2018 ESC/ESH

Guidelines for the management

of arterial hypertension

A key message: The need to do better on BP control

 The diagnosis of hypertension
Should not be based on a single set of BP readings at a single office visit
(BP can be highly variable)
It is recommended to base the diagnosis of hypertension on:
 repeated office BP measurements
 on more than one visit
 except when hypertension is severe (especially in high-risk patients)

Wider use of out-of-office BP measurement with ABPM and/or HBPM,

especially HBPM
provided that these measurements are logistically and economically feasible

 To confirm the diagnosis

 To detect white coat and masked hypertension
 To monitor BP control
 Screening for the detection of hypertension is recommended in all
adults
 IN ALL ADULTS, at least every 5 years and more frequently in people with a high-normal BP
 In older patients (> 50 years), more
frequent screening of office BP should be considered for
each BP category (rise in SBP with ageing)

Optimal BP Normal BP High-normal BP Hypertension

<120/80* 120-129/80-84* 130-139/85-89* ≥140/90

Out-of-office BP
Consider masked measurement
hypertension (ABPM or HBPM) Use
either to
confirm
diagnosis

Repeated visits Out-of-office BP

Repeat BP at least Repeat BP at least Repeat BP at least
for office BP measurement
every 5 years every 3 years annually
measurement (ABPM or HBPM)

Indications for
ABPM or HBPM see Table 11

 Telemonitoring and smart phone applications may offer additional advantages

AMBULATORY BLOOD PRESSURE MONITORING
Interventions that may improve drug
adherence in hypertension
Physician level
Provide informations on the risk of hypertension and the benefit of treatment, as well as agreeing a treatment strategy to
achieve and maintain BP control using lifestyle measure and a single-pill-based treatment strategy when possible
(information material, programmed learning, computer-aided counseling)
Empowerment of the patient
Feedback on behavioural and clinical improvement
Assesment and resolution of individual barriers to adherence
Collaboration with other healthcare providers, especially nurses and pharmacist

Patient level
Self monitoring of BP (including telemonitoring)
Group sessions
Instruction combined with motivational strategies
Self management with simple patient-guided systems
Use of reminders
Obtain family, social, or nurse support
Provision of drugs at worksite

Williams, Mancia, et al. Eur Heart J. 2018; 00, 1-98

Interventions that may improve drug
adherence in hypertension

Drug treatment level

Simplification of the drug regimen favouring the use of SPC therapy
Reminder packaging

Health-system level
Support the development of monitoring systems (telephone follow up, home visits, telemonitoring of home BP)
Support financially the collaboration between healthcare providers (pharmacists, nurses)
Reimbursement of SPC pills
Development of national databases, including prescription data, available for physicians and pharmacist
Accessibility to drugs

Williams, Mancia, et al. Eur Heart J. 2018; 00, 1-98

“Pusing, „Mak…Lelah hayati…”
 SUMMARY
 Start treatment in most patients with two drugs, not one
 ESC/ESH Guideline 2018 sets out to normalize the concept that initial therapy for the majority of patients with
hypertension should be with a combination of two drug, not a single drug
 The only exception would be in a limited numbers of patients with a lower baseline BP close to their recommended
target, who might achieve that target with a single drug, or in some frailer old or very old patients, in whom more
gentle reduction of BP may be desirable.

 A Single Pill Combinations (SPC) strategy to treat hypertension

 Research had shown a direct correlation between the number of BP-lowering pills and poor adherence to
medications, and SPC therapy has been shown to improve adherence to treatment.
 SPC therapy is the preferred strategy for two-drug combination treatment of hypertension.
 This strategy will control the BP in most patient with a single pill and could transform BP control
 Considering RAAS blockade and evidence based, ARB+CCB is favored option in hypertension management.

 Strong emphasis on the importance of evaluating treatment adherence is

needed as a major cause of poor BP control

 A key role for nurses, pharmacist in the longer term management of

hypertension to improve BP control
Controlling hypertension based on new
guideline ESC/ESH 2018: Benefits of SPC
AMLODIPINE/VALSARTAN

NVS/SLID/092018/0263
dr. Rinelia Minaswary Sp. JP, FIHA
 Contents:

 New 2018 European Guidelines (ESC/ESH) for the

treatment of high blood pressure
 The Real World Evidence for Dual Combination
Amlodipine/Valsartan (EXCITE Study)
 Summary
 Single-pill Concept to Treatment Goal

Step 1 Monotherapy Simplicity1

Medication
adjustment
Adherence1
2 in 1 Single-Pill Tolerance1
Step 2 Combination
Single-Pill Efficacy1,2
Medication Treatment
adjustment
Lower Cost2
3 in 1 Single-Pill
Step 3
Combination

