Hypertension is the most common condition seen in primary care and leads to myocardial infarction, stroke, renal failure, and death if not detected early and treated appropriately. Patients want to be assured that blood pressure (BP) treatment will reduce their disease burden, while clinicians want guidance on hypertension management using the best scientific evidence. This report takes a rigorous, evidence-based approach to recommend treatment thresholds, goals, and medications in the management of hypertension in adults. Evidence was drawn from randomized controlled trials, which represent the gold standard for determining efficacy and effectiveness. Evidence quality and recommendations were graded based on their effect on important outcomes.
There is strong evidence to support treating hypertensive persons aged 60 years or older to a BP goal of less than 150/90 mm Hg and hypertensive persons 30 through 59 years of age to a diastolic goal of less than 90 mm Hg; however, there is insufficient evidence in hypertensive persons younger than 60 years for a systolic goal, or in those younger than 30 years for a diastolic goal, so the panel recommends a BP of less than 140/90 mm Hg for those groups based on expert opinion. The same thresholds and goals are recommended for hypertensive adults with diabetes or nondiabetic chronic kidney disease (CKD) as for the general hypertensive population younger than 60 years. There is moderate evidence to support initiating drug treatment with an angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, calcium channel blocker, or thiazide-type diuretic in the nonblack hypertensive population, including those with diabetes. In the black hypertensive population, including those with diabetes, a calcium channel blocker or thiazide-type diuretic is recommended as initial therapy. There is moderate evidence to support initial or add-on antihypertensive therapy with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker in persons with CKD to improve kidney outcomes.
Although this guideline provides evidence-based recommendations for the management of high BP and should meet the clinical needs of most patients, these recommendations are not a substitute for clinical judgment, and decisions about care must carefully consider and incorporate the clinical characteristics and circumstances of each individual patient.
Hypertension remains one of the most important preventable contributors to disease and death. Abundant evidence from randomized controlled trials (RCTs) has shown benefit of antihypertensive drug treatment in reducing important health outcomes in persons with hypertension.1-3 Clinical guidelines are at the intersection between research evidence and clinical actions that can improve patient outcomes. The Institute of Medicine Report Clinical Practice Guidelines We Can Trust outlined a pathway to guideline development and is the approach that this panel aspired to in the creation of this report.4
The panel members appointed to the Eighth Joint National Committee (JNC 8) used rigorous evidence-based methods, developing Evidence Statements and recommendations for blood pressure (BP) treatment based on a systematic review of the literature to meet user needs, especially the needs of the primary care clinician. This report is an executive summary of the evidence and is designed to provide clear recommendations for all clinicians. Major differences from the previous JNC report are summarized in Table 1. The complete evidence summary and detailed description of the evidence review and methods are provided online (see Supplement).
The panel members appointed to JNC 8 were selected from more than 400 nominees based on expertise in hypertension (n = 14), primary care (n = 6), including geriatrics (n = 2), cardiology (n = 2), nephrology (n = 3), nursing (n = 1), pharmacology (n = 2), clinical trials (n = 6), evidence-based medicine (n = 3), epidemiology (n = 1), informatics (n = 4), and the development and implementa- tion of clinical guidelines in systems of care (n = 4).
The panel also included a senior scientist from the National In- stitute of Diabetes and Digestive and Kidney Diseases (NIDDK), a se- nior medical officer from the National Heart, Lung, and Blood Insti- tute (NHLBI), and a senior scientist from NHLBI, who withdrew from authorship prior to publication. Two members left the panel early in the process before the evidence review because of new job com- mitments that prevented them from continuing to serve. Panel mem- bers disclosed any potential conflicts of interest including studies evaluated in this report and relationships with industry. Those with conflicts were allowed to participate in discussions as long as they declared their relationships, but they recused themselves from vot- ing on evidence statements and recommendations relevant to their relationships or conflicts. Four panel members (24%) had relation- ships with industry or potential conflicts to disclose at the outset of the process.
In January 2013, the guideline was submitted for external peer review by NHLBI to 20 reviewers, all of whom had expertise in hypertension, and to 16 federal agencies. Reviewers also had expertise in cardiology, nephrology, primary care, pharmacology, research (including clinical trials), biostatistics, and other important related fields. Sixteen individual reviewers and 5 federal agencies responded. Reviewers’ comments were collected, col- lated, and anonymized. Comments were reviewed and discussed by the panel from March through June 2013 and incorporated into a revised document. (Reviewers’ comments and suggestions, and responses and disposition by the panel are available on request from the authors.)
