10/13/2014

1

JNC 8: Too Little Too LateHypertension Guidelines 2014

Ed Kersh, MD, FACCChief of Cardiology, St. Luke’s Hospital, SF

Clinical Professor of Medicine, UCSF, Touro and Dartmouth U.

Medical Director for Telemedicine, SCAH

Disclosures

Speaker’s Bureau or Advisory Board:Boeringher-Ingelheim, Jansenn, Pfizer, Lantheus, Alive-Cor, BMS

What is Normal Blood Pressure?

• 120/80

• 140/90

• 100 plus age

• 150/90

• 115/75

• 165/95

FDR signs Social Security Act 1935Blood Pressure 140/95

Frances Perkins

No treatment prescribed

FDR at Yalta 1944 BP 186/108

Dx Hypertensive Heart Failure Rx = Digitalis, Na restriction, phenobarbital

1945 FDR Dies BP = 300/190

10/13/2014

2

1948 Truman signs National Heart ActEstablishes NIH and Framingham

Framingham: CV Mortality Risk Doubles WithEach 20/10 mm Hg BP Increment

Lewington S et al. Lancet. 2002;360:1903-1913.

CVmortality

risk

SBP/DBP (mm Hg)

0

1

2

3

4

5

6

7

8

115/75 135/85 155/95 175/105

NHANES III(Phase 2)

1991-1994

NHANES III(Phase 1)

1988-1991

51%

73% 68%

31%

55% 54%

10%

29% 27%

Ad

ult

s(%

)

Awareness

NHANES II1976-1980

Treatment

Control

NHANES1999-2000

70%

59%

34%

NHANES: Prevalence of Hypertension in the US

National Health and Nutrition Examination Survey (NHANES)

High Blood Pressure: 140/90Prevalence in Different Patient Groups

National Health and Nutrition Examination Survey (NHANES)

Source: Yoon SS et al. NCHS Data Brief 2012;107:1-7

*High blood pressure defined as bloodpressure140/90 mmHg or treatment

Association Between Hypertensionand Heart Failure

Incidence of ESRD by SBP: MRFIT

100

80

60

40

20

0

SBP (mm Hg)

Incidence ofESRD/

100,000person-yrs

(%)

White

African American

ESRD, end-stage renal disease.Klag MJ et al. JAMA. 1997;277:1293-1298.

<117 117-123 124-130 131-140 >140

15.8

5.4

27.3

5.4

26.2

9.1

37.2

14.2

83.1

32.4

10/13/2014

3

Association between blood pressure andrisk of first-ever stroke

Vokó Z et al. Hypertension. 1999;34:1181-1185

Association between treated blood pressureand risk of first-ever stroke

Vokó Z et al. Hypertension. 1999;34:1181-1185

Veterans Administration, 1967

Veterans Administration, 1970

Hypertension Stroke Study, 1974

USPHS Study, 1977

EWPHE Study, 1985

Coope and Warrender, 1986

SHEP Study, 1991

STOP-Hypertension Study, 1991

MRC Study, 1992

Syst-Eur Study, 1997

Total

0 0.5 1.0 1.5 2.0

0.79(0.69 to 0.90)

Source: He J et al. Am Heart J 1999;138:211-219

Better than placebo Worse than placebo

CHD=Coronary heart disease

High Blood Pressure Evidence:Prevention of Cardiovascular Disease withTreatment Benefits of Lowering BP

Average Percent Reduction

Stroke incidence 35–40%

Myocardial infarction 20–25%

Heart failure 50%

CVD Survival in Treated Hypertensivesat Goal and Not at Goal

Benetos et al. J Hypertens. 2003;21:1635-1640.

Follow-up (Years)

Su

rviv

al(

%)

1

0.96

0.92

0.88

0.84

0.81 3 5 7 9 11 1315 17 19 21 23 25

P=.03

P<.0001

P=.001

Treated BP not at goal 140/90 mm Hg

Untreated BP <140/90 mm Hg

Untreated BP 140/90 mm Hg

Treated BP at goal <140/90 mm Hg

What is JNC?

• Joint National Committee of NHLBI

• JNC 1 1976

• JNC 7 2003

• JNC 8 2014 – too late

• There will be no JNC 9

10/13/2014

4

What did JNC 7 say?

