hypertension 2016: are we hypertension up or down? peter

Hypertension 2016: Are we up or down?

Peter LibbyBrigham & Women’s Hospital

Harvard Medical School

Pri-Med Updates for CardiologistsPhiladelphia September 12, 2016

Hypertension Guidelines

Where do we stand?

New hypertension practice guidelines from 10 expert committees in the US, Canada, and Europe have emerged since 2010. The guideline recommendations have become more evidence-based and but also more controversial.

Hypertension GuidelinesWhere do we stand?

So, where were the new hypertension guidelines?

March, 2013

The 2014 Report of Panel Members Appointed to the Eighth Joint National Committee (“JNC 8”) is the most strictly evidence-based set of hypertension guidelines produced to date. Yet, unlike past JNCs, “JNC 8” is not a comprehensive set of practice guidelines and was neither reviewed nor endorsed by NIH/HHS or any professional medical society.

Hypertension GuidelinesWhere do we stand?

JAMA. doi:10.1001/jama.2013.284427. Published online December 18, 2013.

2014 BP Guideline: Recommendation #1 1. In patients aged ≥60 years, initiate

pharmacologic treatment in systolic BP ≥150mmHg or diastolic BP ≥90mmHg and treat to a goal systolic BP <150mmHg and goal diastolic BP <90mmHg.

(Strong Recommendation – Grade A) In other words: Ease up on Hypertension Treatment in Older Adults (60 years of age or older)

BP goal <150/90

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2014 BP Guideline: Recommendations #2 & #3 2. In patients aged <60 years, initiate pharmacologic

treatment at DIASTOLIC BP ≥90mmHg and treat to a goal <90mmHg.

For ages 30–59 years, Strong Recommendation–Grade A For ages 18–29 years, Expert Opinion–Grade E

3. In patients aged <60 years, initiate pharmacologic treatment at SYSTOLIC BP ≥140mmHg and treat to a goal <140mmHg.

Expert Opinion–Grade E

For Adults under 60 years of age

BP goal <140/90 There’s strong evidence for treating high diastolic BP in patients

30-59 years of age. Everything else is “Expert Opinion”

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2014 BP Guideline: Recommendations # 4 & 5

4. In patients aged ≥18 years with chronic kidney disease, initiate pharmacologic treatment at systolic BP ≥140mmHg or diastolic BP ≥90mmHg and treat to goal systolic BP <140mmHg and goal diastolic BP <90mmHg. (Expert Opinion–Grade E)

Earlier HTN guidelines lowered treatment goals for adults with CKD and DM; but “JNC 8” gives the same BP goals in these patients as in the

general population. BP goal <140/90

5. diabetes mellitus

K. Watson UCLA

2014 BP Guideline: Recommendation # 8

8. In the population aged ≥18 years with chronic kidney disease, initial (or add-on) antihypertensive treatment should include an ACE inhibitor or ARB to improve kidney outcomes.

(Moderate Recommendation–Grade B)

In adult patients with CKD, make sure an ACE-I or an ARB is part of the

antihypertensive regimen K. Watson UCLA

ACE-I or ARB in CKD reduces progression of kidney disease

Study Pts Design RR for kidney disease progression

Maschio et al 1996 583 Benazapril v. placebo 53%

Gisen group 1997 166 Ramapril v. placebo 48%

Hou et al 2006 224 Benazapril v placebo 43%

Brenner et al 2001 1513 Losartan v. placebo 22%

2014 BP Guideline: Recommendation # 9 9. If goal BP is not reached within a month of treatment,

increase the dose of the initial drug or add a second drug from one of the classes in Recommendation 6. If goal BP cannot be reached with two drugs, add and titrate a third drug from the list provided. Do not use an ACEI and an ARB together in the same patient. If goal BP cannot be reached using only the drugs in Recommendation 6 … antihypertensive drugs from other classes can be used. (Expert Opinion–Grade E)

Thiazide-type diuretic, CCB, ACE-I or ARB

Don’t dilly dally. If BP is not at goal within a month, use one of these 3 strategies :

1. Increase the dose of the initial drug 2.  Add a 2nd, then a 3rd drug (Rec #6)

(Never an ACE + ARB together) 3. Add a drug from other classes K. Watson UCLA

Why Did The Goals For Patients Over 60 Change (the minority report?)

