JNC 8 and Older Adults: A Review of the Evidence

New Guideline for Blood Pressure Management in Older Patients

Introduction

Blood pressure (BP) goals have been the subject of ongoing debate for years and are arguably even more controversial in the elderly. Many factors must be taken into consideration, such as life expectancy, fall risk, and medication adverse effects. This article will review select special considerations in BP management in the elderly, as well as the evidence surrounding the more lenient older adult BP goal recommended in the recently published Eighth Joint National Committee (JNC 8) hypertension guideline.¹

Considerations in the Elderly

Orthostatic Hypotension

Orthostatic hypotension (OH) is defined as a decrease in systolic blood pressure (SBP) by more than 20 mm Hg or a more than 10 mm Hg decrease in diastolic blood pressure (DBP) from supine to standing position.² OH has been shown to be an independent risk factor for falls in the older adult population and is highly age dependent. This is mostly due to hardening of the arteries with age, causing a decreased baroreceptor response. OH has also been shown to be associated with a significant increase in morbidity and mortality.^2-6

Isolated Systolic Hypertension

Isolated systolic hypertension (ISH) is most prevalent in the older adult population and appears to be due to hardening of the large arteries. It has been found that there is a linear increase in systolic blood pressure (SBP) with age, but that diastolic blood pressure (DBP) plateaus and may decrease around the fifth or sixth decade of life. A trial reviewing the correlation between blood pressure and coronary heart disease found that DBP was superior to pulse pressure (PP) and SBP in predicting heart disease in patients younger than 50 years, whereas SBP was superior to PP in patients older than 60 years and DBP was negatively correlated to coronary heart disease.⁹ Treating ISH can be challenging when the DBP is low, as it has been shown that there may be possible harm with DBP less than 55 to 60 mm Hg.^{2, 7-14} See Online Table 1 for a list of pre-JNC 8 guidelines.

Table 1: Previous Hypertension Guideline Recommendations

Guideline

BP Goal

(mm Hg)

Comments

Specific for Older Adults: Yes/No

CHEP¹⁵ (Canadian Hypertension Education Program)

2013

<150/90

· In patients ≥ 80 years of age without diabetes and target organ damage, drug therapy should be initiated when SBP is ≥160 mm Hg to a target of <150 mm Hg (C)

· Antihypertensives should be considered regardless of age (B)

· Caution should be exercised in initiating antihypertensives in frail elderly patients

· In ISH in the elderly, recommended therapy is a thiazide-like diuretic, CCB (A) or an ARB (B)

· Avoid BB or alpha-blockers as first line therapy in ISH in the elderly (A)

Yes

(80 years of age)

ESH/ESC¹⁶ (European Society of Hypertension/European Society of Cardiology)

2013

<150/90

· Recommend diuretic or calcium antagonist in elderly with ISH based on SHEP¹⁷, Syst-Eur¹⁸, SystChina¹⁹ (IA)

· Recommended to treat all elderly with SBP >160mmHg to 140 to 150mmHg (IA), largely based on HYVET²⁰

· Consider SBP goal of <140mmHg in fit older adult patients (IIbC)

· However, in frail elderly patients clinical judgment is advised (IC)

Yes

(80 years of age or fragile older adult)

NICE²¹ (National Institute for Health and Care Excellence)

2011

<150/90

· Same medications should be offered for patients’ ≥ 80 years of age as younger patients, based on comorbidities

· Not recommended to initiate treatment in patients ≥80 years of age if only stage I HTN (<160/100 mm Hg)

Yes

(≥ 80 years of age)

JNC 7 ² (Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure)

2003

<140/90

· ISH is the predominant form of HTN in older adults

· Alpha and non-selective beta-blockers can cause ISH

· Treating HTN in the elderly has been shown to be beneficial via multiple trials including SHEP,²⁰ Syst-Eur,²¹ Staessen et al meta-analysis,²² Hansson et al,²³ Gueyffier et al,²⁴ and Neal et al²⁵

· SBP provides more appropriate classification in the older adult population versus DBP

· Weight loss and reduced sodium intake are particularly beneficial in the elderly, based on the TONE²⁶ trial

· Diuretics have been found to be associated with a decreased risk of hip fracture

No

ARB = angiotensin receptor blocker; CCB = calcium channel blocker; DBP = diastolic blood pressure; ISH = isolated systolic hypertension; SBP = systolic blood pressure; HTN = hypertension; HYVET = Hypertension in the Very Elderly Trial; SBP = systolic blood pressure; TONE = Trial of Nonpharmacologic Interventions in Elderly.

