Hypertension – JNC 8 Guideline: Henry R. Black, MD, Michael A. Weber, MD and Raymond R. Townsend, MD
Reporter: Aviva Lev-Ari, PhD, RN
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http://www.medscape.com/viewarticle/820407?src=wnl_edit_specol&uac=93761AJ
Hypertension Guidelines: Same Data, Different Conclusions
February 11, 2014
Henry R. Black, MD: Hi. I’m Dr. Henry Black. I’m an adjunct professor of medicine at the Langone NYU School of Medicine and a former president of the American Society of Hypertension. I’m here today with 2 of my colleagues. Michael, would you introduce yourself?
Michael A. Weber, MD: Yes. I’m Michael Weber. I’m a professor of medicine at State University of New York Downstate College of Medicine and the editor of the Journal of Clinical Hypertension.
Dr. Black: Ray?
Raymond R. Townsend, MD: I’m a professor of medicine at the University of Pennsylvania. I carry a card that says I’m a nephrologist but I mostly do hypertension care. I was lately part of the appointed JNC 8 panel and also served on the US advisory board for the Medtronic SYMPLICITY-HTN 3 hypertension trial, and I’m current vice president of the American Society of Hypertension (ASH).
Dr. Black: One of the things I want to talk about today is guidelines. Both of you have authored and been part of guideline committees. I was part of the so-called JNC 6 and JNC 7 but not a part of JNC 8. So, Michael, could you review what your guideline said and where it came from?
Dr. Weber: Yes. I was involved as the coordinator of a large group of expert authors of the ASH and the International Society of Hypertension (ISH) guidelines. [1] They were written primarily to provide what you might call a curriculum on how to manage hypertension in the community. That said, they were very much based on the available evidence, so they do constitute guidelines. But we wrote them in such a way as to be easily usable by people working on the frontlines of medicine.
Dr. Black: Ray, what about JNC 8, which, by the way, I’m not sure should be called JNC 8. [2] The Joint National Committees were appointed by the National High Blood Pressure Education Program, and that was disbanded several years ago. So how come you can still call yourself JNC 8?
Dr. Townsend: Well, if I understand the phenomenon correctly, Henry, the National Heart, Lung, and Blood Institute (NHLBI) actually convened this panel. My understanding is that they convened several of the previous Joint National Committee panels as well.
Dr. Black: All of them, in fact.
Dr. Townsend: Exactly. So we really saluted the NHLBI in 2008 when the 18 or so of us were first put in a room in Bethesda and were charged with writing the next hypertension guideline in the United States — and to do it in a somewhat different manner such that it would be entirely, to the best it can be, evidence-based as opposed to being consensus-based. At least that was the charge that we were given in September 2008 when we first met.
Dr. Black: I’d like to talk about that a little bit. You had 11 recommendations, I believe, in what was published. Six of them — more than half — ended up as expert opinion anyway. How come that happened? Why were so few recommendations based on trial evidence?
Dr. Townsend: We began the process in the JNC 8 by developing what were called the critical questions. We came up with 23 critical questions from our parlay with the various primary care doctors in our various institutions across the country. We felt that these were pretty important questions in the current management and evaluation of blood pressure. We couldn’t do 23 questions so we decided on 5, and of those 5, the 3 most critical ones are the core of what became the US guidelines in 2014 by the panel appointed to the Joint National Committee. The issues that we faced with respect to making the recommendations began first with the summation of the evidence. So each of the questions that we developed for JNC 8 had to have a certain process laid out by which a query was made through all of the different databases. It wasn’t just a PubMed search; this was fully vetted, and all the background information is available. You will see that we searched a wide range of sources.
Once the question was written and we had the data back, we had to manually go through the thousands of hits that we got through the process and grade them based upon preset criteria for what is an acceptable-, good-, fair-, or poor-quality randomized clinical trial. We consciously made the choice from the get-go that we would only accept clinical trial evidence for the report itself. We looked at meta-analyses. We looked at other things. But for distilling it down to what became the evidence base, we only used randomized clinical trials. That’s been a difference, for example, between our approach and the European approach.
ASH/ISH Guidance
Dr. Black: How about yours, Michael? How different was what you did in your report, which I won’t call a guideline?
