The New A merican Guidelines on Hypertension: A Favorable Opinion

I am grateful to The Journal of Clinical Hypertension for asking me to comment on the recently published Joint National Committee (JNC) guidelines on hypertension,1 thus giving me a chance to express the reasons for my overall favorable opinion on this document. First, I am impressed by the format and style of these guidelines, ie, by the fact that they deal with the recommendations they focus on in a condensed yet clear fashion without avoiding mention of the evidence on which the recommendations are based. Simplicity is achieved without making the guidelines prescriptive and thus missing the educational purpose they should always have. Second, I substantially agree with the more conservative threshold and target blood pressure (BP) values recommended for treatment, ie, with the recommendation that in all middle-aged patients, including those with diabetes and chronic kidney disease: (1) a systolic BP ≥140 mm Hg is where antihypertensive drugs should be started; (2) BP <140/90 mm Hg is where antihypertensive treatment should go to; and (3) 150 mm Hg rather than 140 mm Hg systolic BP should be the threshold or target cutoff value in the elderly hypertensive population. My agreement on this issue has an element of bias because the BP threshold and target recommended by the JNC guidelines do not substantially differ from the ones recently published by the guidelines on hypertension of the European Society of Hypertension and the European Society of Cardiology,2 to which I contributed. Yet, it can hardly be denied that these threshold and target BPs reflect the evidence made available by randomized controlled trials, which both guidelines rightly consider as the best evidence achievable in clinical medicine. It is hoped that the agreement of the American and European guidelines on this crucial aspect of hypertensive management will be favorably received by physicians who often express confusion, when not irritation, at the discrepancies of guidelines claiming to be evidence-based on issues importantly affecting their daily-life practice. Finally, I find myself in agreement with the recommendations of the present JNC guidelines on the drugs to be used for treatment initiation. The agreement does not extend to the “apriori” exclusion of β-blockers from the list of first-choice drugs, which I believe to be a mistake because, although not immune from inconveniences (which all drug classes have) β-blockers (1) have been found to exert cardiovascular protection in hypertension, as acknowledged by the JNC guidelines, and (2) the overall protective effect has been shown in large meta-analyses3, 4 to be not substantially different from that of other drug classes. What I find entirely agreeable is, on the other hand, the present JNC refusal to confirm the recommendations of the previous JNC guidelines, which restricted the first-choice options to diuretics only5 based on a questionable interpretation of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) data.6 The choice is now extended to include, beside diuretics, calcium channel blockers, angiotensin-converting enzyme inhibitors, and angiotensin receptor antagonists, which reflects the evidence that these classes provide overall similar cardiovascular protection in the hypertensive population. The liberal attitude to the choice of drugs in the present JNC guidelines is further emphasized by their recommendation to consider first-choice diuretics, not only thiazides, but also indapamide and thiazide-like agents, which is again in line with the data provided by randomized trials,7 and all drugs mentioned as first choice also as suitable “add-on” drugs for combination treatment. This offers physicians a large number of options from which to select not only the monotherapy but also the multiple-drug regimen to be eventually used. Guidelines can never avoid criticism and the present JNC document is no exception. For example, although the evidence made available by randomized controlled trials justifies the recommendation to lower systolic BP to <150 mm Hg in patients aged between 60 and 80 years, it might have been appropriate to consider or at least discuss some other options. After all, the randomized trials that have been performed in the elderly have not directly compared higher vs lower on-treatment BP values, which means that recommendations are based on which BP values happened to be reached in the actively treated groups.8 Furthermore, although their limitations are well-known, it may perhaps be excessive to completely dismiss observational data from post-hoc analysis of randomized trials which suggest that elderly patients aged up to 80 years may have fewer cardiovascular events if systolic BP is reduced to <140 mm Hg.9 Again, with the caveat of my conflict of interest, I believe that the European guidelines may have taken a wiser position by (1) emphasizing that, within this age range, the most solid evidence is in favor of a systolic BP target of 150 mm Hg; (2) with a lower level of evidence, also mentioning that a target of <140 mm Hg “may be considered” in fit elderly individuals. The word “fit” referring to the fact that, for obvious reasons, trials in elderly hypertensives have avoided recruitment of patients with bad general health conditions that could have compromised their adherence to the treatment plan during follow-up; and (3) highlighting that in fragile elderly patients, including those older than 80 years, no evidence exists and thus the BP treatment goal is left to the physician's clinical judgement. Few other points of criticism may also be mentioned. For example, limiting the recommendations to only a few issues helped make the guidelines easily readable. It left out, however, many conceptual and practical aspects of hypertension in which physicians may expect help, such as why, when, and how to use out-of-office BP in untreated and treated patients; which weight to give to diagnostic and on-treatment data on subclinical organ damage; and how to quantify the total cardiovascular risk of the patient as well as which reflection this should have on prescription and nonantihypertensive drugs, frequency of follow-up visits, and laboratory or instrumental examinations. Also, the choice of the JNC to derive recommendations only from outcome-based randomized clinical trials on hypertensive patients may have been too restrictive. BP has a unimodal distribution in the population as well as a continuous relationship with cardiovascular morbid and fatal events, which makes the distinction between hypertension and normotension arbitrary. Furthermore, landmark trials that recruited patients with a BP above but also below 140/90 mm Hg (Perindopril Protection Against Recurrent Stroke Study [PROGRESS], Heart Outcomes Prevention Evaluation [HOPE], Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial [ONTARGET], and many others) have fundamentally contributed to current knowledge of what BP-lowering interventions do (or do not) in different clinical conditions or at different entry BPs. Finally, as mentioned above, dismissal of observational studies from evidence on which recommendations were based may have also be questionable because observational studies provide information on issues that are outside the range and complementary to those of randomized trials, such as the long-term persistence of the beneficial effects of treatment. This is also the case for endpoints other than morbidity and mortality, such as delayed progression or regression of subclinical organ damage, prevention of hypertension or diabetes, and adherence to the prescribed treatment regimen, which are also important aspects of daily-life practice as well as of the physician-patient interaction. It might have been preferable, in my opinion, to consider these data and deal with their weaker scientific value vis-à-vis outcome-based randomized trials by the instrument offered by evidence grading. After all, the JNC committee made frequent use of this instrument in the document and graded several recommendations as “expert opinion” rather than evidence-based. In conclusion, despite some limitations, I find the new JNC guidelines an effective document because it addresses few fundamental questions on the treatment of hypertension and gives them a clear and easy-to-apply answer. I hope this will have a positive impact on the management of this condition, which remains a major health problem worldwide because (1) despite some improvement, hypertension is poorly controlled by current treatment,10 and (2) uncontrolled hypertensive patients remain at high cardiovascular risk,11, 12 which keeps hypertension still the first cause of death in the world.13