Feldman, Harvey MD; Zuber, Kim PA-C; Davis, Jane S. DNP
Determining the ideal BP goal is a clinician's dream. The ink was barely dry on the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC 7) in 2003 when clinicians began to anticipate the JNC 8 report, which was released in late 2013.1 The new guideline is a major departure from previous JNC guidelines in its methodology, focus, and content. This article reviews the design and content of the new document as well as its similarities and differences from JNC 7 and other recently published hypertension guidelines.
WHAT'S DIFFERENT ABOUT JNC 8?
The newest guideline is titled, “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),” rather than the “Eighth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure.”2 The JNC 8 panel, like all of its predecessors, was originally commissioned by the National Heart, Lung, and Blood Institute (NHLBI). However, in June 2013, the NHLBI decided to transfer the task of guideline writing to the American College of Cardiology (ACC) and the American Heart Association (AHA). ACC and AHA recently published guidelines on assessing cardiovascular risks, lifestyle management to reduce those risks, treating blood cholesterol, and managing overweight and obesity. The JNC panel decided to publish its report independently, rather than partner with the ACC and AHA, so a change in the guideline title was needed.
The JNC panel's makeup also reflects a significant change from previous groupings. In the past, panel members were primarily experts in cardiology and hypertension with a small contingent of family practitioners. Because the JNC 8's guidelines are directed toward primary care, a significant portion of panel members are from that area of practice.
The JNC 8 document is much more narrowly focused in both its search methodology and in its content than previous JNC reports. Key differences include:
* Previous JNC guidelines were based on nonsystematic literature reviews that included a variety of study types, ranging from randomized controlled clinical trials to various types of observational studies, meta-analyses, and expert consensus recommendations. For JNC 8, the panel decided to perform a rigorous systematic review limited solely to randomized controlled trials deemed to be of fair to high quality. Based on stringent criteria, low-quality randomized controlled trials were excluded. The panel members believe that randomized controlled trials are “less subject to bias than other study designs and represent the gold standard for determining efficacy and effectiveness.”2
* The panel chose to focus its evidence review on three questions relating to hypertension management in adults (patients age 18 years and older). These questions were deemed the most critically important for practicing clinicians. Unlike JNC 7, the JNC 8 report does not cover definitions of prehypertension and hypertension, methods of BP measurement (such as home BP monitoring or ambulatory BP monitoring), patient evaluation, secondary hypertension, resistant hypertension, or lifestyle interventions (but accepts the recent ACC/AHA lifestyle guidelines and recommends that these be continued throughout the duration of management). JNC 7 included a comprehensive list of antihypertensive drugs and dosage ranges; JNC 8 lists only drugs and doses that were reported in the randomized controlled trials reviewed by the panel.
The three questions that form the basis of the JNC 8 report are (paraphrased):
1. Does initiating drug therapy at specific BP thresholds improve health outcomes?
2. Does drug treatment to specified goals improve health outcomes?
3. Do different drugs or drug classes differ in benefits and harms?
This restrictive evaluation of the literature has implications and consequences.
The major implication of the restrictive literature search is shown in Table 1, the yield from the panel's literature search. Due to the rigorous exclusion criteria used by the panel, only 1.7% to 2.4% of the articles initially screened for each of the three questions were considered acceptable for critical review. Of the total number of acceptable randomized controlled trials, only 0.6% (38 out of 6,146) were deemed to be of good quality. This implies that when subjected to rigorous analysis, almost all of the literature on hypertension management published over the past several decades fails to meet standards that can provide definitive answers to the panel's critical questions. The yield also predicts gaps in evidence needed to answer these three questions and that recommendations derived from this evidence will be made with less than optimal confidence. Finally, these data strongly point to the need for more robust research in the future.
