DR. BASILE: I appreciate your points, Dr. Izzo, they’re very important for the clinician. Regarding guidelines overall, I like Dr. Gradman’s points about the individualization versus the population strategy. The one-size-fits-all guidelines just do not apply to the many heterogeneous patients we see.
The JNC 8 tried to be an evidence-based document in that they only looked at randomized controlled hypertension trials, which in itself is a limitation. These were very strict criteria that prevented the group from including certain evidence bases. But ultimately, more than half of the guideline recommendations ended up being expert opinion. And the reason they ended up addressing only the 3 questions presented is because there just isn’t the kind of clinical trial-based evidence required to answer questions on issues such as resistant hypertension, the value of combination therapy, and contrasting differences in BP measurement techniques to detect which is best. Accordingly, we end up with a somewhat narrow perspective. In fact, JNC 8 ended up with a lot of expert opinion and failed to be as evidence-based as they would’ve liked to have been. At the end of the day, JNC 8 just doesn’t provide the clinician with the answers to many of the controversial issues that we face each and every day.
DR. IZZO: I’m with you on that last point, Dr. Basile. Speaking of evidence, although we know that systolic BP rises linearly with age, where is the study justifying that after age 60, your BP threshold should be relaxed immediately? JNC 8 said there is “no evidence of a BP benefit here”; I say there is no evidence of common sense here.
DR. BASILE: The recent American Society of Hypertension/International Society of Hypertension (ASH/ISH) guideline suggests that “elderly” means 80 years of age and older. The JNC 8 panel decided that while some trials had higher thresholds for eligibility than the BP goals tested, in an effort to simplify the message they decided that the threshold for initiating antihypertensive treatment should be made the same as the BP treatment goal. So their answer to the second question, “What should be the goal for BP reduction in patients who are 60 years of age and older?” is that it should be less than 150/90 mm Hg, the same as the threshold for starting antihypertensive therapy.
DR. MOSER: Well, the evidence doesn’t actually support this. None of the BP cutoffs were ever truly “evidence-based,” but the new guidelines do not acknowledge this. Clearly, evidence from randomized trials of any therapeutic benefit from having a systolic BP under 150 mm Hg isn’t very good, but expert opinion, clinical judgment, and epidemiologic data suggest very strongly to me that we should have kept the threshold for diagnosis and treatment at 140/90 mm Hg at any age. If a systolic pressure under 140 mm Hg is achieved in the elderly and therapy is well-tolerated, then therapy should be continued as before.
DR. GRADMAN: The targets for patients with diabetes and renal disease have been changed and that must be discussed. The revised goal of <140/90 mm Hg for diabetics was based primarily on the results of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial which compared that goal to a goal of <120/80 mm Hg and found no net advantage of very aggressive treatment. The JNC 7 goal of <130/80 mm Hg was never evaluated. It is of interest that the newest Canadian guidelines retain the <130/80 mm Hg recommendation.7 The JNC 8 document ignored individual patient differences, which might influence treatment decisions. In patients at increased risk for stroke, such as Asian populations or patients who have a history of cerebrovascular events, lower targets may be a rational treatment decision. As ACCORD demonstrated once again, stroke risk is exquisitely BP sensitive and those in the 120/80 mm Hg target group had fewer strokes; this consideration may trump others in specific patients. The JNC 8 document was certainly not for experts or specialists in the treatment of hypertension. Guidelines are also needed to address the “hard-to-treat patient” who may be defined in a number of ways.
DR. MOSER: Well, let me just embellish that, Dr. Izzo, for a second. If you ask who is going to use this document as a metric, or who is going to hold clinicians to these recommendations, at the end of the day, it may be no one. This is because JNC 8 was, unfortunately, not endorsed by any major group; it is a standalone document. It was sent out to a number of hypertension specialists who had an opportunity to give comments, but it wasn’t posted for either the professional community or the public community to see if there were any concerns before it was published.
I don’t necessarily mean this as a harsh criticism because it seems the JNC group was forced to go it alone. But there’s a possibility that not all major organizations, including the government, may actually accept the recommendations, especially the one relating to age and target BPs.
