In the JournalsPerspective

New guideline for management of high BP in adults released

A new guideline for the management of high BP in adults, developed by the Eighth Joint National Committee and containing nine recommendations and a treatment algorithm, has been published online in JAMA.

The guideline provides evidence-based recommendations for the management of high BP, with different BP goals and treatments recommended for patients based on age, race/ethnicity, kidney function and diabetes status.

Most notably, the Eighth Joint National Committee (JNC 8) loosened the recommended goal for systolic BP in older adults.

Target goals changed in some patients

The committee aimed to base recommendations on evidence from randomized clinical trials and found no evidence that setting a systolic BP goal <150 mm Hg in the general population aged at least 60 years provided any additional clinical benefit. Therefore, the guideline recommends that if treatment of high BP is to be started in this population, the treatment goal should be systolic BP <150 mm Hg and diastolic BP <90 mm Hg.

However, if a patient in that population is already being treated for high BP and has achieved a lower systolic BP, such as <140 mm Hg, treatment need not be adjusted if no adverse effects on health or quality of life are observed, according to the guideline.

The committee found no evidence for a systolic BP goal in patients younger than 60 years with hypertension or for a diastolic BP goal in patients younger than 30 years with hypertension. The guideline advises treating patients younger than 60 years with hypertension to a goal of systolic BP <140 mm Hg and diastolic BP <90 mm Hg.

“In the absence of any [randomized controlled trials] that compared the current [systolic] BP standard of 140 mm Hg with another higher or lower standard in this age group, there was no compelling reason to change current recommendations,” Paul A. James, MD, of the University of Iowa, and colleagues wrote in the guideline. Further, they wrote, participants in studies showing clinical benefits to achieving diastolic BP <90 mm Hg also usually achieved systolic BP <140 mm Hg, and there was no way to determine whether the clinical benefit was a result of improved diastolic BP, improved systolic BP or both.

The recommended treatment goal for patients aged at least 18 years with chronic kidney disease (CKD) and diabetes is systolic BP <140 mm Hg and diastolic BP <90 mm Hg. The committee noted insufficient evidence of BP treatment goals for patients aged at least 70 years with CKD; for this group, “antihypertensive treatment should be individualized, taking into consideration factors such as frailty, comorbidities and albuminuria.” The common recommendation of a systolic BP goal <130 mm Hg in patients with diabetes and hypertension is not supported by results from high-quality randomized clinical trials, according to the committee.

Four drug classes recommended

Initial antihypertensive treatment in the general nonblack population, including those with diabetes, is supported, based on moderate evidence. The treatment plan should include:

  • Thiazide-type diuretics.
  • Calcium channel blockers.
  • ACE inhibitors.
  • Angiotensin receptor blockers.

Beta-blockers are not recommended for initial treatment because one study showed that use was associated with a higher rate of stroke compared with use of angiotensin receptor blockers (ARBs). Alpha-blockers are not recommended for initial treatment because one study showed that patients who used them had worse cerebrovascular, HF and other CV outcomes compared with those who used diuretics.

The following classes of drugs are not recommended for first-line therapy because of a lack of good clinical evidence comparing them with the four recommended classes: dual alpha1- and beta-blocking agents, vasodilating beta-blockers, central alpha2-adregenic agonists, direct vasodilators, aldosterone receptor antagonists, peripherally acting adrenergic antagonists and loop diuretics.

For black patients with hypertension, including those with diabetes, the committee recommended first-line therapy with a thiazide-type diuretic or a calcium channel blocker (CCB). This recommendation is based on an analysis of the black patient subgroup of the ALLHAT trial, in which diuretics were more effective at improving cerebrovascular, HF and other CV outcomes in that subpopulation than ACE inhibitors, and those using ACE inhibitors had a 51% higher rate of stroke than those using CCBs, whereas clinical outcomes for those using diuretics and those using CCBs were similar.

For adults with CKD and hypertension, regardless of race or diabetes status, “initial (or add-on) antihypertensive treatment should include an ACE [inhibitor] or [angiotensin receptor blocker] to improve kidney outcomes,” the committee wrote.

