Permanente 3 Grading System Grade Strength of recommendation Grade Strength of recommendation Grade Intended action Strong Recommendation (Grade A) There is high certainty based on evidence that the net benefit is substantial. Grade A The USPSTF recommends the service. There is high certainty that the net benefit is substantial. Strong Strong affirmative Provide the intervention. Most individuals should receive the intervention; only a small proportion will not want the intervention. Recommendation language: start, initiate, prescribe, treat, provide, offer, evaluate Recommendation Against (Grade D) There is at least moderate certainty based on evidence that it has no net benefit or that risks/harms outweigh benefits. Grade D The USPSTF recommends against the service. There is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits. Strong negative Do not provide the intervention. Most individuals should not receive the intervention; only a small proportion will want the intervention. Recommendation language: do not start, initiate, prescribe treat, provide, offer, evaluate The evidence quality rating system used in this guideline was developed by the National Heart, Lung, and Blood Institute s (NHLBI s) Evidence-Based Methodology Lead (with input from NHLBI staff, external methodology team, and guideline panels and work groups) for use by all the NHLBI CVD guideline panels and work groups during this project. As a result, it includes the evidence quality rating for many types of studies, including studies that were not used in this guideline. Additional details regarding the evidence quality rating system are available in the online Supplement. 11
JNC 8 1 Grading System USPSTF 2 Grading System Kaiser Permanente 3 Grading System Grade Strength of recommendation Grade Strength of recommendation Grade Intended action Moderate Recommendation (Grade B) Grade B Weak Weak Recommendation (Grade C) Expert Opinion (Grade E) There is moderate certainty based on evidence that the net benefit is moderate to substantial or there is high certainty that the net benefit is moderate. There is at least moderate certainty based on evidence that there is a small net benefit. ( There is insufficient evidence or evidence is unclear or conflicting, but this is what the committee recommends. ) Net benefit is unclear. Balance of benefits and harms cannot be determined because of no evidence, insufficient evidence, unclear evidence, or conflicting evidence, but the committee thought it was important to provide clinical guidance and make a recommendation. Further research is recommended in this area. Grade C The USPSTF recommends the service. There is high certainty that the net benefit is moderate or there is moderate certainty that the net benefit is moderate to substantial. The USPSTF recommends selectively offering or providing this service to individual patients based on professional judgment and patient preferences. There is at least moderate certainty that the net benefit is small. Weak affirmative Assist each patient in making a management decision consistent with personal values and preferences. The majority of individuals in this situation will want the intervention, but many will not. Different choices will be appropriate for different patients. Recommendation language: consider starting, initiating, prescribing, treating, providing, offering, evaluating Weak negative Assist each patient in making a management decision consistent with personal values and preferences. The majority of individuals in this situation will not want the intervention, but many will. Different choices will be appropriate for different patients. Recommendation language: consider stopping, consider not starting, initiating, prescribing, treating, providing, offering, evaluating 12
JNC 8 1 Grading System USPSTF 2 Grading System Kaiser Permanente 3 Grading System Grade Strength of recommendation Grade Strength of recommendation Grade Intended action No recommendation for or against (Grade N) ( There is insufficient evidence or evidence is unclear or conflicting. ) Net benefit is unclear. Balance of benefits and harms cannot be determined because of no evidence, insufficient evidence, unclear evidence, or conflicting evidence, and the committee thought no recommendation should be made. Further research is recommended in this area. Grade I Statement The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of the service. Evidence is lacking, of poor quality, or conflicting, and the balance of benefits and harms cannot be determined. No recommendation for or against Given that the balance between desirable and undesirable effects, the evidence quality, the values & preferences, and the resource allocation implications of an intervention do not drive a recommendation in one particular direction, recommendations will be made at the discretion of the individual clinician. Recommendation language: No recommendation for or against 13