DR. GRADMAN: I wouldn’t agree with that entirely. I think people will latch onto the JNC document, in particular to the idea that patients don’t need to be treated as intensively as was recommended in the past. So these guidelines will reduce the number of people who are seen to require treatment and will lower the intensity of treatment for those who are receiving therapy. Computerized medical records will soon be almost universal and it will be easily determined if the practitioner is in compliance with a cutoff of 140/90 mm Hg in general or less than 150 mm Hg if a patient is over 60. So I think it could have more effect than you seem to think, Dr. Moser. Many people will conclude that lower really isn’t better. The cost of treatment to insurance companies and managed care organizations will go down as a lower intensity of treatment becomes the standard of care.
DR. BASILE: I agree with you, Dr. Gradman. The ASH/ISH and European Society documents have also abandoned the <130/80 mm Hg threshold for diabetic and chronic kidney disease (CKD) patients, in favor of a goal of <140/90 mm Hg (European Society <140/85 mm Hg in diabetes [Table]), so there is additional weight behind the new metrics in addition to JNC 8.
DR. MOSER: In response to Dr. Gradman, when you increase the target for treatment to 150 mm Hg you eliminate an enormous number of people in the “difficult-to-treat” category. Another point, some of the new guidelines are not user-friendly as Dr. Izzo pointed out. They may not be helpful for the practicing doctor. The European guidelines, for example, are too long and have too many references. I believe that JNC 8 should have been 6 or 7 pages. Physicians do not care about an A-rating, B-rating, or C-rating; they want to know what experts believe.
DR. IZZO: The European guidelines are unnecessarily complex and have other flaws, such as conflating hypertension treatment with risk scores. Interpretation and perspective are the jobs of an expert panel and those traits, labeled for what they are, need to be integral to the framework of any good guideline. That’s what JNC 7 had in greater measure and that’s what people want.
DR. IZZO: Maybe we can slightly reframe this same discussion in light of another vexing problem that seems to continue to surface. Is there a J-curve? Are there different J-curves for different organs or diseases?
DR. MOSER: The issue of J-curves has never been covered effectively.
DR. BASILE: It’s not discussed in most of the guidelines because it’s a very controversial area. In principle, there is a J-curve because when you get to a BP of 0 mm Hg, you can’t sustain life. I don’t have a problem with the JNC group or other groups not really looking into this J-curve issue but it’s a terrible problem for the clinician, never knowing what level you might put the patient in danger as you continue to lower BP.
DR. GRADMAN: I agree with you, Dr. Basile. I think the possibility that the J-curve is real underlies the changes the new guidelines made in target BPs. Higher BP targets will promote less aggressive BP-lowering, so maybe the J-curve “risk” will be diminished somewhat. Different endpoints appear to have different J-curves. You may reduce strokes, for example, but increase myocardial infarctions, and the latter seems to be related more to low diastolic BP. This risk-benefit balance of intensive treatment really underlies a lot of the changes that we’ve seen in target BPs in many guidelines, not just JNC 8. Overall attention to this equation is positive but guidance to clinicians faced with patients with specific risk factors, co morbidities, circadian BP patterns, or other clinical characteristics is completely lacking.
DR. BASILE: I totally agree with you, Dr. Gradman. Increasing the systolic BP goals will also lead to some increases in diastolic BP and perhaps less concern about J-curves, if they really exist.
One important point that I’ve been making with clinical groups is that the “ideal” BP for most patients depends on whether that patient is most at risk for stroke, heart attack, or kidney disease. These differing target organs do not all prefer to see the same amount of BP reduction. For example, the brain seems to prefer a lower target and does better with more systolic BP reduction than does the heart. Yet our antihypertensive agents are not organ specific when we use them so we have to accept a “sweet spot” that is most beneficial to the patient and causes little harm. Accordingly, I think there is a “best” BP range for most patients; the European guidelines suggest that when you keep the systolic BP for most patients between 130 and 139 mm Hg, you’re really doing the best for the patient. I agree with this. I believe this should be our “sweet spot” for most patients with hypertension except for the oldest of the old, especially those with isolated systolic hypertension, where the spot appears to be 140–149 mm Hg.