Individual management of arterial hypertension Doumas Michael, Internist Doumas Michael, Internist Lecturer, Aristotle University, Thessaloniki Lecturer, Aristotle University, Thessaloniki
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.”
∆υστυχώς
είναι
πραγματικότητα…
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