Questions Guiding the Evidence Review
This evidence-based hypertension guideline focuses on the pan- el’s 3 highest-ranked questions related to high BP management iden- tified through a modified Delphi technique.5 Nine recommenda- tions are made reflecting these questions. These questions address thresholds and goals for pharmacologic treatment of hypertension and whether particular antihypertensive drugs or drug classes im- prove important health outcomes compared with other drug classes.
۱٫ In adults with hypertension, does initiating antihypertensive pharmacologic therapy at specific BP thresholds improve health outcomes?
۲٫ In adults with hypertension, does treatment with antihypertensive pharmacologic therapy to a specified BP goal lead to improvements in health outcomes?
۳٫ In adults with hypertension, do various antihypertensive drugs or drug classes differ in comparative benefits and harms on specific health outcomes?
The Evidence Review
The evidence review focused on adults aged 18 years or older with hypertension and included studies with the following prespecified subgroups: diabetes, coronary artery disease, peripheral artery dis- ease, heart failure, previous stroke, chronic kidney disease (CKD), proteinuria, older adults, men and women, racial and ethnic groups, and smokers. Studies with sample sizes smaller than 100 were ex- cluded, as were studies with a follow-up period of less than 1 year, because small studies of brief duration are unlikely to yield enough health-related outcome information to permit interpretation of treat- ment effects. 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 fail- ure, stroke
• Coronary revascularization (includes coronary artery bypass sur- gery, coronary angioplasty and coronary stent placement), other revascularization (includes carotid, renal, and lower extremity re- vascularization)
• End-stage renal disease (ESRD) (ie, kidney failure resulting in di- alysis or transplantation), doubling of creatinine level, halving of glomerular filtration rate (GFR).
The panel limited its evidence review to RCTs because they are less subject to bias than other study designs and represent the gold standard for determining efficacy and effectiveness.6 The studies in the evidence review were from original publications of eligible RCTs. These studies were used to create evidence tables and sum- mary tables that were used by the panel for their deliberations (see Supplement). Because the panel conducted its own systematic re- view using original studies, systematic reviews and meta-analyses of RCTs conducted and published by other groups were not in- cluded in the formal evidence review.
Initial search dates for the literature review were January 1, 1966, through December 31, 2009. The search strategy and PRISMA dia- gram for each question is in the online Supplement. To ensure that no major relevant studies published after December 31, 2009, were excluded from consideration, 2 independent searches of PubMed and CINAHL between December 2009 and August 2013 were con- ducted with the same MeSH terms as the original search. Three panel members reviewed the results. The panel limited the inclusion cri- teria of this second search to the following. (1) The study was a ma- jor study in hypertension (eg, ACCORD-BP, SPS3; however, SPS3 did not meet strict inclusion criteria because it included nonhyperten- sive participants. SPS3 would not have changed our conclusions/ recommendations because the only significant finding supporting a lower goal for BP occurred in an infrequent secondary outcome).7,8 (2) The study had at least 2000 participants. (3) The study was mul- ticentered. (4) The study met all the other inclusion/exclusion cri- teria. The relatively high threshold of 2000 participants was used because of the markedly lower event rates observed in recent RCTs such as ACCORD, suggesting that larger study populations are needed to obtain interpretable results. Additionally, all panel mem- bers were asked to identify newly published studies for consider- ation if they met the above criteria. No additional clinical trials met the previously described inclusion criteria. Studies selected were
rated for quality using NHLBI’s standardized quality rating tool (see Supplement) and were only included if rated as good or fair.
An external methodology team performed the literature re- view, summarized data from selected papers into evidence tables, and provided a summary of the evidence. From this evidence re- view, the panel crafted evidence statements and voted on agree- ment or disagreement with each statement. For approved evi- dence statements, the panel then voted on the quality of the evidence (Table 2). Once all evidence statements for each critical question were identified, the panel reviewed the evidence state- ments to craft the clinical recommendations, voting on each rec- ommendation and on the strength of the recommendation (Table 3). For both evidence statements and recommendations, a record of the vote count (for, against, or recusal) was made without attribu- tion. The panel attempted to achieve 100% consensus whenever possible, but a two-thirds majority was considered acceptable, with the exception of recommendations based on expert opinion, which required a 75% majority agreement to approve.
The following recommendations are based on the systematic evi- dence review described above (Box). Recommendations 1 through 5 address questions 1 and 2 concerning thresholds and goals for BP treatment. Recommendations 6, 7, and 8 address question 3 con- cerning selection of antihypertensive drugs. Recommendation 9 is a summary of strategies based on expert opinion for starting and add- ing antihypertensive drugs. The evidence statements supporting the recommendations are in the online Supplement.