Hypertension Management 2017

Dr Monkez M YousifProfessor of Internal Medicine

Member of AGA, EASL and ISC-Hepatitis WG

Zagazig University

October 16, 2017

AGENDA

• Epidemiology of HTN in Egypt

• Accurate diagnosis of HTN

• Presentation of evidence-based threshold and target BPs.

• Update in Pharmacotherapy.

Did you know??

35 000 000people died from

chronic diseases

in 2005

Preventing

CHRONIC DISEASESa vital investment

Cardiovascular disease,

mainly heart disease, stroke

Cancer

Chronic respiratory diseases

Diabetes

Chronic diseases

Preventing

CHRONIC DISEASESa vital investment

Causes of chronic diseases

Preventing

CHRONIC DISEASESa vital investment

• One of the key risk factors for cardiovascular disease is hypertension or raised blood pressure.

• Hypertension already affects 1.1 billion people worldwide, leading to heart attacks and strokes. By 2025, it is estimated over 1.5 billion people will have hypertension.

• Researchers have estimated that raised blood pressure currently kills nine million people every year.

Epidemiology of Hypertension in Egypt

1.002.00

2008

2015

55-59 Y 15-59 Y

20082015

Prevalence of HTN among adults 15-59 years: EDHS 2008 vs 2015

53.5 % 45.6%

17% 12.8%

Awareness of condition and treatment status among hypertensive women and men age 15-59

EHIS 2015

Figure 2

The Lancet 2002 360, 1903-1913DOI: (10.1016/S0140-6736(02)11911-8)

Stroke mortality rate in each decade of age versus usual blood pressure at the start of that decade

Figure 4

The Lancet 2002 360, 1903-1913DOI: (10.1016/S0140-6736(02)11911-8)

IHD mortality rate in each decade of age versus usual blood pressure at the start of that decade

CV benefits of treating HTN

Hebert et al, Archives Int Med 1993

Hypertension Guidelines

1. Joint National Committee: (JNC VIII): 2014 2. ASH/ISH 20153. Australian: 2016 4. Canadian 20175. Egyptian: 2014 6. European (ESC/ ESH): 20137. Indian: 2007 , 20138. Japanese: 2009 , 20149. Latin America: 2009, 2017 10. Malaysian: 2008 , 2013 11. NICE (British): 2011 12. Sub-Saharan Africa (SSA): 2014 13. WHO/ISH: 2003 14. South African Hypertension Guideline 2011

What is New in Guidelines?

• Appropriate methods for making a diagnosis of hypertension

• Evidence-based threshold and target BPs

• Drug Therapy for HTN

Diagnosis of HTN

USPSTF Draft Statement, January, 2015:

• “The USPSTF recommends screening for HTN in adults ≥18y old.

• Ambulatory BP monitoring is recommended to confirm high BP before the diagnosis of HTN, except in cases for which immediate initiation of therapy is necessary…

• Good quality evidence suggest that confirmation of hypertension using home BP monitoring may be acceptable…

• More research is needed on the best home BP monitoring protocols for follow-up of elevated office BP measurements…”

www.uspreventiveservicestaskforce.org/page/Document/RecommendationStatementDraft

BP measurement methods

• Office (attended, OBPM)

– Oscillometric (electronic) – preferred method

– Auscultatory (mercury, aneroid)

• Office Automated (unattended, AOBP)

– Oscillometric (electronic)

• Ambulatory blood pressure monitoring (ABPM)

• Home blood pressure monitoring (HBPM)

Auscultatory OBPM is inaccurate!

• In the real world, the accuracy of auscultatory OBPM can be adversely affected by provider, patient and device factors such as:– too rapid deflation of the cuff– digit preference with rounding off of readings to 0 or 5– also, mercury sphygmomanometers are being phased

out– and aneroid devices are less likely to remain calibrated

• Consequence: Routine auscultatory OBPMs are 9/6 mm Hg higher than standardized research BPs (primarily using oscillometric devices)

Myers MG, et al. Can Fam Physician 2014;60:127-32.

