Why new BP targets and threshold · The decision to use BP-Lowering treatment should not be based...

Why new BP targets and threshold

Costas TsioufisProfessor of Cardiology,

University of Athens, Greece

President of European Society of Hypertension (ESH) (2017-19)

No outcome-based RCT has used ABPM or HBPM to guide the treatment of HTN

Thresholds/Targets of antihypertensive treatment should be based on office BP or ABPM?

OFFICE BP - ABPM - HBPM

COMPLEMENTARY

NOT

ALTERNATIVE APPROACHES

But…Hypertension is more than just Blood Pressure!

Recommendations Class Level

CV risk assessment with the SCORE system is recommended forhypertensive patients who are not already at high or very high riskdue to established CV or renal disease or diabetes or a markedlyelevated single risk factor (e.g. cholesterol), or hypertensive LVH.

I B

2018 ESC/ESH Hypertension Guidelines

Hypertension and CV assessment

Williams et al, European Heart Journal (2018) 39, 3021–3104

The decision to use BP-Lowering treatment should not be based solely on the level of CV

risk because the benefits of BP-lowering treatment

> Are at best marginal even in patients at the highest CV risk when baseline BP is below

140/90mmH while are

>Most evident in patients with CAD at the upper end of the high-normal BP range

Thresholds/Targets of antihypertensive treatment should be based on BP values or level of total CV risk?



Why new BP thresholds?

18832 M

Drug treatment in:

- Grade 3 HTN

- Grade 2 HTN

- Grade 1 HTN with high/very high CV risk

Drug treatment uncertain/excluded:

- Grade 1 HTN with low/moderate CV risk

- Grade 1 HTN of the elderly

- High normal BP (130-139/85-89 mmHg)

USE OF DRUGS IN 2013 ESH/ESC GUIDELINES

Mancia et al, European Heart Journal (2013) 34, 2159–2219

CV Death, MI, Stroke, Cardiac Arrest, Revasc, HF

0.5 1.0 2.0

Candesartan + HCTZ Better Placebo Better

3.5

4.6

7.5

1.25 (0.92-1.70)

1.02 (0.77-1.34)

0.76 (0.60-0.96)

0.009

HR (95% CI) P Trend

HOPE 3. Prespecified Subgroups:By Thirds of SBP (T:22%)

SBP

Mean

≤131.5

131.6-143.5

>143.5

Diff

6.1

5.8

5.6

Cutoffs

122

138

154

Placebo

Event Rate%

Lonn EM, et al. N Engl J Med. 2016; 374(21):2009-20

Effects of BP Lowering (10/5 mmHg SBP/DBP) in Trials with

Average Baseline BP in Grade 1 and Average Low-to-Moderate CV Risk

19385 M Thomopoulos et al., J Hypertens 2014; 32: 2296

Outcome

Stroke

CHD

Stroke + CHD

CV Death

All-cause Death

Trials

(n)

4

5

4

4

4

Baseline

SBP/DBP

(mmHg)

146/91

145/91

146/91

146/91

146/91

Difference

SBP/DBP

(mmHg)

-7.1/-4.5

-6.5/-4.2

-7.1/-4.5

-7.1/-4.5

-7.1/-4.5

Absolute

Risk Reduction

1000 pts/5 years

(95%CI)

-21 (-26, -1)

-12 (-18, -2)

-34 (-43, -19)

-9 (-14, +1)

-19 (-25, -8)

NNT

5 years

(95% CI)

47 (39, 1301)

86 (55, 531)

29 (23, 54)

110 (72, -2223)

54 (40, 119)

Standardized RR

(95% CI)

0.1 0.2 0.5 1 2 5

Active better Control better

Standardized RR

(95% CI)

0.33 (0.11-0.98)

0.68 (0.48-0.95)

0.51 (0.36-0.75)

0.57 (0.32-1.02)

0.53 (0.35-0.80)

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CHANGE IN RECOMMENDATIONS

2013 2018

Treatment thresholds

Treatment of low-risk grade 1 hypertension:

Initiation of antihypertensive drug treatment should

also be considered in grade 1 hypertensive patients

at low to moderate risk, when BP is within this range

at several repeated visits or elevated by ambulatory

BP criteria, and remains within this range despite a

reasonable period of time with lifestyle measures.