•  “However, the panel did not reach unanimous consensus on the recommendation for persons older than 60 years who do not have DM or CKD. The majority embraced the view that in the absence of definitive evidence, increasing the SBP goal was the optimum approach. We, the panel minority, believed that evidence was insufficient to increase the SBP goal from its current level of less than 140 mm Hg because of concern that increasing the goal may cause harm by increasing the risk for CVD and partially undoing the remarkable progress in reducing cardiovascular mortality in Americans older than 60 years.”

Wright, JT, Ann Intern Med. 2014;160:499-503

Approaches to Prevention Guidelines:

• Expert opinion• Strict RCT evidence based approach

• Consider also a wealth of observational data

Summary: New HBP Guideline(s)•  Clinicians have improved significantly the

control of hypertension•  The “JNC 8” Committee responded to the

recommendations of the IOM in making the new guidance

•  The change in BP goals by age does not match that in Canada or Europe and has engendered debate

•  Salt reduction is still important in BP control and stroke reduction

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“JNC8” guidelines status

•  Minority view published in Annals:–  Insufficient evidence to support target of <150

–  Higher goal would apply to some at highest CV risk (blacks, multiple RFs, clinical CVD)

–  Higher SBP goal in >60 years old could reverse decades-long declude in CVD, especially stroke mortality

•  Not endorsed by the NHLBI, AHA, or ACC

•  ACC/AHA in collaboration with ASH plan to release new guidelines in 2016-2017?

–  Anticipated goals are 130-140/80-90, with >150 permitted in >80 years old and/or frail

“JNC8” guidelines status•  Minority view published in Annals:

–  Insufficient evidence to support target of <150– Higher goal would apply to some at highest CV risk

(blacks, multiple RFs, clinical CVD)– Higher SBP goal in >60 years old could reverse

decades-long declude in CVD, especially stroke mortality

•  Not endorsed by the NHLBI, AHA, or ACC•  ACC/AHA in collaboration with ASH plan to release new

guidelines in 2016-2017?– Anticipated goals are 130-140/80-90, with >150

permitted in >80 years old and/or frail

ASH and ISH guidelines

Journal of Clinical Hypertension 2013

ASH & ISH guidelines

Dietary Therapy in Hypertension Frank M. Sacks, M.D.,

and Hannia Campos, Ph.D.

N Engl J Med Volume 362(22):2102-2112

June 3, 2010

Mechanisms Linked to Increases in Blood Pressure and the Therapeutic Effects of Healthful Dietary Patterns, Sodium Reduction, and Weight Loss

Sacks F, Campos H.N Engl J Med 2010;362:2102-2112

Sacks F, Campos H. N Engl J Med 2010;362:2102-2112

Na Reduction, the DASH Diet, and Changes in SBP The older you are the more diet influences blood pressure


Recommended Weekly and Occasional Food Purchases for One Person Following a Healthful Diet Containing 2100 kcal and 1500 mg of Sodium per Day


2014 BP Guideline: Recommendation # 9 9. If goal BP is not reached within a month of treatment,

increase the dose of the initial drug or add a second drug from one of the classes in Recommendation 6. If goal BP cannot be reached with two drugs, add and titrate a third drug from the list provided. Do not use an ACEI and an ARB together in the same patient. If goal BP cannot be reached using only the drugs in Recommendation 6 … antihypertensive drugs from other classes can be used. (Expert Opinion–Grade E)

Thiazide-type diuretic, CCB, ACE-I or ARB

Don’t dilly dally. If BP is not at goal within a month, use one of these 3 strategies :

1. Increase the dose of the initial drug 2.  Add a 2nd, then a 3rd drug (Rec #6)

(Never an ACE + ARB together) 3. Add a drug from other classes K. Watson UCLA

Should we prefer hydrochlorothiazide or chlorthalidone for HBP Rx?