• Defined hypertension stages and prehypertension

• Defined standards for BP measurement

• Defined 130/80 for diabetic and CKD subsets

• Outlined effective lifestyle changes

• Recommended initial therapy and workup

• Defined compelling indications

• Guidelines for special populations

• Addressed resistant hypertension and adherence

JNC 7: Classification and Management of BP

Class Lifestyle

Modification

No CompellingIndications

With CompellingIndications

Normal BP Encourage None

Pre – HTN

(135/85)

Yes None

Stage 1

>140/90

Yes Thiazide Drug forIndication

Stage2

>160/100

Yes 2 drugs Drug(s) forIndication

Clinical-Trial BasisCompelling Indication

ALLHAT, HOPE, ANBP2,LIFE, CONVINCE

High CAD Risk

ACC/AHA Post-MI Guidelines,BHAT, SAVE, Capricorn, EPHESUS

Post-MI

MERIT-HF, COPERNICUS, CIBIS,SOLVD, AIRE, TRACE, Val-HeFT,

RALES

Initial Therapy Options

Diuretic, BB, ACE-I, CCB

BB, ACE-I, Aldo ANT

Diuretic, BB, ACE-I,ARB, Aldo ANT

Heart Failure

Recurrent Stroke Prevention PROGRESSDiuretic, ACE-I

NKF-ADA Guideline,UKPDS, ALLHAT

NKF Guidelines, Captopril Trial,RENAAL, IDNT, REIN, AASK

Diuretic, BB, ACE-I,ARB, CCB

ACE-I, ARB

Diabetes Mellitus

Chronic Kidney Disease

Source: ChobanianAV et al. JAMA 2003;289:2560-2572

ACE-I=Angiotensin converting enzyme inhibitor, Aldo ANT=Aldosterone antagonist,ARB=Angiotensin receptor blocker, BB=Beta-blocker, CAD=Coronary artery disease,

CCB=Calcium channel blocker, MI=Myocardialinfarction

JNC VII Guidelines:Compelling Indications for Drug Classes

What is JNC 8?

• Joint National Committee

• 17 members

• 8th time

• Appointed by the NHLBI in 2008

• Disbanded by the NHLBI in June 2013

• Published in JAMA in December 2013

• “Not an NHLBI-sanctioned report and doesnot reflect the views of the NHLBI”

JNC8: Methods

• Only included randomized, controlled trials• Excluded sample size < 100 and f/up period < 1 year• Only included studies reporting effects of

interventions on:– MI– Stroke– Renal Function– Heart failure (HF) or hospitalization for HF– Coronary revascularization or other

revascularization– Mortality

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

Strength of Recommendation

10/13/2014

5

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

Evidence Quality Rating What does JNC 8 say?

Too Little

150/90 for those over age 60

Hypertension Conspiracy Theory:lower diagnostic thresholds mean that more people are

diagnosed with a disease

In 1993, JNC V lowered from the guideline from 160/95 to140/90 in non-diabetic patients.

In 1998, the hypertension blood pressure definition fordiabetics was lowered to 130/80.

Lower targets led to an additional 22 million customers for thepharmaceutical industry. Much of the research onhypertension is industry funded, hence the conspiracy theory.

JNC 8: Asks 3 Key Questions

• In adults with HTN, does initiating antihypertensivepharmacologic therapy at specific BP thresholdsimprove health outcomes?

• In adults with HTN, does treatment withantihypertensive pharmacologic therapy to a specifiedBP goal lead to improvements in health outcomes?

• In adults with HTN, do various antihypertensive drugsor drug classes differ in comparative benefits andharms on specific health outcomes?

JNC 8 – 9 recommendations

• Age > 60, 150/90• Age< 60, <diastolic 90• Age < 60, <systolic 140• CKD, 140/90• Diabetes, 140/90• Non-black: diuretic, CCB, ACE/ARB• Black: diuretic, CCB• CKD: ACE/ARB regardless of race or diabetes• Goal in 1 month/titration

#1 = < 150/90 for those 60 and older

• Start Rx at 150/90

• Aim for 150/90

• Trials• HYVET

• SHEP

• Syst-Eur

• JATOS

• VALISH

• CARDIO-SIS

• Grade A – strong recommendation

10/13/2014

6

3,845 patients >80 years with SBP >160 mm Hg randomized to treatment toindapamide (1.5 mg) and perindopril (2-4 mg if needed) vs. placebo for 2 years