Appendix C: Rationale for KP-Modified Recommendation Topic: Diastolic Blood Pressure Targets Recommendation In the general population <60 years, initiate pharmacologic treatment to lower BP at DBP 90 mmhg and treat to a goal DBP < 90 mmhg. (Strong Recommendation) Basis of Recommendation There is strong evidence for this recommendation for ages 30 to 59. There is insufficient evidence to determine an optimal DBP goal in people ages 18 to 29. No high quality outcome trials assessing optimal diastolic blood pressure targets included large numbers of adults ages 18 to 29. The balance between benefit and harm from a DBP goal lower than < 90 mmhg for ages 18 to 29 cannot be determined; however, expert opinion favors the use of this goal, and risk of harm is expected to be low. Despite the low quality of evidence and the unknown balance of desirable and undesirable effects, a strong recommendation is warranted based on the discourse of the JNC 8 and its implications for health care delivery implementation. GRADE criteria Balance of desirable and undesirable effects Quality of Evidence Values and Preferences Resource Implications GRADE assessment Outcome evidence for patients aged 30 to 59 demonstrates that lower DBP is associated with lower rates of CVD. However, for patients 18 to 29 the optimal goal DBP has not been determined in wellconducted randomized controlled trials. The balance between risks of overtreatment of younger individuals versus the potential benefits of a lower DBP target is unknown but expected to be significant. Strong for ages 30 to 59. For ages 18 to 29: Expert opinion- while there is insufficient/unclear evidence we agree with the discourse of the JNC 8 committee and its recommendations. 1 This recommendation places a low value on preventing undertreatment of younger people and a higher value on the potential high expected reduction of CV events with DBP targets. Values and preferences were derived by polling the GDT. Uncertainty around and variability of values and preferences regarding hypertension therapy among patients are estimated to be high. Low to moderate because agents are of low-to-moderate cost and therapy of hypertension has been shown in some populations to becost effective with reduced morbidity and mortality. Uncertainty: Moderate because net benefits are unknown and outcome studies of comparative effectiveness are lacking. 14
Topic: Systolic Blood Pressure Targets Recommendation Basis of Recommendation GRADE criteria Balance of desirable and undesirable effects Quality of Evidence Values and Preferences Resource Implications In the general population < 60 years, initiate pharmacologic treatment to lower BP at SBP < 140mmHg and treat to a goal SBP < 140 mmhg. (Strong recommendation) There is insufficient evidence to determine an optimal SBP goal in people aged < 60 years. No high quality outcome trials assessing optimal systolic blood pressure targets included large numbers of adults younger than 60 years. The balance between benefit and harm from a BP goal < 140 mmhg cannot be determined; however, expert opinion favors the use of this goal and risk of harm is expected to be low. Despite the low quality of evidence and the unknown balance of desirable and undesirable effects, a strong recommendation is warranted based on the discourse of the JNC 8 and its implications for health care delivery implementation. GRADE assessment Pathophysiological evidence in younger people suggests that lower SBP is associated with lower rates of CVD. However, the optimal goal SBP has not been determined in well-conducted randomized controlled trials. The balance between risks of overtreatment of younger individuals versus the potential benefits of a lower SBP target is unknown but expected to be significant. Expert opinion-although there is insufficient/unclear evidence, we agree with the discourse of the JNC 8 and its recommendations. 1 This recommendation places a low value on preventing undertreatment of younger people and a higher value on the potential high expected reduction of CV events with SBP targets. Values and preferences were derived by polling the GDT. Uncertainty around and variability of values and preferences regarding hypertension therapy among patients are estimated to be high. Low to moderate because agents are of low-to- moderate cost and therapy of hypertension has been shown in some populations to be cost-effective with reduced morbidity and mortality. Uncertainty: Moderate because net benefits are unknown and outcome studies of comparative effectiveness are lacking. 15
