1. New Guidelines for the Management of Hypertension- Is the Pressure Off?
Pranay Kathuria, MD, FACP, FASN, FNKF
Director, Division of Nephrology
Director, Nephrology Fellowship
Professor of Medicine
University of Oklahoma College of Medicine

2. Objectives
Review the 2014 evidence-based guidelines for the management of hypertension in adults for patients aged 60 years or more
Review the “The Minority View” on targeting systolic blood pressure goal of less than 150 mmHg in patients aged 60 years or older
Summarize relevant studies
Comment on other hypertension guidelines

3. Hypertension is a Major Health Problem
• Affects 1 billion people worldwide
• US – about 1 in 3 adults
–73 million have hypertension (SBP >140/90)
• A 55-yo normotensive person has up to a 90% lifetime risk of developing hypertension (Vasan 2001)
• Number one reason listed for office visits
• Causes/contributes to 457,000 admissions per year
• A leading cause/contributor to death (MI, stroke, vascular disease)

4. Development of JNC-8 Commissioned by the NHLBI in 2008
Panel members appointed
Developed focused critical questions relevant to practice
In 2013, the NHLBI decides that it will no longer publish clinical guidelines
Proposes to work collaboratively with other organizations
The panel members appointed to the JNC-8 decided to publish their findings independently
Published online in JAMA in December 2013
Received no endorsements from other organizations

5. And then we waited…and waited…
Development of JNC-8
And then we waited…and waited…

6. also got known as JNC-Late
Development of JNC-8
also got known as JNC-Late

8. 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults
2014 Hypertension Guideline Management AlgorithmSBP indicates systolic blood pressure; DBP, diastolic blood pressure; ACEI, angiotensin-converting enzyme; ARB, angiotensin receptor blocker; and CCB, calcium channel blocker.aACEIs and ARBs should not be used in combination.bIf blood pressure fails to be maintained at goal, reenter the algorithm where appropriate based on the current individual therapeutic plan.
JAMA. 2014;311(5): doi: /jama

9. New Hypertension Guidelines in 2013
A multitude of other hypertension guidelines were also published in 2013:
AHA/ACC/CDC advisory algorithm
American Society of Hypertension/International Society of Hypertension (ASH/ISH)
European Society of Hypertension and European Society of Cardiology (ESH/ESC)
Canadian Hypertension Education Program (CHEP)

10. Comparison of Recent Guideline Statements
Adapted from Salvo M et al. Ann Pharmacother 2014;48:

11. Recommendation 1 Patients aged 60+
Treatment threshold and BP goal 150/90+
Strong Recommendation – Grade A
If treatment achieves BP <150/90, do not step- down medication (i.e. if already controlled <140, don’t change treatment)
Expert Opinion – Grade E

12. Hypertension in the Elderly
Fastest growing segment of the population
Prevalence of hypertension is very high
Several issues make managing HTN unique:
Often present with isolated systolic HTN
More likely to present with comorbidities
Many clinical trials in HTN have excluded these patients (particularly for those 80 years and older)
Elderly are more susceptible to certain adverse effects (orthostatic hypotension)

13. JNC-8 Implications for the USA
ALL US Adults
Ages 18-59
Ages 60+
JNC 7: HTN
66.6 M
32.8 M
33.8 M
Controlled
26 (39.9%)
13.3 (40.5%)
13.3 (39.3%)
JNC 8: HTN
60.8 M
30.8 M
30.0 M
34.3 (56.4%)
14.6 (47.4%)
19.7 (65.7%)