Blood pressure control in patients >80 years of age provides benefit

Hypertension in the Very Elderly (HYVET) Trial

Source: Beckett NS et al. NEJM 2008;358:1887-1898

CV=Cardiovascular, CVA=Cerebrovascular accident

Rat

e/1

00

0p

atie

nty

ears

(%)

P=0.06

P=0.05

P=0.02

P<0.001

P<0.001

(Primary end point)

Indapamide +perindopril

Placebo

VALISH Trial – examined 140 systolic goal

Angeli F et al. Hypertension. 2010;56:182-184

JATOS<140 vs 140-160

age 65-85efondipine T channel CCB

• Goal <140 systolic

• N=2212

• 136/75

• Endpoints = 86

• Deaths = 54

• Goal 140-160 systolic

• N=2206

• 146/78

• Endpoints = 86

• Deaths = 42

Jatos Study Group Hypertension Res 2008; 31:2115-2127Source: Verdecchia P et al. Lancet 2009;374:525-533

Cardio-SIS Trial

AF=Atrial fibrillation, ESRD=End stage renal disease, CHF=Congestive heart failure,CVA=Cerebrovascularaccident, LVH=Left ventricular hypertrophy, MI=Myocardial infarction,

PAD=Peripheral artery disease, SBP=Systolic bloodpressure, TIA=Transient ischemic attack

Incid

ence

ofL

VH

(%)

Usual Control

17.0

Tight Control

21

14

7

0

11.4

P=0.013

Co

mpo

site

ofC

Ve

ve

nts

*(%

)

Usual Control

9.4

Tight Control

15

10

5

0

4.8

P=0.003

*Composite of death, MI, CVA, TIA, CHF, angina, new AF,revascularization, aortic dissection, PAD, and ESRD

1,111 patients >55 years with SBP >150 mm Hg randomized totreatment to achieve usual BP control (SBP <140 mm Hg) or intensive

BP control (SBP <130 mm Hg)

More intensive blood pressure control provides greater benefit

Corollary to #1

• No need to down titrate doses or medicationsif SBP is lower than 140

• Therapy can be down titrated in patients on>3 medications

• Expert opinion

Recommendation #2:Age <60, Diastolic <90

• Prevalence of diastolic hypertension is higher inyounger patients

• Start if diastolic BP > 90• Aim for diastolic < 90• Trials:

• HDFP• Hypertension-Stroke• MRC• ANBP• VA Coop

• Level of evidence A for 30-59• Level of evidence E for 18-29

10/13/2014

7

Hypertension-Stroke Trial

• 523 male VA patients with diastolic BPbetween 90 and 104

• Randomized to Serapes vs placebo

• Followed for avg. 3.3 years

• 20 strokes in placebo group

• 5 strokes in treatment group

Fries, Stroke 1974

HDFP trialEntry diastolic BP >90.

Stepped Care vs Referred Care

Reommendation 3:Age <60, Systolic <140

• Start if SBP > 140

• Aim for SBP< 140

• There are no RCT’s that address this question

• Expert Opinion

Recommendation 4:CKD < 140/90

• CKD defined as GFR<60 or albuminuria >30mg/g creatinine

• Raises goal from 130/80 (JNC 7)

• Conflicting evidence

• Strength of recommendation E

JAMA. 2002;288(19):2421-2431.1

No difference in CV events or mortality

AASK

JAMA. 2002;288(19):2421-2431.

No significant difference between usual and lower BP goal

AASK : Usual vs Lower BP Goal

10/13/2014

8

JAMA. 2002;288(19):2421-2431

AASK: Changes in glomerular filtration rate(GFR) by therapy

amlodipine

metoprolol

ramipril

ACE inhibitor was better

Recommendation 5:Diabetes, <140/90

• Raises goal from 130/80 (JNC 7)

• ACCORD – BP trial – outcomes at SBP < 140were the same as SBP < 120

• Strength of Recommendation E

StrokeAny

diabeticendpoint

Death fromdiabetes

Microvascularcomplications

Riskreduction

(%)

UKPDS: Benefits of BP Control in Type 2 Diabetes:

*P<0.05 vs tight glucose control.

Bakris GL et al. Am J Kidney Dis.2000;36:646-661.