JNC 8 Appointed Panel Members Blood Pressure Guideline¹

Older Adult Recommendation

“In the general population aged 60 years or older, initiate pharmacologic treatment to lower BP at systolic blood pressure (SBP) of 150 mm Hg or higher or diastolic blood pressure (DBP) of 90 mm Hg or higher and treat to a goal SBP lower than 150 mm Hg and goal DBP lower than 90 mm Hg.” (Strong Recommendation—Grade A)

“In the general population aged 60 years or older, if pharmacologic treatment for high BP results in lower achieved SBP (for example, <140 mm Hg) and treatment is not associated with adverse effects on health or quality of life, treatment does not need to be adjusted.” (Expert Opinion—Grade E)

Evidence Review

It is evident that even the very elderly can benefit from treatment of hypertension. What is not as well established is what goal is safe and effective at preventing cardiovascular (CV) outcomes. Per the recently published 2014 hypertension guideline,¹ the recommended goal blood pressure for patients older than 60 years is less than 150/90 mm Hg. The trials this decision was based on include HYVET,²⁰ Syst-Eur,¹⁸ SHEP,¹⁷ JATOS,²⁷ VALISH,²⁸ and Cardio-Sis.²⁹

A summary table of the following trials is included as an appendix (Online Table 2).

Table 2: A Summary of Hypertension Trial Data

Trials

Average Age (years)

Duration (years)

Treatment Intervention

BP Goal

(mm Hg)

Findings

Comments

HYVET²⁰

83.6

1.8 (median)

Indapamide (diuretic) vs placebo (plus perindopril [ACEI] or placebo if needed for BP control)

<150/80; BP difference b/w groups at year 2 15.0/6.1 mm Hg

Total Stroke: P = .06 (30% reduction)

Death from stroke: P = .046* (39% reduction)

Death from any cause: P = .02* (21% reduction)

Baseline BP: 173/90.8 mm Hg; Europe, China, Australasia, Tunisia

Syst-Eur¹⁸

70.3

2 (median)

Nitrendipine (CCB) vs placebo (plus enalapril [ACEI] and/or HCTZ [diuretic] if needed for BP control)

Goal: SBP reduction at least 20 mm Hg to <150 mm Hg; change in BP

(-23/-7 mm Hg active vs -13/-2 mm Hg placebo)

Total stroke P = .003*

All-cause mortality P = .22

All fatal and nonfatal CV end points (P <.001)*

Patients with ISH

Baseline BP (sitting): 173/85.5 mm Hg

.

SHEP¹⁷

71.6

4.5 (mean)

Chlorthalidone (diuretic) vs placebo (plus atenolol [BB] or reserpine if needed for BP control)

If baseline SBP > 180 mm Hg, the goal BP was <160 mm Hg; if baseline SBP 160 to 179 mm Hg, the goal BP was a reduction of 20 mm Hg; mean BP difference between groups 11.1/3.4 mm Hg at year 5

1°: total stroke:

P = .0003*

All-cause mortality: RR (95% CI) 0.87 (0.73-1.05)

Baseline BP: 170.3/76.6 mm Hg

JATOS²⁷

73.6

2

Efonidipine (CCB) (plus antihypertensive per provider discretion, if needed for BP control)

SBP: <140 mm Hg (strict) vs <160 mm Hg (mild)

Results: 135.9/74.8 vs 145.6/78.1 mm Hg; P <.001*

Composite end point of CV events and renal failure: P = .99

Deaths: (strict) 54 vs (mild) 42 P = .22

Japanese patients;

baseline BP: 171.6/89.1 mm Hg

Limitation: observed rate of primary outcome was half of that expected

VALISH²⁸

76.1

2.85 (mean)

3.07

(median)

Valsartan (other antihypertensives added at providers discretion)

SBP <140 mm Hg vs ≤140 to <150 mm Hg;

BP difference between the 2 groups was 5.6/1.7 mm Hg (P <.001)*

CV events and renal dysfunction: P = .38

All-cause mortality: P = .362

Japanese patients; baseline BP: 169.6/81.5 mm Hg

Cardio-Sis²⁹

67

2

Furosemide, ramipril, telmisartan, amlodipine, bisoprolol, transdermal clonidine (providers’ discretion)

SBP <140 mm Hg (n = 553) vs <130 mm Hg (n = 558);

between-group difference 3.8 mm Hg systolic (P <.0001)*; and 1.5 mm Hg diastolic (P = 0.041)*

LVH: (OR 0.46, 0.26-0.84)*

Composite end point of death from any cause, MI, stroke, TIA, A fib, heart failure admission, angina or coronary revascularization: P = .003*

Death from any cause: 0.70

Baseline BP: 163.3/89.7 mm Hg

Italy; nondiabetic patients

* Statistically significant

ACEI = angiotensin-converting enzyme inhibitors; A fib = atrial fibrillation; BP = blood pressure; CCB = calcium channel blocker; CV = cardiovascular; ISH = isolated systolic hypertension; MI = myocardial infarction; SBP = systolic blood pressure; TIA = transient ischemic attacks.