Dr. Weber: Well, it was intended to be more than just a report, but that said, it’s strange that we were influenced predominantly by the same trials that the JNC 8 panelists were influenced by. In other words, we looked at SHEP. [3] We looked at Syst-Eur. [4] We looked at HYVET. [5] We looked at all of the studies that we’re all very familiar with and decided how to be influenced. We were more liberal, though. We were not as rigid (or as meticulous, depending on which word you want to use), as the JNC 8 group. We were willing to be influenced by what we thought was credible and useful information. Ray, in the end, wasn’t your dilemma that you wanted it to be evidence-based rather than consensus-based? But when the evidence wasn’t as complete as it should have been to answer these questions, you didn’t have a consensus and you didn’t quite have the evidence you wanted. You must have been aware that it was a difficult assignment. The further you went into it, you must have become aware that it was getting harder and harder to do what you had set out to do.
Dr. Townsend: Of course. The other charge we had, besides writing a guideline based on evidence, was to identify gaps in the knowledge base. We felt that that was one of the contributions that we should make as a group after sifting through what amounted to mountains of information, much of which was chaff and not wheat. The number of really useful trials that are rigorous enough to come to a conclusion that helped us define what is and what is not elevated blood pressure. When does the risk of treating it exceed the risks of benefit so that we have a cut-off for what is and is not hypertension? What goal should we treat blood pressure to? How should we do that with medication? Those were the 3 critical questions that we came down to, but one of the problems that we faced — and we all knew this going in — is that we have fairly good evidence for diastolic blood pressure thresholds and diastolic blood pressure treatment goals. However, there is very little on systolic, aside from the 160 mm Hg and higher that was popularized in the late ’80s when SHEP, [3] Syst-Eur, [4] STONE, [6] Syst-China,[7] HYVET, [5] and all of the other trials were either in their pilot phase or actually in their full clinical trial stage. What we lacked was really definitive evidence on the 140-160 mm Hg range for systolic blood pressure, particularly in the population at greatest risk of having that kind of blood pressure: those who are 60 years of age and older.
150 vs 140 mm Hg in Patients Aged 60-80 Years
Dr. Black: So, what’s a doctor to do who has to face patients like that getting conflicting advice? I would hate to be in that position for a condition I didn’t know anything about. How do the doctors out there who treat most everybody — how are they supposed to deal with these seemingly conflicting guidelines? For example, the 150 mm Hg recommendation for people over 65 — that really wasn’t tested either. [ Editor’s Note: For people ≥ 60 years of age, JNC 8 recommends a goal of < 150/90 mm Hg, whereas the ASH/ISH guidance recommends < 140/90 mm Hg. ] The ACCORD study, [8] for example, which was an important study and a relatively recent one, didn’t test 150 against 140 mm Hg; it tested 140 against 120 mm Hg. So where did the 150 come from?
Dr. Townsend: The 150 mm Hg came from the following: Trials like SHEP and Syst-Eur enrolled people at systolic pressures of 160 mm Hg or higher and randomly assigned them either to active drug therapy or to placebo. The blood pressure during drug therapy in Syst-Eur and in SHEP was in the 140s range.
Dr. Black: But that wasn’t what was tested.
Dr. Townsend: We tried to address the question based upon our understanding of the best way to interpret what evidence we do have in the clinical trial. We acknowledge that there are no good- or fair-quality randomized clinical trials (particularly in the United States) that tested 140 mm Hg vs 160 mm Hg as a systolic blood pressure goal. So we acknowledged that from the get-go, but you’ve got to say something about what to do in that particular situation and base it as best as you can on your understanding of what we do have in terms of clinical trial data. I won’t call it evidence at this point; I’ll simply call it data. Those were the achieved levels of blood pressure in the treatment group, whereas it was in the high 150s in the placebo group. So there is a 10-15 mm Hg spread. It appeared safe to lower the blood pressure down into the 140s range in those 60 years of age and older, and it had benefit associated with it. Now, the trial didn’t test 140 mm Hg vs 160 mm Hg, but at the end of the day what we had that we could tether to was that at least it seemed to us that when you got blood pressure below 150 mm Hg, you did benefit without excessive harm. That was the message from the first recommendation.
Dr. Black: Michael, would you like to comment on that?
Dr. Weber: To be fair to the JNC 8 report or the report of the JNC 8 panelists, they acknowledge throughout the document — almost to a point, Ray, where I wonder whether the same authors wrote different parts of the report — they acknowledge that there were gaps. They do acknowledge that they could not exclude the possibility that 140 mm Hg might be a better outcome than 150 mm Hg but there just isn’t the evidence. There were a couple of trials that looked at 140 mm Hg vs 150 mm Hg. They were underpowered. They were poorly performed. The data were basically useless. Ray is absolutely correct. Anything we know about less than 140 mm Hg compared with higher achieved blood pressures comes from analysis of trials where this was not the, as it were, primary endpoint. So you have to use a somewhat lower level of evidence.
