Blood Pressure

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The International Society of Hypertension

Guidelines 2020 – a new drug treatment
recommendation in the wrong direction?

Sverre E. Kjeldsen, Krzysztof Narkiewicz, Michel Burnier & Suzanne Oparil

To cite this article: Sverre E. Kjeldsen, Krzysztof Narkiewicz, Michel Burnier & Suzanne
Oparil (2020) The International Society of Hypertension Guidelines 2020 – a new drug
treatment recommendation in the wrong direction?, Blood Pressure, 29:5, 264-266, DOI:
10.1080/08037051.2020.1806494

To link to this article: https://doi.org/10.1080/08037051.2020.1806494

Published online: 18 Aug 2020.

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BLOOD PRESSURE
2020, VOL. 29, NO. 5, 264–266
https://doi.org/10.1080/08037051.2020.1806494

EDITORIAL

The International Society of Hypertension Guidelines 2020 – a new drug

treatment recommendation in the wrong direction?

The 2020 International Society of Hypertension (ISH)
Global Hypertension Practice Guidelines [1] were devel-
oped by the ISH Hypertension Guidelines Committee to
be evidence-based and, in addition, (a) to be used glo-
bally; (b) to be fit for application in low-resource and
high-resource settings by advising on both basic/essential
and optimal standards; and (c) to be concise, simplified,
and easy to use.
The ISH has a long tradition of issuing hypertension
guidelines, either stand-alone or jointly with other
organisations such as the World Health Organisation
(WHO). The jointly written 1999 WHO/ISH hyperten-
sion guidelines were the source of inspiration for devel-
oping the first European Society of Hypertension (ESH)
Guidelines issued as an ESH Scientific Newsletter [2].
The first full guidelines from ESH were issued jointly
with the European Society of Cardiology (ESC) and pub-
lished in the Journal of Hypertension. This publication
was the most widely cited paper in the medical literature
in 2003 and 2004 [3]. In the United States the National
High Blood Pressure Education Program (NHBPEP) was
founded in 1972 and its subsidiary Joint National
Committee on Detection, Evaluation and Treatment of
High Blood Pressure (JNC) began issuing hypertension
guidelines in 1977 and updated them regularly until the
task was taken over in 2017 by the American College of
Cardiology (ACC) and the American Heart Association
(AHA), in partnership with several other professional
societies [4].
Modern hypertension guidelines are evidence-based
in the sense that they recommend medical treatments
that have been proven effective in lowering blood pres-
sure and preventing cardiovascular disease outcomes
and death in randomised controlled clinical trials and/or
in well-designed observational studies with large patient
populations. The evidence base for these guidelines is
extensive, and guidelines typically include many hun-
dreds of references. Their complexity and the extensive
background literature on which they are based is over-
whelming to most practicing physicians, and most
guidelines have drawn criticisms for being impractical
for everyday use. The 2020 ISH guidelines were designed
to solve this problem by being concise, simplified, and
easy to use for the busy practitioner [1]. The most recent
ESC/ESH practice guidelines were also simplified for
similar reasons [5].
Since the various hypertension guidelines generally
refer to the same clinical trials and observational studies
as their evidence base, they might be expected to make
similar treatment recommendations. However, there are
differences between guidelines regarding important
issues, e.g. the choice of first line treatment. The recom-
mended treatment algorithm by ISH is shown in Figure
1. Step 1 and step 2 include angiotensin converting

Step 1 Consider monotherapy in low-risk grade 1

Ideally hypertension (systolic BP <150 mmHg), or in
1 pill
Dual low-dose ACEi or ARB + CCB very old (≥80years) or frailer patients.
combination
Consider a thiazide-like diuretic in post-
stroke, very old, incipient heart failure or
Step 2 CCB-intolerant patients.
Ideally
1 pill
Dual full-dose ACEi or ARB + CCB Step 1 only: Consider ACEi or ARB + CCB or
combination
CCB+ thiazide-like diuretic in black patients

Ideally Step 3 ACEi or ARB + CCB

1 pill Triple combination + thiazide-like diuretic

Step 4 Resistant hypertension Caution with spironolactone or other

2 pills Triple combination + Add spironolactone (12.5–50 mg OD) or potassium sparing diuretics when eGFR
2 pills spironolactone or other drug <45 mL/min/1.73 m2 or K+ >4.5 mmol/L
other drug

Beta-blockers
Consider beta-blockers at any treatment step, when there is a specific indication for their use, e.g. heart failure, angina,
post-MI, atrial fibrillation, or younger women with or planning pregnancy

Figure 1. Treatment Algorithm of the International Society of Hypertension. ACEi: angiotensin-converting enzyme inhibitor; ARB:
angiotensin II receptor blocker; CCB: calcium channel blocker; OD: once a day; eGFR: estimated glomerular filtration rate; MI: myo-
cardial infarction.
 BLOOD PRESSURE 265

Initial therapy Consider monotherapy in low-risk grade 1

1 pill Dual combination ACEi or ARB + CCB or diuretic hypertension (systolic BP <150 mmHg), or in
very old (≥80years) or frailer patients