HYVET²⁰

HYVET (Hypertension in the Very Elderly Trial) is a significant trial in the geriatric community and is frequently cited in hypertension management in the elderly reviews. HYVET’s objective was to resolve some of the uncertainty of the risk versus benefit in the use of antihypertensive therapy in the very elderly. The HYVET trial was a large randomized controlled trial consisting of 3845 patients in Europe, China, and Tunisia with a sustained SBP equal to or greater than 160 mm Hg. The primary end point was fatal and nonfatal stroke, not including transient ischemic attacks, with a secondary end point of death from all causes, death from CV causes, death from cardiac causes, and death from stroke. Indapamide or placebo was given, with perindopril or placebo added if necessary, to reach the target BP goal of less than 150/80 mm Hg.

The average age was approximately 84 years with CV disease in about 11% of patients and diabetes in about 7% of patients. Of note, patients with diagnosis of clinical dementia or requirement of nursing home care were excluded. Mean sitting blood pressure was 15.0/6.1 mm Hg lower in the active treatment group versus placebo. Target blood pressure was reached in 19.9% of patients in the placebo group and 48.0% in the active group at 2 years (P <.001). A significant decrease was seen in total stroke, death from stroke, death from any cause, any heart failure, and any CV event in the active treatment group versus the placebo group. The number of serious adverse events reported was 448 in the placebo group versus 358 in the active-treatment group (P = .001). Overall, the HYVET study showed it was beneficial for the very elderly with an SBP of >160 mm Hg to have a blood pressure goal of <150/80 mm Hg.

Syst-Eur¹⁸

The Syst-Eur (Systolic Hypertension in Europe) trial is a randomized doubleblind controlled trial in patients 60 years and older with ISH. This study included 4695 patients in several centers throughout Europe. Patients were assigned to either nitrendipine or placebo and, if necessary, treatment was combined or replaced with enalapril and/or hydrochlorothiazide to reach a target sitting SBP reduced by at least 20 mm Hg to less than 150 mm Hg. The baseline mean BP was 173.9/85.5 mm Hg. The primary end point was stroke. Other end points included the following: death, stroke, retinal hemorrhage, and myocardial infarction (MI). A mean decrease in sitting SBP and DBP of 13 mm Hg and 2 mm Hg, respectively, in the placebo group and 23 mm Hg and 7 mm Hg in the active treatment group was seen at 2 years.

At median follow-up, 21.4% of patients in the placebo group and 43.5% in the active group had reached target blood pressure (P <.001). There was a significant reduction seen in stroke (P = .003), all fatal and nonfatal CV end points (P <.001), and angina pectoris (P = .04). The trial was stopped early due to a significant decrease in stroke occurrence in the active treatment group at the second interim analysis. The median duration of exposure to active treatment was 1.7 years. Overall, there was a reduction in fatal stroke of 33% and CV mortality of 22% in the active treatment group, which was similar to the results in the Systolic Hypertension in the Elderly Program (SHEP) trial.

SHEP¹⁷

The SHEP trial included 4736 patients, at multiple sites within the United States, 60 years and older, with ISH. Patients were assigned to either chlorthalidone or placebo. Chorthalidone dose was increased, then atenolol was added, if needed, to get to goal (reserpine could be substituted if atenolol was contraindicated). For patients with a baseline SBP of more than 180 mm Hg, the goal BP was less than 160 mm Hg and if the baseline SBP was 160 to 179 mm Hg, the goal BP was a reduction of 20 mm Hg. The primary outcome was total stroke, and secondary outcomes included CV and coronary morbidity and mortality, all-cause mortality, and quality-of-life measures. Overall baseline mean BP was 170.3/76.6 mm Hg with mean BP at year 5 for active and placebo group of 144/67.7 mm Hg and 155.1/71.1 mm Hg, respectively. Goal BP was reached in 65% to 72% in active treatment group and 32% to 40% in placebo group. A significant decrease was seen in total stroke, non-fatal stroke,non-fatal MI, non-fatal left ventricular failure, coronary heart disease (CHD), nonfatal MI or CHD death, and CV disease. Overall, a 36% risk reduction in stroke and a 20% risk reduction in CV death were seen in the active treatment group compared with placebo.