Topic: Hypertension Treatment in Patients with CKD Recommendation In the population aged 60 years with chronic kidney disease (CKD), consider initiating pharmacologic treatment to lower BP at SBP 140 mmhg or DBP 90 mmhg and treat to goal SBP <140 mmhg and goal DBP <90 mmhg. (Weak Recommendation)** **When weighing the risks and benefits of a lower BP goal for people aged 70 years with estimated GFR < 60 ml/min/ 1.73m2, antihypertensive treatment should be individualized, taking into consideration factors such as frailty, comorbidities, albuminuria, and estimation of non-age-related egfr decline (for example egfr + 1/2 age < 85). Basis of Recommendation For individuals aged < 60 years, regardless of comorbidity of CKD, the prior strong recommendations apply. There is insufficient evidence to determine an optimal BP goal in people aged 70 years with CKD and on the diagnostic criteria for CKD that would identify people who would benefit from a BP goal lower than <150/90 mmhg. No outcome trials included large numbers of adults aged 70 years with CKD. The balance between benefit and harm from a BP goal lower than <150/90 mmhg cannot be determined; however, some expert opinions favor more aggressive treatment of people aged 70 years with CKD. Thus, when weighing the risks and benefits of a lower BP goal for people aged 70 years with estimated GFR < 60 ml/min/ 1.73m2, antihypertensive treatment should be individualized. Given the low quality of evidence and the unknown balance of desirable and undesirable effects, a weak recommendation is warranted. GRADE criteria Balance of desirable and undesirable effects GRADE assessment Pathophysiological evidence in younger people suggests that lower BP is associated with less progression of renal disease. However, the optimal goal BP goal has not been determined in high-quality randomized controlled trials. Those trials excluded people aged 70 years, so the effect of a more aggressive BP goal is unknown in elderly people with CKD. There is also no evidence on the definition of CKD that would identify elderly people who might benefit from BP goal lower than the strong recommendation of <150/90 mmhg for the general population aged 60 years. The commonly used estimating equations for GFR were not developed in populations with significant numbers of people aged 70 years and have not been validated in older adults. Observational data suggest that a modified definition of CKD (for example, egfr + (age/2) < 85) may indicate individuals more likely to progress to ESRD who may be candidates for a lower BP goal. The balance between risk of overtreatment of older individuals with CKD versus the potential benefits of a lower SBP target is unknown. Quality of Evidence Very low quality (indirect evidence) 1,5,6 Values and Preferences Resource Implications This recommendation places a high value on preventing overtreatment of elderly people and a lower value on the small risk of harms of increased CV and renal risk potentially associated with slightly higher SBP targets. Values and preferences were derived by polling the GDT. Uncertainty around and variability of values and preferences regarding hypertension therapy among patients in whom a treatment decision for lower SBP target is unclear are estimated to be high. Low to moderate because agents are of low-to-moderate cost and therapy of hypertension has been shown in some populations to be costeffective with reduced morbidity and mortality. Uncertainty: Moderate because net benefits are unknown and outcome studies of comparative effectiveness are lacking. 16
Topic: Blood Pressure Targets in the Diabetic Population 60 years Recommendation Basis of Recommendation GRADE criteria Balance of desirable and undesirable effects Quality of Evidence Values and Preferences Resource Implications In the population aged 60 years with diabetes, initiate pharmacologic treatment to lower BP at SBP 140mmHg or DBP 90 mmhg and treat to a goal SBP <140 mmhg and goal DBP <90 mmhg. (Strong Recommendation) For individuals aged 60 years, regardless of comorbidity of DM, the prior strong recommendations apply. There is insufficient evidence to determine an optimal BP goal in adults with DM aged > 60 years. No high-quality outcome trials comparing systolic blood pressure targets of 140 vs. 150 mm Hg included large numbers of adults with DM. The balance between benefit and harm from a SBP goal <140 mmhg cannot be determined; however, expert opinion favors the use of this goal and risk of harm is expected to be low. Despite the low quality of evidence, and the unknown balance of desirable and undesirable effects, a strong recommendation is warranted as based on the discourse summarized by the JNC 8 and its implications for health care delivery implementation. GRADE assessment Pathophysiological evidence suggests that lower BP is associated with lower rates of CVD. However, the optimal goal BP has not been determined in well-conducted randomized controlled trials including individuals with diabetes. The balance between risks of overtreatment versus the potential benefits of a lower BP target is unknown but expected to be significant. Expert opinion-although there is insufficient/unclear evidence, we agree with the discourse of the JNC 8 and its recommendations. 1 This recommendation places a low value on preventing undertreatment of adults with diabetes and a higher value on the potential high expected reduction of CV events with lower SBP targets. Values and preferences were derived by polling the GDT. Uncertainty around and variability of values and preferences regarding hypertension therapy among patients are estimated to be high. Low to moderate because agents are of low-to-moderate cost and therapy of hypertension has been shown in some populations to be cost-effective with reduced morbidity and mortality. Uncertainty: Moderate because net benefits are unknown and outcome studies of comparative effectiveness are lacking. 17
