DR. IZZO: I am honored to moderate today’s discussion with 3 very well recognized experts in hypertension: true “doctor’s doctors,” if you will. Our panelists include Dr. Jan Basile from South Carolina, Dr. Alan Gradman from Pittsburgh, and Dr. Marvin Moser from New York. Welcome, gentlemen.
The first part of our discussion focuses on the issue of guidelines and guideline proliferation. Over the last several years, multiple professional groups and health-associated agencies have issued guidelines for the diagnosis and treatment of hypertension. It is not clear to me that these competing documents provide a rational platform for improved care. Despite some recent claims, no guideline can be fully “evidence-based” because we cannot afford clinical trials for each relevant clinical question. Furthermore, the current batch of new guidelines has yielded conflicting recommendations. For example, the definition of “elderly” as age 60 in the Eighth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 8) and age 80 in the recent joint guidance from the International and American Societies of Hypertension. I fear that the guideline process has essentially broken down—this benefits no one.
First, a little history. Prior JNC documents were produced under the auspices of the National High Blood Pressure Education Program, a consortium of about 3 dozen healthcare professional organizations. As a participant in JNC VI and JNC 7, I can assure you that all participants were dedicated scientists and clinicians whose common goal was to synthesize the best and most robust information into a document that provided practitioners with the most reliable guidance possible. JNC 7 was released in 2003 and was soon widely adopted; it truly stood the test of time. After that, everything changed. Dr. Basile, what has been happening since?
DR. BASILE: Thanks, Dr. Izzo. I agree with you about your concerns with guidelines. This is a very difficult issue for the practicing clinician.
With regard to JNC 8, in 2008, the National Heart, Lung, and Blood Institute (NHLBI) decided to develop its own comprehensive “evidence-based” disease prevention portfolio that included a coordinated cholesterol guideline, obesity guideline, hypertension guideline, as well as a lifestyle/risk factor modification guideline. Following the recommendations put forth by the Institute of Medicine on guidelines, the NHLBI mandated that strict rules of evidence be used for its guideline development. After the JNC 8 committee established the clinical trial criteria for use in their hypertension guideline, the NHLBI hired a professional vendor to vet the literature. The process was essentially going nowhere so a second vendor for hypertension had to be hired. In the end, few clinical trials passed the criteria used to form the basis of JNC 8. And near its completion, after the JNC 8 group toiled for over 5 years putting their report together, they learned in 2013 that the NHLBI withdrew its support for the guideline and asked the American College of Cardiology/American Heart Association to establish a joint task force (to include the JNC 8 group) to assume responsibility for the guideline process. Declining this collaborative opportunity, the JNC 8 group decided on their own to have their work submitted and it was published without organizational support in JAMA.1
Meanwhile, the Centers for Disease Control published an overall systems approach for primary care clinicians in which they released the Kaiser Permanente algorithm for effective blood pressure (BP) control.2
Of note, there are several other competing guidelines: one which is issued annually by the Canadian Hypertension Education Program. This approach is now extremely well developed and comprehensive with multiple web-based programs and information sources (www.hypertension.ca/en/chep). In addition, there is the recent effort by the European Society of Hypertension/European Society of Cardiology in 2013,3 and a newer, less formal document from the International Society of Hypertension and supported by a working group comprised of members of the American Society of Hypertension.4 Finally, there are other national guidelines around the world, perhaps most prominent among these being the British Hypertension Society National Institute for Clinical Excellence or the NICE guidelines.
DR. IZZO: That’s a good summary, Dr. Basile. What constitutes a useful guideline? Who is the audience? I don’t believe that a good guideline should be hidebound by unduly restrictive ‘evidence rules’ that ignore all but a tiny fraction of the available scientific information. A good guideline must synthesize complex data in a clear and concise way and must address the kinds of questions that real doctors need answered every day. Dr. Gradman, do you have an opinion on guidelines?
DR. GRADMAN: Part of what is going on in the revised hypertension guidelines is a worldwide shift from the treatment of individual patients to the treatment of patient populations. Such guidance for treating large groups is of great interest to governments and insurance companies but is less useful for making treatment decisions for individual patients with individual problems.
