THE IMPORTANCE OF 24-HOUR BP CONTROL FOR MANAGING CV RISK dr. Hendro PIT VII IDI Kota Bogor, 1-2 November 2014

1. THE IMPORTANCE OF 24-HOUR BP CONTROL
FOR MANAGING CV RISK
Hendro Darmawan, 2 November 2014

3. 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
HTNglobally 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, WheltonM, Reynolds K, MuntnerP, WheltonPK, He J. Global burden of hypertension: analysis of worldwide data. Lancet. 2005 Jan 15-21;365(9455):217-23. GazianoTA, AsafB, S Anand, et.al. The global cost of nonoptimalblood pressure. J Hypertens2009; 27(7): 1472-1477.
1.6 Billion
HTN patients estimated by 2025
PrevalensiHipertensiRISKESDAS (2007) 31,7%  RISKESDAS (2013) 25.8%

4. 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
Telahmendapatterapiatauminumobatantihipertensi24.2 %
Yang terkontrol18 %
Yang belumterjangkaupelayanankesehatan75.8 % (RISKESDAS 2013)

5. 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

6. 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

7. Peripheral VascularResistance
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
Doumaset al. Am J Cardiol2010;105:570-576, Cleveland Clinic Journal of Medicine 2012; 79: 501-10

8. Risk Factors for Cardiovascular Disease
•Smoking
•Hyperlipidaemia
•High salt intake
•Homocysteinaemia
•Lack of exercise
•Obesity
•Diabetes
•Alcohol >4pints of beer/day
•Genetic

9. 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. 10
Initial Drug TherapyBP ClassificationSBP* (mm Hg) DBP* (mm Hg) Lifestyle ModificationWithout Compelling IndicationsWith Compelling IndicationsNormal<120and <80EncourageNo antihypertensive drug indicated. Drug(s) for compelling indications.Prehypertension120–139or 80–89YesStage 1 hypertension140–159or 90–99YesThiazide-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 hypertension 160or 100YesTwo-drug combinationfor most (usuallythiazide-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.

11. JAMA. 2013;():. doi:10.1001/jama.2013.284427
Guideline
Population
Goal BP,
mm Hg
Initial Drug Treatment Options
JNC 8
2014 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 orARB
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. 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

13. 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

14. 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

16. 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

17. DBP change from baseline (mmHg)
-14
-12
-10
-8
-6
-4
-2
0
Telmisartan 80 mg
Ramipril 10 mg
Time after dosing (h)
2 4 6 8 10 12 14 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

18. -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 6 8 10 12 14 16 18 20 22 24
(n = 430)
(n = 447)

19. 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. 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

21. 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