Individual management of arterial hypertension Doumas Michael, - - PowerPoint PPT Presentation

Individual management of arterial hypertension

Doumas Michael, Internist Doumas Michael, Internist Lecturer, Aristotle University, Thessaloniki Lecturer, Aristotle University, Thessaloniki

From Population to I ndividual From Population to I ndividual Management of Arterial Management of Arterial Hypertension Hypertension

Epidemiologic impact on mortality of blood pressure reduction in the population

Reduction in SBP

(mmHg)

% Reduction in Mortality Stroke CHD Total 2

• 6
• 4
• 3

3

• 8
• 5
• 4

5

• 14
• 9
• 7

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

After Intervention Before Intervention

Reduction in BP Prevalence %

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 woman non smoker TC: 202 mg/dL HDLC: 61 mg/dL No diabetes BP: 162/94 mmHg 10y CV risk: 0.6% BP: 157/89 mmHg 10y CV risk: 0.5%

Mrs Ariadni Low-risk

67 yr old man Diabetes Smoker TC: 268 mg/dL HDLC: 28 mg/dL BP: 160/95 mmHg 10y CV risk: 5.3% BP: 155/90 mmHg 10y CV risk: 5.3%

Mr Thrasivoulos High-risk Smoking cessation BP – lipid control

3.7%

"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

• r

DBP 80‐84 High normal SBP 130‐139 or DBP 85‐89 Grade 1 HT SBP 140‐159 or DBP 90‐99 Grade 2 HT SBP 160‐179 or DBP 100‐109 Grade 3 HT SBP ≥180 or DBP ≥110 No other risk factors Average risk Average risk Low added risk Moderate added risk High added risk 1‐2 risk factors Low added risk Low added risk Moderate added risk Moderate added risk Very high added risk 3 or more risk factors, MS, OD

• r diabetes

Moderate added risk High added risk High added risk High added risk Very high added risk Established CV

• r renal disease

Very high added risk Very high added risk Very high added risk Very high added risk Very 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

• f Hypertension

• How to improve prognosis to identify the

patients in need of further treatment?

• How to identify more effective therapeutic
• pportunities 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 treatment

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 HT SBP 140‐159 or DBP 90‐99 Grade 2 HT SBP 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 changes Lifestyle changes and consider drug treatment Lifestyle changes + drug treatment Lifestyle changes + drug treatment Lifestyle changes + immediate drug treatment Diabetes Lifestyle changes Lifestyle changes + drug treatment Established CV

• r 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%

TNT TNT

(CAD pts) (CAD pts)

5 10 15 20 25 30 35 1 2 3 4 5

≤ ≤ 60 60 61 61-

• 70

70 71 71-

• 80

80 81 81-

• 90

90 91 91-

• 100

100 > 100 > 100

On On-

• treatment DBP (mmHg)

treatment DBP (mmHg) CV events (%) CV events (%) Adjusted HR Adjusted HR

ONTARGET ONTARGET

(high risk pts, mainly with CAD) (high risk pts, mainly with CAD) On On-

• treatment SBP (mmHg)

treatment SBP (mmHg)

112 121 126 130 133 136 140 144 149 160 10 20 30 1 2 3

CV events (%) CV events (%) Adjusted HR Adjusted HR

VALUE VALUE

(High risk pts) (High risk pts) On On-

• treatment SBP (mmHg)

treatment SBP (mmHg)

INVEST INVEST

(CAD pts) (CAD pts) On On-

• treatment SBP (mmHg)

treatment SBP (mmHg)

110 110 >110 >110 to 120 to 120 >120 >120 to 130 to 130 >130 >130 to 140 to 140 >140 >140 to 150 to 150 >150 >150 to 160 to 160 >160 >160 10 20 30 40 50 60

CV events (%) CV events (%) Cardiac events (%) Cardiac events (%)

10 20 30 < 120 < 120 >120 >120 to 130 to 130 >130 >130 to 140 to 140 >140 >140 to 150 to 150 >150 >150 to 160 to 160 >160 >160 to 170 to 170 >170 >170 to 180 to 180 ≥ ≥ 180 180

J hypertension 2009;

2009;27: 27:2121–58 121–58

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 name Drug name Cost for 30 day supply Cost for 30 day supply Enalapril 5 mg Enalapril 5 mg -

• 20 mg

20 mg $4 $4 HCTZ 12.5 HCTZ 12.5-

• 25 mg

25 mg $4 $4 Atenolol 25 mg Atenolol 25 mg-

• 100 mg

100 mg $4 $4 Amlodipine (Norvasc) 5 mg Amlodipine (Norvasc) 5 mg $75 $75 Amlodipine (generic) 5 mg Amlodipine (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
• pportunities 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 agents Centrally acting agents Diuretics Diuretics Beta blockers Beta blockers C C B s C C B s ARBs ARBs ACE ACE – – inhibitors inhibitors

Hypertension Hypertension

Reductions in Systolic Blood Pressure Among All Patients Reductions in Systolic Blood Pressure Among All Patients

VA Cooperative Study of Responses to Single VA Cooperative Study of Responses to Single-

• Drug Therapy

Drug Therapy

Materson BJ, et al. N Engl J Med. 1993;328:914-921.