The gaps in evidence become apparent when one looks at the quality of the numerous evidence statements generated to address each question. These evidence statements, based on the selected randomized controlled trials, relate to each of the questions and outcomes noted above and were directed at different populations of patients based on age, race, and the presence of diabetes and/or chronic kidney disease (CKD). Fourteen evidence statements were identified for question 1, 21 for question 2, and 48 for question 3. Each statement was graded on quality based on information in the randomized controlled trials pertinent to that statement. Quality ratings were high, moderate, low, or indeterminate due to insufficient evidence.2 Figure 1 shows the distribution of evidence quality for the statements related to each of the three questions. Quality of evidence could not be determined for a preponderance of statements due to insufficient information in the randomized controlled trials that were available for analysis. The reason for this again reflects the inadequacies of the available literature. Even high- to fair-quality randomized controlled trials do not fully address the questions raised by the panel.
Nonetheless, the panel was able to generate nine recommendations from its analysis of these randomized controlled trials. Because three recommendations contain subcategories, the guideline actually contains 12 recommendations. The strength of each recommendation was graded according to specified criteria: A (strong), B (moderate), C (weak), or E (expert opinion). Recommendations 1 through 5 address questions 1 and 2 and recommendations 6 through 8 address question 3. Because the panel's evidence-based systematic review was focused only on initial therapy, recommendation 9 and a treatment algorithm, both based on expert opinion, were added “for further guidance to assist in implementation of recommendations 1 through 8.”2
WHAT ARE THE JNC 8 RECOMMENDATIONS?
The complete set of recommendations (modified from the JNC 8 document) and their respective strength grades are listed in Table 2. Briefly, the major points are:
* In patients age 60 years and older, start treatment for BP of 150 mm Hg systolic or 90 mm Hg diastolic or greater, and treat to under those thresholds. However, if the patient tolerates a lower BP (for example, less than 140 mm Hg systolic), do not adjust treatment to raise BP closer to 150 mm Hg.
* In patients under age 60 years, treatment thresholds and goals should be 140/90 mm Hg. Use this same guideline for patients with diabetes or CKD.
* In nonblack patients with hypertension, initial treatment can be a thiazide diuretic, calcium channel blocker, angiotensin-converting enzyme (ACE) inhibitor, or angiotensin receptor blocker (ARB). For black patients, initial therapy should be a thiazide diuretic or calcium channel blocker. The latter recommendation is based on a large clinical trial that showed that in black patients, thiazide diuretics were more effective in improving cerebrovascular, heart failure, and combined cardiovascular outcomes and that a calcium channel blocker reduced BP and rate of stroke to a greater degree than an ACE inhibitor.2
* In patients with CKD, initial or add-on therapy should be an ACE inhibitor or ARB, regardless of race or diabetes status.
Table 2 reveals a paradox in the guideline. The panel attempted to rely solely on randomized controlled trials, which it called the “gold standard for determining efficacy and effectiveness,” in order to use the strongest evidence for its recommendations. However, because of its stringent standards and inadequacies in many of the randomized controlled trials, the panel was compelled to rely heavily on expert opinion to provide therapeutic guidance.
COMPARISON TO OTHER GUIDELINES
By far the recommendation causing most comment so far is relaxing the systolic BP threshold and goal for treating patients age 60 years and older from 140 to 150 mm Hg (Table 2, recommendation 1). JNC 7 did not assign a different threshold or goal systolic BP for older adults; a systolic BP of 140 mm Hg applied to all.1
Other recently published guidelines recommend a systolic BP cutoff of 150 mm Hg only for people age 80 years and older, based mainly on the results of the Hypertension in the Very Elderly Trial (HYVET).3 That trial showed favorable outcomes for patients age 80 years and older with systolic BP of 160 mm Hg or greater who were targeted to a systolic BP of less than 150 mm Hg and achieved an average systolic BP of 146 mm Hg.3 These guidelines come from Britain (2011), Canada (2013), Europe (2013), and the American and International Societies of Hypertension (ASH/ISH), which published its guideline simultaneously with JNC 8.4–7 The concern is that the higher systolic BP goal in JNC 8 will produce a “speed limit” mentality, resulting in an upward shift of BP values in the general older population. The contention of the JNC 8 panel is that there is no evidence that a systolic BP goal of less than 140 mm Hg is better than less than 150 mm Hg for patients over age 60 years.