Treatment of low-risk grade 1 hypertension:

In patients with grade 1 hypertension at low–

moderate risk and without evidence of HMOD, BP-

lowering drug treatment is recommended if the

patient remains hypertensive, after a period of

lifestyle intervention.



Initiation of drug therapy in older patients with grade 1 Hypertension

>Various definitions of old (>65) and very old (>80)

> Chronological age is often a poor surrogate for biological age (frailty, independence )

> Physically and mental frail and institutionalized patients have been excluded from RCT

> Older Patients participating in RCT with baseline BP in lower range showing beneficial

effects of drugs, were often on background antihypertensive treatment



Data from HDFP/HOPE/PATS (n=8389)

Entry SBP=140-159 mmHg, Age >60 yrs

CV death: 0.55 (95%CI 0.36-0.85)

All cause death: 0.79 (0.67-0.94)

Stroke/CHD/HF: 0.58 (0.45-0.74)

Thomopoulos et al., J Hypertens 2017; 35: 2150

BENEFITS OF TREATMENT

80+ years

The most « hypertensive » population (prevalence of HTN over 80 yrs >75%)1

The most growing population (5% in 2015, 10% in 2050 will be over 80 yrs)2

The most heterogeneous population3

1. Bromfield, et al. J Clin Hypertens 2014;16(4): 270-6

2. OECD Health Policy Studies. Published on May 18, 2011

3. Williams, et al. Eur Heart J 2018; 39: 3021-3104

Recommendations Class Level

BP-lowering drug treatment and lifestyle intervention are recommended in the fit older patients (> 65 years but not over 80 years) when SBP is in the grade 1 range (140–159 mmHg), provided that treatment is well tolerated.

I A

Antihypertensive treatment may also be considered in frail older patients if tolerated. IIb B

Withdrawal of BP-lowering drug treatment on the basis of age, even when patients attain an age of ≥ 80 years, is not recommended, provided that treatment is well tolerated.

III A



Initiation of drug therapy in patients with high-normal BP

➢ In many RCTs, the ‘’baseline BP’’ was measured on a background of

antihypertensive drugs

➢ HOPE-3 trial was negative for those at high normal levels

➢ 2 Meta-analyses did not show a beneficial effect on outcome in patients with

high-normal BP and low-moderate risk


Thomopoulos et al, J Hypertens 2017;35:2150-2160Brunstrom M, et al. JAMA Intern Med 2018;178:28-36

Relative risk of morbidity and mortality outcomes in individuals with high-normal or normal BP:

comparison of individuals at low–moderate and high–very high CV risk

Trials

(n)

4

8

4

6

1

5

3

8

5

6

3

6

10

6

Outcome

Stroke

CHD

HF

Stroke + CHD

Stroke + CHD + HF

CV Death

All Death

CV

risk

L-M

H-VH

L-M

H-VH

L-M

H-VH

L-M

H-VH

L-M

H-VH

L-M

H-VH

L-M

H-VH

Standardized RR

(95% CI)

1.20 (0.51-2.78)

0.40 (0.20-0.81)

1.25 (0.82-1.92)

1.00 (0.60-1.84)

-

0.82 (0.38-1.81)

1.27 (0.88-1.81)

0.65 (0.52-0.80)

1.02 (0.73-1.39)

0.91 (0.66-1.29)

1.23 (0.74-2.06)

0.66 (0.40-1.09)

1.18 (0.88-1.60)

0.77 (0.54-1.13)

P-value

interaction

0.006

0.089

-

<0.001

0.32

0.001

0.016

Standardized RR

(95% CI)

Treated better Control better

0.2 1.0 2.00.5 5.0


2013 2018


High-normal BP (130–139/85–89 mmHg):

Unless the necessary evidence is obtained it is not

recommended to initiate antihypertensive drug therapy

at high-normal BP.