Automated Office BP Measurement

• Automated office blood pressure (AOBP) is the preferred method of performing in-office BP measurement

• More closely approximates ABPM than routine office BPs (mitigates white coat effect)1-3

• Is more predictive of end organ damage (LVMI, proteinuria and cIMT), similar to ABPM4-6

1. Beckett L, et al. BMC Cardiovasc Disord 2005;5:18; 2. Myers MG, et al. J Hypertens 2009;27:280-6; 3. Myers MG, et al. BMJ 2011;342;d286;4. Campbell NRC, et al. J Hum Hypertens 2007;21:588-90; 5. Andreadis EA, et al. Am J Hypertens 2011;24:661-6; 6. Andreadis EA, et al. Am J Hypertens 2012;25:969-73.

ABPM = ambulatory blood pressure measurementLVMI = left ventricular mass indexcIMT = carotid intima media thickness

Keys to accurate OBPM

• Use standardized measurement techniques and validated equipment

• Measurement using electronic (oscillometric) upperarm devices is preferred over auscultation

• The first reading should be discarded and the two averaged.

Mean blood pressure* (mmHg)

Centre for Studies in Primary Care1

ABPM referral unit2

CAMBO trial3

Routinemanual office BP

151/83 152/87 150/81

Automatedoffice BP

140/80 132/75 135/77

Awakeambulatory BP

142/80 134/77 133/74

AOBP Readings are Lower than OBP Readingsand are More Similar to ABP Readings

*The automated office blood pressure (BP) and awake ambulatory BP were similar, and both were lower than the routine manual BP obtained in community practice.

1. Beckett L et al , BMC Cardiovasc. Disord. 2005; 5: 18. 2. Myers MG et al, J. Hypertens. 2009; 27: 280. 3. Myers MG, et al. BMJ 2011; 342: d286.

Correct BP measurement technique

Mean Office, Home, AmbulatoryBlood Pressures: Equivalence Numbers

• An office blood pressure of 140/90 mmHg is comparable to:

Blood Pressure mmHgDescription

135/85Home BP

135/85Daytime Ambulatory BP

130/8024-hour Ambulatory BP

135/85Automated office BP

Criteria for the diagnosis of hypertensionand recommendations for follow-up: overview

Out-of-Office BP Measurements

• Out-of-office measurement identifies white coat hypertension and masked hypertension

• ABPM has better predictive ability than OBPM and is the recommended out-of-office measurement method

• HBPM has better predictive ability than OBPM and is recommended if ABPM is not tolerated, not readily available or due to patient preference

ABPM = ambulatory blood pressure measurementHBPM = home BP measurementOBPM = office BP measurement

-0.1 0. 0.1 0.2 0.3 0.4 0.5 0.6

OBP

HBPM

ABPM

Mulè G, et al. J Cardiovasc Risk 2002;9:123-9.

-0.1 0. 0.1 0.2 0.3 0.4 0.5 0.6

OBP

HBPM

ABPM

0. 0.1 0.2 0.3 0.4 0.5

0. 0.1 0.2 0.3 0.4 0.5

SBP

DBP

LVH Albumin excretion ratio

SBP

DBP

Indexes of hypertensive target organ damage Indexes of hypertensive target organ damage

Out-of-Office BP Measurements are More Highly Correlated With BP-Related Risk

Masked Hypertension

BP (mm Hg)

Office BPAutomated office BP

< 140/90< 135/85

Awake Ambulatory ≥ 135/85

24-hour Ambulatory BP ≥ 130/80

• Definition:– The term ‘masked hypertension’ is defined as having non-

elevated clinical (office) BP with elevated out-of-clinic average BP, typically determined by ambulatory BP monitoring.

• Criteria of Diagnosis

10%about

in the general

population

30%about

in treated

hypertensive

patients

diabetes

in patients with

and

higher

chronic kidney

disease patients

One out of three treated hypertensive patients has masked hypertension

Andalib A, et al. Int Med J 2012;42:260-6

Prevalence of Masked Hypertension

0

5

10

15

20

25

30

35

Normal White coat Uncontrolled Masked

CV

eve

nts

pe

r 1

00

0 p

atie

nt-

year CV Events

Okhubo T, et al. J Am Coll Cardiol 2005;46;508-15

The Prognosis of White Coatand Masked Hypertension

Clinical and Laboratory Evaluation

Objectives

• Identify high risk patients

– Detect other cardiovascular risk factors.

– Assess target organ damage.

