JNC 7: The debate begins

Susan Jeffrey

May 21, 2003

New York, NY - Authors presented new JNC 7 guidelines for the first time at a medical meeting at the American Society of Hypertension's 18th Annual Scientific Meeting and Exposition and received some live feedback from other hypertension experts, not all of it positive.

The new national hypertension guideline, known as the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7), was first published online last week and released officially at a press conference at the National Heart Lung and Blood Institute (NHLBI).

Dr Aram V Chobanian
(Source: Boston University Medical Center)

Dr Aram V Chobanian (Boston University School of Medicine, MA) was first author on JNC 7 and gave the presentation here. "There was a feeling that the classification of blood pressure needed to be simplified," Chobanian said of the new document. "The direction of the report was to come up with precise, streamlined guidelines for practicing clinicians. The consensus that was achieved was remarkable on the report; there were no dissenting votes on the part of the coordinating committee members," he said.

Dr Edward J Roccella
(Source: Online NewsHour/PBS)

Coauthor Dr Edward J Roccella (NHLBI), who also cochaired the session, said, "JNC 7 was a very labor-intensive effort, but this effort won't matter unless the results are applied in clinical practice. The recommendations must be used."

The guidelines are the work of the National High Blood Pressure Education Program Coordinating Committee, coordinated by NHLBI, a coalition of 39 major professional, public, and voluntary organizations and seven federal agencies. A truncated version of JNC 7 is available online now [see Ref 1] and will be published in the May 21, 2003 issue of the Journal of the American Medical Association. The full report will appear in Hypertension: Journal of the American Heart Association later this summer.

Diuretics first . . .

At the meeting, however, the new guidelines were met with some reservations. During the question-and-answer period after their presentation, debate was raised on several pointsamong these was the strong recommendation that "most" patients with hypertension be on diuretics.

JNC 7 authors put forward basically the same conclusion as that from the recently published Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)that, given the economic advantage of diuretics and similar benefits from each of other drugs, treatment should probably begin with a diuretic. However, their recommendation is not inflexible, they pointed out.

"Without compelling indications, for stage 1 hypertension, the committee is recommending thiazide-type diuretics for most, but ACE inhibitors, angiotensin-receptor blockers, beta blockers, and calcium channel blockers still may be considered," Chobanian said. "All five classes of drugs are very effective in lowering blood pressure, and all five classes of drugs have been shown to decrease complications in a variety of clinical trials."

Why start with diuretics first? If you restrict your salt intake, which is one of the recommendations, you double the efficacy of an ACE or ARB. Why not use that?

But during the discussion period, Dr Graham MacGregor (St George's Hospital, London, UK) expressed concern that the new guidelines actually look like British guidelines from a few years ago. "But we didn't have the benefit then of knowing that all drugs reduce cardiovascular events. We now know they're all equal. Why start with diuretics first? If you restrict your salt intake, which is one of the recommendations, you double the efficacy of an ACE or ARB. Why not use that?"

He speculated most doctors would not choose themselves to start with a diuretic if they were hypertensive. In particular, he said, "Is it really right to make a large number of males who won't complain about it impotent as first-line therapy?" drawing applause from the audience.

Dr Alberto Zanchetti (University of Milan, Italy) who cochaired the JNC 7 session with Roccella, told doctors here that new European guidelines will be released in Milan next month at the European Society of Hypertension meeting.

"The very fact that the European society is preparing its own guidelines and is not simply taking the JNC 7 means there are probably some major or minor forms of disagreement in how hypertension may be seen on the other side of the ocean."

Zanchetti added that he anticipates less rigid guidelines about drug choice, for example, saying, "there are many more things under the heavens than cost."

Dr Hans R Brunner (Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland) was more blunt. "I can only say, how are you going to convince me that I should start every hypertensive patient on a diuretic? I wouldn't want it myself; I wouldn't want to give it to my patients."

The authors reply

Dr William C Cushman
(Source: World Medical Leaders [wml.com])

In an interview with heartwire , Dr William C Cushman (University of Tennessee Health Science Center, Memphis), who was a member of the ALLHAT steering committee and of the writing committee for JNC 7, discussed some of the resistance on this point.

"We didn't just base this recommendation on ALLHAT," Cushman said. "We've got a wealth of data over many decades of how well diuretics in particular lower events. But when you do a head-to-head study and the other drugs don't beat them, I think people just need to accept that and get on with doing what's best for our patients. And that means for most people, why not include the diuretic in the regimen?"