High-normal BP (130–139/85–89 mmHg):

Drug treatment may be considered when CV risk is very

high due to established CVD, especially CAD

CHANGE IN RECOMMENDATIONS



Why new BP targets?

General hypertensive population

(regardless the CV risk level)

< 140/90

Elderly patients(Both below and above

80 years of age)

150-140/90

2013 ESH/ESC Hypertension GuidelinesBP targets for treatment

Mancia et al, European Heart Journal (2013) 34, 2159–2219

Post hoc analyses of large outcome RCTs in patients at high CV risk

Registries in patients with CAD

SPRINT Trial

New meta analyses of all available RCTs

Why new BP targets?

Mean achieved SBP and outcomes in Ontarget/Transcend patients

Boehm, et al, Lancet 2017; 389: 2226

Risk Reduction (%) for 10 mm Hg fall in SBP -613,815 patients

20

17

2728

13

0

5

10

15

20

25

30

Major CVD CHD Stroke CCF Mortality

% risk reduction

Irrespective of

Baseline BP within the hypertensive range

Level of CV risk

Comorbidities

Age

Sex

Ethnicity

Ettehad D et al, Lancet. 2016,387:957-967


Stroke

CHD

HF

Stroke + CHD + HF

CV death

All-cause death

SBP*Risk reduction (%)

-21 (-34/-6)

-16 (-29/+1)

-19 (-44/+20)

-22 (-31/-11)

-20 (-36/+2)

-12 (-26/+6)

DBP*Risk reduction (%)

-27 (-41/-7)

-16 (-29/+1)

-23 (-43/+5)

-18 (-25/-10)

-27 (-45/-10)

-22 (-38/-3)

* Mean BP in more and less intensely treated patients: 122.1/72.5 vs 135.0/75.6 mmHg

Risk reduction (%, 95% CI) by an achieved SBP of <130 mmHg or DBP of <80 mmHg vs less intense treatment

Relationships of mortality and morbidity outcome reductions and increase in discontinuations for adverse events

to the extent of SBP and DBP reductions


Vidal-Petiot et al. The Lancet 2016; 388(10056): 2142–2152.

Office BP treatment target range

Age group

Office SBP treatment target ranges (mmHg) Diastolic treatment

target range (mmHg)

Hypertension + Diabetes + CKD + CAD + Stroke/TIA

18−65 years

Target to 130

or lower if tolerated

Not < 120

Target to 130


Not < 120

Target to

< 140 to 130

if tolerated

Target to 130


Not < 120

Target to 130


Not < 120< 80 to 70

65−79 yearsTarget to < 140 to

130

if tolerated

Target to

< 140 to 130

if tolerated

Target to

< 140 to 130

if tolerated

Target to

< 140 to 130

if tolerated

Target to < 140 to

130

if tolerated

< 80 to 70

≥ 80 yearsTarget to < 140 to

130

if tolerated

Target to < 140 to

130

if tolerated

Target to < 140 to

130

if tolerated

Target to < 140 to

130

if tolerated

Target to < 140 to

130

if tolerated

< 80 to 70

Diastolic treatment target range(mmHg)

< 80 to 70 < 80 to 70 < 80 to 70 < 80 to 70 < 80 to 70



Reducing SBP <140/90 mmHg not easy, even in the setting controlled trials

Incremental benefit of BP lowering decreases as target BP is lowered

Target BP: crucial points to be considered

Precision Medicine is coming but today doctors cannot determine the

optimal BP target in individual patients unless there are clinical

markers of treatment inconveniences

Treat the patient and not only BP numbers

Why new BP targets and threshold · The decision to use BP-Lowering treatment should not be based...

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