THE IMPORTANCE OF 24-HOUR BP CONTROL FOR MANAGING CV RISK

Hendro Darmawan, 2 November 2014

Hypertension (HTN) is a major public health concern, affecting

26% of adults worldwide1

Number of

people with HTN

worldwide in 20001

972 million

Increase in the

number of adults with

HTN globally by 20251

60%

Percent of all global

healthcare spending

attributable to high

blood pressure2

10%

Annual worldwide cost of

hypertension2$370 billion

1. Kearney PM, Whelton M, Reynolds K, Muntner P, Whelton PK, He J. Global burden of hypertension: analysis of worldwide data. Lancet. 2005 Jan 15-21;365(9455):217-23. Gaziano TA, Asaf B, S Anand, et.al. The

global cost of nonoptimal blood pressure. J Hypertens 2009; 27(7): 1472-1477.

1.6 Billion

HTN patients estimated

by 2025

Prevalensi Hipertensi

RISKESDAS (2007) 31,7%

RISKESDAS (2013) 25.8%

EU Prevalence of Hypertension

~81 Million Adults have elevated Blood Pressure

Lloyd-Jones D: Circulation 2010;121:e46 – e215

Persell SD: Hypertension 2011;57:1076-1080

EU Patients with HTN 81.0M

Diagnosed HTN 78%

Treated HTN 68%

Uncontrolled HTN 38%

Resistant HTN 9% - $7.2M

81M

Patients with HTN

Diagnosed HTN

Treated HTN

Uncontrolled HTN

HTN=Hypertension

Telah mendapat terapi atau minum obat antihipertensi 24.2 %

Yang terkontrol 18 %

Yang belum terjangkau pelayanan kesehatan 75.8 %

(RISKESDAS 2013)

Each 20/10 mmHg BP increase doubles the

risk of CV mortality

1-fold

2-fold

4-fold

8-fold

0

2

4

6

8

10

135/85 155/95 175/105

* Individuals aged 40–69 years

Lewington S, et al. Lancet. 2002;360:1903–1913.

Fold Increase in Relative CV Risk*

115/75

SBP/DBP, mmHG

A meta-analysis of individual data from 1 million

adults without previous vascular disease from

61 prospective observational studies of BP and

mortality addressed the cause-specific death

rate during a 10-year period

Uncontrolled hypertension carries the same

CV risk as untreated hypertension

35%

(n = 1,756)

48%

(n = 2,458)

17%

(n = 872)

Third National Health and Nutrition Examination Survey (NHANES III)

Gu Q, et al. Am J Hypertens 2010;23(1):38-45

Both are at equally

increased risk compared

with controlled BP

(p>0.05)

Not treated

BP

uncontrolled

BP controlled

Risk1.57

Risk 1.34

Peripheral Vascular

Resistance Cardiac Output

Renal Function

Efferent: from the brain

Afferent: to the brain

Cardiac Effects:

- LV Hypertrophy

- Systolic HF

- HFpEF

- Arrhythmia

Kidney Effects:

- Sodium &

Volume Retention

- Decreased Renal

Blood Flow due to

Vasoconstriction

- RAS Activity

Hyperactive Sympathetic Nervous System

Drives Hypertension

Doumas et al. Am J Cardiol 2010;105:570-576, Cleveland Clinic Journal of Medicine 2012; 79: 501-10

Risk Factors for Cardiovascular Disease

• Smoking

• Hyperlipidaemia

• High salt intake

• Homocysteinaemia

• Lack of exercise

• Obesity

• Diabetes

• Alcohol >4pints of beer/day

• Genetic

Start one drug, titrate to maximum dose, and then add a second drug

Start one drug and then add a second drug before achieving maximum dose of the initial drug

Begin with 2 drugs at the same time, either as 2 separate pills or as a single pill combination

Strategies to Dose of Antihypertensive Drugs

10

Initial Drug Therapy

BP

Classification

SBP*

(mm

Hg)

DBP*

(mm

Hg)

Lifestyle

Modification

Without

Compelling

Indications

With

Compelling

Indications

Normal <120 and <80 Encourage

No antihypertensive

drug indicated.

Drug(s) for

compelling

indications.Prehypertension 120–139 or 80–89 Yes

Stage 1

hypertension140–159 or 90–99 Yes

Thiazide-type diuretic

for most. May consider

ACEI, ARB, BB, CCB,

or combination.

Drug(s) for

compelling

indications.

Other

antihypertensive drugs

(diuretic, ACEI, ARB,

BB, CCB) as needed.

Stage 2

hypertension160 or 100 Yes

Two-drug combination

for most (usually

thiazide-type diuretic

and ACEI or ARB or

BB or CCB).

JNC 7: Classification and Management

of Blood Pressure for Adults

JNC 7. May 2003. NIH publication 03-5233.