Finally, if goal BP is not achieved 1 month after initial therapy, the dose should be increased or a second drug from one of the four recommended classes should be added. A third drug should be added if adding the second drug does not enable the patient to reach goal BP, but ACE inhibitors and ARBs should not be used in the same patient, according to the guideline.

If three drugs from the recommended classes do not enable the patient to reach goal BP or the patient is contraindicated for any of those drugs, a drug from a nonrecommended class may be prescribed. If goal BP still cannot be attained or the patient’s case is considerably complex, a referral to a hypertension specialist is recommended.

The guideline contains an algorithm for hypertension management. However, the committee noted that the algorithm “has not been validated with respect to achieving patient outcomes.”

A break from JNC 7

In a related editorial, Eric D. Peterson, MD, MPH, of Duke University Medical Center, J. Michael Gaziano, MD, of Brigham and Women’s Hospital, and Philip Greenland, MD, of Northwestern University Feinberg School of Medicine, said the new guideline differs from JNC 7, which was released in 2003. The new guideline raises target systolic BP goals in patients aged at least 60 years from <140 mm Hg to <150 mm Hg and eliminates the JNC 7 recommendation of a target systolic BP of <130 mm Hg for those with diabetes and kidney disease.

According to the editorialists, despite the JNC 7 target goal of systolic BP <140 mm Hg, only about half of US patients with hypertension have achieved that goal, and the JNC 8 recommendation of a target goal of systolic BP <150 mm Hg in those aged at least 60 years could mean that only about half of that population attains that mark. “Whether this change will have adverse consequences for population health is unclear, but it should be recalled that in the SHEP study, a 5-year lowering of average [systolic BP] from 155 mm Hg to 143 mm Hg resulted in a 32% reduction in cardiovascular events,” they wrote.

Additionally, they wrote, the JNC 8 guideline focus on BP target levels differs in stark contrast to the American College of Cardiology/American Heart Association guidelines on cholesterol management, which eschew specifying target levels in favor of focusing on treating those at greatest risk with more aggressive therapy. “Such divergent philosophies may cause confusion among clinicians and patients alike,” they wrote.

For more information:

James PA. JAMA. 2013;doi:10.1001/jama.2013.284427.

Peterson ED. JAMA. 2013;doi:10.1001/jama.2013.284430.

Disclosure: See the full text of the guideline for the committee members’ relevant financial disclosures. Peterson, Gaziano and Greenland report no relevant financial disclosures.

A new guideline for the management of high BP in adults, developed by the Eighth Joint National Committee and containing nine recommendations and a treatment algorithm, has been published online in JAMA.

The guideline provides evidence-based recommendations for the management of high BP, with different BP goals and treatments recommended for patients based on age, race/ethnicity, kidney function and diabetes status.

Most notably, the Eighth Joint National Committee (JNC 8) loosened the recommended goal for systolic BP in older adults.

Target goals changed in some patients

The committee aimed to base recommendations on evidence from randomized clinical trials and found no evidence that setting a systolic BP goal <150 mm Hg in the general population aged at least 60 years provided any additional clinical benefit. Therefore, the guideline recommends that if treatment of high BP is to be started in this population, the treatment goal should be systolic BP <150 mm Hg and diastolic BP <90 mm Hg.

However, if a patient in that population is already being treated for high BP and has achieved a lower systolic BP, such as <140 mm Hg, treatment need not be adjusted if no adverse effects on health or quality of life are observed, according to the guideline.

The committee found no evidence for a systolic BP goal in patients younger than 60 years with hypertension or for a diastolic BP goal in patients younger than 30 years with hypertension. The guideline advises treating patients younger than 60 years with hypertension to a goal of systolic BP <140 mm Hg and diastolic BP <90 mm Hg.

“In the absence of any [randomized controlled trials] that compared the current [systolic] BP standard of 140 mm Hg with another higher or lower standard in this age group, there was no compelling reason to change current recommendations,” Paul A. James, MD, of the University of Iowa, and colleagues wrote in the guideline. Further, they wrote, participants in studies showing clinical benefits to achieving diastolic BP <90 mm Hg also usually achieved systolic BP <140 mm Hg, and there was no way to determine whether the clinical benefit was a result of improved diastolic BP, improved systolic BP or both.