1. Sison J et al. Real-world clinical experience of amlodipine/valsartan and

amlodipine/valsartan/hydrochlorothiazide in hypertension:the EXCITE study Curr Med Res Opin 2014; 30: 1937- 54
1945
2. Tung YC et al. J Clin Hypertens (Greenwich). 2015 Jan;17(1):51-8
Calcium Channel Blocker
Conditions favoring the use of CCBs and ARBs according
to guidelines for the management of hypertension

CCBs ARBs

ARB angiotensin receptor

blocker;
CCB, calcium channel blocker
Waeber B et al. Vasc Health Risk Manag. 2009; 5: 165–174
 CCBs and ARBs Interact Synergistically on Vascular and Renal
Function, Sympathetic Nervous System and Renin-Angiotensin
System Activity

negative
Natriuresis sodium balance
reinforces the
effects of the
ARB

Vasodilation
Arterial +
Arterial
Venous

CCB (Amlodipine) ARB (Valsartan)

• ↑ SNS  ↑ RAS • ↓ RAS  ↓ SNS
• Arteriodilation • Arterio- and venodilation
• Effective in low-renin patients • Effective in high-renin patients
• No renal or congestive heart failure benefits • Congestive heart failure and renal benefits
• Peripheral edema • Attenuates peripheral edema
• Reduces cardiac ischemia
SNS = sympathetic nervous system; RAS = renin-angiotensin system
Cummings, DM. Arch Intern Med, 1991; Vol 151 p 250-259
Amy Barreras et al. BUMC Proceedings 2003; 16:123-6
5 Grassi G, J Hypertens 2001:19:1713-16
 Real world effectiveness and safety of
AML/VAL single-pill combinations

The EXCITE study:

clinical EXperienCe of amlodIpine and
valsarTan in hypErtension

Objective:
To assess effectiveness and safety and tolerability of AML/VAL SPCs as
antihypertensive therapy under daily-life conditions during a planned observation
period of ≥26 weeks in adult patients with hypertension

Sison J et al. Real-world clinical experience of amlodipine/valsartan and amlodipine/valsartan/hydrochlorothiazide

in hypertension:the EXCITE study Curr Med Res Opin 2014; 30: 1937-1945.
 EXCITE: prospective, multinational,
non-interventional, ‘real-world’ study

Amlodipine/valsartan†

Visit 1 Optional Visit 2 Visit 3

Baseline 13 weeks 26 weeks
End of study

Observational period of 26 weeks ± 8 weeks‡

Therapy was prescribed according to the treating clinician and was clearly separated from the decision to include the patient in the study
†Prescribed at any dosage in compliance with local prescribing information

for arterial hypertension, administered as single therapy,

or as add-on therapy to diuretics, beta blockers (BBs), calcium channel blockers (CCBs), angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor
blockers (ARBs).‡Only data from routine medical practice collected – no imposed visit schedule, or required diagnostic or therapeutic procedures or tests

Sison J et al. Real-world clinical experience of amlodipine/valsartan and

amlodipine/valsartan/hydrochlorothiazide in hypertension:the EXCITE study Curr Med Res Opin 2014; 30:
1937-1945.
59
EXCITE: data analyzed from 8.603 HTN patients
received Amlo/Val pooled from 13 countries

Kuwait
Bahrain

Qatar
Lebanon
UAE South Korea

Taiwan

Hong Kong

Oman
Pakistan Philippines

Egypt
Indonesia

n=500

Sison J et al. Real-world clinical experience of amlodipine/valsartan and

amlodipine/valsartan/hydrochlorothiazide in hypertension:the EXCITE study Curr Med Res Opin 2014; 30:
1937-1945.
60
1
EXCITE: incremental BP reductions with AML/VAL across
prior antihypertensive monotherapy classes
Prior antihypertensive Overall ACEi ARB CCB Beta-blocker Diuretic
monotherapy (n=2575) (n=653) (n=581) (n=781) (n=546) (n=14)

BL msSBP/msDBP 158.7/96.5 160.0/97.0 158.3/96.2 157.3/95.8 159.6/97.0 162.9/102.9

(mmHg) 0

–5

–10
Change in mean sitting

–15
BP (mmHg)

–16.2 –15.5 –15.8

–20 –16.6 –17.2
–19.3
–25

–30
–28.6 –28.7
–29.9 –30.7
–35 –31.2 –31.3

–40
128.8 / 80.3
mmHg

Post-hoc analysis. Baseline defined as prior to start of AML/VAL. End of study defined as Visit 3 (Week 26). Included only patients who did not
take any antihypertensive medication during the observational period, in addition to AML/VAL, and did not switch to AML/VAL/HCT. No
additional treatment prior to study entry was received .