Tight glucose control (HgbA1c 7.0%)

Tight BP control (<150/85 mm Hg)

24*

44*

37*32*

11

12

25

10

UKPDS Group 38. BMJ. 1998;317:703-713.UKPDS Group 33. Lancet. 1998;352:837-853.

-50

-40

-30

-20

-10

0

10

20

ACCORD BP: Using an average of 3 drugs, the study achieved a SBP of 119 mmHg vs. 133 mmHg

ACCORD BP: Results

Conclusions: “In patients with type 2 diabetes at high risk for cardiovascular events,targeting a systolic blood pressure of less than 120 mmHg, as compared with lessthan 140 mmHg, did not reduce the rate of fatal and nonfatal major CVD events.”

N Engl J Med April 29th, 2010

Cochrane review 2009

Four trials looked at major CVD outcomes based on randomized BP control;Two trials (ABCD) were exclusively in patients with diabetes

10/13/2014

9

Source: Hansson L et al. Lancet 1998;351:1755-1762

Hypertension Optimal Treatment (HOT) Study

Diastolic BP goal

Patients withoutDiabetes

Ma

jor

CV

eve

nts

pe

r1

00

0pa

tient-

yea

rs

Patients withDiabetes

Diastolic BP goal

18,790 patients with a baseline diastolic BP of 100-115 mm Hg randomizedto a target diastolic BP of <90 mm Hg, <85 mm Hg, or <80 mm Hg

More intensive blood pressure control provides greater benefit in diabetics

Blood Pressure Lowering Therapy Evidence:Effect of Intensive Blood Pressure Control Recommendation #6

Non-black: diuretic, CCB, ACE/ARB

• In the general non-black population, initial RXshould include a thiazide diuretic, CCB, ACE orARB.

• Most require 2 agents

• Studies: VA Coop. HDFP, SHEP

• Moderate Recommendation, Grade B

• Diuretic>ACE>CCB in preventing CHF

33,357 patients with HTN and >1 CHD risk factor randomized tochlorthalidone, amlodipine, or lisinopril for 5 years

All three BP lowering agents providesimilar efficacy

0 1 2 3 4 5 6 70

.04

.08

.12

.16

.20

Ra

teo

fM

Io

rfa

talC

HD

Antihypertensive and Lipid-Lowering Treatment to Prevent HeartAttack Trial (ALLHAT)

Source: ALLHAT Investigators. JAMA 2002;288:2981-2997

Years to CHD Event

BP=Blood pressure, CHD=Coronary heart disease,HTN=Hypertension, MI=Myocardial infarction

Chlorthalidone

Amlodipine

Lisinopril

RR (95% CI) P-value

A/C 0.98 (0.90-1.07) 0.65

L/C 0.99 (0.91-1.08) 0.81

Blood Pressure Lowering Therapy Evidence:Primary Prevention

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

Evidence-Based Dosing for Antihypertensive Drugs

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

Comparison of Current Recommendations

With JNC 7 Guidelines

Eliminates Beta Blockers as initial choice

Modification Recommendation Approximate SBPReduction Range

Weight reduction Maintain normal body weight (BMI=18.5-25)

5-20 mmHg/10 kg weightlost

DASH eating plan Diet rich in fruits, vegetables, low fat dairyand reduced in fat

8-14 mmHg

Restrict sodiumintake

<2.4 grams of sodium per day 2-8 mmHg

Physical activity Regular aerobic exercise for at least 30minutes most days of the week

4-10 mmHg

Moderate alcohol <2 drinks/day for men and <1 drink/dayfor women

2-4 mmHg

Source: ChobanianAV et al. JAMA 2003;289:2560-2572

BMI=Body mass index, BP=Blood pressure, SBP=Systolic blood pressure

JNC VII Guidelines:Lifestyle Modifications for BP Control

10/13/2014

10

Recommendation #7:Black: diuretic, CCB

• Subgroup analysis from ALLHAT

• 51% higher stroke rate in ALLHAT with ACE

• Black patients have lower renin levels

• Moderate Recommendation, Grade B

• Weak recommendation with diabetes, Grade C

Heart Disease Mortality Among Women by Race

Deathsper

100,000women

per year*

Black White NativeAmerican

Hispanic Asian

110.6

77.6

53.0 51.844.2

*Women >35 years of age; 1991-1995.American Heart Association. 2001 Heart and Stroke Statistical Update.Casper ML et al. Women and Heart Disease: An Atlas of Racial and Ethnic Disparities in Mortality. 2nd

ed. 2001.