"Even though it's unpopular perhaps among many of my colleagues for me to be a proponent of diuretics, that's what the data show," he added. "Can you tell doctors, 'Well, this is what the clinical trials clearly show, but we don't believe it, so go do what you want to do, and we hope that it will be good for your patients even though we haven't proved that in trials?'"

Cushman added that, despite general impressions to the contrary, trials of diuretics have shown no significant increase in impotence over placebo. "I know it does cause impotence," he acknowledged, "but it's really rare."

Dr Jackson T Wright, Jr
(Source: ISHIB)

Fellow JNC 7 writing committee member and ALLHAT investigator Dr Jackson T Wright Jr (Case Western Reserve University, Cleveland) also pointed out that ALLHAT was not the only source for this conclusion and that their results have been replicated in a large variety of studies.

"Everyone has the right to their opinion, and I think thoughtful people will have differences in opinion," Wright told heartwire . "But I have no difficulty in suggesting that both the findings of ALLHAT and JNC 7 are valid and a reasonable interpretation of the data."

Rocella said he thinks some of the resistance is coming from people who may care for a very ill patient population with other comorbidities, where other agents may be the first choice. Their recommendation "is not to indicate that other drugs can't be used and don't have a role," he told heartwire . However, "all of the randomized trials have used diuretics to control blood pressure. They're tested, they're safe, and they have been unsurpassed in the management of hypertension."

Piling on the agents
All of the randomized trials have used diuretics to control blood pressure. They're tested, they're safe, and they have been unsurpassed in the management of hypertension.

Other concerns included the potential impact of more diabetes with the diuretic and the recommendation by the committee that after diuretics were tried and failed, other drugs should be added; that is, that both drugs should be used going forward, rather than substituting one for the other.

One questioner from the floor during the presentation pointed out that while only 30% of patients may respond adequately to any given antihypertensive drug, many more could be controlled on monotherapy if they were allowed to switch to another drug to which they might respond adequately. "I believe it's a mistake to have everyone on a diureticnot that the diuretic is a bad drug, but that it's often unnecessary to be continued in patients, many of whom can be controlled by a different drug." These patients could also then be spared the other side effects of diureticshypokalemia, hyperglycemia, gout, he added.

"It's pretty clear from the report that we are not advocating substitutions of classes of drugs across the board," Chobanian acknowledged. "The emphasis from the practical standpoint is to combine therapy to get blood pressure down and keep it down."

The emphasis from the practical standpoint is to combine therapy to get blood pressure down and keep it down.

In terms of side effects, he said, "No matter what the side effects areand I wouldn't restrict it to diureticsif gout is aggravated, if potassium can't be controlled, then certainly those drugs should not be used."

Cushman elaborated on this point. "We think it's better for public health to encourage people to use more drugs within reason than to try one and stop it and try another," he told heartwire . "The reason is that . . . they [might] stop a drug that might have beneficial effects on cardiovascular events and that we've proven in studies does and . . . use something that's inferior in preventing cardiovascular events, [and] even though it lowers blood pressure better in that patient, we don't know that that's the better way to go. It makes sense that if you lower blood pressure better that's going to be better on outcomes, but that's not true in all analyses. That's one of the most hotly debated things at this meeting."

Prehypertension: A new disease state?

Another area of some concern for many was the new classification of BP between 120 mm Hg and 139 mm Hg systolic and 80 mm Hg and 89 mm Hg diastolic as "prehypertension" in place of the previous designation of "high normal" and the removal of a recommendation for global cardiovascular risk assessment that had been included in JNC 6.

Dr Jay N Cohn
(Source: University of Minnesota Medical School)

Dr Jay N Cohn (University of Minnesota Medical School, Minneapolis) professed himself "delighted" at the committee's emphasis on the high-normal group because of their risk for cardiovascular morbid events. However, Cohn added, "I'm a little troubled by calling it prehypertension. It's creating a good deal of anxiety around the country and we certainly know not all of these people are at risk for development of high blood pressure and certainly not all of them are at risk for cardiovascular morbid events, which I think should be the focus of our therapeutic efforts anyway."