14. The Data Behind the JNC 8 Recommendations

16. HYpertension in the Very Elderly Trial
International, multi-centre, randomised, double-blind, placebo-controlled
Inclusion Criteria: Exclusion Criteria:
Aged 80 or more, Standing SBP < 140mmHg
Systolic BP; mmHg Stroke in last 6 months
+ diastolic BP; <110 mmHg, Dementia
Informed consent Need daily nursing care
Primary Endpoint:
All strokes (fatal and non-fatal)
Background
Whether the treatment of patients with hypertension who are 80 years of age or older is beneficial is unclear. It has been suggested that antihypertensive therapy may reduce the risk of stroke, despite possibly increasing the risk of death.
Full Text of Background...
Methods
We randomly assigned 3845 patients from Europe, China, Australasia, and Tunisia who were 80 years of age or older and had a sustained systolic blood pressure of 160 mm Hg or more to receive either the diuretic indapamide (sustained release, 1.5 mg) or matching placebo. The angiotensin-converting–enzyme inhibitor perindopril (2 or 4 mg), or matching placebo, was added if necessary to achieve the target blood pressure of 150/80 mm Hg. The primary end point was fatal or nonfatal stroke.
Full Text of Methods...
Results
The active-treatment group (1933 patients) and the placebo group (1912 patients) were well matched (mean age, 83.6 years; mean blood pressure while sitting, 173.0/90.8 mm Hg); 11.8% had a history of cardiovascular disease. Median follow-up was 1.8 years. At 2 years, the mean blood pressure while sitting was 15.0/6.1 mm Hg lower in the active-treatment group than in the placebo group. In an intention-to-treat analysis, active treatment was associated with a 30% reduction in the rate of fatal or nonfatal stroke (95% confidence interval [CI], −1 to 51; P=0.06), a 39% reduction in the rate of death from stroke (95% CI, 1 to 62; P=0.05), a 21% reduction in the rate of death from any cause (95% CI, 4 to 35; P=0.02), a 23% reduction in the rate of death from cardiovascular causes (95% CI, −1 to 40; P=0.06), and a 64% reduction in the rate of heart failure (95% CI, 42 to 78; P<0.001). Fewer serious adverse events were reported in the active-treatment group (358, vs. 448 in the placebo group; P=0.001).
Full Text of Results...
Conclusions
The results provide evidence that antihypertensive treatment with indapamide (sustained release), with or without perindopril, in persons 80 years of age or older is beneficial. (ClinicalTrials.gov number, NCT )
Target blood pressure
150/80 mmHg

17. HYVET: ITT Analysis HR 95% CI 0.70 (0.49, 1.01) 0.61 (0.38, 0.99) 0.79
(0.65, 0.95)
0.81
(0.62, 1.06)
0.77
(0.60, 1.01)
0.71
(0.42, 1.19)
0.36
(0.22, 0.58)
0.66
(0.53, 0.82)
All Stroke
Stroke Death
All cause mortality
NCV/Unknown death
CV Death
Cardiac Death
Heart Failure
CV events
0.1
0.2
0.5 2

18. Hypertension in the Elderly
HYVET demonstrated that treatment of HTN to goal BP less than 150/80 mm Hg in patients >80 years old was safe and effective But…what about a lower BP goal? And…what about the patients age 60-80?

19. Hypertension in the Elderly Trials – Stroke, HF, & CHD Reduction
SHEP
Syst-Eur
Year
1991
1997
Sample Size (N)
4, 736
4,695
Sample Characteristics
Adults ≥60 yo
SBP
DBP <90
DBP <95
Goals
SBP >180: <160
SBP : ↓20
SBP <150 AND↓≥20
Median f/u
4.5 years
2 years
Quality Rating
Good*
*Good = least risk of bias, results considered valid
JAMA. 2013;():doi: /jama

20. Results – Cardiovascular Disease
Combined fatal and non-fatal stroke
SHEP ↓36% (p=0.0003)
Syst-Eur ↓42% (p=0.003)
Combined fatal and non-fatal HF
SHEP ↓49% (p<0.001)
Syst-Eur ↓29% (p=0.12)
Combined fatal/non-fatal MI, CHD death, sudden death
SHEP
CHD events ↓25% (95% CI 0.60, 0.94)
Non-fatal MI ↓33% (95% CI 0.47, 0.96)
Non-fatal MI+CHD death ↓27% (95% CI 0.57, 0.94)
Syst-Eur - CHD component outcomes not significant w/o HF inclusion
JAMA. 2013;():doi: /jama

21. Trials Addressing SBP <150 vs <140
JATOS*
VALISH**
Year
2008
2010
Sample Size (N)
4,418
3,260
Sample Characteristics
Adults 65-85
SBP ≥ 160
DBP <120
Adults 70-85
SBP ≥160
DBP <90
Goals
Strict: <140
Moderate: ≥140-<160
Strict: SBP <140
Moderate: ≥140-<150
Median f/u
2 years
2.85 years
Quality Rating
Good
*Japanese Trial to Assess Optimal SBP (JATOS)
**Valsartan in Elderly Isolated Systolic Hypertension
JAMA. 2013;():doi: /jama

