The 2017 Hypertension Guidelines: Approaches to Mild Hypertension and Combination Therapy

Editor's Note: Please see the accompanying Expert Analysis, "Response to 'The 2017 Hypertension Guidelines: Approaches to Mild Hypertension and Combination Therapy.'"

The 2017 ACC/AHA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults is a landmark achievement. The committee reviewed thousands of publications to produce a truly comprehensive guideline.1 The document is also successful in remaining accessible to clinicians with straightforward coherent algorithms. An important new concept is the tailoring of treatment to 10-year atherosclerotic cardiovascular disease (ASCVD) risk. While the idea was adopted from cholesterol guidelines and previously existed in a rudimentary capacity in the Joint National Committee (JNC)-7 algorithm,2,3 this is the first time that the calculation of ASCVD risk has been promulgated in hypertension guidelines. Another major change is the lowering of the definition of stage I hypertension to 130/80 mm Hg. I applaud the committee for their truly remarkable work overall. However, there are a few recommendations, specifically the approach to mild hypertension and combination therapy, where I would like to offer some differences in opinion.

The guidelines espouse using an ASCVD risk-based approach. Unfortunately, this concept only impacts the treatment algorithm insofar as it is used to justify initial drug treatment of "stage 1 hypertension" (130-139/80-89 mm Hg) in higher-risk patients. The committee chose not to incorporate a similar approach for patients at the other end of the hypertensive disease spectrum. It follows that there is an over-simplification of the management of lower-risk patients with "mild hypertension." All patients with high blood pressure (BP) historically-considered mild (140-159/90-99 mm Hg) are now instructed to immediately begin pharmacologic therapy in addition to lifestyle changes.3,4 This apparently applies to everyone—even to young people (18-55 years old) and individuals with a low 10-year risk <10% (Table 8.1.2 classification of recommendation [COR]: 1; level of evidence [LOE]: C-LD). This strong COR is clearly discordant from the weak LOE. It may be that the authors wished to provide uniform thresholds for treatment to avoid overly-complicated algorithms. They may have also aimed to curtail the problem of therapeutic inertia. However, as the committee members know, the evidence to justify immediate drug-treatment at a BP level of 140/90 mm Hg in a low-risk population is completely lacking. The rationale was clearly based upon extrapolations from trials that involved much older and higher-risk patients.5 This is because trials in young low-risk patients are not feasible from a sample size or time-frame perspective to show benefits. That being the case, how can clinicians defend drug treatment to individual patients in real-world practice? The authors also provided reasoned (but speculative) arguments regarding the self-amplifying nature of hypertension and the heightening of lifetime risk when BP goes untreated. These conjectures can logically be used to support earlier attention to milder forms of high BP in general, but I fail to see how they justify a COR-1 for universal immediate drug-treatment.

Ironically, the guidelines may result in more widespread "non-evidence-based" treatment. Nearly half of patients with "stage-2 hypertension" (BP ≥140/90 mm Hg) are low-risk (30.5% and 15.3% with 10-year risks <5% and 5-9%, respectively).6 No outcome trial has ever explicitly tested (let alone proven) the benefits of drug-therapy in younger patients (18-59 years old) or "mild-hypertensives" (BP <160/100 mm Hg) with a low estimated 10-year ASCVD risk.7 Older trials including some germane patients with "mild hypertension" exist; however, they enrolled individuals who were on average >50-60 years old who typically had many other ASCVD risk factors (including diabetes) and BP levels much closer to 160/100 mm Hg.4 Even so, meta-analyses of these data provided mixed results at-best. Moreover, the feasibility and risk/benefit ratio of decades of drug-treatment in young lower-risk people main unknown.4 Serious risks due to antihypertensive medications are typically low. However, the possibility remains that more low-risk hypertensives could suffer adverse events (e.g., hypotension, syncope, azotemia, electrolyte disorders, allergy/angioedema) than reduction in ASCVD events. The case for health care providers to advocate to their patients in support of immediate drug treatment would be strengthened by providing a favorable estimation of the number-needed-to-treat versus number-harmed in this lower risk strata.