In fact, the JNC 8 guidelines specifically say that they are aimed at primary care physicians, not specialists or people who have a lot of experience with the treatment of hypertension. I think JNC 8 is to be commended for trying to make the fundamental concepts of the guidelines completely evidence-based. The guidelines delineate general targets and thresholds for treatment and also suggest the best drugs to use for most patients. Unfortunately, the exercise showed that it is not really possible to answer a lot of specific treatment questions using a strict evidence-based approach. For these we must rely on less definitive evidence and expert opinion.
I think there are different audiences; a good general guideline today should be aimed at primary care physicians but I think specialists need their own guidelines. As a cardiologist, I would want a very different set of guidelines than is presented in JNC 8.
DR. IZZO: Dr. Moser, given your long association with the highly successful parent of the JNC process, the National High Blood Pressure Education Program, I think your perspective is invaluable. Do you think any of the current guidelines hit the mark or what do you think should have been done differently?
DR. MOSER: Well, that’s a broad question. JNC 8 doesn’t differ much from JNC 7 except for one or 2 items. JNC 8 set out to answer several questions with a strict evidence-based methodology, and when they were finished, after a long period of time and substantial expenditure of money, they only ended up addressing 3 questions. The first question was when to initiate treatment, the second was related to the target or goal BPs, and the third was how to achieve goal pressures. They did address the question of whether people with comorbidities, especially diabetes and kidney disease, needed to have lower goal BPs.
On the issue of targets for BP, it was decided that 140/90 mm Hg was good enough for most people and that there was no compelling evidence that BP should be lowered below 130/80 mm Hg in diabetics or people with kidney disease. But we all know that in practice, you can’t adjust BPs to exact numbers. JNC 8 also said that the threshold for a diagnosis and target BP in people over the age of 60 was 150/90 mm Hg. This is quite different from other guidelines.
The guidelines also point out a difference in black and white patients. We’ve known for years that calcium-channel blockers (CCBs) and thiazide-type diuretics are more effective in blacks and angiotensin-converting enzyme (ACE) inhibitors or beta blockers are more effective in whites, so I don’t think JNC 8 provided any new information on this. Otherwise, you’ll find very little difference between JNC 8 and 7. What they didn’t address were possible changes in the diagnostic evaluation or nonpharmacologic therapy and they failed to discuss issues related to the delivery of care and adherence, etc. Some physicians have said that the changes are important and different, but when you look at it very carefully they’re not substantive compared to other reports.
Dr. IZZO: Is that a result of their strict rules of evidence?
Dr. MOSER: The report was supposed to be all evidence-based. They hired an outside vendor that reviewed about 6100 English-language papers. The experts on that panel could have picked up the 40 papers that they finally rated as acceptable within a few days. It took the vendors several years. As everyone has mentioned, they used the data from evidence-based trials and reached conclusions, but they also had an “out” on all of them, including the 150 mm Hg BP target in the elderly, which was arbitrarily defined as age 60. As in their other recommendations, they then said that you could rely on “expert opinion,” meaning clinical judgment. This is the basis of the major recommendation: “If you treat below 140/90 mm Hg and everybody’s happy and there are no side effects, then just continue treatment.”
Regarding their approach to the treatment of resistant patients, the proposed algorithm is almost the same as it has been for many, many years. So I’m very disappointed in what they have accomplished, especially since it took such a long period of time and cost so much money.
DR. IZZO: I echo your disappointment, especially on very fundamental grounds. First, a guideline constrained by the suffocating rules applied by the JNC 8 group is enormously biased, especially when over 99% of the potentially relevant information was ignored because it did not come from a randomized trial. Did they not understand just how biased randomized clinical trials really are? A true expert does better than that, prioritizing the value and relevance of all evidence, from bench science to randomized trials. The real test for a guideline is then in the projection of that synthesis, that is translating expert interpretation into understandable and workable recommendations. One other issue: absence of evidence should not imply a negative recommendation. If there is no definitive study proving that a lower BP target is warranted for people with kidney disease, it should also be very clear that there is existing evidence that lowering BP to 130/80 mm Hg instead of 140/90 mm Hg may be a good idea. JNC 8 chose to ignore studies of achieved (not intention-to-treat) BP values that identified better renal outcomes in diabetics5 and fewer recurrent strokes6 in trial participants with the lowest BPs. While it is true that such benefits are not achieved by all trial participants, it should be recognized that “lower is better” is probably true in at least some people.
Are there any comments or concerns that the narrow definition of evidence can actually lead us astray?