Individual management of arterial hypertension

Doumas Michael, InternistDoumas Michael, InternistLecturer, Aristotle University, ThessalonikiLecturer, Aristotle University, Thessaloniki

From Population to Individual From Population to Individual Management of Arterial Management of Arterial HypertensionHypertension

Epidemiologic impact on mortality of blood pressure reduction in the population

Reduction in SBP

(mmHg)

% Reduction in Mortality

Stroke CHD Total

2 -6 -4 -33 -8 -5 -45 -14 -9 -7

Adapted from Whelton, P. K. et al. JAMA 2002;288:1882-1888

AfterIntervention

BeforeIntervention

Reduction in BPPrev

alen

ce %

BP Reductions as Small as 2 mmHg Reduce the Risk of CV Events by Up to 10%

•

Meta-analysis of 61 prospective, observational studies

•

1 million adults

•

12.7 million person-years

Prospective Studies Collaboration. Lancet. 2002;360:1903-

1913.

2 mmHg decrease in mean SBP 10% reduction

in risk of stroke mortality

7% reduction in risk of IHD mortality

52 yr old womannon smokerTC: 202 mg/dLHDLC: 61 mg/dLNo diabetesBP: 162/94 mmHg

10y CV risk: 0.6%

BP: 157/89 mmHg

10y CV risk: 0.5%

Mrs AriadniLow-risk

67 yr old manDiabetesSmokerTC: 268 mg/dLHDLC: 28 mg/dLBP: 160/95 mmHg

10y CV risk: 5.3%

BP: 155/90 mmHg

10y CV risk: 5.3%

Mr ThrasivoulosHigh-risk

Smoking cessationBP –

lipid control3.7%

"Individualized Care"

• Risk factors considered• Non-pharmacological therapy tried• Monotherapy or combination therapy is

instituted• Considerations for choice of initial

therapy: Renin status Age Coexisting cardiovascular conditions Other conditions

Stratification of CV risk in four categories

SBP: systolic blood pressure; DBP: diastolic blood pressure; CV:

cardiovascular; HT: hypertension. Low, 

moderate, high, very high risa refer to 10year risk of a CV fatal or non‐fatal event. The term “added”

indicates 

that in all categories risk is greater than average. OD: subclinical organ damage; MS: metabolic syndrome.

Blood pressure (mmHg)

Other risk 

factors, OD or 

disease

Normal SBP 120‐129 

or

DBP 80‐84

High normal SBP 130‐139 or

DBP 85‐89

Grade 1 HTSBP 140‐159 or

DBP 90‐99

Grade 2 HTSBP 160‐179 or

DBP 100‐109

Grade 3 HT 

SBP ≥180 or DBP ≥110

No other risk 

factorsAverage risk

Average risk

Low added risk

Moderate 

added riskHigh added 

risk

1‐2 risk factorsLow added risk

Low added risk

Moderate 

added riskModerate 

added riskVery high 

added risk

3 or more risk 

factors, MS, OD 

or diabetes

Moderate 

added riskHigh added 

risk High added risk High added 

riskVery high 

added risk

Established CV 

or renal diseaseVery high 

added riskVery high 

added riskVery high 

added riskVery high 

added riskVery high 

added risk

Einstein

“Not everything that can be counted counts, and not everything that counts can be counted.“

Αυτά

που

είναι

μετρήσιμα

δεν

είναι

πάντα

χρήσιμα

και

αυτά

που

είναι

χρήσιμα

δεν

είναι

πάντα

μετρήσιμα

Addressing the Complexity of Hypertension

• How to improve prognosis to identify the patients in need of further treatment?

• How to identify more effective therapeutic opportunities tailored to the individual patient?

The Challenge of Personalized Antihypertensive

Treatment

Who to treat?Who to treat?

How to treat?How to treat?

