Hypertension Guidances Published in 2013: A Busy Year With More to Follow
An early entry into the 2013 hypertension literature was the affirmation by Lim and colleagues of high blood pressure (BP) as the greatest contributor to the global burden of disease. However, while there is general consensus on the link between high BP and adverse cardiovascular (CV) outcomes, the benefits of lowering BP in appropriate patients, and the availability of multiple classes of drugs with excellent efficacy and safety profiles, there are substantial differences of opinion related to classification of hypertension, thresholds and targets for BP-lowering treatment regimens, and the choice of initial drug therapy given that CV benefits of certain classes of drugs may extend beyond BP-lowering effects. Last year saw a dizzying array of guidance documents, expert consensus documents, position papers, and scientific statements published in the United States and Europe, which are represented in the Table.[2-14] Discussions in the papers ranged broadly as exemplified by the following topics: methodological recommendations for the assessment of BP; the assessment of CV risk; the pharmacologic and device-based management of hypertension; and considerations of obesity, lifestyle modifications, and pet ownership.
Table . Notable Guidelines/Consensus Documents/Position Papers/Scientific Statements From Professional Societies Related to High Blood Pressure Published in 2013
|Landsberg et al||Obesity-Related Hypertension: Pathogenesis, Cardiovascular Risk, and Treatment: A Position Paper of The Obesity Society and the American Society of Hypertension|
|Goff et al||2013 ACC/AHA Guideline on the Assessment of Cardiovascular Risk: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines|
|Eckel et al||2013 AHA/ACC Guideline on Lifestyle Management to Reduce Cardiovascular Risk: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines|
|Jensen et al||2013 AHA/ACC/TOS Guideline for the Management of Overweight and Obesity in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society|
|Stone et al||2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Risk in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines|
|Brook et al||Beyond Medications and Diet: Alternative Approaches to Lowering Blood Pressure: A Scientific Statement From the American Heart Association|
|Levine et al||Pet ownership and Cardiovascular Risk: A Scientific Statement From the American Heart Association|
|Weber et al||Clinical Practice Guidelines for the Management of Hypertension in the Community: A Statement by the American Society of Hypertension and the International Society of Hypertension|
|James et al||2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults: Report From the Panel Members Appointed to the Eighth Joint National Committee (JNC 8)|
|Mancia et al||ESH/ESC Guidelines for the Management of Arterial Hypertension|
|Schmeider et al||Updated ESH Position Paper on Interventional Therapy of Resistant Hypertension|
|O'Brien et al||European Society of Hypertension Position Paper on Ambulatory Blood Pressure Monitoring|
|Mahfoud et al||Expert Consensus Document From the European Society of Cardiology on Catheter-Based Renal Denervation|
With regard to clinical practice guidelines in general, Cook and Gould commented as follows: “In the face of an overwhelmingly large and growing medical literature, providers often turn to clinical practice guidelines to inform the decisions they make with patients. By systematically appraising the evidence and providing transparent recommendations for practice, guidelines have the potential to improve both bedside decision-making and health policy.” This is indeed a very positive potential. However, these authors also noted that, to be of optimal quality, such documents must be transparent and not tainted by conflicts of interest, and their authors must employ rigorous methodologies to evaluate the evidence before them. Indeed, we now have ‘guidelines on writing guidelines,’ perhaps most saliently from the National Academies, and an Editorial discussed their adoption during the preparation of the evidence-based guidelines for the management of high BP in adults that were published online by James and colleagues in December 2013.
In this Commentary we take a look backward by offering two case studies involving guidelines released in 2013, and then take a look forward by using these studies to illuminate the challenges facing authors of subsequent new and revised guidelines.
Case Study I
Since 1977, the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC) has published seven reports, with JNC 7 released in 2003. We learned in 2013 that following the withdrawal of the US National Heart, Lung, and Blood Institute (NHLBI) from the ‘guideline writing business,’ an eighth report per se would not be released. In a follow-up paper, Gibbons and colleagues announced that the American Heart Association (AHA) and the American College of Cardiology (ACC) would “assume the governance and management” of various prevention guidelines and would “ensure their completion and dissemination to the public.” Four of these have been released and are included in the Table,[3-6] and a fifth, focusing on hypertension, is currently in preparation as discussed in due course.
However, a remarkable two-step scenario was witnessed at the end of 2013 and the beginning of 2014. Step one: In December 2013 James and colleagues published a guideline whose subtitle included the term “JNC 8,” ie, “Report from the panel members appointed to the Eighth Joint National Committee (JNC 8).” Step two: In January 2014, Wright and colleagues published a paper entitled “Evidence supporting a systolic blood pressure goal of less than 150 mm Hg in patients aged 60 years or older: the minority view.” The authors of this paper, four of whom were authors on the guidelines paper by James and colleagues, expressed their disagreement with that guidelines’ recommendation to increase the target systolic BP in persons 60 years or older without diabetes mellitus or chronic kidney disease from 140 mm Hg to 150 mm Hg. The outcome: two publications that both lack the authority of NHLBI, and that in part say different things. See references for additional discussion of the guidelines.[22, 23]
Case Study II
The second case study concerns renal sympathetic denervation (RDN) as a purported treatment option for resistant hypertension (see Gulati and White for a well-balanced review of the rationale for the technique and the state-of-affairs at the time their paper was published in 2013). The hypertension literature has recently witnessed an explosion of publications addressing this topic. Notably, the Editors of Hypertension published a “Hypertension Editors’ Picks” paper as a service to their readers given the considerably increased rate of publications indexed on PubMed using the search term “renal denervation/ablation,” in which they collated all full-length articles on RDN published in their journal in 2012 and the first half of 2013.