– Diagnose associated cardiovascular or renal disease.

• Identify secondary causes of hypertension and comorbid conditions.

Laboratory Tests• Essential (in all patients):

– Urine: dipstick for protein, blood, sugar

– Blood tests: sugar, creatinine

• Recommended (if facilities are available)– Blood lipid profile: total cholesterol, LDL, HDL, triglycerides

– Uric acid

– Serum potassium

– Hemoglobin

– ECG

– Special investigations in resistant or suspected secondary forms of hypertension.

– Optic fundus in patients with severe hypertension.

Cardiovascular Risk Factors• DM• Males >55 years or Females >65 years.• Total S-Cholesterol> 240 mg/dl, HDL-C <40 mg/dl

or LDL-C >160 mg/dl.• Cigarette smoking.• Obesity • Serum creatinine >2 mg/dl.• Metabolic syndrome• Family history of ASCVD in a first degree relative

(parents, siblings or brothers) before the age of 40 years in males and 50 years in females.

Silent Target Organ Damage

• Left ventricular hypertrophy (LVH):– ECG criteria (Sokolow-Lyon SV1+RV5 or V6 > 35 mm,

tall R in AVL> 11 mm) .

– Echo criteria (wall thickness 12 mm or LVMI in males 125 gm/m2 or in females 110 gm/m2 .

• Carotid bruits

• Proteinuria: microalbuminurea 30–300 mg/24 h

• Increased serum creatinine >1.4 mg/dl in females and >1.5 mg/dl in males

• Optic fundus changes: >grade I retinopathy

Cardiovascular Risk Categorization

• Risk Group A (low risk): patients with – no other cardiovascular risk factors, – no target organ damage or associated ASCVD.

• Risk Group B (moderate/intermediate risk): patients with – additional 1 or 2 risk factors (not including diabetes) but

with no target organ damage or associated ASCVD.

• Risk Group C (high risk): patients with – diabetes, – target organ damage or – associated asymptomatic ASCVD or – patients with 3 or more risk factors or – a very high level of a single risk factor.

• Risk Group D (very high risk): Patients with symptomatic established cardiovascular or renal disease:

– Coronary artery disease (angina, MI, CABG, PCI).

– Cerebrovascular disease (stroke, TIA).

– Peripheral arterial disease.

– Heart failure.

– Abdominal aortic aneurysm.

– Renal failure: serum creatinine >2 mg/dl.

Threshold and Target of BP

Definitions of hypertension by different types of blood pressure measurement

JNC-7 Treatment Algorithm

Chobanian AV et al. JAMA 2003;289:2560-72.

JNC-8 Recommendations

• In patients >60 years of age, start medications

at blood pressure of >150/90mm Hg and treat to

goal of <150/90mm Hg

• In patients >60 years of age, treatment does

not need to be adjusted if achieved blood

pressure is lower than goal and well-tolerated

James PA et al. JAMA 2014;311:507-20.

HYVET trialbenefit of target < 150/90 in very elderly

VALISH trialno benefit of target < 140/90 in elderly

JATOS trialJapanese Trial to Assess Optimal SBP

JNC-8 Recommendations

• In patients <60 years of age, start

medications at blood pressure of >140/90mm

Hg and treat to goal of <140/90mm Hg

• In all adult patients with diabetes or chronic

kidney disease, start medications at blood

pressure of >140/90mm Hg and treat to goal of

<140/90mm Hg

James PA et al. JAMA 2014;311:507-20.

ACCORD Trialintensive HTN Tx in DM

Population SBP DBP

High Risk (SPRINT population) # ≥130 NA

Diabetes ≥ 130 ≥ 80

Moderate* ≥ 140 ≥ 90

Low risk (no TOD or CV risk factors) ≥ 160 ≥ 100

Usual Office BP Threshold Values for Initiation of Pharmacological Treatment

AOBP = automated office blood pressure TOD = target organ damageSBP = systolic blood pressureDBP = diastolic blood pressure