JAMA. 2013;():. doi:10.1001/jama.2013.284427

Guideline Population Goal BP,

mm Hg

Initial Drug Treatment Options

JNC 82014 Hypertension

guideline

General ≥60 y <150/90 Nonblack: thiazide-type diuretic, ACEI, ARB, or CCB

General <60 y <140/90 Black: thiazide-type diuretic or CCB

Diabetes <140/90 Thiazide-type diuretic, ACEI, ARB, or CCB

CKD <140/90 ACEI or ARB

NICE 2011 General <80 y <140/90 <55 y: ACEI or ARB

General ≥80 y <150/90 ≥55 y or black: CCB

KDIGO 2012 CKD no

proteinuria

≤140/90 ACEI or ARB

CKD + proteinuria ≤130/80

12

24 hour BP variabillity associated with

increased target organ damage

- During the course of 24 hours, BP fluctuate dramatically, starting with a rapid rise in the morning between 6am and 10 am and falling at night

-Even though office BP is controlled, many patients may still have uncontrolled early morning BP

- Acute Myocardial Infarction has been shown to be three times more common at 9 am than at 11 pm

- 44% of Ischaemic strokes occur in the morning period

Mead M,et al.Br J Cardiol 2008,15:31-34

ARB’s were associated with the lowest rate

of discontinuation

ARB, angiotensin II receptor blocker; CI, confidence interval* Relative to ACE inhibitors after 1 year of treatment

0.5 1.0 2.0

Diuretics

β-blockers

α-blockers

Calcium channel blockers

ACE inhibitors

ARBs

1.83 (1.81-1.85)

1.64 (1.62-1.67)

1.23 (1.20-1.27)

1.08 (1.06-1.09)

1.00 (reference)

0.92 (0.90-0.94)

- +Cause-specific hazard ratio (95% CI) for discontinuation*

Total n = 445,356

Mancia G,et al.European heart journal supplements 2009;11:1093

HR CI

Cohort study in Lombardia,

Italy, in 445,356 subjects

aged 40–80 years.1

MICARDIS unique molecular structures :

Unique pharmacokinetic properties &

pharmacodynamic effects

As evidenced, differences of MICARDIS was :

lipid solubility, volume of distribution, bioavailability, plasma half life,

receptor-binding affinity, and different ways of elimination

Verdecchia, et al.Expert review of clinical pharmacology 2011,4(2):151-161

MICARDIS® Telmisartan is a long-lasting ARB that

effectively controls BP over the full 24-hour period

Asmar M.European Cardiology 2012;8:10-16

DBP change from baseline (mmHg)

-14

-12

-10

-8

-6

-4

-2

0Telmisartan 80 mg

Ramipril 10 mg

Time after dosing (h)

2 4 10 14126 8 16 18 20 22 24

Chambers S.Drugs in context 2008;4(1):1-14;

Telmisartan is superior to ramipril

in 24 hour ABPM reduction

*** P<0.0001 24-h mean Telmisartan vs Ramipril

***

PRISMA II

(n = 405)

(n = 407)

Study PRISMA II

-14

-12

-10

-8

-6

-4

-2

0

Valsartan 160 mg

Telmisartan 80 mg

Telmisartan is superior to Valsartan

in 24 hour ABPM reduction especially in last 6 hours

P values are for Telmisartan vs Valsartan comparison

Pooled analysis of two independent studies (MICADO I & II)

Lacourcière et al. Blood Press Monit 2004:9;203–210

P = 0.0286

P=0.0040 P = 0.0002

P < 0.0001

SBP change from baseline (mmHg)

Time after dosing (h)

2 4 10 14126 8 16 18 20 22 24

(n = 430)

(n = 447)

The cardiovascular and renal continua of disease & studies evaluating the

efficacy of Telmisartan

Galzerano D,et al.Vascular health and risk management 2010;6:113-133

20

Lo-

sartan

Epro-

sartan

Irbe-

sartan

Olme-

sartan

Val-

sartan

Cande-

sartan

Telmi-

sartan

Hypertension ✔ ✔ ✔ ✔ ✔ ✔ ✔

Treatment of renal disease ✔ ✔

Prevention of stroke in LVH ✔

High cardiovascular risk ✔

Type 2 diabetes with target

organ damage✔

Atherothrombotic CVD,e.g.,

corinary heart disease ✔

Peripheral vascular disease ✔

Stroke

HF or LV dysfunction ✔ ✔ ✔

Telmisartan, with the broadest CV prevention in class (based on the ONTARGET trial program)

Asmar M.European Cardiology 2012;8:10-16

Summary

1. Hypertension is the most powerful risk factor for the cardiovascular

diseases, including stroke, coronary aretery disease, heart failure, chronic

kidney disease, aortic and peripheral arterial diseases1

2. “Uncontrolled” and “Untreated” hypertension was associated with

increased risk of total and cardiovascular mortality2

3. Antihypertensive agents that minimise the fluctuations in BP observed

over a 24-hour cycle are likely to be most effective in maintaining

reductions in BP and potentially offer the greatest cardiovascular

protection3

4. Telmisartan’s unique pharmacological profile, including highest receptor

affinity, most lipophilic, a long elimination half life (24-h), results in an

sustained control of BP over a 24-hour throughout the once-daily dosing

interval4

5. The powerful and sustained BP control, together with broadest

cardiovascular protection and also better tolerability of Micardis®

(Telmisartan) demonstrated in “ONTARGET” study5

Reference

1.Kario K,et al.Hypertension 2010;56:765-773

2.Gu Q, et al. Am J Hypertens 2010;23(1):38-45

3.Battershill AJ,et al.Drugs 2006;66(1):51-83

4.Verdecchia, et al.Expert review of clinical pharmacology 2011,4(2):151-161

5.Galzerano D,et al.Vascular health and risk management 2010;6:113-133