The Critics of ALLHAT Also Reject JNC 7

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http://www.medscape.com/viewarticle/455990

 

The Critics of ALLHAT Also Reject JNC 7Linda Brookes, MSc

Three New York researchers, including John H Laragh, MD (New York

Hospital/Cornell University Medical Center, New York, NY), founder of the

American Society of Hypertension (ASH), recently challenged the findings of

ALLHAT (the Antihypertensive and Lipid-Lowering treatment to prevent Heart

Attack Trial) in the American Journal of Hypertension.[1-3] Subsequently, at a

press briefing held in New York City during the 18th Annual Scientific Meeting

of ASH, they extended their criticisms to the recently released Seventh Report

of the Joint National Committee on Prevention, Detection, Evaluation, and

Treatment of High Blood Pressure (JNC 7).[4,5] They believe that JNC 7 has been

inappropriately based on the ALLHAT results. Dr. Laragh, along with Lawrence M

Resnick, MD (Weill College of Medicine, New York, NY) and Jay Meltzer, MD

(Columbia University of Physicians and Surgeons, New York, NY) all expressed

their opposition to the way the JNC guidelines have been produced and spoke out

about what they see as intimidation toward any criticism of the

government-produced JNC 7 report.

The " Two Basic Types " Theory of Hypertension Was Ignored

Dr. Laragh is highly critical of the overall development of the JNC guidelines.

Over the past 25 years during which JNC reports have been produced, science has

leaped forward but JNC has leaped nowhere, he declared, adding that the latest

recommendations are little different from the first JNC report,[6] published in

1977 after it was discovered that blood pressure could be lowered with

diuretic-based therapy. Since that time, JNC has repeatedly recommended the use

of diuretics. In JNC 5, ACE inhibitors and beta-blockers were added as

first-line therapy, but although the recommendations were based on evidence from

clinical trials, these 2 classes of agents were removed in JNC 6 and JNC 7,

respectively, he noted.

 

Dr. Laragh proposes that 2 causes of hypertension be recognized: salt and

increased plasma renin. According to Laragh, salt accounts for 30% to 35% of the

incidence of hypertension, so many patients only need a desalting drug such as

chlorthalidone or hydrochlorothiazide (HCTZ), or spironolactone, which Dr.

Laragh prefers as a safer alternative and which is also off patent and therefore

inexpensive. The other 50% to 60% of people with high blood pressure have

hypertension caused by high plasma renin (plasma renin activity [PRA] > 0.65

ng/mL/h).

 

According to Dr. Laragh, the only reason to treat high blood pressure is not to

correct the blood pressure levels per se, but rather to avoid the future

occurrence of MI, stroke, renal failure, or heart failure, and the only drugs

that are known to protect against these are the anti-renin system drugs, ie, ACE

inhibitors, angiotensin receptor blockers (ARBs), and beta-blockers. All of

these agents lower or block renin and all give measurable and immediate

protection from MI, stroke, heart and kidney failure. Dr. Laragh takes issue

with the fact that although the literature on this is extensive, none of it was

mentioned in the ALLHAT or the JNC 7 reports.

 

As a result of this simple dichotomous analysis of hypertension, patients in

whom diuretics like chlorthalidone, HCTZ, or spironolactone are not effective

should be switched to an antirenin drug. Renin testing, which is now widely

available, can be used to more quickly identify whether a patient has salt

(low-renin) hypertension or high-renin hypertension. Thus, two thirds of all

hypertension can be corrected with monotherapy, according to Dr. Laragh. This

can be done because it involves using a drug mechanistically, which it is only

possible to do with the correct drug. However, there can be no such certainty

when patients are given 3 drugs. Dr. Laragh noted that in ALLHAT, the diuretic

was continued indefinitely throughout the duration of the trial, with other

drugs added on. Thus the negative effects of the diuretic canceled out the value

of the antirenin drug. Around 63% of patients in ALLHAT took 3 drugs to control

their blood pressure, whereas, according to Dr. Laragh, 65% of his patients are

controlled with 1 drug.

 

In support of his theory and practice, Dr. Laragh cites ANBP2 (the Second

Australian National Blood Pressure Study),[7] which compared treatment with a

desalting drug, hydrochlorothiazide (HCTZ), to treatment with an antirenin

agent, enalapril. Patients who did not respond to the first drug were switched

to the other. After 5 years, the ACE inhibitor was found to be superior to a

diuretic for correcting hypertension, and monotherapy in two thirds of patients

was not only found to be possible but superior. This result was achieved because

each patient received the right drug, thus confirming his theory, Dr. Laragh

concludes.

ALLHAT and JNC 7 Express -- Unbelievably Fast?

In his critique, Dr. Melzer questioned why both the ALLHAT and JNC 7 reports

appeared as " JAMA express, " for which the peer-review process time is 24-48

hours and the time for authors' response is 72 hours. In the case of ALLHAT, Dr.

Meltzer doubts that the report could have been reviewed within this period of

time or that all the many authors could have responded within 72 hours. In the

case of JNC 7, he questions the need for an express version of a report that

essentially made only 2 changes since JNC 6: the creation of the category

" prehypertension " and the recommendation, based on ALLHAT, that most patients

should be started on a diuretic.