JATOS²⁷

The JATOS (Japanese Trial to Assess Optimal Systolic Blood Pressure in Elderly Hypertensive Patients) study was designed to compare 2 years of strict antihypertensive treatment of SBP less than 140 mm Hg with mild treatment of SBP less than 160 mm Hg. Patients were between 65 and 85 years of age with an SBP of more than 160 mm Hg during run-in period. Of note, exclusion criteria included patients with DBP equal to or greater than 120 mm Hg and poorly controlled diabetes mellitus (fasting blood glucose equal to or greater than 200 or A1C equal to or greater than 8%). Patients received efonidipine with an additional antihypertensive agent(s) added, if needed, to reach their assigned SBP goal. Primary end point was combined incidence of CV disease, cardiac and vascular disease, and renal failure. Secondary end points were death from any causes and any safety problems. The average BP was 135.9/74.8 mm Hg in the strict group and 145.6/78.1 mm Hg in the mild group (P <.001). There was no significant difference between the strict and mild treatment group in primary and secondary outcomes.

VALISH²⁸

The (Valsartan in Elderly Isolated Systolic Hypertension (VALISH) study was an open-label, randomized Japanese trial with an objective of establishing whether strict blood pressure control (less than 140 mm Hg) versus moderate blood pressure control (140 to less than 150 mm Hg) is superior in reducing CV mortality and morbidity in elderly patients with ISH. Valsartan was given to all patients with the addition of another antihypertensive if needed to achieve goal. The primary end point was a composite of CV events (sudden death, total stroke, total MI, CV death, unplanned hospitalization for CV disease, and renal dysfunction). BP difference between the 2 groups was 5.6/1.7 mm Hg (P <.001). No significant difference between strict versus moderate control was found in the primary end point or any of the secondary end points.

Cardio-Sis²⁹

The Italian Study on the Cardiovascular Effects of Systolic Blood Pressure Control (Cardio-Sis) trial was an openlabeled randomized study that included 1111 patients 55 years or older with SBP equal to or greater than 150 mm Hg. Of note, patients with any disease that reduces life expectancy or with diabetes were excluded. Patients were then randomized into 2 groups, less than 140 mm Hg (usual control) versus less than 130 mm Hg (tight control). The primary outcome was the prevalence of electrocardiographic left ventricular hypertrophy (LVH). Per Verdecchia et al, this end point was chosen as it is a strong predictor of CV outcomes. Providers had the choice of furosemide, ramipril, telmisartan, amlodipine, bisoprolol, or transdermal clonidine and the medications were added at the providers’ discretion in order to reach the patients’ blood pressure goal. In the usual control group 66.9% of patients reached goal at 2 years versus 78.7% in the tight control group. Between-group difference SBP was 3.8 mm Hg (P <.0001) and DBP 1.5 mm Hg (P = .041). The likelihood of LVH was significantly decreased in the tight control group versus usual control group (OR 0.46, 95% CI 0.26- 0.84). Diuretic drugs were significantly more frequently used in the tight control group versus the usual control group (P = .009).

Summary

Older adults have a more lenient BP goal in many hypertension guidelines. However, none of the reviewed hypertension guidelines start this goal as young as 60 years, as JNC 8 does.^1,15,16,21 Almost all of the trials cited by the new hypertension guidelines regarding the goal of less than 150/90 for patients 60 years and older (reviewed above) included patients 70 years and older. The above evidence indicates that BP control in the elderly is beneficial, although all of the trials, except for CardioSis,²⁹ support a less strict blood pressure goal versus tight blood pressure control.

Key Considerations

It is important to remember that each older adult patient is unique, which may affect how aggressively blood pressure goals are set. Clinical judgment should always be used when determining risk versus benefit of reaching a blood pressure goal versus possible harm (such as falls, medication burden, side effects, and low diastolic pressure) [Figure].

Jamie Rickards, PharmD, MBA, BCPS, CPP, is a PGY-2 pharmacy resident specializing in geriatrics at UNC Medical Center in Chapel Hill, North CarolinaJena Ivey Burkhart, PharmD, BCPS, CPP, is a clinical assistant professor in the division of pharmacy practice and experiential education at the UNC Eshelman School of Pharmacy and a geriatric clinical pharmacist practitioner at UNC Hospitals and Clinics.

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