Reaching a consensus on any threshold for drug treatment can inevitably be criticized as arbitrary because the risks due to high BP levels increase in a monotonic fashion above 115/75 mm Hg. However, rather than drawing a line in the sand at 140/90 mm Hg and advocating immediate universal drug-treatment, the authors should have followed their own precedent and outlined a global ASCVD risk-based approach. In the absence of outcome trial data to support a departure from prior standards-of-practice,3 I advocate that young (18-55 years old) and low-risk patients (<5-7.5%/10 years) with a BP <160/100 mm Hg should have the option to try a period of lifestyle therapy prior to starting medications. This is in accord with all prior guidelines and expert opinion recommendations.3,8 Using a shared-decision making process, these patients should at least be offered 3-12 months of lifestyle alone. The new guidelines go to great length to laud the merits of lifestyle treatments, yet in no circumstances are they offered alone once BP is above 140/90 mm Hg. This is a major departure from prior guidelines without an evidential basis. Perhaps unintentionally, this gives the dismissive characterization that lifestyle alone can never be effective to control mild hypertension. I believe this is a strangely contradictory line of reasoning given the clear attention the guidelines pay to reviewing their potential effectiveness. Not only is short-term (3-12 months) lifestyle treatment a safe option given the extraordinarily low risk for events in this healthy/younger population, it may reduce the number of patients ultimately requiring drug therapy. Granted, the long-term success rate for controlling even mild hypertension with lifestyle alone may not be well-established. However, this is not a reason to universally exclude the possibility, most notably for highly-motivated individuals who have a realistic chance of achieving goals.

Immediate drug-treatment for low risk mild hypertensives could certainly remain a credible option. However, I believe it should receive a lower strength of recommendation (COR IIA or IIB). This downgrade would circumvent the potential for inappropriate penalization of clinicians who decide with their patients to delay drug-therapy for a few months. The failure of the authors to account for this period of lifestyle treatment alone that existed in previous guidelines also led them to under-estimate the number of additional patients who will receive drug-therapy following new guidelines.3,8 The new approach (perhaps unintendedly) also limits shared decision-making processes. A COR 1 "should" be followed. This means there is no opportunity to discuss with patients the potential for lifestyle change alone. In my experience, many patients appreciate a lifestyle option over the relegation to being "condemned to drug therapy" without so much as first even having a realistic discussion about the possible success of "natural" (non-drug) treatments. The immediate surrendering to the inevitability of drug-treatment at a BP level of 140/90 mm Hg might also feed into the narrative that health care providers are in collusion with pharmaceutical industries and not willing to involve patients in decisions regarding their own health. An alternative option would be to acknowledge these arguments and add a section on the approach to weaning anti-hypertensive medications. Some of my anxiety would be mitigated if the committee outlined an algorithm for when/how to "step-down" drug therapy among individuals who appear able to maintain BP control using lifestyle alone.

A second aspect of the guidelines that I would have addressed differently is the approach to combination therapy. A wealth of data supports that >75% of patients require two or more medications to achieve BP control.8 Given new targets <130/80 mm Hg, an even larger percentage of patients will require more intense treatment. I applaud the promotion of using early combination therapy. However, the guidelines (with a few notable exceptions) provide the false sense that all combinations are created equal.

Clinical outcome trial evidence supports that optimal first-line therapy should consist of combined renin-angiotensin-system (RAS)-calcium channel blockade (CCB) if possible.9-11 This combination has proven superior to both beta blocker-diuretic (ASCOT: Anglo Scandinavian Cardiac Outcomes Trial) and RAS-blocker-hydrochlorothiazide (Avoiding Cardiovascular Events Through Combination Therapy in Patients Living With Systolic Hypertension [ACCOMPLISH]) treatment.9,10 A 20% reduction in the composite outcome occurred in ACCOMPLISH despite equal on-treatment and well-controlled BP levels (adjudicated by ambulatory monitoring). The benefits were observed across most outcomes (e.g., cardiovascular and renal) and subgroups of patients (e.g., diabetics, kidney disease, coronary artery disease).9-11 We reviewed in detail the totality of evidence favoring this combination.11