 

Dr. Meltzer also criticized the ALLHAT report for basing its conclusion on a

secondary endpoint when the trial was originally intended to make

recommendations only on the basis of the results of its primary endpoints.

Secondary endpoints constitute useful data, but are collected mainly for

hypothesis generation and the elucidation of possibilities for further studies,

Dr. Meltzer pointed out. Another change in ALLHAT since its rationale and design

was published[8] was its appearance as a study of first-step therapy. However,

ALLHAT could not be a first-step study because 90% of patients were already on

antihypertensive medications for an unknown number of years before they were

entered into the trial. In contradistinction to most other studies of this

nature, there was no washout period in ALLHAT, Dr. Meltzer noted. Initial blood

pressure was never recorded, so there was no baseline on which to judge

first-step response, he declared. To call ALLHAT a study of first-step response

is post hoc reasoning, he believes.

Prehypertension: Creating More Patients " by Fear "

Dr. Laragh referred to the new JNC 7 category of prehypertension as " creating 45

million more patients by fear. " No one knows whether " prehypertension " really

exists. It does not define anything; it only guesses at what might happen, he

stated. His colleague, Dr. Resnick, said that the idea of calling people with

blood pressure of 120/80 mm Hg prehypertensive is " the biggest garbage I have

ever heard in my life. " He stated that in the early years of treating

hypertension, the aim was to treat the people who need to be treated and to

leave the others alone, not make their lives more difficult. That focus has been

lost now, because everyone in a population is regarded as the same. Instead of

this general approach, however, the approach should be tailored for individual

people, according to Dr. Resnick, and he hopes that most doctors will not take

this new category seriously and that the population will not be worried about

" this stuff. "

 

Dr. Meltzer pointed out that there is nothing new about prehypertension, since

it was previously called high normal. It was associated with an increased

cardiovascular risk, but the degree of risk is very small and patients are not

always willing to change their lives in order to improve a statistic that may be

far in the future.

 

Dr. Laragh strongly believes that the lifestyle changes recommended for

prehypertensive individuals will not work because they are too difficult for

people to follow. Dr. Resnick agreed, saying that they will only work in a

formal program.

Individual Therapy for Individual Patients

Dr. Resnick believes that physicians are being told to practice as if every

patient were the same, whereas the underlying principle of practice over the

past 30 years has been to find out about each individual patient and decide what

the best drug or advice is for that patient. Large numbers of patients are not

needed to demonstrate an effect; in fact, the larger the clinical trial, the

more irrelevant it is for the doctor treating patients, Resnick believes. Such

trials are not a good basis for guidelines as to what is the best drug for

patients. The best a physician can do is to look at the individual. It is easy

to see whether patients are young or old, black or white, etc, and to do tests

such as renin measurement to find out something that allows the physician to

judge what is best for that patient. This is the normal medical approach and in

the long term it will be cheaper; the patient will be on fewer medicines and on

lower doses, Dr. Resnick believes.

Conflict of Interest

The JNC guidelines were originally suggestive and now they are becoming

coercive, Dr. Laragh believes. He sees a major conflict of interest in the

governmental operation. He claims that physicians are not free to criticize the

National Institutes of Health. " I no longer need huge government grants, so I

can tell them to go to hell, " he joked, but stressed that other researchers may

risk their livelihood in doing so.

References

Laragh JH, Sealey JE. Relevance of the plasma renin hormonal control system

that regulates blood pressure and sodium balance for correctly treating

hypertension and for evaluating ALLHAT. Am J Hypertens. 2003;16:407-415.

Abstract

Meltzer JI. A specialist in clinical hypertension critiques ALLHAT. Am J

Hypertens. 2003;16:416-420. Abstract

Resnick LM. Why we can't translate clinical trials into clinical practice in

hypertension. Am J Hypertens. 2003;16:421-425. Abstract

US Department of Health and Human Services. JNC 7 Express. The Seventh Report

of the Joint National Committee on Prevention, Detection, Evaluation, and

Treatment of High Blood Pressure. Available on the NHLBI web site at

http://www.nhlbi.nih.gov or from the NHLBI Health Information Center, PO Box

30105, Bethesda, MD 20824-0105. Phone: 301-592-8573 or 240-629-3255 (TTY); Fax:

301-592-8563.

Chobanian AV, Bakris GL, Black HR, et al, and the 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. 2003;289:3560-3572.

Report of the Joint National Committee on Detection, Evaluation, and

Treatment of High Blood Pressure. JAMA. 1977;237:255-261. Abstract

Wing LMH, Reid CM, Ryan P, et al, for the Second Australian National Blood

Pressure Study Group. A comparison of outcome with angiotensin-converting-enzyme

inhibitors and diuretics for hypertension in the elderly. N Engl J Med.

2003;348:583-592. Abstract

Davis BR, Cuttter JA, Gordon DJ, et al. Rationale and design for the

Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack trial

(ALLHAT). Am J Hypertens. 1996;9:342-360. Abstract

 

 

2003 Medscape.

 

 

 

 

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