The recommended treatment goal for patients aged at least 18 years with chronic kidney disease (CKD) and diabetes is systolic BP <140 mm Hg and diastolic BP <90 mm Hg. The committee noted insufficient evidence of BP treatment goals for patients aged at least 70 years with CKD; for this group, “antihypertensive treatment should be individualized, taking into consideration factors such as frailty, comorbidities and albuminuria.” The common recommendation of a systolic BP goal <130 mm Hg in patients with diabetes and hypertension is not supported by results from high-quality randomized clinical trials, according to the committee.

Four drug classes recommended

Initial antihypertensive treatment in the general nonblack population, including those with diabetes, is supported, based on moderate evidence. The treatment plan should include:

  • Thiazide-type diuretics.
  • Calcium channel blockers.
  • ACE inhibitors.
  • Angiotensin receptor blockers.

Beta-blockers are not recommended for initial treatment because one study showed that use was associated with a higher rate of stroke compared with use of angiotensin receptor blockers (ARBs). Alpha-blockers are not recommended for initial treatment because one study showed that patients who used them had worse cerebrovascular, HF and other CV outcomes compared with those who used diuretics.

The following classes of drugs are not recommended for first-line therapy because of a lack of good clinical evidence comparing them with the four recommended classes: dual alpha1- and beta-blocking agents, vasodilating beta-blockers, central alpha2-adregenic agonists, direct vasodilators, aldosterone receptor antagonists, peripherally acting adrenergic antagonists and loop diuretics.

For black patients with hypertension, including those with diabetes, the committee recommended first-line therapy with a thiazide-type diuretic or a calcium channel blocker (CCB). This recommendation is based on an analysis of the black patient subgroup of the ALLHAT trial, in which diuretics were more effective at improving cerebrovascular, HF and other CV outcomes in that subpopulation than ACE inhibitors, and those using ACE inhibitors had a 51% higher rate of stroke than those using CCBs, whereas clinical outcomes for those using diuretics and those using CCBs were similar.

For adults with CKD and hypertension, regardless of race or diabetes status, “initial (or add-on) antihypertensive treatment should include an ACE [inhibitor] or [angiotensin receptor blocker] to improve kidney outcomes,” the committee wrote.

Finally, if goal BP is not achieved 1 month after initial therapy, the dose should be increased or a second drug from one of the four recommended classes should be added. A third drug should be added if adding the second drug does not enable the patient to reach goal BP, but ACE inhibitors and ARBs should not be used in the same patient, according to the guideline.

If three drugs from the recommended classes do not enable the patient to reach goal BP or the patient is contraindicated for any of those drugs, a drug from a nonrecommended class may be prescribed. If goal BP still cannot be attained or the patient’s case is considerably complex, a referral to a hypertension specialist is recommended.

The guideline contains an algorithm for hypertension management. However, the committee noted that the algorithm “has not been validated with respect to achieving patient outcomes.”

A break from JNC 7

In a related editorial, Eric D. Peterson, MD, MPH, of Duke University Medical Center, J. Michael Gaziano, MD, of Brigham and Women’s Hospital, and Philip Greenland, MD, of Northwestern University Feinberg School of Medicine, said the new guideline differs from JNC 7, which was released in 2003. The new guideline raises target systolic BP goals in patients aged at least 60 years from <140 mm Hg to <150 mm Hg and eliminates the JNC 7 recommendation of a target systolic BP of <130 mm Hg for those with diabetes and kidney disease.

According to the editorialists, despite the JNC 7 target goal of systolic BP <140 mm Hg, only about half of US patients with hypertension have achieved that goal, and the JNC 8 recommendation of a target goal of systolic BP <150 mm Hg in those aged at least 60 years could mean that only about half of that population attains that mark. “Whether this change will have adverse consequences for population health is unclear, but it should be recalled that in the SHEP study, a 5-year lowering of average [systolic BP] from 155 mm Hg to 143 mm Hg resulted in a 32% reduction in cardiovascular events,” they wrote.