Assaad-Khalil SH et al. Real-world effectiveness of amlodipine/valsartan and

amlodipine/valsartan/hydrochlorothiazide in high-risk patients and other subgroups Vasc Health Risk Manag
2015; 11: 71-78.
61
2
EXCITE Indonesia:
meaningful BP reductions from baseline across all EXCITE
INDONESIA
hypertension severities
Stage 1 Stage 2 Stage 3
140- <160 160 - < 180 ≥ 180
(n=131) (n=229) (n=111)
Baseline TDD/TDS (mmHg) 147.5 / 91.7 164.1 / 96.2 189.2 / 103.7

Perubahan Tekanan Darah dari

baseline selama 26 minggu

Tekanan
Darah
Sistolik

Tekanan
Darah
Diastolik

128.3/ 81.4 130 / 81.3 135.5 / 83.2

mmHg mmHg mmHg

Setiowati, A, et al. Clinical Effectiveness, Safety, and Tolerability of Amlodipine/Valsartab in Hypertensive

Patients: the Indonesian Subset of the EXCITE Study. Acta Medica Indonesiana.2015; (47) : 223-233
3
EXCITE Indonesia:
EXCITE
meaningful BP reductions from baseline across all treatment dosage
INDONESIA

Penurunan SBP dari baseline1

Dosis AML/VAL (mg) Overall 5/80 mg 5/160 mg 10/160 mg
(n=487) (n=334) (n=94) (n=58)
Baseline TDD/TDS (mmHg) 164.1/96.4 161.0/95.0 171.2/99.1 170.6/99.9
Perubahan Tekanan Darah dari
baseline selama 26 minggu

Tekanan
Darah
Sistolik

Tekanan
Darah
Diastolik

130.4 / 81.6
mmHg

Setiowati, A, et al. Clinical Effectiveness, Safety, and Tolerability of Amlodipine/Valsartab in Hypertensive Patients: the
Indonesian Subset of the EXCITE Study. Acta Medica Indonesiana. 2015; (47) : 223-233

63
4
EXCITE Indonesia:
EXCITE
meaningful BP reductions from baseline across risk factorsINDONESIA

ISH Lansia ≥ 65 tahun DM Obesitas (BMI > 30)

(n=46) (n=100) (n=134) (n=62)
Baseline TDD/TDS (mmHg) 159.7 / 79.1 168.4 / 95.2 165.5 / 94.7 162.4 / 96.3

dari baseline selama 26 minggu

Perubahan Tekanan Darah

Tekanan
Darah
Sistolik

Tekanan
Darah
Diastolik
134.2 / 81.7 129.9 / 79.7
mmHg mmHg

Setiowati, A, et al. Clinical Effectiveness, Safety, and Tolerability of Amlodipine/Valsartab in Hypertensive Patients:
the Indonesian Subset of the EXCITE Study. Acta Medica Indonesiana. 2015; (47) : 223-233

64
5
EXCITE: 70% of patients achieved the BP goal
of <140/90 mmHg and ~90% achieved SBP/DBP response

AML/VAL
N= 8603
BP target achieved n (%)

Therapeutic goal
SBP<140 mmHg and DBP <90 mmHg 5822 (69.9)

SBP response
SBP <140 mmHg or a reduction of ≥20 mmHg 7305 (89.5)
from baseline

DBP response
DBP <90 mmHg or a reduction of ≥10 mmHg 6876 (91.8)
from baseline

1. Sison J et al. Real-world clinical experience of amlodipine/valsartan and

amlodipine/valsartan/hydrochlorothiazide in hypertension:the EXCITE study Curr Med Res Opin 2014; 30:
1937-1945.
65
6
EXCITE: AML/VAL was generally well tolerated

AML/VAL
N=8603
Adverse events (AEs) by preferred term* n (%)
Total AEs 963 (11.2)
Oedema 173 (2.0)
Peripheral oedema 99 (1.2)
Headache 87 (1.0)
Cough 52 (0.6)
Nausea 41 (0.5)

• SAEs were reported in a 49 (0.6%) patients with AML/VAL. Most of the AEs and SAEs were assessed
by the study investigators as being unrelated to the medication of interest.
• A total of 12 deaths (AML/VAL) were reported during the study, none were considered to be related to
the medication of interest by the study investigator

1. Sison J et al. Real-world clinical experience of amlodipine/valsartan and

amlodipine/valsartan/hydrochlorothiazide in hypertension:the EXCITE study Curr Med Res Opin 2014; 30:
1937-1945.
66
 Classification of office BP and definitions of
hypertension grade
The classification of BP and the definition of hypertension is unchanged
 Still defined as an office SBP ≥ 140 and/or DBP ≥ 90 mm Hg
 Equivalent to a 24-h ABPM average of ≥ 130/80 , or a HBPM average ≥ 135/85 mm Hg

BP have to be classified as optimal, normal, high-normal, or grades 1–3

hypertension according to office BP.

