DR. IZZO: I think that’s a valid point. And just to summarize, the data show clearly that in an African-American population, you get about the same degree of BP reduction by using either a thiazide-type diuretic or CCB, and you do tend to have a more limited response to RAS blockers. The reverse could be stated for whites. But then again, if you use a thiazide-type diuretic and an RAS blocker together, the race issue is moot.
DR. MOSER: For years we have been studying black patients around the world, and there’s no question that there is a different response. I also want to return to something mentioned earlier: we are losing sight of the value of so-called “experts.” Simple guidelines work for the vast majority of patients. The complicated patient should probably be referred to an expert.
DR IZZO: Are there other issues when it comes to managing the hard-to-treat patient?
DR. GRADMAN: There are many reasons why a patient may be difficult to treat. Some may truly not respond to drugs but others have hypertension in the office and not at home. They may be difficult to treat because they don’t take their medications for various reasons. The other thing, of course, is to ask whether patients are taking any interfering substances like nonsteroidal antiinflammatory drugs. Most often, if you have people who are truly poorly responsive to antihypertensive therapy, it is worth reviewing whether adequate doses of preferred agents (RAS blockers, thiazide-type diuretics, and CCBs) have been used.
Most people these days also use aldosterone antagonists as the fourth drug, recognizing the danger of hyperkalemia particularly in patients receiving renin-angiotensin aldosterone system inhibitors. If patients have renal insufficiency, using a sufficient dose of thiazide-type diuretics is extremely important, and for patients with advanced renal disease, a loop diuretic is required. There may also be some intraclass differences among drugs, as between losartan and azilsartan.
DR. BASILE: I’m now running a resistant hypertension clinic, seeing only difficult-to-treat patients. As we saw in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), there is no question that the difficult-to-treat patient may be a little more likely to be black with left ventricular hypertrophy, CKD, obese, and elderly.
But the reality is there are patients in our practices that are called resistant that really only have white-coat hypertension and may have markedly reduced BPs when they’re out of the office. These are the same patients that complain of being periodically light headed or lethargic when their pressures are low outside of the office and often have minimal target organ disease with benign eyegrounds, no left ventricular hypertrophy on electrocardiogram, and minimal if any protein in the urine.
Another major issue is the use of inadequate doses of agents such as amlodipine when started at 2.5 mg daily and never up-titrating to the standard doses of 5 or 10 mg daily because of the concern of edema. I also find that replacing hydrochlorothiazide 25 mg with chlorthalidone at the same dose can improve BP control. And we have already mentioned the important role of spironolactone.
DR. MOSER: Let me emphasize that about half of the patients referred to as “resistant” respond when you increase the thiazide-type diuretic; this also seems to be true for the addition of spironolactone to hydrochlorothiazide. Combinations have a clear advantage in terms of a meaningful response.
DR. IZZO: It still begs the question to me of whether or not we’ve given enough guidance to well-meaning practitioners in this tougher-to-treat group of patients.
DR. GRADMAN: Let me point out the paper on resistant hypertension from the American Heart Association14 as a useful comprehensive reference, but perhaps we need a relatively simple document that could be used by practicing physicians who regularly treat these patients.
DR. BASILE: I would agree with Dr. Gradman that we need to continue to provide more information on the resistant patient.
DR. IZZO: Dr. Moser, you have the last word.
DR. MOSER: If you look at the general approach in JNC 8 and the algorithm in JNC 7, you’ll find a perfectly good and reasonable approach to the management of hypertension, including for the so-called resistant or difficult-to-treat patient. It seems physicians have been afraid to lower BP, especially in the elderly. This may be one of the reasons why JNC 8 recommends a target of 150 mm Hg and not to go below that. There’s an unfounded fear of the J-curve, of causing fainting or falling in patients, especially the elderly, that does not appear to be too much of a problem if BP is reduced gradually.15
It’s unlikely that we will cause much harm and may actually reduce cardiovascular events more in the elderly if we lower the goals to what we had before. But the JNC 8 algorithm is out there and probably will be followed by many physicians.
DR. IZZO: Thank you all very much for your valuable insights. The acid test, however, is what practitioners think and what they will do. We have recent insight into this area (Table). As is readily apparent, the opinion piece we call JNC 8 does not fully resonate with the majority of primary care providers or cardiologists. What will fill the need remains to be determined.
Disclosures: Joseph Izzo has been a consultant for Novartis and Bristol-Myers Squibb, has received a research grant from Forest Laboratories, and has received speakers’ honoraria from the American Society of Hypertension. Alan Gradman is a consultant for Daiichi-Sankyo, Novartis, Forest Laboratories, and Takeda. He is a member of the Speakers Bureau for Daiichi-Sankyo, Novartis, Forest Laboratories, Takeda, and Arbor. Over the past year, he has also received honoraria for lectures sponsored by The American Society of Hypertension and The American College of Cardiology. Jan Basile is a consultant for Daiichi-Sankyo, Forest, Arbor, Eli-Lilly, and Medtronic. He has received grant/research support from NHLBI (SPRINT). He is a member of the speakers’ bureau at Daiichi-Sankyo, Forest, and Arbor.
Addendum: The concerns raised during this discussion have been echoed by clinicians in the field. Cardiologists have indicated that they are waiting for yet another hypertension guideline proposed by the American Heart Association/American Society of Cardiology for 2014–2015 (Figure). 16 Clearly the fractionation continues.
—Joseph L. Izzo, Jr., MD