Additionally, they wrote, the JNC 8 guideline focus on BP target levels differs in stark contrast to the American College of Cardiology/American Heart Association guidelines on cholesterol management, which eschew specifying target levels in favor of focusing on treating those at greatest risk with more aggressive therapy. “Such divergent philosophies may cause confusion among clinicians and patients alike,” they wrote.

For more information:

James PA. JAMA. 2013;doi:10.1001/jama.2013.284427.

Peterson ED. JAMA. 2013;doi:10.1001/jama.2013.284430.

Disclosure: See the full text of the guideline for the committee members’ relevant financial disclosures. Peterson, Gaziano and Greenland report no relevant financial disclosures.

    Perspective
    Randall Zusman

    Randall Zusman

    The biggest take-away from the guideline is that patient care can be individualized to meet the goals of reducing stroke, MI, HF and renal disease in a hypertensive patient population.

    It’s hard to disagree with the overall recommendations in terms of the importance of BP control. I, personally, am more aggressive in terms of treatment, and would use the lower target of 140 mm Hg/90 mm Hg rather than 150 mm Hg/90 mm Hg in elderly patients, but I think that the focus on the need to identify patients to initiate therapies that are effective when used alone or in combination and to follow patients in a focused fashion to achieve BP control is something we can all agree upon and support.

    The only thing that I found surprising was the failure to support the use of ACE inhibition and/or angiotensin receptor blockade in African-American patients with diabetes. The authors recommend starting with a thiazide diuretic or a CCB, and I think that reflects a longstanding — but perhaps not convincing — feeling that African-American patients do not respond to ACE inhibition. I think it’s a matter of dosage and titration. The evidence for the nephroprotective effect of ACE inhibitors and ARBs in diabetic patients is well established, and I would afford the African-American population that same benefit, even if it may not be associated with as great a BP-lowering effect as in the white patient population.

    I think the differentiations are very appropriate. As a cardiologist, I might have added a few others, for example the presence or absence of CAD, evidence of left ventricular dysfunction and history of arrhythmias, because under those circumstances there might be a preference for the selection of one drug over another. But the demographic subpopulations that the authors have identified are quite appropriate and apply to the largest number of hypertensive subjects.

    I would have emphasized more the potential for lifestyle modification, and perhaps at least included peripherally non-drug therapies that are potentially beneficial in resistant patient populations. The guideline also doesn’t focus much on resistant hypertension. This is an ever-expanding group of people that’s worth mentioning, and might have warranted a discussion of multidrug regimens, how to improve compliance, the importance of diet, and the use of non-drug therapies such as relaxation response, which can be very helpful in some of these patients. The authors also didn’t talk about emerging strategies, including renal denervation therapy and what role that might play in the next decade.

    Many of us were disappointed that it took so long for this document to be developed. Because these guidelines come out so infrequently, I might have taken the opportunity to broaden the scope of the commentary. Given that the number of people who have hypertension is increasing, this would have been an opportunity to provide a more forward-looking thought about where we might end up in another decade.

    People with strong family histories of hypertension or others who believe they may have symptoms related to high BP should take the opportunity to have their BP measured. If they find their values to be abnormal, they should seek to aggressively lower those numbers, given their tight correlation with CV complications, starting with lifestyle modification and moving on to drug therapy if needed.

    • Randall Zusman, MD
    • Director of Hypertension, Massachusetts General Hospital Associate Professor of Medicine, Harvard Medical School Consultant in Cardiology, Massachusetts Institute of Technology

    Disclosures: Zusman reports no relevant financial disclosures.

    Perspective
    George Bakris

    George Bakris

    The document has its pluses and minuses. The problem is that the authors were so true to the tenets of the rules of everything being evidence-based, that they put out a guideline that is written like a physics equation. Unfortunately, we are dealing with biology, not physics. My fear is that non-academic clinicians in the trenches taking care of patients are going to look at this and say ‘what are we supposed to do with this?’ The saving grace is the algorithm. It gives you a reasonable approach and is a good summary of what was trying to be said in the document. If you actually read the document, it has issues.