Another major departure from guidelines published before 2010 is that JNC 8 applies the same treatment goal for the general population under age 60 years to all patients with diabetes or CKD age 18 years or older. The goal for patients with hypertension and CKD or diabetes is now less than 140/90 mm Hg (Table 2, recommendations 4 and 5). JNC 8 is in line with the other recent guidelines, including those from the American Diabetes Association.8 Although multiple organizations and consensus panels endorsed the lower systolic BP for more than a decade, recent critical analyses found that the evidence for this lower BP target is very weak. Previous guidelines were based on post hoc analyses of achieved BP levels in randomized controlled trials not designed to assess this outcome. Also, the ACCORD Trial of patients with type 2 diabetes showed that a systolic BP less than 120 mm Hg was no better than one less than 140 mm Hg, except for a slightly reduced rate of stroke.9 Some experts believe that a goal of less than 130/80 mm Hg should still be retained for patients with CKD and proteinuria. The JNC 8 writers acknowledge possible benefit of a lower BP in patients with proteinuria but the evidence comes from post hoc analyses that did not meet the stringent criteria for inclusion in their evidence-based review.
With respect to drug therapy, JNC 8 differs from JNC 7 in the following ways:
* Beta-blockers are no longer listed as a first-line choice, leaving only thiazide diuretics, ACE inhibitors, ARBs, and calcium channel blockers. The panel based its decision on evidence that beta-blockers are less effective than other drugs in stroke protection. This change was foreshadowed by the British guideline reducing beta-blockers to fourth-line status in its treatment algorithm 2 years ago.4 The new ASH/ISH guideline also relegates beta-blockers to fourth-line status.7 The Canadian and European guidelines retain beta-blockers as first-line drugs but only in patients under age 80 years.5,6
* JNC 7 favored thiazide diuretics as first-line treatment in most patients. JNC 8 places this class of drugs on an equal footing with the other three classes. Thiazides have an advantage over the other antihypertensive drug classes only for prevention of heart failure; this was an insufficient reason for the panel to retain the favored status of thiazides. Similarly, all other recent guidelines do not favor thiazides over other first-line drugs.4–7
* JNC 7 recommended specific drug classes for “compelling indications,” including coronary heart disease, stroke, left ventricular dysfunction, heart failure, diabetes, and CKD.1 JNC 8 recommends specific drug classes for patients based on race, diabetes, and CKD because these were the only subpopulations for which evidence from randomized controlled trials was sufficient.2 Other recent guidelines incorporate these three subpopulations into their treatment algorithms, but some also include age as a determinant of drug selection.4,7 Most recent guidelines favor ACE inhibitors or ARBs for patients with diabetes and CKD, and thiazides or calcium channel blockers for black patients.2,4–7 British and ASH/ISH guidelines favor thiazides or calcium channel blockers as initial therapy for patients over ages 55 to 60 years, respectively.4,7 Both older age and black race are associated with low plasma renin levels, rendering drugs that inhibit the renin-angiotensin-aldosterone system (RAAS) less effective as monotherapy. In black patients with CKD, however, the panel recommends ACE inhibitors or ARBs as initial or add-on therapy (Table 2, recommendation 8).
* JNC 7 did not address the combined use of drugs that block the RAAS, especially in patients with CKD.1 JNC 7 was published before three seminal randomized controlled trials that pointed out the dangers of the combined approach. Hypotension, acute renal failure, and hyperkalemia have been reported with combinations of ACE inhibitors and ARBs, or the combination of either drug class with a direct renin inhibitor such as aliskiren.10–12 JNC 8 (Table 2, recommendation 9) and the other recent guidelines all contain warnings about combining ACE inhibitors and ARBs.2,4–7
Table 3 summarizes the similarities and differences between the JNC 8 recommendations and those of other recently published guidelines. Figure 2 is a simplified version of the JNC 8 treatment algorithm for use in primary care.