Arguments have also been made that the usage of chlorthalidone instead of hydrochlorothiazide in ACCOMPLISH would have provided similar or better outcomes. This is only speculation. It is also largely irrelevant because the only germane single pill combination is not available as a generic. Given the superior BP-lowering effect of chlorthalidone compared to hydrochlorothiazide, it may also have resulted in greater BP-lowering. This defeats the basis for the argument. In other words, if it requires a greater reduction in BP to provide an equal degree of cardiovascular protection, then why would a clinician choose to start that combination? Moreover, guidelines do not specify that a RAS-blocker plus chlorthalidone should be used as first line, only that therapy should consist of a rationale combination across drug classes. I strongly believe that the overall evidence supports that health care providers should start with a RAS-blockade plus CCB whenever possible. Thereafter, should BP remain uncontrolled then chlorthalidone is an obvious choice for the third agent. Unfortunately, it is unlikely that there will ever be another outcome study to corroborate the landmark results of ACCOMPLISH. However, in my mind the totality of evidence is already more than adequate to start with RAS-blockade plus CCB as first line therapy in most patients.11

Overall, the new hypertension guidelines are outstanding and a remarkable step forward. I recognize difficult task involved in reaching a consensus on dozens of topics. I hope that I have outlined in this brief commentary a reasoned case for the consideration of minor changes to their recommendations.

References

  1. Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines. J Am Coll Cardiol 2018;71:e127-248.
  2. Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association task force on practice guidelines. J Am Coll Cardiol 2014;63:2889-934.
  3. Chobanian AV, Bakris GL, Black HR, et al. Seventh report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure. Hypertension 2003;42:1206-52.
  4. Viera AJ, Hawes EM. Management of mild hypertension in adults. BMJ 2016;355:i5719.
  5. Brunstrom M, Carlberg B. Association of blood pressure lowering with mortality and cardiovascular disease across blood pressure levels: a systematic review and meta-analysis. JAMA Intern Med 2018;178:28-36.
  6. Muntner P, Whelton PK. Using predicted cardiovascular disease risk in conjunction with blood pressure to guide antihypertensive medication treatment. J Am Coll Cardiol 2017;69:2446-56.
  7. Musini VM, Gueyffier F, Puil L, Salzwedel DM, Wright JM. Pharmacotherapy for hypertension in adults aged 18 to 59 years. Cochrane Database Syst Rev 2017;8:CD008276.
  8. Mancia G, Fagard R, Narkiewicz K, et al. 2013 ESH/ESC guidelines for the management of arterial hypertension: the task force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J 2013;34:2159-219.
  9. Dahlof B, Sever PS, Poulter NR, et al. Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding Bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT_BPLA): a multicenter randomized controlled trial. Lancet 2005;366:895-906.
  10. Jamerson K, Weber MA, Bakris GL, et al. Benazepril plus amlodipine or hydrochlorothiazide for hypertension in high-risk patients. N Engl J Med 2008;359:2417-28.
  11. Brook RD, Weder AB. Initial hypertension treatment: one combination fits most? J Am Soc Hypertens 2011;5:66-75.

Clinical Topics: Arrhythmias and Clinical EP, Diabetes and Cardiometabolic Disease, Dyslipidemia, Heart Failure and Cardiomyopathies, Prevention, Pulmonary Hypertension and Venous Thromboembolism, Vascular Medicine, Atherosclerotic Disease (CAD/PAD), EP Basic Science, Lipid Metabolism, Nonstatins, Heart Failure and Cardiac Biomarkers, Pulmonary Hypertension, Exercise, Hypertension

Keywords: Adrenergic beta-Antagonists, Angioedema, Angiotensin Receptor Antagonists, Angiotensin-Converting Enzyme Inhibitors, Antihypertensive Agents, Blood Pressure, Blood Pressure Determination, Calcium Channel Blockers, Calcium Channels, Coronary Artery Disease, Diabetes Mellitus, Exercise, Goals, Drug Therapy, Combination, Cholesterol, Health Personnel, Hypertension, Hypertension, Pulmonary, Hypotension, Life Style, Myocardial Infarction, Myocardial Ischemia, Peptidyl-Dipeptidase A, Risk, Risk Factors, Syncope, Primary Prevention, Secondary Prevention


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