He pointed out that it is now possible to stratify risk more effectively within that normal range by looking at other factors such as arterial elasticity or microalbuminuria. "We know a lot more about vascular health today, and I wish the committee would have at least paid lip service to the fact that this opens the door for performing a more comprehensive assessment of vascular health before we embark on lifestyle and drug intervention for the life of the individual," Cohn said.

Dr Curt Furberg

Dr Curt Furberg (Wake Forest University, Baptist Medical Center, Winston-Salem, NC) was also uncomfortable about the label of prehypertension but was more concerned about the lack of emphasis on global risk assessment. "You can have the same blood pressure, and the risk of heart attack or stroke can differ by a factor of 20, which means that you really should go after the people who are at high risk," he told heartwire . "That's what the Europeans do, [that's what they do] in New Zealand and Australiahere, we don't. We are so narrow minded and compartmentalized."

How can I tell my wife I've been unfaithful to her?

Another audience member made a similar point with a bit more humor. "How can I tell my wife I've been unfaithful to her? All my life I've had patients who had blood pressures of 120/80 walk out of my office very, very happy. Now I have tell them they have prehypertension syndrome or some such. You're not making things too easy for us, because the patient is going to interpret it as hypertension."

Opportunity too good to pass up

"We spent an awful lot of time trying to come up with the right term, we went back and forth," Chobanian acknowledged. "Finally, and remarkably after about three sessions, everyone decided that prehypertension was the best term. We then presented it to members of the coordinating committee to get their reaction and also to others, and it seems to be a better term than high normal, which was not as much of an action-oriented item. But it's a difficult issue that we grappled with."

He also emphasized that these guidelines are for clinicians in more general practice. "This is not a guide for the specialists in this room, because all of you have had a lot of experience; we wanted to make it simple and straightforward."

The opportunity is there for really affecting the lifelong risk of hypertension, and I think that's worth it in the long run.

He acknowledged that it may take time and education before people understand the idea that prehypertension is something they can do something about. "On the other hand, the opportunity is there for really affecting the lifelong risk of hypertension, and I think that's worth it in the long run. We're not recommending drugs, we're recommending lifestyle changes that are not just healthy for blood pressure but for other things as well."

Another question from the floor related to the potential insurance implications of this new diagnosis. Chobanian noted they had contacted insurers and employers to gauge reaction and, similar to the new designation of "prediabetes," they felt it would not have an impact on insurability issues.

Cushman told heartwire they were a little surprised about reaction to this aspect of the guidelines. "I guess we weren't expecting as much attention and interest in the prehypertension designation, but I think I understand," he said. "We're not saying it's a disease. It really is to help identify a large segment of our population who, almost all of them, are going to develop hypertension eventually."

He said that the use of global risk assessment was dropped purposely from the new guidelines. "What risk stratification would actually do would be to say there's a group of people with hypertension that you shouldn't treat, and really right now, there's not much sympathy for that perspective within the United States, and trials have really not distinguished that."

Organized resistance

In the May 2003 issue of the American Journal of Hypertension, three editorials appear questioning the validity of findings from ALLHAT and of using large clinical trials as the basis for clinical practice guidelines. At this meeting, the reservations about ALLHAT and its interpretation expressed in these editorials became more generalized to include the new JNC 7 guidelines.

First among the editorials was one coauthored by Drs John H Laragh and Jean E Sealey (New York Hospital/Cornell University Medical Center, New York). In it Laragh and Sealey discuss a hypothesis about the nature of hypertension, maintaining that high blood pressure is caused either by an excess of renin, in about 65% of cases, or by a sensitivity to sodium, in about 35%. Any given case of hypertension, they say, relates to one or the other of these basic problems, and treatment for one type of hypertension will be ineffective for the other. Antirenin drugs include ACE inhibitors, ARBs, and beta blockers; salt-reducing drugs include diuretics and calcium channel blockers.

By determining whether a given hypertensive patient has one or the other type of hypertension by testing renin levels before beginning treatment, they say they can control patients to target BP levels with monotherapy in 65% of cases. The guidelines recommend starting with diuretics and then adding drugs without taking them away. "We don' t believe in that strategy because we believe those 50 million people with high blood pressure don't all have the same cause," Laragh told a press conference on this topic here.

Laragh and Sealey presented further data on this theory of hypertension at another session later this meeting that will be reported by heartwire .