SUMMARY AND CONCLUSIONS
The JNC 8 panel took a very different approach than other expert panels have taken in writing its guidelines for hypertension management. JNC 8 is more narrowly focused because of its self-imposed limits: addressing only three important questions and attempting to rely solely on critical assessment of randomized controlled trials for evidence in support of its recommendations. Those seeking a more comprehensive document resembling JNC 7 should refer to one of the other recently published guidelines.4–7 However, JNC 8 is a simpler guideline than either its predecessor or other recent guidelines, with a single BP recommendation (140/90 mm Hg) for both the pharmacologic treatment threshold and treatment goal for patients between ages 18 and 60 years and patients with diabetes or CKD.2 JNC 8 also reduces the number of first-line drugs from five to four while recommending specific drug preferences for only three subpopulations: black patients, patients with diabetes, and patients with CKD. One shortcoming is that because of a gap in evidence, half of the panel's recommendations are based on expert opinion rather than on the results of high-quality randomized controlled trials. By uncovering these evidence gaps through its meticulous systematic review of the literature, the panel has done the medical community an important service by pointing the way to further research in the field. The JNC 8 guideline, incorporating 10 years of knowledge since JNC 7, is a much-welcomed update that should help primary care clinicians better manage patients with hypertension.
Clinicians should not be confused or driven to inaction by the discrepancies between JNC 8 and the other recent guidelines mentioned in this review. Guidelines are the product of their writers, who bring to the table their own biases, viewpoints, and experience. Differences between guidelines are to be expected, and a one-size-fits-all approach may not be appropriate for all patients. As pointed out by the JNC 8 panel, guidelines are not a substitute for clinical judgment, and clinicians must consider each patient's circumstances and clinical condition when making decisions about medical care.2
In the United States, only about 50% of patients with hypertension are being treated to target BP levels. Of those with uncontrolled hypertension, nearly 90% have a usual source of healthcare and have health insurance.12 This suggests that a major reason for this shortcoming is clinician inertia, or the failure to take appropriate action to drive BPs down to guideline-recommended levels.13 We suggest that clinicians select one of the current guidelines and follow its recommendations. All of these guidelines, if followed correctly, will achieve better outcomes than we have seen thus far.
1. Chobanian AV, Bakris GL, Black HR, et al. National Heart, Lung, and Blood Institute Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; National High Blood Pressure Education Program Coordinating Committee. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA
2. 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
3. Beckett NS, Peters R, Fletcher AE, et al. Treatment of hypertension in patients 80 years of age or older. N Engl J Med
5. Dasgupta K, Quinn RR, Zarnke KB, et al. The 2014 Canadian Hypertension Education Program recommendations for blood pressure measurement, diagnosis, assessment of risk, prevention, and treatment of hypertension. Can J Cardiol
6. Mancia G, Fagard R, Narkiewicz K, et al. 2013 ESH/ESC guidelines for the management of arterial hypertension: the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology. Eur Heart J
7. Weber MA, Schiffrin EL, White WB, et al. Clinical practice guidelines for the management of hypertension in the community: a statement by the American Society of Hypertension and the International Society of Hypertension. J Clin Hypertens (Greenwich)
8. American Diabetes Association. Standards of medical care in diabetes—2013. Diabetes Care
. 2013;36(suppl 1):S11-S66.
9. ACCORD Study Group, Cushman WC, Evans GW, et al. Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med
10. ONTARGET Investigators, Yusuf S, Teo KK, et al. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med
11. Parving HH, Brenner BM, McMurray JJ, et al. Cardiorenal end points in a trial of aliskiren for type 2 diabetes. N Engl J Med
12. Fried LF, Emanuele N, Zhang JH, et al. Combined angiotensin inhibition for the treatment of diabetic nephropathy. N Engl J Med
13. Go AS, Bauman MA, Coleman King SM, et al. An effective approach to high blood pressure control: a science advisory from the American Heart Association, the American College of Cardiology, and the Centers for Disease Control and Prevention. J Am Coll Cardiol
© 2014 American Academy of Physician Assistants.