Appendix D: Systematic Review Topic: Screening and Diagnosis of High Blood Pressure The NGP methodology calls for the KP guideline development process to first seek high-quality external guidelines for adoption or adaption and to conduct additional evidence review only as needed. 3 The Hypertension National Guideline Lead Team conducted a review of existing KP regional guidelines and potential high-quality existing guidelines on hypertension available for adaption or adoption. The Lead Team determined that the USPSTF recommendations for screening and diagnosis for high blood pressure best addressed the needs of the NGP and proceeded to analyze the quality and content of this guideline for comprehensiveness and adoption to the KP NGP. The final product of this KP recommendation is based on the USPSTF recommendation. Screening frequency is addressed as a clinical consideration by USPSTF and is therefore presented similarly in the KP clinician guide. AGREE II Summary The AGREE (Appraisal of Guidelines Research and Evaluation) 4 II tool is used to assess the methodological quality of existing clinical practice guidelines being considered for adoption into the NGP portfolio. An AGREE assessment was completed on the USPSTF recommendations in 2016 (using the completed 2014 evidence review) 7 and it was considered to be of good quality and rigor; no additional evidence review was conducted by KP. To access the link to the completed AGREE II assessment click below: 2016 USPSTF Blood Pressure Screening and Diagnosis AGREE II Assessment Following are the key questions addressed by the USPSTF recommendations: Key Questions 1. Does screening for high blood pressure reduce cardiovascular disease and mortality in adults aged 18 years or older? 2. What is the best way to screen for high blood pressure in adults in the primary care setting? a. How accurate (i.e., sensitivity, specificity, and predictive value) are clinic-based blood pressure measurement methods (e.g., manual vs. automated) in provisionally diagnosing hypertension within a single visit? b. What screening protocol characteristics within a single encounter (e.g., sitting quietly for 5 minutes or number of readings) define the best diagnostic accuracy? 3. What is the best way to confirm hypertension in adults who initially screen positive for high blood pressure? a. How well do home and ambulatory blood pressure monitoring methods predict cardiovascular events compared with clinic-based blood pressure measurement methods? What confirmation protocol characteristics define the best prediction of cardiovascular events? Which methods and associated protocols best predict cardiovascular events? b. How accurate are other noninvasive blood pressure measurement methods in establishing or confirming the diagnosis of hypertension, compared with these best methods and associated protocols? Does diagnostic accuracy vary by protocol characteristics (i.e., characteristics not reviewed in key question 2b, such as the number of visits)? c. Does changing the measurement method from that used during the initial screening improve diagnostic accuracy for some specific patient subgroups (e.g., those with suspected white-coat hypertension)? 4. What is the clinically appropriate rescreening interval for patients who have previously been screened and found to have normal blood pressure? a. What is the shortest interval in which clinically significant, diagnosed hypertension may develop? b. Does the rescreening interval vary by patient characteristics (e.g., age, sex, race/ethnicity, cardiovascular risk, blood pressure, or screening history)? 5. What are the adverse effects of screening for high blood pressure in adults? Inclusion/Exclusion Criteria USPSTF conducted a comprehensive literature search for existing systematic reviews from various databases including MEDLINE and PubMed from January 1, 2005 to March 19, 2013. Various databases including MEDLINE and PubMed were searched for randomized controlled trials (Questions 1 and 5), cohort studies (Questions 4 and 5), and diagnostic accuracy studies (Question 2 and 3) published between 1966 and February 24, 2014. A full list of databases searched for each question can be found in the published evidence review. 7 Reference lists of included studies were also reviewed. A total of 19,309 titles and abstracts and 1,171 full-text articles were reviewed. In general, studies were included if they were conducted in adult populations (i.e., > 80% of the study population was aged 18 years) in primary care settings. If conducted in adults and children, results had to be stratified by age group. Participants must not have been taking antihypertensive medications (except for Question 3a). Studies with pregnant women, institutionalized persons, inpatients, and persons with an underlying cause 18