CATEGORY SYSTOLIC (mm DIASTOLIC (mm

Hg) Hg)
Optimal <120 and <80
Normal 120-129 and/or 80-84
High normal 130-139 and/or 85-89
Grade 1 hypertension 140-159 and/or 90-99
Grade 2 hypertension 160-179 and/or 100-109
Grade 3 hypertension ≥180 and/or ≥110
Isolated systolic ≥140 and ≥90
hypertension
Same classification in younger, middle-aged, and older people
 Initiation of BP-lowering treatment
(lifestyle changes and medication) at different initial office BP
levels

High Normal BP Grade 1 hypertension Grade 2 hypertension Grade 3 hypertension

BP 130-139 / 85-89 BP 140-159 / 90-99 BP 150-169 / 100-109 BP >180/110

Lifestyle advice Lifestyle advice Lifestyle advice Lifestyle advice

Immediate drug treatment in

Consider drug treatment
high or very high risk Immediate drug treatment in
in very high risk patients Immediate drug treatment
patients with CVD, renal all patients
with CVD, especially CAD in all patients
disease or HMOD

Aim for BP control within Aim for BP control within 3

Drug treatment in low months
moderate risk patients 3 months
without CVD, renal disease,
or HMOD after 3-6 months
of lifestyle intervention if BP
not controlled

Williams, Mancia, et al. Eur Heart J. 2018; 00, 1-98

 The importance of cardiovascular risk assessment
and detection of HMOD
• SCORE CV risk assessment is recommended,
• SCORE system alone may underestimate the risk
SCREENING FOR PRESENCE OF HMOD, especially LVH, CKD, or advanced retinopathy

Classification of hypertension stages according to BP levels, presence of CV risk factors, HMOD, or comorbidities

Hypertensi Other risk BP (mmHg) grading

on disease factors, High- Grade 1 Grade 2 Grade 3
staging HMOD, or normal SBP 140−159 SBP 160−179 SBP ≥ 180
disease SBP DBP 90−99 DBP 100−109 DBP ≥ 110
130−139
DBP 85−89
Stage 1 No other risk factors Low risk Low risk Moderate risk High risk
(uncomplica
ted) 1 or 2 risk factors Low risk Moderate risk Moderate − high High risk
risk
≥ 3 risk factors Low – Moderate − high High risk High risk
moder risk
ate risk
Stage 2 HMOD, CKD grade 3, or Moderate − high High risk High risk High – very high
(asymptom diabetes mellitus risk risk
atic without organ damage
disease)

Stage 3 Symptomatic CVD, CKD Very high risk Very high risk Very high risk Very high risk
(establis grade ≥ 4, or diabetes
hed mellitus with organ
disease) damage
 Thresholds for Initiation of BP-lowering treatment less conservative
High normal BP Grade 1 hypertension Grade 2 hypertension Grade 3 hypertension
BP 130-139 / 85-89 BP 140-159 / 90-99 BP 160-179 / 100-109 BP ≥ 180/ 110

Lifestyle advice Lifestyle advice Lifestyle advice Lifestyle advice

Consider drug treatment
in very high risk patients
with CVD, especially CAD
Immediate drug
treatment in high or very
high risk patients with Immediate drug Immediate drug
CVD, renal disease or treatment in all patients treatment in all patients
HMOD

Drug treatment in low-

moderate risk patients Aim for BP control Aim for BP control
without CVD, renal disease within 3 months within 3 months
NO Prompt initiation of or HMOD after 3-6 months
BP-lowering drug of lifestyle intervention
treatment if BP not controlled
Prompt initiation of BP-lowering drug treatment is
recommended in patients with grade 2 or 3 HT
• At any level of CV risk,
• Simultaneous with the initiation of lifestyle changes
Treatment thresholds : Special considerations in frail and
older patients

Withdrawal of BP-lowering drug treatment on the basis of age,

even when patients attain age of ≥ 80 y,
is not recommended,
provided that treatment is well tolerated.
IN FIT OLDER PATIENTS
LIFESTYLE INTERVENTION + BP-LOWERING DRUG TREATMENT
if well tolerated

> 65 years but not > 80 years

when SBP is in the grade 1 range Over 80 years
(140–159 mm Hg) when SBP is ≥ 160
Office BP THRESHOLDS FOR treatment

Summary of office BP thresholds for treatment