Change in SBP (mm Hg) from Baseline

• 35
• 30
• 25
• 20
• 15
• 10
• 5

*P ≤ 0.05 vs. captopril

* * *

177 188 182 186 176 188 186 Clonidine Captopril Hydrochlorothiazide Diltiazem Prazosin Atenolol Placebo n =

SBP = systolic blood pressure

25 50 75 100 25 50 75 100

Successful Treatment (%)

C l

• n

i d i n e

White Men <60 yr

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

VA Cooperative Study of Responses to Single VA Cooperative Study of Responses to Single-

• Drug Therapy

Drug Therapy

White Men ≥60 yr

A t e n

• l
• l

C a p t

• p

r i l

Diltiazem

P r a z

• s

i n

HCTZ

P l a c e b

• *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.

Successful Treatment (%)

C l

• n

i d i n e A t e n

• l
• l

Diltiazem

P r a z

• s

i n

HCTZ

C a p t

• p

r i l P l a c e b

• *

* *

0% 20% 40% 60% 80% 100%

6 mon 1 yr 3 yr 5 yr

ALLHAT Medication Use and BP Control ALLHAT Medication Use and BP Control*

*

Patients (%) # of Drugs/Patient

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

2 1.8 1.6 1.4 1.2 1 0.8 0.6 0.4 0.2 1 Drug 2 Drugs 3 Drugs Average #

• f Drugs

≥4 Drugs 72 72 22 27 32 36 18 18 14 14 6 6 63 63 48 48 37 37

One tool fits all One drug for everybody

2007 ESH/ESC Guidelines

 Subclinical organ damage

LVH ACEI, CA, ARB Microalbuminuria ACEI, ARB Atherosclerosis (asympt) CA, ACEI Renal dysfunction ACEI, ARB

 Clinical event

Previous stroke Any BP lowering agent Previous MI BB, ACEI, ARB Angina pectoris BB, CA Heart failure Diu, BB, ACEI, ARB, Antialdo Atrial fibrillation Recurrent ARB, ACEI Permanent BB, non-dihydropiridine CA ESRD/Proteinuria ACEI, ARB, Loop DIU Peripheral Artery Disease CA

Antihypertensive Treatment: Preferred Drugs Antihypertensive Treatment: Preferred Drugs

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

• 1187

1187

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, 54y BP: 156/88 mmHg No comorbidities LVMI: 152 g/m2 Lisinopril 20mg BP: 138/84 mmHg 9mon - Cough Valsartan 160mg-6mo BP: 141/83 mmHg LVMI: 149 g/m2 Manidipine 20mg BP: 140/85 mmHg LVMI: 123 g/m2

K.E., man, 62y BP: 155/95 mmHg No comorbidities LVMI: 163 g/m2 Irbesartan 150 to 300 2 mon BP: 154/92 mmHg Amlo 5 to 10mg- 9mon BP: 138/86 mmHg LVMI: 165 g/m2 Edema Indapamide 2.5 mg BP: 143/88 mmHg LVMI: 131 g/m2

Peeking at the Future Peeking at the Future

Be yo nd the HGP: What’s Next?

HapMap Pro te- Metabo l-o mic s

Exploring Microbial Genomes for Energy and the Environment Chart genetic variation within the human genome

Diuretics B-blockers Ca-antag ARBs ACE-inhibit Renin-inh Other

The Future…

Edema Cough Hypokalemia Sexual Dysf

Pharmacogenomics Pharmacogenomics

• “

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

• Increased efficacy

Increased 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.in

43

Dr.Sarma@works

DH Lawrence's DH Lawrence's The Third Thing The Third Thing (Pansies 1929) (Pansies 1929) Water is H20 Water is H20 Hydrogen two parts Hydrogen two parts Oxygen one Oxygen one But there is a third thing But 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

20 40 60 80 Smoking BMI 25+ Inactive Alcohol 9+ P e r c e n t A B

• 1.6%

+1.4%

• 2.4%
• 0.1%

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

∆υστυχώς είναι πραγματικότητα…

www.drsarma.in

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