.

Comparative Evaluation of Safety and Efficacy of Hydrochloro-thiazide CR with Hydrochloro-thiazide and Chlorthalidone in Patients With Stage I Essential Hypertension

J Am Coll Cardiol 2016;67:379–89

Disposi&onofStudyPar&cipantsCR=controlledrelease;ITT=inten3on-to-treat

Comparative Evaluation of Safety and Efficacy of Hydrochlorothiazide CR with Hydrochlorothiazide and Chlorthalidone in Patients With Stage I Essential Hypertension J Am Coll Cardiol 2016;67:379–89

Mean Change From Baseline to Week 12 in Average Ambulatory Systolic Blood Pressure

.

Comparative Evaluation of Safety and Efficacy of Hydrochlorothiazide CR with Hydrochlorothiazide and Chlorthalidone in Patients With Stage I Essential HypertensionJ Am Coll Cardiol 2016;67:379–89

.

Comparative Evaluation of Safety and Efficacy of Hydrochlorothiazide CR with Hydrochlorothiazide and Chlorthalidone in Patients With Stage I Essential HypertensionJ Am Coll Cardiol 2016;67:379–89 .

Comparative Evaluation of Safety and Efficacy of Hydrochlorothiazide CR with Hydrochlorothiazide and Chlorthalidone in Patients With Stage I Essential HypertensionJ Am Coll Cardiol 2016;67:379–89

Visit-to-VisitMeanOfficeSBP

.

Low-Dose Thiazides in Hypertension: 24-h and Nighttime Ambulatory BP After 12 Weeks of Therapy. A significant decrease of both 24-h and nighttime ambulatory BP with chlorthalidone, 6.25 mg/day, was observed. There was no significant decrease with HCTZ, 12.5 mg/day. ��p < 0.001; �p < 0.01; Wilcoxon signed rank tests were used for comparison. CTD = chlorthalidone; HCTZ = hydrochlorothiazide; SBP = systolic blood pressure.

CONCLUSIONS: Low-dose chlorthalidone, 6.25 mg daily, significantly reduced mean 24-h ABP as well as daytime and nighttime BP. Due to its short duration of action, no significant 24-h ABP reduction was seen with HCTZ,12.5 mg daily, which merely converted sustained hypertension into masked hypertension. Thus, low-dose chlorthalidone, 6.25 mg, could be used as monotherapy for treatment of essential hypertension, whereas low-dose HCTZ monotherapy is not an appropriate antihypertensive drug. Comparative Evaluation of Safety and Efficacy of Hydrochlorothiazide CR with Hydrochlorothiazide and Chlorthalidone in Patients With Stage I Essential HypertensionJ Am Coll Cardiol 2016;67:379–89

What Happened to Beta Blockers?

Lindholm, L Lancet 2005;366:1545-53

The US Institute of Medicine (IOM) and Salt•  The available evidence on associations between

sodium intake and direct health outcomes is consistent with population-based efforts to lower excessive dietary sodium intakes.

•  The evidence on health outcomes is not consistent with efforts that encourage lowering of dietary sodium in the general population to 1,500 mg/day.

•  There is no evidence on health outcomes to support treating population subgroups differently from the general U.S. population.

IOM Report Brief May 2013 on Sodium Intake

Clinical studies have changed the landscape since 2014

SPRINTHOPE-3CLARIFY RegistryARIC Analysis



Intensive vs. Standard BP treatment: SPRINT

SPRINT trialists. NEJM 2015;737:2103-16.