There’s no question that Ray is right, that SHEP did show that less than 150 mm Hg was better than more than 150 mm Hg. [3] I’m not sure you can say that about Syst-Eur because they didn’t give their on-treatment values. [4] As best as I can calculate, Ray, using the data that you published as the appendix — hundreds and hundreds of pages, and thank you that you did — that they were probably comparing 151 vs 161 mm Hg. So they technically showed that less than 160 mm Hg is better than more than 160 mm Hg. The only trial that showed that less than 150 mm Hg is better than more than 150 mm Hg as a prespecified endpoint was HYVET. [5] But that trial was in people over 80 years of age. In the ASH/ISH guideline — and also in the JNC 8 and European guidelines — it’s implicit; everyone agrees that if you’re over the age of 80, less than 150 mm Hg is good enough. The dispute, of course, Ray, is between 60 and 80 years. I guess the argument would be — and I don’t want to sound like I’m an advocate for the minority group who dissented with the opinion — the argument would be that if it turns out that 140 mm Hg really is better than 150 mm Hg (ie, that you’re better off being at, let’s say, 135 mm Hg rather than 145 mm Hg in terms of strokes, heart attacks, and major outcomes), aren’t we taking perhaps an unnecessary risk in relaxing the goal? Wouldn’t we be more responsible and prudent to say, “Let’s stay with 140 mm Hg until we can be sure that it’s okay to go with 150 mm Hg”?
Dr. Townsend: We debated this for over a year, Michael, and you can imagine that it was not a very placid give-and-take. There was passion on all sides with this particular recommendation. We uniformly agreed on most things in JNC 8 with the sole exception of recommendation #1, to the point where we acknowledged as a committee exactly what you just said, which is why we put the corollary recommendation in after recommendation #1. We made the point in the abstract and in the end of the article that clinical judgment trumps a guideline. The one thing we never said was that it was okay to take drug away from someone who is over age 60 years and let their blood pressures come up. There are no data on that. We were careful to make sure that in our message to primary care providers (JNC 8 was written for primary care), we were not recommending taking people off drug in order to let their blood pressures drift up, but I acknowledge that what you said may have merit. But when we had to come down with a number that we would choose for the systolic blood pressure, the thing we felt we could defend the most was the 150 mm Hg.
Dr. Black: I just want to highlight one thing that you said that we also said in JNC 6 and in JNC 7: that the individual clinician’s judgment when dealing with the individual patient will always trump whatever a guideline says about a population. I think that’s very critical. So if the doctor or practitioner thinks that the patient is doing fine at 138 mm Hg, don’t take away the medicine. If they think they’re doing fine at 128 mm Hg, don’t take away the medicine. I think that’s a message that we have to reinforce until we can prove convincingly that the higher goal is better.
I’d like to thank you both for your time. This is a very interesting issue. I don’t think this is over, and I think it’s very nice that we can talk about it. Thank you very much.
References
- Weber MA, Schiffrin EL, White WB, et al. Clinical Practice Guidelines for the Management of Hypertension in the Community. J Clin Hypertens (Greenwich). 2014;16:14-26.
- 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. 2013 Dec 18. [Epub ahead of print]
- SHEP Cooperative Research Group. Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). JAMA. 1991;265:3255-3264. Abstract
- Staessen JA, Fagard R, Thijs L, et al; The Systolic Hypertension in Europe (Syst-Eur) Trial Investigators. Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension. Lancet. 1997;350:757-764. Abstract
- Beckett NS, Peters R, Fletcher AE, et al; HYVET Study Group. Treatment of hypertension in patients 80 years of age or older. N Engl J Med. 2008;358:1887-1898. Abstract
- Gong L, Zhang W, Zhu Y, et al. Shanghai trial of nifedipine in the elderly (STONE). J Hypertens. 1996;14:1237-1245.Abstract
- Wang J, Staessen JA, Gong L, Liu L, for the Systolic Hypertension in China Collaborative G. Chinese trial on isolated systolic hypertension in the elderly. Arch Intern Med. 2000;160:211-220. Abstract
- Cushman WC, Evans GW, Byington RP, et al; ACCORD Study Group. Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med. 2010;362:1575-1585. Abstract
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