J Hypertension, November 2009

Initiation of antihypertensive treatmentOther risk 

factors, OD or 

disease

Normal SBP 120‐129 or

DBP 80‐84

High normal SBP 130‐139 or

DBP 85‐89

Grade 1 HTSBP 140‐159 or

DBP 90‐99

Grade 2 HTSBP 160‐179 or

DBP 100‐109

Grade 3 HT 

SBP ≥180 or

DBP ≥110

No other risk 

factors

No BP 

intervention

No BP 

intervention

Lifestyle changes 

for several 

months then drug 

treatment if BP 

uncontrolled

Lifestyle changes 

for several weeks 

then drug 

treatment if BP 

uncontrolled

Lifestyle 

changes + 

immediate 

drug 

treatment

1‐2 risk factors Lifestyle changes Lifestyle changes

Lifestyle changes 

for several weeks 

then drug 

treatment if BP 

uncontrolled

Lifestyle changes 

for several weeks 

then drug 

treatment if BP 

uncontrolled

Lifestyle 

changes + 

immediate 

drug 

treatment

3 or more risk 

factors, MS, 

OD or diabetes

Lifestyle changesLifestyle changes 

and consider 

drug treatment Lifestyle changes 

+ drug treatment

Lifestyle changes 

+ drug treatment

Lifestyle 

changes + 

immediate 

drug 

treatmentDiabetes Lifestyle changes Lifestyle changes 

+ drug treatment

Established CV 

or renal 

disease

Lifestyle changes 

+ immediate drug 

treatment

Lifestyle changes 

+ immediate 

drug treatment

Lifestyle changes 

+ immediate drug 

treatment

Lifestyle changes 

+ immediate drug 

treatment

Lifestyle 

changes + 

immediate 

drug 

treatment

Beckett NS et al. N Engl J Med 2008;358:1887-1898

-30% -21%

-23% -39%

TNTTNT(CAD pts)(CAD pts)

0

5

10

15

20

25

30

35

0

1

2

3

4

5

≤≤ 6060 6161--7070 7171--8080 8181--9090 9191--100100 > 100> 100

OnOn--treatment DBP (mmHg)treatment DBP (mmHg)

CV

eve

nts (

%)

CV

eve

nts (

%)

Adj

uste

d H

RA

djus

ted

HR

ONTARGET ONTARGET (high risk pts, mainly with CAD)(high risk pts, mainly with CAD)

OnOn--treatment SBP (mmHg)treatment SBP (mmHg) 112 121 126 130 133 136 140 144 149 160

0

10

20

30

0

1

2

3

CV

eve

nts (

%)

CV

eve

nts (

%)

Adj

uste

d H

RA

djus

ted

HR

VALUEVALUE(High risk pts)(High risk pts)

OnOn--treatment SBP (mmHg)treatment SBP (mmHg)

INVESTINVEST(CAD pts)(CAD pts)

OnOn--treatment SBP (mmHg)treatment SBP (mmHg)

110110 >110>110to 120to 120

>120>120to 130to 130

>130>130to 140to 140

>140>140to 150to 150

>150>150to 160to 160

>160>1600

10

20

30

40

50

60C

V e

vent

s (%

)C

V e

vent

s (%

)C

ardi

ac e

vent

s (%

)C

ardi

ac e

vent

s (%

)

0

10

20

30

< 120< 120 >120>120to 130to 130

>130>130to 140to 140

>140>140to 150to 150

>150>150to 160to 160

>160>160to 170to 170

>170>170to 180to 180

≥≥ 180180

J hypertension 2009;27:2121–58

Should low-risk hypertensive patients be treated?

Young patients?Mild hypertension?