# Based on AOBP*AOBP threshold 135/85 mmHg

Hypertension Canada’s 2017 Guidelines

Treatment consists of health behaviour ± pharmacological management

Population SBP DBP

High Risk # < 120 NA

Diabetes < 130 < 80

All others* < 140 < 90

Recommended Office BP Treatment Targets

# Based on AOBP*AOBP threshold 135/85 mmHg

New Guideline Post-SPRINT

• For high-risk patients, aged ≥ 50 years, withsystolic BP levels ≥130 mm Hg, intensive management to target a systolic BP ≤120 mm Hg should be considered

• Intensive management should be guided by automated office BP measurements

• Patient selection for intensive management isrecommended and caution should be taken in certain high-risk groups

Average no. of medications

Intensive care: 2.8Standard care: 1.8

The SPRINT Research Group, NEJM, Nov 9th, 2015

SPRINT: SBPs Achieved

NNT=61

SPRINT Primary Outcome

The SPRINT Research Group, NEJM, Nov 9th, 2015

25% relative risk reduction (P<0.001) with intensive treatment, with the two curves beginning to separate by 1 year.

New Thresholds/Targets for the High-Risk Patient Post-SPRINT: Who does this apply to?

• There was an increased risk of renal deterioration, potassium abnormalities and hypotension with intensified therapy

• Patients with one or more clinical indications should consent to intensive management

Clinical or sub-clinical cardiovascular diseaseOR

Chronic kidney disease (non-diabetic nephropathy, proteinuria <1 g/d, *estimated glomerular filtration rate 20-59 mL/min/1.73m2)

OR†Estimated 10-year global cardiovascular risk ≥15%

ORAge ≥ 75 years

* Four variable MDRD equation† Framingham Risk Score, D'Agastino, Circulation 2008

New Thresholds/Targets for the High-Risk PatientPost-SPRINT: Who does this NOT apply to?

Limited or No Evidence:• Heart failure (EF <35%) or recent MI (within last 3 months)• Indication for, but not currently receiving, a beta-blocker• Institutionalized elderly

Inconclusive Evidence: • Diabetes mellitus• Prior stroke• eGFR < 20 ml/min/1.73m2

Contraindications: • Patient unwilling or unable to adhere to multiple medications• Standing SBP <110 mmHg• Inability to measure SBP accurately• Known secondary cause(s) of hypertension

Pharmacologic Therapy of HTN

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

Panel Members Appointed to the Eighth Joint National Committee (JNC 8)

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

Guideline Comparisons of Goal BP and Initial Drug Therapy for Adults With Hypertension

Hypertension 2017

What’s new?

• Longer acting (thiazide-like) diuretics are preferred vs. shorter acting (thiazides)

• Single pill combinations should be used as a first line treatment (regardless of the extent of BP elevation)

Leung AA, et al. Hypertension Canada’s 2017 Guidelines. Can J Cardiol. 2017.

Longer-acting Diuretics Should be Preferred(i.e., thiazide-like are preferred to thiazides)

•Longer-acting (thiazide-like): –chlorthalidone,

–indapamide

•Shorter-acting (thiazides): –hydrochlorothiazide

• Design: Meta-analysis of 21 RCTs of BP lowering comparing thiazide-type or thiazide-like diuretics vs. placebo or another antihypertensive on CV events and mortality

• >500,000 person-years of observation combined

• Thiazide-type:

– Hydrochlorothiazide

– Bendrofluazide

– Chlorothiazide

• Thiazide-like:

– Indapamide

– Chlorthalidone

Thiazide-type vs. Thiazide-like Diuretics: CV Events and Mortality Meta-analysis

Olde Engberink RH. Hypertension 2015;65(5):1033-40

Diuretic Type Meta-Analysis vs. Placebo

• Both types of diuretics reduced CV events, cerebrovascular events, and HF

• Only thiazide-like diuretics additionally reduced coronary events and all-cause mortality

Event Thiazide-Type Thiazide-Like

CV 0.67 (.56-.81) 0.67 (0.60-0.75)

Coronary 0.81 (0.63-1.05) 0.76 (0.61-0.96)

Cerebrovascular 0.52 (0.38-0.69) 0.68 (0.57-0.80)

Heart Failure 0.36 (0.16-0.84) 0.47 (0.36-0.61)

All-cause Mortality 0.86 (0.75-1.00) 0.84 (0.74-0.96)

Olde Engberink RH. Hypertension 2015;65(5):1033-40

• Design: Meta-analysis of 14 RCTs (n=883) comparing HCTZ vs. indapamide/chlorthalidone on BP reduction