In our opinion, based on the methodological limitations of the studies conducted and reported to date, the majority of the RDN literature published across all journals during 2013 could arguably be regarded as displaying unreasonable rapture, and papers extolled its likely virtues not only for severe resistant hypertension but also for a seemingly ever-lowering level of hypertension. A much smaller group of authors voiced their concern,[26-30] with two noting that “In our opinion, one cannot countenance using these techniques in ‘mild to moderate, non-resistant hypertension’ until they have been shown unequivocally to be effective in resistant hypertension.” Several factors likely contributed to excitement about RDN, one of them being a refusal to pay due respect to BP data collected via ambulatory BP monitoring when assessing the intervention's efficacy: when collected and reported, such data consistently demonstrated considerably less reduction attributed to RDN than did office BP data.
A position paper and an expert consensus document were published in 2013 by the European Society of Hypertension (ESH) and the European Society of Cardiology.[12, 14] In a section entitled “Limitation and Unresolved Issues,” the ESH position paper noted appropriately that “As of April 2013 only one randomised trial has been published…. Clearly, a larger set of patients and randomised trials are urgently needed.” The trial referred to was the Renal Denervation in Patients With Uncontrolled Hypertension (SYMPLICITY HTN-2) study, which randomized just over 100 participants in a one-to-one ratio to either the treatment group, ie, RDN with previous (pharmacologic) treatment, or to the control group, ie, previous treatment alone. Study reports from both the SYMPLICITY HTN-1[32-34] and HTN-2[31, 35] trials have interpreted their results as demonstrating efficacy.
On January 9, 2014, a press release of remarkable import announced that SYMPLICITY HTN-3, the first single-blind, randomized, fully controlled clinical trial evaluating RDN (ie, the control group experienced a sham procedure that was as similar as possible without ablation of the renal nerves actually occurring) and having approximately 5 times as many participants as SYMPLICITY HTN-2, had failed its primary efficacy endpoint.
It should be noted here that treatment-resistant hypertension is an important clinical concern, and, with RDN currently appearing to be unlikely to be added to the physician's armamentarium in the United States (its future use or otherwise in geographic regions where it has already received regulatory approval remains to be seen), issues surrounding successful pharmacologic interventions resurface with renewed vigor. One of these is physician adherence to the prescribing recommendations in whichever guideline(s) they choose to read. Physician adherence is far from optimal in numerous geographic regions, and therapeutic inertia is widely discussed in the literature.[38-44] Another is patient adherence to prescribed treatment regimens.[38, 45] Addressing both via educational initiatives should be a priority for all professional societies in the field of hypertension, both for treatment-resistant hypertension and for all other categories of hypertension.
Looking Forward to 2014 and Beyond
As noted at the beginning of the first case study, 4 AHA/ACC papers (one in conjunction with The Obesity Society) have been released. Additionally, and in partnership with the American Society of Hypertension (ASH), they are preparing a new hypertension guideline. Given the increasing array of existing guidance documents, how can diligent hypertension specialists who nonetheless wish to write more documents best serve community physicians who are on the front lines of the global fight against hypertension? This is not an easy question to answer: a slew of new reports of randomized controlled clinical trials that would provide a broad range of additional evidence and insights is not expected in the near future, and so it seems that the evidence base of such trials to be considered will not dramatically differ. Of course, existing evidence that has not been considered part of the evidence base used by previous guidelines may become part of it for future documents (eg, the guidelines from James and colleagues noted that “This report does not comment on home or ambulatory BP monitoring”), and additional topics may be addressed within the broad rubric of the prevention and management of hypertension.
Medical practices vary considerably in different geographies and communities based on ethnic, sociocultural, and economic factors that limit the universal applicability of guideline recommendations originating from specific regions, which may not take these differences into account. Coupled with this is an increasing tendency to view guidelines as a prescriptive rather than an informative framework enabling physicians to treat hypertension, which we must remember is a multifactorial disease, on a patient-by-patient basis. Existing guidelines typically acknowledge this, but in caveat format: empowering community physicians to equate their clinical skills with the advice conveyed in guidelines may be a powerful strategy, as long as everything possible is done to enhance those skills with appropriate professional education.
In addition, writing styles employed by authors of guidelines must always be tailored to their target audience. By definition, community physicians are not typically employed in the academic or institutional halls of privilege enjoyed by some of the authors. As Mitchie and Johnston observed 10 years ago in the British Medical Journal, “Efforts to get doctors to follow guidelines have overlooked the importance of clear and concise recommendations.” More recently, Rümenapf expressed the view that physicians’ time is too limited to read guidelines that are written in a complicated manner, and that they often “provide no reading pleasure because the language and style they are written in is too far removed from clinical practice.” The guidelines from ASH and the International Society of Hypertension concerning clinical practice guidelines for the management of hypertension in the community (which are also endorsed by the Asia Pacific Hypertension Society) are, in our opinion, written in a reader-friendly manner and may be particularly useful to physicians in low-resource settings.
The authors of guidance documents on RDN now face a difficult question: how does one begin to reconcile guidance on the use of an interventional technique with the observation that, according to the brief current statement based on the strongest level of evidence to date, the technique is ineffective? One guesses that these guidelines will be revisited. In fairness, the full dataset and results from SYMPLICITY HTN-3 are not yet known, being expected in the first or second quarter of 2014: full examination of these data will better permit authors of the guidelines to implement potential modifications than is possible on the basis of a limited statement in a press release.
Calm, collected, and comprehensive evaluations of approaches to any medical need are a sine qua non of clinical research and clinical practice, and perhaps even more so in the preparation of clinical practice guidelines, which fall at their intersection with clinical research informing clinical practice. We wish the writers of new and revised hypertension guidelines every success in their challenging tasks ahead.
The authors report no specific funding in relation to the preparation of this paper. No editorial support was used.