One point of view

“individual treatment can only be justified if there is individual benefit”

Stroke and blood pressure lowering: subgroup analysis from 17 RCTs

Trial % Events

Odds ratio (Relative risk red.)group

control treatment

Older

34 %patients

Younger 43 %patients

0 0.5 1.0 1.5

1º

prev. 38 %

2º

prev. 38 %

MacMahon & Rogers J Vasc Med Biol 1993;4:265-71

Stroke and blood pressure lowering: subgroup analysis from 17 RCTs

Trial % Events

Odds ratio (Relative risk red.)group

control treatment

Older 7.0 % 4.6 %

34 %

patients

Younger 2.3 % 1.3 %

43 %patients

0 0.5 1.0 1.5

1º

prev. 3.2 % 2.0 %

38 %

2º

prev. 27.3 % 18.8 %

38 %

MacMahon & Rogers J Vasc Med Biol 1993;4:265-71

1%

2.4%

1.2%

8.5%

Drug Costs in the US Drug Costs in the US Drug nameDrug name Cost for 30 day supplyCost for 30 day supply

Enalapril 5 mg Enalapril 5 mg --20 mg20 mg $4$4

HCTZ 12.5HCTZ 12.5--25 mg25 mg $4$4

Atenolol 25 mgAtenolol 25 mg--

100 mg100 mg $4$4

Amlodipine (Norvasc) 5 mgAmlodipine (Norvasc) 5 mg $75$75

Amlodipine (generic) 5 mgAmlodipine (generic) 5 mg $21$21

To treat or not to treat “mild hypertension”

“treat risk not blood pressure”

“only absolute risks and benefits are relevant to patients”

“the payer should

choose the threshold”

High-risk patients

‘The earlier –

The better’Attention to all CV risks

To treat or not to treat “mild hypertension”

“the payer should not choose the threshold”

• How to improve prognosis to identify the patients in need of further treatment?

• How to identify more effective therapeutic opportunities tailored to the individual patient?

The Challenge of Personalized Antihypertensive

Treatment

How to treat?How to treat?

The Many Faces of HT Therapy Today

Centrally acting agentsCentrally acting agents

DiureticsDiuretics

Beta blockers

Beta blockers

CCBsCCBs

ARBsARBs

ACE ACE –– inhibitorsinhibitors

HypertensionHypertension

Reductions in Systolic Blood Pressure Among All PatientsReductions in Systolic Blood Pressure Among All Patients VA Cooperative Study of Responses to SingleVA Cooperative Study of Responses to Single--Drug TherapyDrug Therapy

Materson BJ, et al. N Engl J Med.

1993;328:914-921.

Ch

ang

e in

SB

P (

mm

Hg

)fr

om B

asel

ine

-35

-30

-25

-20

-15

-10

-5

0

*P ≤

0.05 vs. captopril**

*

177 188 182 186 176 188 186

Clonidine

CaptoprilHydrochlorothiazide

Diltiazem

Prazosin

Atenolol Placebo

n =

SBP = systolic blood pressure

0

25

50

75

100

0

25

50

75

100

Su

cces

sfu

l Tre

atm

ent

(%)

Clonid

ine

White Men <60 yr

Rates of Successful Treatment Were Rates of Successful Treatment Were Similar for Most Single Drugs in White MenSimilar for Most Single Drugs in White Men

VA Cooperative Study of Responses to SingleVA Cooperative Study of Responses to Single--Drug TherapyDrug Therapy

White Men ≥60 yr

Atenol

ol

Capto

pril

Diltia

zem

Prazo

sinHCTZ

Place

bo

*There were no clinically important differences (<15%) between the treatment groups spanned by the arrows. Treatment was considered to be successful if the

diastolic blood pressure measured <95 mm Hg after 1 year.

Su

cces

sfu

l Tre

atm

ent

(%)Clo

nidin

e

Atenol

ol

Diltia

zem

Prazo

sin HCTZ

Capto

pril

Place

bo

*

*

*

0%

20%

40%

60%

80%

100%

6 mon 1 yr 3 yr 5 yr

ALLHAT Medication Use and BP ControlALLHAT Medication Use and BP Control**P

atie

nts

(%

)#

of D

rug

s/P

atient

Cushman WC, et al. J Clin Hypertens. 2002;4:393-404.