– Compared according to 3 different dose levels: HCTZ 12.5, 25, 50 mg; chlorthalidone 6.25, 12.5, 25 mg; indapamide 1.5, 2, 2.5 mg

• SBP reduction:

– Indapamide vs. HCTZ: −5.1 mmHg (p=0.004)

– Chlorthalidone vs. HCTZ: −3.6 mmHg (p=0.052)

• Metabolic effects:

– No differences between HCTZ vs. indapamide in adverse effects (K+, Na+, Cr, BG, cholesterol, uric acid); no data for HCTZ vs. chlorthalidone

Roush GC, et al. Hypertension. 2015 May;65(5):1041-6

• Meta-analysis

• Used 3 dose levels to try to standardize dosing

– Hydrochlorothiazide (12.5/25/50 mg)

– Chlorthalidone (6.25/12.5/25 mg)

– Indapamide (1.5/2.0/2.5 mg)

– Outcomes:

• BP lowering

• Metabolic

• CV events

Head-to-Head for BP Lowering: HCTZ vs. Chlorthalidone or Indapamide

Roush GC et al. Hypertension 2015;65:1041-6

Summary: Longer-Acting Diuretics Preferred

• Longer-acting (thiazide-like) diuretics appear

more effective at reducing CV events and SBP

& DBP than shorter-acting (thiazide) diuretics

Hypertension 2017

What’s new?

• Longer acting (thiazide-like) diuretics are preferredvs. shorter acting (thiazide)

• Single pill combinations should be used as a first line treatment (regardless of the extent of BP elevation)

TARGET < 140 mmHg systolic AND < 90 mmHg diastolic

First Line Recommandations Circa 1999-2016

Thiazidediuretic

ACEiLong-acting

CCBARB Beta-

blocker*

*Not indicated as first line therapy for patients over 60 yrs.

A combination of 2 first line drugs may be considered as initial therapy if the blood pressure is ≥20 mmHg systolic or ≥10 mmHg diastolic above target

Health behaviour management

Thiazide/thiazide-like*

ACEI§ Long-actingCCB

TARGET <135/85 mmHg (automated measurement method)

ARB § Beta-blocker†

First Line Treatment of Adults with Systolic/DiastolicHypertension Without Other Compelling Indications

Health behaviour management

Single pill combination**

† BBs are not indicated as first line therapy for age 60 and above

§Renin angiotensin system (RAS) inhibitors are contraindicated in pregnancy and caution is required in prescribing to women of child bearing potential

* Longer-acting (thiazide-like) diuretics are preferred over shorter-acting (thiazide) diuretics

INITIAL TREATMENT

**Recommended SPC choices are those in which an ACE-I is combined with a CCB,an ARB with a CCB, or an ACE-I or ARB with a diuretic

Advantages of Single Pill Combinations (SPCs)

• SPC therapy is associated with better adherence vs. free combinations1

• A regimen featuring initial prescription of SPC leads to better BP control2

• Initial combination therapy is associated with ↓ risk of CV events than monotherapy3,4

1. Sherrill B, et al. J Clin Hypertens 2011;13:898-909;2. Feldman RD, et al. Hypertension 2009;53:646-53;3. Corrao G, et al. Hypertension 2011;58:566-72;4. Gradman AH, et al. Hypertension 2013;61(2):309-18.

Study or SubgroupSinge Pill Free Equivalent Mean Difference

IV, Random, 95% CIMean Difference

IV, Random, 95% CIMean SD N Mean SD N Weight

Naive patients

Brixner 2008 64.2 58.67 1628 57.6 30.21 561 14.2% 6.60 (2.81, 10.39)

Jackson 2008 73.1 35.42 619 60.5 35.42 65 10.3% 12.60 (3.55, 21.65)

Subtotal (95% CI) 2247 626 24.5% 8.13 (3.00, 13.26)

Heterogeneity: Tau2 = 5.47; Chi2 = 1.44, df = 1 (P=0.23); I2 = 30%Test for overall effect: Z = 3.11 (P=0.002)

Experienced patients

Dickson 2008 58.6 35.42 3363 48.1 35.42 713 14.7% 10.50 (7.64, 13.36)