    I have a problem saying that if you’re an older individual, you should not be given any treatment unless your systolic BP is above 150 mm Hg. I don’t and won’t do that in clinical practice. There is a big bone of contention. Everyone agrees that if you lower systolic BP below 160 mm Hg, there is a benefit. No one’s arguing that point, and it’s certainly implicit in the guidelines. But the argument is, if your systolic BP is 148 mm Hg, and you lower it to 138 mm Hg, how much risk reduction did you get? It’s obviously less than going from more than 160 mm Hg down to 140 mm Hg, but is it still worth doing? There is no cost-benefit analysis. One is limited in saying what you can do from this. All you can say is the strength of the evidence to support these statements is what it is, and there are more unanswered practical questions than there are answered questions. The lack of an answer is not satisfying to anybody. Moreover, when you make a statement that a goal of <140 mm Hg systolic BP over 90 mm Hg diastolic BP in the general population reduces CV risk, and then you say that’s expert opinion, that’s a problem.

    It would have been nice to have a lot more on combination therapy, especially as initial therapy, and on other aspects of disease states that clinicians are faced with all the time, but either there wasn’t enough time or evidence to cover those things. I also would have liked to have seen more on ethnic groups, though there was something.
    • George Bakris, MD
    • Cardiology Today Editorial Board member

    Disclosures: Bakris is a consultant for AbbVie, Medtronic, Novartis, Relypsa and Takeda and a principal investigator for Medtronic and Relypsa.

    Perspective
    Franz H. Messerli

    Franz H. Messerli

    This report takes a rigorous, evidence-based approach to recommend treatment thresholds and medications. Supposedly, it’s very evidence-based, but when you look at the recommendations, six of them are based on consensus of opinion and only two receive a grade of A for the strongest evidence. The guidelines were promised to be evidence-based, but when you scrutinize them, they are not.

    By and large, they are very thorough, but I have a few points of contention. One, 24-hour ambulatory BP monitoring is nowhere to be found. That’s a concern, because that’s a very useful tool to assess need for treatment, white-coat hypertension, secondary hypertension, etc. Two, they used the term `thiazides.’ That’s very disappointing, because there’s absolutely no morbidity and mortality evidence for hydrochlorothiazide in its usual dose of 12.5 mg to 25 mg. There’s only evidence for chlorthalidone and indapamide, and to lump them together is in my opinion not acceptable. Instead of saying in Recommendation 6 that a thiazide-type diuretic was more effective than a calcium channel blocker or an ACE inhibitor, why not say that chlorthalidone was more effective than amlodipine or lisinopril? This may not be a class effect. This most likely is an individual drug effect, which should be identified as such. Three, they still recommend thiazides as initial therapy. This may be acceptable in the elderly patient, but in my way of thinking, given the obesity epidemic that we are facing in this country and the high risk for developing new-onset diabetes, a thiazide should not be initial therapy in any patient who is at risk. We have CCBs, angiotensin receptor blockers and ACE inhibitors, all of which are metabolically much more patient-friendly than all the thiazides.

    What is good to see is that beta-blockers have been relegated to add-on fourth-line therapy. But again, this is based on pure consensus; there’s no good evidence that they should be fourth-line at all. Nor is there any evidence for any other fourth-line therapies except possibly for spironolactone.

    The authors tried to be so strict in going with only randomized trials, and they failed to a certain extent. Unfortunately, they completely neglected meta-analyses. Those have their drawbacks and are not as convincing as powerful randomized trials, but nevertheless they can be helpful in giving us some hints on what should be done.

    Another issue is that Table 4, “Evidence-Based Dosing for Antihypertensive Drugs,” is purely cherry-picked. I don’t understand why, for instance, among the CCBs, diltiazem is there but felodipine is not; among the thiazide-type diuretics, they list bendroflumethiazide, which is not available in the US; and among the ACE inhibitors, ARBs, and beta-blockers, there are some that are left out. “Evidence-based” here means what? That they reduce morbidity and mortality? That’s certainly not true for the entire list, especially for hydrocholorothiazide. If it means evidence that they lower BP, then yes, I agree, but numerous other drugs not in the table also have been shown to lower BP.

    These authors were hand-picked by the National Heart, Lung and Blood Institute, and then for one reason or another, that institution no longer wanted to be part of it, and shifted it to the American Heart Association, the American College of Cardiology and the CDC. Subsequently, those bodies decided to come up with their own guidelines, which were published in November. Not surprisingly, the hand-picked authors have now decided to publish their own version on which they worked for years.