Intensive better than standard

blood pressure treatment:

SPRINT


Do people > 75 fare better with intensive BP therapy? Subgroup skuldugery with SPRINT


“SPRINT vs. ACCORD”“SPRINT vs. ACCORD”

“SPRINT vs. ACCORD”

SPRINT•  Age 68±10 with no diabetes•  Randomized: SBP<120 vs <140•  # Meds needed: 3.0 vs 1.9•  BP measure: Omron 907 auto-cuff

x3, quiet room, after 5 min rest•  25% lower CV events, 27% lower

mortality, at 3.3 years

•  Could SPRINT have been especially effective for preventing arterial stiffness in non-diabetics? (marked difference seen for HF events and non-CV deaths)

ACCORD•  Age 62±7 with diabetes•  Randomized: SBP<120 vs <140•  # Meds needed: 3.4 vs 2.3•  BP measure: Omron 907 auto-cuff

x3•  No difference at 4.7 years

•  Could ACCORD have been less effective or too aggressive for persons with greater arterial stiffness? (despite more adverse events in SPRINT given older age)

SPRINT BP measurement technique: relevant to our busy practices?


Clinic vs. Home BP Measures

Clinic Measures Home Measures

Niiranen et al. Hypertension 2013;61:27-34

Clinic BP Home BP120/80 120/75140/90 135/85

160/100 145/90



Published April 2, 2016, at NEJM.org.DOI: 10.1056/NEJMoa1600175

Antihypertensive therapy reduces the risk of cardiovascular events among high-risk persons and among those with a systolic blood pressure of 160 mm Hg or higher, but its role in persons at intermediate risk and with lower blood pressure is unclear….We randomly assigned 12,705 participants at intermediate risk who did not have cardiovascular disease to receive either candesartan at a dose of 16 mg per day plus hydrochlorothiazide at a dose of 12.5 mg per day or placebo.

Blood-Pressure Lowering in Intermediate-Risk Persons without Cardiovascular Disease HOPE-3

HOPE-3BP ArmApril 2, 2016, NEJM.org.DOI: 10.1056/NEJMoa1600175


Blood-Pressure Lowering in Intermediate-Risk Persons without Cardiovascular DiseaseEva M. Lonn,.. Salim Yusuf, for the HOPE-3 Investigators†

HOPE-3 NEJM.org.DOI: 10.1056/NEJMoa1600175




The “J-shaped-curve”

Dogma Disputed: Can Aggressively Lowering Blood Pressure inHypertensive Patients with Coronary Artery Disease Be Dangerous? Messerli, Mancia, Conti, Hewkin, Kupfer, Champion, Kolloch, Benetos, Pepine

Ann Intern Med. 2006;144:884-893.

Cardiovascular event rates and mortality according toachieved systolic and diastolic blood pressure in patients withstable coronary artery disease: an international cohort study

Emmanuelle Vidal-Petiot, Ian Ford, Nicola Greenlaw, Roberto Ferrari, Kim M Fox, Jean-Claude Tardif, Michal Tendera, Luigi Tavazzi,Deepak L Bhatt, Philippe Gabriel Steg, for the CLARIFY Investigators*

Published OnlineAugust 30, 2016http://dx.doi.org/10.1016/S0140-6736(16)31326-5

More on the “J-shaped curve”


Low diastolic pressure associates with increased

troponin: ARIC Study

Low diastolic pressure associates with increased troponin: ARIC Study McEvoy JACC 2016

h t t p : / / d x . d o i . o r g / 1 0 . 1 0 1 6 / j . j a c c . 20 1 6 . 0 7 . 7 5 4

Coronary blood flow occurs during diastole

D. Bhatt JACC 2016h t t p : / / d x . d o i . o r g / 1 0 . 1 0 1 6 / j . j a c c . 2 0 1 6 . 0 8 .00 7

As diastolic pressure drives coronary perfusion, low diastolic pressure can embarrass coronary flow in atherosclerotic arteries

Low diastolic pressure associates with increased troponin: ARIC Study

Medication Discontinuation One Month After MI on Increases 12-month Mortality

Ho PM, et al. Arch Intern Med. 2006;166:1842-1847

0 vs. Any 1 Medication 3.81 (1.88-7.72)

