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

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

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)

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

JAMA. 2014;311(5):507-520. doi:10.1001/jama.2013.284427

2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults

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)

COMPARISON OF RECENTGUIDELINE STATEMENTS

Adapted from Salvo M et al. Ann Pharmacother 2014;48:1242-8.

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

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)

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

Controlled 34.3 (56.4%) 14.6 (47.4%) 19.7 (65.7%)

THE DATA BEHIND THE JNC 8 RECOMMENDATIONS

Placebo

Placebo

+ Placebo

+ Placebo

Indapamide SR 1.5 mg

+ Perindopril 2 mg

+ Perindopril 4 mg

M-2 M-1 M0 M3 M6 M9 M12 M18 M24 M60

International, multi-centre, randomised, double-blind, placebo-controlled

Inclusion Criteria: Exclusion Criteria:Aged 80 or more, Standing SBP < 140mmHgSystolic BP; 160 -199mmHg Stroke in last 6 months+ diastolic BP; <110 mmHg, DementiaInformed consent Need daily nursing care

Primary Endpoint: All strokes (fatal and non-fatal)

Target blood pressure

150/80 mmHg

HYpertension in the Very Elderly Trial

0 20.50.20.1

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

HYVET: ITT ANALYSIS

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?

HYPERTENSION IN THE ELDERLYTRIALS – STROKE, HF, & CHD REDUCTION

SHEP Syst-Eur

Year 1991 1997

Sample Size (N) 4, 736 4,695

Sample Characteristics

Adults ≥60 yoSBP 160-219

DBP <90

Adults ≥60 yoSBP 160-219

DBP <95

Goals SBP >180: <160SBP 160-179: ↓20

SBP <150 AND↓≥20

Median f/u 4.5 years 2 years

Quality Rating Good* Good*

JAMA. 2013;():doi:10.1001/jama.2013.284427.

*Good = least risk of bias, results considered valid

RESULTS – CARDIOVASCULAR DISEASECombined 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:10.1001/jama.2013.284427.

TRIALS ADDRESSING SBP <150 vs <140

JATOS* VALISH**

Year 2008 2010

Sample Size (N) 4,418 3,260

Sample Characteristics Adults 65-85SBP ≥ 160DBP <120

Adults 70-85SBP ≥160DBP <90

Goals Strict: <140Moderate: ≥140-<160

Strict: SBP <140Moderate: ≥140-<150

Median f/u 2 years 2.85 years

Quality Rating Good Good

JAMA. 2013;():doi:10.1001/jama.2013.284427.

*Japanese Trial to Assess Optimal SBP (JATOS)**Valsartan in Elderly Isolated Systolic Hypertension

JAPANESE TRIAL TO ASSESS OPTIMAL SBP (JATOS)

Hypertens Res. 2008;31(12):2115-2127

VALSARTAN IN ELDERLY ISOLATED SYSTOLIC HYPERTENSION

Hypertension. 2010;56(2):196-202

Dissension among the ranks!

Wright JT Jr et al. Ann Intern Med 2014;160:499-504.

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”

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

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 yoSBP 160-219

DBP <90

Adults ≥60 yoSBP 160-219

DBP <95

Adults ≥80 yoSBP ≥160DBP <110

Goals SBP >180: <160SBP 160-179: ↓20

SBP <150 AND↓≥20

<150/80

BP achieved 143 mm Hg 150 mm Hg 144 mm HgMedian f/u 4.5 years 2 years 2.1 years

Quality Rating Good* Good* Good*

JAMA. 2013;():doi:10.1001/jama.2013.284427.

*Good = least risk of bias, results considered valid

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)

Rate per 1000 patient year:13.7 vs 12.9

VALISH(n=3260)

99 HR: 0.89P=0.383

HR: 0.68P=o.237

LACK OF HARM WITH SBP < 140

VALISH

JATOS

HYVET

SHEP

THE AGE GROUP 60 YEARS AND OLDER IS A HIGH RISK POPULATION

Ann Intern Med. 2014;160(7):499-503. doi:10.7326/M13-2981

U.S. Cardiovascular Disease Death Rates for Persons Younger and Older Than 65 yrs

Ann Intern Med. 2014;160(7):499-503. doi:10.7326/M13-2981

Reproduced from Lackland and colleagues (4). NHANES = National Health and Nutrition Examination Survey; NHES = National Health Examination Survey.

Smoothed Weighted Frequency Distribution, Median and 50th Percentile of SBP for persons aged 60-74 years

NHANES Data Showing Progress in Treatment of Hypertension

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

WHAT WILL RESOLVE THE CONTROVERSY?BP< 140/90 OR < 150/90

More data is needed

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!

SUMMARYSignificant 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