21.81.61.41.210.80.60.40.20

1 Drug 2 Drugs 3 Drugs Average # of Drugs

≥4 Drugs

7272

22 27

3236

1818141466

63634848

3737

One tool fits allOne drug for everybody

2007 ESH/ESC Guidelines

Subclinical organ damageLVH

ACEI, CA, ARB

Microalbuminuria

ACEI, ARBAtherosclerosis (asympt)

CA, ACEI

Renal dysfunction

ACEI, ARB Clinical event

Previous stroke

Any BP lowering agentPrevious MI

BB, ACEI, ARB

Angina pectoris

BB, CAHeart failure

Diu, BB, ACEI, ARB, Antialdo

Atrial fibrillationRecurrent

ARB, ACEI

Permanent

BB, non-dihydropiridine CAESRD/Proteinuria

ACEI, ARB, Loop DIU

Peripheral Artery Disease

CA

Antihypertensive Treatment: Preferred DrugsAntihypertensive Treatment: Preferred Drugs

2007 ESH/ESC Guidelines. J Hypertens 2007; 25: 11052007 ESH/ESC Guidelines. J Hypertens 2007; 25: 1105--11871187

Benjamin Franklin

“Keep your eyes wide open before marriage, half shut afterwards.”

“Keep your eyes wide open before treatment, and keep doing this afterwards.”

M.T., woman, 54yBP: 156/88 mmHgNo comorbiditiesLVMI: 152 g/m2Lisinopril 20mgBP: 138/84 mmHg9mon -

Cough

Valsartan 160mg-6moBP: 141/83 mmHgLVMI: 149 g/m2

Manidipine 20mgBP: 140/85 mmHgLVMI: 123 g/m2

K.E., man, 62yBP: 155/95 mmHgNo comorbiditiesLVMI: 163 g/m2Irbesartan 150 to 3002 monBP: 154/92 mmHg

Amlo 5 to 10mg-

9monBP: 138/86 mmHgLVMI: 165 g/m2Edema

Indapamide 2.5 mgBP: 143/88 mmHgLVMI: 131 g/m2

Peeking at the FuturePeeking at the Future

Beyond the HGP: What’s Next?

HapMap Prote- Metabol-omicsExploring Microbial Genomes for

Energy and the EnvironmentChart genetic variation

within the human genome

DiureticsB-blockersCa-antagARBsACE-inhibitRenin-inhOther

The Future…

EdemaCoughHypokalemiaSexual Dysf

PharmacogenomicsPharmacogenomics

““The right drug to the right patientThe right drug to the right patient””

Increased efficacyIncreased efficacy

Decreased toxicity Decreased toxicity

Mission not accomplished (yet)Mission not accomplished (yet)

Erdine. European Society of Hypertension Scientific Newsletter 2000

Hypertension poorly controlled worldwide Percentage of patients with controlled BP (<140/90 mm Hg)

Belgium 25% Canada 16% China 3% England 6% France 33%

Italy 9% Poland 4% Russia 6% Spain 16% USA 24%

www.drsarma.in43 Dr.Sarma@works

DH Lawrence's DH Lawrence's The Third ThingThe Third Thing (Pansies 1929)(Pansies 1929)

Water is H20Water is H20

Hydrogen two partsHydrogen two parts

Oxygen oneOxygen one

But there is a third thingBut there is a third thing

That makes it water.That makes it water.

And nobody knows what that is.And nobody knows what that is.

NPHS (1994-2002): More Lifestyle Changes After Hypertension Diagnosis Are Needed

Can J Cardiol, 2008. 24; 3: 199-204.

Age Standardized Rates of Lifestyle Change After a Hypertension Diagnosis

0

20

40

60

80

Smoking BMI 25+ Inactive Alcohol 9+

Perc

ent

A B

-1.6%

+1.4%-2.4%

-0.1%

“Let’s just go in and see what happens.”

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είναι

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