of high BP were excluded. In addition, studies that enrolled a highly selected group of participants (e.g. renal transplant recipients or those with chronic kidney disease) were excluded. Blood pressure measurements had to be taken on the upper arm. Studies with measurements using the wrist, ankle, finger, and toe blood pressure monitors were excluded. Studies using blood pressure measurement methods not commonly used in routine screening practices (e.g. invasive methods or noninvasive central blood pressure measurements) were excluded. Details regarding inclusion/exclusion criteria can be found in the published evidence review. 7 USPSTF Analytic Framework Legend: ABPM = ambulatory blood pressure monitoring; BP = blood pressure; CHD = coronary heart disease; CVD = cardiovascular disease; ESKD = end-stage kidney disease; HBPM = home blood pressure monitoring; HF = heart failure. * Defined as the threshold for pharmacologic treatment. Topic: Treatment Initiation and Blood Pressure Targets The NGP methodology calls for the KP guideline development process to first seek high-quality external guidelines for adoption or adaption, and to conduct additional evidence review only as needed. 3 The Hypertension National Guideline Lead Team conducted a review of existing KP regional guidelines and potential high-quality existing guidelines on hypertension available for adaptation or adoption. The Lead Team determined that the JNC 8 1 guideline best addressed the needs of the NGP and proceeded to analyze the quality and content of this guideline for comprehensiveness and adoption to the KP NGP. The final product of the KP guideline is based primarily on the JNC 8 guideline. AGREE II Summary The AGREE (Appraisal of Guidelines Research and Evaluation) 4 II tool is used to assess the methodological quality of existing clinical practice guidelines being considered for adoption into the NGP portfolio. An AGREE assessment was completed on the JNC 8 guideline in 2014 and it was considered to be of good quality and rigor; no additional evidence review was conducted by KP. Following are the key questions addressed by the JNC 8 guideline: Key Questions 1. In adults with hypertension, does initiating antihypertensive pharmacologic therapy at specific blood pressure thresholds improve health outcomes? 2. In adults with hypertension, does treatment with antihypertensive pharmacologic therapy to a specified BP goal lead to improvements in health outcomes? 3. In adults with hypertension, do various antihypertensive drugs or drug classes differ in comparative benefits and harms on specific health outcomes? Inclusion/Exclusion Criteria The JNC 8 1 conducted an evidence review that focused on adults aged 18 years with hypertension and included studies with the following pre-specified subgroups: diabetes, coronary artery disease, peripheral artery disease, heart failure, previous stroke, chronic kidney disease (CKD), proteinuria, older adults, men and women, racial and ethnic groups, and smokers. Studies with sample sizes < 100 were excluded, as were studies with a follow-up period of less than a year, because small studies of brief duration are unlikely to yield enough health-related outcome information to permit interpretation of treatment effects. 19
Studies were included in the evidence review only if they reported the effects of the studied interventions on any of these important health outcomes: Overall mortality, cardiovascular disease (CVD)-related mortality, CKD-related mortality Myocardial infarction, heart failure, hospitalization for heart failure, stroke Coronary revascularization (includes coronary artery bypass surgery, coronary angioplasty, and coronary stent placement), other revascularization (includes carotid, renal, and lower extremity revascularization) End-stage renal disease (ESRD) (i.e., kidney failure resulting in dialysis or transplantation), doubling of creatinine level, halving of glomerular filtration rate (GFR). 20
References 1. James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014;311(5):507-520. 2. Siu AL. Screening for high blood pressure in adults: U.S. Preventive Services Task Force recommendation statement. Ann. Intern. Med. 2015;163(10):778-786. 3. Kaiser Permanente. Kaiser Permanente National Guideline Program Process and Methodology for Systematic Development of Clinical Practice Recommendations. 2016. https://wiki.kp.org/wiki/x/_imadg. 4. Brouwers MC, Kho ME, Browman GP, et al. AGREE II: advancing guideline development, reporting and evaluation in health care. Can. Med. Assoc. J. 2010;182(18):E839-842. 5. Rutkowski M, Mann W, Derose S, et al. Implementing KDOQI CKD definition and staging guidelines in Southern California Kaiser Permanente. Am. J. Kidney Dis. 2009;53(3 Suppl 3):S86-99. 6. Kidney Disease; Improving Global Outcomes (KDIGO) Blood PressureWork Group. KDIGO clinical practice guideline for the management of blood pressure in chronic kidney disease. Kidney Int Suppl,. 2012;2(5):337-414. 7. Piper MA, Evans CV, Burda BU, et al. Screening for High Blood Pressure in Adults: A Systematic Evidence Review for the U.S. Preventive Services Task Force. Rockville MD2014. 21