0

40

60

80

100

120

20

Recommendation #8:CKD: ACE/ARB regardless of race or diabetes

• No studies comparing ACE’s to ARB’s

• Multi drug therapy almost always required

• Monitor creatinine and K+

• Moderate Recommendation, Grade B

Maschio G et al. J Cardiovasc Pharmacol. 1999;3(suppl 1):S16-S20.

Renal Endpoints in Subjects With Moderate Chronic RenalFailure Receiving Benazepril or Placebo: AIPRI

Subjectsnot

reachingendpoint

(%)

0 1 2 3

Benazepril

Years

0

60

80

100

0

70

90

Placebo

JAMA. 2002;288(19):2421-2431.

AASK: percentage changes in the urine protein/creatinine ratio

Better with lower BP

Worse with CCBBest with ACE

AA with CKD should get both a CCB and and ACE or ARB

Recommendation #9: How To

1950’s = Diuretics

1960’s = Sympatolytics

1970’s = Beta Blockers

1980’s = CCB’s

1990’s = ACE’s and ARB’s

2000 = DRI

2010 = Double RAAS

10/13/2014

11

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

Strategies to Dose Antihypertensive Drugs

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

ACEIs and ARBs should not be used in combination.

If blood pressure fails to be maintained at goal, reenter the algorithm where appropriate based on the current individual therapeuticplan.

JNC 8 Algorithm for Treating Hypertension

ACE/ARB Combination Therapy

The ONTARGET Investigators. N Engl J Med 2008;358:1547-1559

Better CV Outcomes but more Renal Failure

The ONTARGET Investigators. N Engl J Med2008;358:1547-1559

Adding Aliskinin to ACE/ARB in Diabetics

Parv ing H-H et al. N Engl J Med 2012;367:2204-2213

Prespecified Primary and Secondary Composite Outcomes and Deaths.

Parving H-H et al. N Engl J Med 2012;367:2204-2213

10/13/2014

12

JNC 8 – too little

What should BP goal be afterstroke, CHF, or MI?

Permissive Hypertension?

• The current guidelines for management of bloodpressure during acute ischemic stroke recommendpermissive hypertension for those patients who havenot received IV-rtPA. The guidelines recommendwithholding antihypertensive treatment unless thesystolic blood pressure is greater than 220 mm Hg orthe diastolic blood pressures greater than 120 mm Hg.When the blood pressure exceeds this threshold andantihypertensive therapy is warranted, blood pressureshould be cautiously reduced by no more than 15%over the initial 24-hour period.

Adams HP Jr, del Zoppo G, Alberts MJ, et al; American Heart Association/AmericanStroke Association Stroke Council Working Group; Circulation 2007;115(20):e478–e534

Effect of antihypertensive therapy in patients with prior stroke on subsequent events

Rashid P et al. Stroke. 2003;34:2741-2748

7 RCT’sBP lowered25/12

AHA/ACC Guidelines 2013:Hypertension should be controlled inaccordance with contemporary guidelines tolower the risk of HF (Level of Evidence: A)

What is the ideal BP in CHF patients?

Blood pressure control in heart failure isReally about afterload reduction

Ideal systolic blood pressure in CHFis 10 points above fainting

What is ideal BP after an MI?

Bangalore et al J- or U-Shaped Curve for Blood Pressure After ACS Circulation.2010;122:2142-2151

Get the heart rate below 70 while maintaining a systolic pressure above 110mmHg

The J Curve of Therapy

0

10

20

30

40

50

60

70

80

90

100

Mortality&

Morbidity

Blood pressureData NOT on File

10/13/2014

13

JNC 8 Summary

• 150/90 for age > 60• 140/90 for CKD , Diabetes and <60• No need to back off tolerated treatment

• ACE/ARB/CCB/Thiazides 1st line• CCB/Thiazides 1st line for AA• Beta-blockers and ACE/ARB combos are out

• Too Little• Too Late

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

Too Controversial

So, what does this all mean to me?

Its just a guideline, it’s not the law!!

• 150/90 is OK

• Lower goals are better

• But, too low is not

• Our control rates will be better at 150/90

• Fewer patients will be dizzy, nauseated and impotent

• Fewer drugs?

• You won’t get sued at 150/90