0 vs. 3 Medications

0 vs. 1 or 2 Medications

Aspirin Discontinuation

β-Blocker Discontinuation

Statin Discontinuation

3.33 (1.52-7.14)

5.00 (1.85-13.50)

1.82 (1.09-3.03)

1.96 (1.10-3.45)

2.86 (1.47-5.55)

Decreased Mortality Increased Mortality 0.125 0.25 0.5 1 2 4 8

Hazard Ratios Were Adjusted for Confounding Factors for Different Patient Subgroups

Are the disputes over guideline cut points a distraction ?

� While the experts argue among themselves about the fine points, practitioners and the public become confused.

� Some therapy is better than none. Simple starting doses of antihypertensive drugs and statins give much benefit.

� Let’s not loose sight of the simple measures that benefit public health, while the guideline groups air their differences.

Risks of Under-Treatment: The Over-Riding Concern

Despite on-going concerns over a J-curve, under-treatment—not over-treatment—accounts for much residual ASCVD risk that remains among most hypertensives. Under-treatment of hypertension and under-utilization of combination drug therapy is common in outpatient office-based practice.

New Hypertension Guidelines: Commentary Ronald G. Victor & Peter Libby

Online supplement to Braunwald’s Heart Disease 9th Edition

THERE IS A LARGE TREATMENT GAP IN HYPERTENSION MANAGEMENT (US DATA)

1988-1994 1999-2004 2007-2008

Awareness (%) 68.5 71.8 80.7

Treatment (%) 53.1 61.4 72.5

Control (%) 26.1 35.1 50.1

Ega, Zhao, Axon. JAMA 2010;303(20):2043-2050.Chobanian AV. N Engl J Med 2007;357:789-796.

Frequency of Untreated Hypertension According to Subtype and Age.

Medication Persistence in CAD Influences Mortality

Ho PM, et al. Arch Intern Med. 2006;166:1842-1847

No. of Months

0 1 (n = 1521)

3 (n = 1509)

6 (n = 1487)

9 (n = 1475)

12 (n = 1450)

100

95

90

85

80

Surv

ival

(%)

3 Medications 2 Medications 1 Medications 0 Medications

Kaplan-Meier Survival Curve Comparing Patients Discontinuing Use of All Medications at 1 MonthWith Patients Continuing Use of 1, 2 or All 3 Medications Among Patients Discharged With All 3

Medications (Log-Rank Test, P<.001).

What I teach our fellows in clinic based on my current synthesis

� Use chlorthalidone, not HCTZ as the thiazide-type diuretic of choice for HBP Rx� Avoid β-blockers for Rx of HBP unless

prior MI� Prefer ACE-I to ARBs� Use spironolactone liberally for

“resistant” hypertension and in conjunction with chlorthalidone to spare K+

What I teach our fellows in clinic based on my current synthesis

� LOOK AT THE PATIENT!!!� Don’t drive diastolic BP below 70 for

those with CAD � Don’t Rx BP over agressively in the

frail, very old, those with autonomic dysfx (e.g. DM), prior falls, or angina or ischemia

Over-zealous treatment of hypertension can cause orthostatic hypotension with falls. This consideration pertains particularly to the hypertensive elderly and to patients with diabetic autonomic neuropathy. Excessive falls in BP can precipitate acute kidney injury in patients with advanced CKD and impaired renal autoregulation, particularly with high-dose ACE-I or ARB therapy if the patient is hypovolemic.

Risks of Over-Treatment of Hypertension

New Hypertension Guidelines: Commentary Ronald G. Victor & Peter Libby

Online supplement to Braunwald’s Heart Disease 9th Edition

Thanks

•  Karol Watson UCLA•  Susan Chang BWH•  Ron Victor Cedars/UCLA

hypertension 2016: are we hypertension up or down? peter

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