In a second editorial, Dr Jay I Meltzer (Columbia University College of Physicians and Surgeons, New York) took issue with the JAMA Express version of the JNC 7, in which peer review of the guidelines was expedited down to a matter of hours. "It's been seven years since the last one, and we're wondering why it has to come out so fast. What is it in this that requires such urgency?" Meltzer told a press conference here.

Most objectionable to him was the change in drug recommendations from diuretics and beta blockers to diuretics in "most." He asserted that the change in recommendation in JNC 7 was based not only just on ALLHAT, but on secondary end points from ALLHAT, namely stroke and heart failure outcomes, since primary outcomes were similar.

Finally, Dr Lawrence M Resnick (Cornell University Weill College of Medicine, New York) reiterated some of the points he made in his editorial about the use of large clinical trials in hypertension that supported those made by Laragh. "For reasons that have nothing to do with medicine, I believe, doctors are being told to practice as though everyone is the same," Resnick told reporters here.

He maintained that treating hypertensive patients without finding out which type of hypertension the patient has is analogous to treating everyone with fever—an abnormal physical sign just like high blood pressure&mash;with penicillin. Not knowing the cause of the fever means the good effects of penicillin would be lost among those whose temperature was caused by other conditions not affected by the drug.

It is good clinical practice, Resnick said, to find out the cause of the fever with a test before treating. When it comes to treating hypertension, "it is the job of the doctor to find out what's best for the patient."

During the session on JNC 7, however, Dr Norman M Kaplan (University of Texas-Southwestern Medical Center, Dallas) called for doctors to throw their support behind the new guidelines, referring pointedly to the editorial by Laragh. He called Laragh "the most remarkable researcher in the field of hypertension" and noted that he would have no objection to dividing hypertensive patients on the basis of a renin assay, "but I would like to see the data, because there are none, based on that approach," Kaplan said.

"As far as I'm concerned what we have in front of us is a very clear, concise, rational, easy way to tell the world that this is how to treat hypertension, and I think that any of us who are going to bite and criticize the basic assumptions that have been made here are making a big mistake," Kaplan said. "I think we ought to get behind it and do what I think the report is all about, and that is to control more patients' hypertension," he concluded, drawing applause from the audience.

Responding to Kaplan's comment, Chobanian implied he would perhaps have been less polite than Kaplan was about the points made by Laragh et al. "I guess if I responded to that, it would only go downhill, so I won't," he said wryly.


Conflict of conspiracy theories

Furberg, who chaired the steering committee for ALLHAT but was not part of the JNC 7 writing committee, told heartwire that he saw some good features of the guidelines but was disappointed that more emphasis was not put on costs associated with hypertension treatment and, in particular, the cost savings that would be offered by using diuretics first.

"We know that one quarter of seniors have no drug benefit in their health insurance; they have to pay for their own drugs, and that the states are having real problems with Medicaid and Medicare because they're spending so much on drugs," Furberg said. "So somehow, cost is important. That's not just in hypertension, but everywhere in medicine, and that should be stated here."

Asked why he felt it was not addressed more overtly in the guidelines, he said, "Typically, we haven't addressed cost; we've been fortunate enough to be able to afford everything, and we've reached a stage now where we can't afford all the expensive drugs." But, he added, "I think the industry has a presence, seen and not seen, that would influence it."

While Furberg was disappointed that more was not made of the cost differential of choosing a diuretic first, Laragh accused the committee of sticking with diuretics to further a government agenda of cost saving. "There is a major conflict of interest in this governmental operation," he told a press conference here. "Virtually the same people have been writing the guidelines for the past 15 years, and they are paid by the governmentthey are on the government payroll big time."

I'm getting on to another age group, so I can tell them to go to hell.

"The only guy in the room able to speak out for them now is me, because I had government grants but now I've stopped doing that," Laragh said. "I'm getting on to another age group, so I can tell them to go to hell."

Cushman dismissed the suggestion that the recommendations hinged on cost savings. "Some people have said that since NHLBI sponsored ALLHAT and JNC 7 that it had a particular agenda, but NHLBI really has no motivation for people to use, say, cheaper drugs, per se. It's not paying for it. Its interest is in public health and using scientific findings to make the best recommendations to patients, so that's what it asked us to do as a committee."

During the session, Roccella noted that the committee members, the executive committee, and the reviewers served as volunteers without remuneration.


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