Dickson-elderly 2008 63.4 29.4 2336 49 23.4 3368 15.2% 14.40 (12.97, 15.83)

Gerbino 2007 87.9 35.42 2839 69.2 35.42 3367 15.1% 18.70 (16.93, 20.47)

Hess 2008 76.9 35.42 7224 54.4 35.42 7225 15.3% 22.50 (21.34, 23.66)

Taylor 2003 80.8 35.42 2754 73.8 35.42 2978 15.1% 7.00 (5.16, 8.84)

Subtotal (95% CI) 18516 17651 75.5% 14.66 (8.97, 20.36)

Heterogeneity: Tau2 = 41.31; Chi2 = 236.93, df = 4 (P0.00001); I2 = 98%Test for overall effect: Z = 5.05 (P0.0001)

Total (95% CI) 20763 18277 100.0% 13.31 (8.26, 18.35)

Heterogeneity: Tau2 = 42.94; Chi2 = 264.57, df = 6 (P0.00001); I2 = 98%Test for overall effect: Z = 5.17 (P0.00001)Test for subgroup differences: Chi2 = 26.20, df = 1 (P0.00001); I2 = 96.2%

Favors free equivalents Favors single pill

-20 -10 0 10 20

SPCs Improve Adherence

Sherrill B, et al. J Clin Hypertens. 2011;13(12):898-909

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Incremental BP-Lowering Effect at Standard Doses: Combine or Double?

Wald DS, et al. Am J Med 2009;122:290-300

Dose as a proportion of the standard dose

Sid

e ef

fect

pre

vale

nce

(%

-pla

ceb

o r

ate)

30

20

10

0

-101/4 1/2 1 2 4

30

20

10

0

-101/4 1/2 1 2 4

Calcium Channel Blockers Thiazides

At Low Doses the Adverse Effects of Most Antihypertensives Approach those of Placebo

Law, M R et al. BMJ 2003;326:1427

• Cluster randomized controlled trial - hypertension in family practices

• Simplified algorithm featuring initial therapy with low-dose antihypertensive single drug combinationvs. conventional guideline-based care

• Low-dose - by splitting usual starting dose in half

• Practitioners randomly assigned to use STITCH care or usual stepwise management according to CHEP guidelines

Initial SPC Therapy ImprovesBP Control Rates: STITCH Study

Feldman RD, et al. Hypertension 2009;53(4):646-53

Absolute difference: 12.0%95% CI 1.5-22.4%P = 0.026Relative difference: 23%

STITCH Study: Results

Feldman RD, et al. Hypertension 2009;53(4):646-53

Ross D. Feldman et al. Hypertension. 2009;53:646-653

Copyright © American Heart Association, Inc. All rights reserved.

STITCH-care algorithm

Initial Combination Therapy Reduces CV Risk(observational study)

Corrao G, et al. Hypertension 2011;58(4):566-72

Thiazide/thiazide-like*

ACEI§ Long-actingCCB

TARGET <135/85 mmHg (automated measurement method)

ARB Beta-blocker†

First Line Treatment of Adults With Systolic/DiastolicHypertension Without Other Compelling Indications

Health behaviour management

Single pill combination**

† BBs are not indicated as first line therapy for age 60 and above

§Renin angiotensin system (RAS) inhibitors are contraindicated in pregnancy and caution is required in prescribing to women of child bearing potential

* Longer-acting (thiazide-like) diuretics are preferred over shorter-acting (thiazide) diuretics

INITIAL TREATMENT

**Recommended SPC choices are those in which an ACE-I is combined with a CCB,an ARB with a CCB, or an ACE-I or ARB with a diuretic

Conclusion

• Out of Office BP measurement is more accurate than In-Office BP measurement.

• Unattended Automated Office Blood Pressure (AOBP) measurement is the preferred method of performing in-office BP measurement vs auscultatory sphygmomanometer method.

• Threshold and Target BPs in eldely patients are unequivalent in different guidelines.

• Long-acting thiazide-like analogues are preferred thanshort-acting thiazides.

• Single pill combinations may (should) be used as a first line treatment (regardless of the extent of BP elevation).

78

Monkez M Yousif

From Next time Don’t feel Lonely….cause you havesome friends inside you to take care of yourself……