Step 2
1 pill Triple combination ACEi or ARB + CCB + diuretic

Step 3 Resistant hypertension Consider referral to a specialist centre

2 pills Triple combination + Add spironolactone (25–50 mg OD) or other for further investigation
2 pills spironolactone or other drug diuretic, alpha-blocker or beta-blocker

Beta-blockers
Consider beta-blockers at any treatment step, when there is a specific indication for their use, e.g. heart failure, angina,
post-MI, atrial fibrillation, or younger women with or planning pregnancy

Figure 2. Treatment Algorithm of the European Society of Cardiology/ European Society of Hypertension. ACEi: angiotensin-con-
verting enzyme inhibitor; ARB: angiotensin II receptor blocker; CCB: calcium channel blocker; OD: once a day; MI: myocar-
dial infarction.

enzyme (ACE) inhibitors or angiotensin receptor block-
ers (ARB) plus calcium channel blockers (CCB) in low-
dose and full-dose combination [1]. The decision to
move thiazide or thiazide-like diuretics such as chlortha-
lidone or indapamide to step 3 was based in part on
results of the Avoiding Cardiovascular Events through
Combination Therapy in Patients Living with Systolic
Hypertension (ACCOMPLISH) trial [6] in which the
ACE inhibitor plus CCB combination prevented cardio-
vascular endpoints more effectively than the ACE inhibi-
tor plus hydrochlorothiazide combination. The ACE
inhibitor plus CCB combination was also the most
effective combination in the Anglo-Scandinavian Cardiac
Outcomes Trial (ASCOT) when compared with the
beta-adrenergic blocker atenolol plus bendroflumethia-
zide combination [7].
It is peculiar that in the ISH Guidelines only two out-
come trials [6,7] performed in the Nordic countries,
United Kingdom and the United States, provided the
evidence base for the most important recommendation,
choice of first line treatment, for hypertensive patients
throughout the world. Numerous outcome trials in
hypertension have shown the benefit of thiazide or thia-
zide-type diuretics in preventing cardiovascular disease
outcomes. All placebo controlled trials of antihyperten-
sive medications have shown that active treatment pre-
vented cardiovascular disease outcomes, including
stroke, heart failure, myocardial infarction, left ventricu-
lar hypertrophy and aortic aneurysm. Outcome trials
that have compared diuretics with beta-blockers have
shown no differences for the primary endpoints.
Further, numerous recent outcome trials have com-
pared antihypertensive drugs of different classes head-to-
head and have shown no inferiority when a diuretic was
administered as the first or second line drug. The only
outcome trial that has shown a difference between first
line drugs for the primary endpoint is the Losartan
Intervention for Endpoint prevention in hypertension
study (LIFE). LIFE showed that losartan was superior to
atenolol for the composite outcome of stroke, myocar-
dial infarction and cardiovascular death, but hydrochlor-
othiazide was given to approximately 90% of study
participants to ensure blood pressure control [8].
Amlodipine was equally effective as valsartan in the
Valsartan Long-term Use for endpoint Evaluation study
(VALUE), but hydrochlorothiazide was given as the
number 2 drug in both arms to ensure blood pressure
control [9]. Thus, many outcome trials of cardiovascular
disease prevention in hypertension have included a diur-
etic as first or second step, clearly supporting the role of
diuretics as a first line antihypertensive treatment, as
recommended in the 2017 American [4] and 2018
European [5] hypertension guidelines (Figure 2).
Importantly, several frequently occurring hyperten-
sion-related conditions including aging, obesity, diabetes
and renal function impairment are associated with salt
sensitivity, which favours diuretic treatment.
Furthermore, insufficient diuretic treatment is one of the
most frequent reasons of not achieving blood pressure
targets. Finally, there is now increasing evidence that all
diuretics are not equal in terms of efficacy and tolerabil-
ity as well as clinical evidence [10].
In conclusion, the ISH hypertension guidelines
diverge from the American and European hypertension
guidelines regarding choice of initial drug treatment.
We are concerned that this could be a step in the wrong
direction because a thiazide type diuretic, e.g. chlorthali-
done or indapamide, is at top of the list of evidence-
based first line antihypertensive drugs.
Disclosure statement
SEK, KN, MB and SO are editors of Blood Pressure and
report no relevant conflicts of interest to disclose related to
this editorial.
266 S. E. KJELDSEN ET AL.
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Sverre E. Kjeldsen
Department of Cardiology, University of Oslo, Ullevaal
Hospital, Oslo Norway
s.e.kjeldsen@medisin.uio.no
Krzysztof Narkiewicz
Department of Hypertension and Diabetology, Medical
University of Gdansk, Gdansk, Poland
Michel Burnier
Service of Nephrology and Hypertension, Centre
Hospitalier Universitaire Vaudois, Lausanne, Switzerland
Suzanne Oparil
Vascular Biology and Hypertension Program,
Department of Medicine, University of Alabama at
Birmingham, AL, USA
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