    • Franz H. Messerli, MD
    • Cardiology Today Editorial Board Member

    Disclosures: Messerli is an ad hoc consultant for Abbott, Daiichi Sankyo, Ipca Laboratories, Medtronic, Pfizer, Servier and Takeda.

    Perspective
    Keith C. Ferdinand

    Keith C. Ferdinand

    Overall, I congratulate the committee for what they have done. The new guideline’s most important message is that evidence based on hard outcomes will be necessary going forward in the crafting of any guideline to assist clinicians in making the best care decisions they can. We have to make sure we’re not only doing the right thing by patients, but that we are avoiding unnecessary harm.

    These recommendations should be integrated with the lifestyle guideline promulgated by the American College of Cardiology and the American Heart Association. Lifestyle remains the bedrock to prevent hypertension and to control the progression of hypertension in most patients.

    I’m concerned that the arbitrary cutpoint in patients 60 years and older for initiating therapy at ≥150 mm Hg systolic BP or ≥90 mm Hg diastolic BP may lead to undertreatment. BP has a direct, linear and persistent relationship to CV outcomes. It’s unreasonable to suggest that a very healthy, active 60-year-old person will lack benefit from earlier intervention when the evidence is that remodeling of the small arteries, progression of LV hypertrophy, renal dysfunction and ischemic heart disease are all directly related to elevated BP at all levels above the optimal. I’m also concerned with the categorical removal of the treatment goal of <130 systolic BP for persons with diabetes. Although the ACCORD primary endpoint was not met, this does not necessarily mean that the secondary endpoint of stroke will not have profound benefit in a large population, especially those persons with a family history of stroke or African Americans, who have a markedly increased risk for stroke, especially at younger ages. Although secondary endpoints can’t be the driving force behind main guideline recommendations, they clearly have clinical importance, and a young person — especially an African American with type 2 diabetes, microalbuminuria or chronic kidney disease — would benefit from protection from decades of exposure. Waiting for 140 mm Hg over 90 mm Hg may not do that.

    The differentiations based on age, race and kidney status are reasonable based on the evidence that has been presented. However, combination therapy, although given as an alternative in the algorithm, probably should be considered more appropriate as a first-step agent for most persons middle-aged and older, and persons with stage II hypertension. Large managed care populations such as Kaiser have been able to show excellent BP control levels using first-step combinations of lower levels of medications. Some of the differentials based on age are clearly supported by the evidence. However, we have an increasingly large cohort of active persons 60 years and older, and I would hate to see them penalized. African Americans have a higher rate of kidney failure, premature stroke, HF and MI, and loosening goals may not be best for that population going forward.

    One of the biggest things that has been overlooked is the fact that this is not the eighth report of a joint national committee. Joint national committees are creatures of the National High Blood Pressure Education Program of the NHLBI. They reflect the 4 decades’ work of the NHLBI in increasing public awareness for the prevention and treatment of high BP. Those efforts cannot be reproduced by simple evidence-based reports of a limited number of trials. Indeed, I applaud the table that compares JNC 7 to JNC 8. It should be pointed out that there were 39 professional, public and voluntary associations; multiple federal agencies; and other reviewers involved in an integrated and complex decision-making process for JNC 7. This new guideline, not exactly JNC 8 per se, is primarily based on a somewhat restricted view of the literature. We don’t have evidence based on a randomized clinical trial that jumping out of an airplane with or without a parachute makes a difference in terms of mortality, but no one would do that study.

    • Keith C. Ferdinand, MD, FACC, FAHA
    • Professor, Tulane University School of Medicine, New Orleans Chair, National Forum for Heart Disease and Stroke Prevention Member, National High Blood Pressure Education Coordinating Committee of the National Heart, Lung and Blood Institute, 1994-2007 Sub-chair, JNC 6

    Disclosures: Ferdinand serves on the speaker’s bureau for AstraZeneca, Forest and Takeda; receives grant/research support from Eli Lilly; and is a consultant for AstraZeneca, Daiichi Sankyo and Forest.