22. Japanese Trial to Assess Optimal SBP (JATOS)
Hypertens Res. 2008;31(12):

23. Valsartan in Elderly Isolated Systolic Hypertension

24. Dissension among the ranks!
Wright JT Jr et al. Ann Intern Med 2014;160:

25. JNC 8 Methodology Excluded Most Studies
Conducted a systematic search of pertinent literature
Limited to randomized controlled trials (RCTs) published between 1966 and 2009
Included patients age 18 or older with hypertension
Sample size of 100 patients or more
Results must have included “hard” outcomes
Subsequent search of studies from 2009 to 2013 required samples of 2000 or more patients
Only 2.05% of reviewed studies formed the basis of the recommendation
Five of the 9 guidelines were opinion-based or “by expert advise only”

26. Other Trials Targeting SBP < 140 mm Hg
Felodipine Event reduction (FEVER) Trial
Chinese population; age range 50-79; mean age 62 yrs
Significant reduction in CVD, mortality, CAD, HF
Secondary Prevention of Subcortical Stroke (SPS3 Trial)
Significant reduction in stroke
2 recent meta-analyses
Observational studies

27. Achieved BP in Studies Included by the JNC 8 was Lower
SHEP
Syst-Eur
HYVET
Year
1991
1997
2008
Sample Size (N)
4, 736
4,695
3,845
Sample Characteristics
Adults ≥60 yo
SBP
DBP <90
DBP <95
Adults ≥80 yo
SBP ≥160
DBP <110
Goals
SBP >180: <160
SBP : ↓20
SBP <150 AND↓≥20
<150/80
BP achieved
143 mm Hg
150 mm Hg
144 mm Hg
Median f/u
4.5 years
2 years
2.1 years
Quality Rating
Good*
*Good = least risk of bias, results considered valid
JAMA. 2013;():doi: /jama

28. Problems with JATOS and VALISH Studies
Performed in Japanese populations Low number of events
Trial (n)
Total Endpoints
Composite CVD
Stroke
JATOS
(n=4418)
172
Rate per 1000 patient year:
22.6 vs 22.7 (p=.99)
13.7 vs 12.9
VALISH
(n=3260) 99
HR: 0.89
P=0.383
HR: 0.68
P=o.237

29. Lack of Harm with SBP < 140
VALISH JATOS HYVET SHEP

30. The age group 60 years and older is a high risk population

31. U.S. Cardiovascular Disease Death Rates for Persons Younger and Older Than 65 yrs
Ann Intern Med. 2014;160(7): doi: /M

32. NHANES Data Showing Progress in Treatment of Hypertension
Smoothed Weighted Frequency Distribution, Median and 50th Percentile of SBP for persons aged years
Reproduced from Lackland and colleagues (4). NHANES = National Health and Nutrition Examination Survey; NHES = National Health Examination Survey.
Ann Intern Med. 2014;160(7): doi: /M

33. Population Impact of Changing BP Goals <150 for Age 60 or Older
High risk population
Risk range for white and AA men aged 60 is 9-30% depending on risk profile
Risk Range for white and AA aged 70 without known CVD or DM with SBP < 140 exceeds 20% at 10-yrs
The “Speed Limit” effect

34. What will resolve the controversy? BP< 140/90 or < 150/90
More data is needed

35. BP Treatment Targets Have Risks Both Ways
If one votes to keep all at 140/90
PM’s and incentives may encourage over-treatment
Worse symptoms, falls, costs in elderly
• If one votes to move to 150/90 in elderly
Risk of under-treatment
Despite existing guideline goals/PM’s, <50% of public reaches goal!

36. Summary
Significant controversy over targets of initiating and goals of hypertension therapy in elderly patients
I recommend the following:
Risk factor stratification
Frail versus non-frail
Chronologic versus physiologic age
Risk of falls
Consideration of adverse effects of anti-hypertensives and polypharmacy