5.2 BP Variability Single Pill Combination - Dr. Budi Bakti Sp.jp(1)
Transcript of 5.2 BP Variability Single Pill Combination - Dr. Budi Bakti Sp.jp(1)
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Telmisartan + Amlodipine Clinical Studies
Single Pill Combination Concept & Why ARB + CCB
Summary
Introduction & Background
Agenda
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Telmisartan + Amlodipine Clinical Studies
Single Pill Combination Concept & Why ARB + CCB
Summary
Introduction & Background
Agenda
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Krishnan A. Regional Health Forum. Vol 17, Number 1;2013;7-11
WHO Age-standardized Estimates of the Prevalence of
Hypertension in Sout East Asia Region
Estimates of age-standardized prevalence (%) of raised blood pressure in adults aged 25+
years in countries of the SEA Region, 2008
Country Men Women Both
Myanmar44.3
(37.7-50.5)
39.8
(33.1-46.5)
42.0
(37.2-46.8)
Indonesia 42.7(35.3-49.9)
39.2(32.5-46.0)
41.0(35.9-45.8)
India36
(29.7-41.8)
34.2
(28.6-39.9)
35.2
(30.9-35.2)
Thailand37.0
(31.3-42.5)
31.6
(26.0-37.1)
34.2
(30.0-38.1)
Asia Tenggara37.6
(32.6-42.4)
35.4
(30.9-39.8)
36.6
(33.1-39.8)
Global40.8
(37.7-43.7)
36.0
(33.3-38.6)
38.4
(36.3-40.5)
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Chobanian A et al. JAMA 2003. 289:2560-72
Classification of Blood Pressure (JNC 7)
BP categorySBP
(mmHg)
DBP
(mmHg)
Normal
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James P et al. JAMA. 2013;289: E1-E14
2014 Hypertension Guideline Management Algorithm (JNC
8)
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2014 Hypertension Guideline Management Algorithm (JNC
8)
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The Relationship Between BP
and Risk of CVD events
*Individuals aged 40-70 years, from BP
115/75 mm Hg to 185/115 mmHg.
Benefits of Lowering BP
35-40%
Stroke
Incidence20-25 %
MI
50 %
HF
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Rate of Controlled Patients
28% ---------------------------------
Unaware of their
hypertension
39% ---------------------------------
Not Receiving therapy
65% ---------------------------------
Do not have their BPcontrolled to levels below
140/90 mmHg
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Poor Compliance with Antihypertensive Treatment
24-51%
Non-
compliant
29-58%
Non-
persistent
- 1/3 – 1/2 patients in US & Canada
with inadequately BP control
- 40-66% with concurrent
hypertension & diabetes
- In Euro : > 2/3 of treated patients
with inadequately BP control
Consequences of poor adherence &
compliance
- Encompasses a higher risk of CVD,
hospitalization and increased
health care utilization cost- Nonpersistence
↑ 15% AMI, ↑ 28% Stroke
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Guidelines worldwide Acknowledge That Most Patients
Need Combination Therapy
to Achieve BP Goals
1. James P et al. JAMA. 2013;289: E1-E142. Mancia et al. Jounal of Hypertension 2013. 31:1281-13573. Weber M et al. The Journal of Clinical Hypertension. 2013. 1-13
• Initiate therapy with ≥ 2 drugs simultaneously
– If SBP is > 20 mmHg above goal and/or DBP is > 10 mmHg
above goal
• Combination of two antihypertensive drugs at fixed doses in a
single tablet may be recommended and favored, because
reducing the number of daily pills improves adherence, which is
low in patients with hypertension.
• If the untreated blood pressure is at least 20/10 mmHg above the
target blood pressure, consider starting treatment immediately
with 2 drugs
JNC 8; 20141
ESH/ESC 20132
ASH/ISH Hypertension Guidelines 20133
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2013 ESH-ESC Guidelines for Arterial Hypertension:
Choice of antihypertensive drugs
Mancia et al. Jounal of Hypertension 2013. 31:1281-1357
ARB+CCB is one of the preffered
antihypertensive combination
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Telmisartan + Amlodipine Clinical Studies
Single Pill Combination Concept & Why ARB + CCB
Summary
Introduction & Background
Agenda
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Monotherapy
1. Monotherapy can effectively reduce BP in only a limited number of hypertensive patients1
Combination Therapy
1. The most patients require the combination of at least two drugs to achieve BP control1
2. The advantage of initiating with combination therapy is potentially beneficial in high-risk
patients1
3. A greater probability of achieving the target BP in patients with higher BP values and a lower
probability of discouraging patient adherence with many treatment changes1
4. Lower drop-out rate than patients given any monotherapy1
5. Fewer side effects and provide larger benefits than those offered by a single agent. (e.g :
RAAS + CCB reduces oedema) 16. Convenient once-daily administration of a single tablet, with potential compliance benefits2
7. Effectively lowers BP in patients with an inadequate response to monotherapy2
Pros and cons of
Monotherapy and combination therapy
Mancia et al. Jounal of Hypertension 2013. 31:1281-1357Drugs The Perspect 2011;Vol.27. No. 5
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Loose Combination or
Single-pill Combination ?
Mancia et al. Jounal of Hypertension 2013. 31:1281-1357Suarez C. Drugs 2011. 71(17):2295-2305Drugs The Perspect 2011;Vol.27. No. 5
Single-pill combination (SPC)1. Reducing the number of pills to be taken daily improves
adherence/patient compliance (Simplify treatment regimens) 1,2,3
2. Provide superior BP-lowering Efficacy2
3. Increases the rate of BP control1
4. Enhanced patient adherence2
5. Reducing healthcare costs3
6. Improved tolerability profile2
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Benefits of Single Pill Combination Concept
Mancia et al. Jounal of Hypertension 2013. 31:1281-1357Suarez C. Drugs 2011. 71(17):2295-2305Drugs The Perspect 2011;Vol.27. No. 5
Single Pill Combination
Good levels of compliance
More rapid and sustained BP control
Reduce cardiovascular morbidity & mortality
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Fixed-dose Combinations Provide a Strong Armamentarium
in Chronic Disease Management
Bangalore S et al. The American Journal of Medicine (2007) 120, 713-719
Effect of fixed-dose combination vs free-drug combination on the risk of
medication non-compliance in cohort with hypertension
Non-compliance
to medication
regimens is
reduced by24-26%
with fixed-dose
combinations
regimens
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Why ARB + CCB ???
Suarez C. Drugs 2011. 71(17):2295-2305
The advantages of ARB+CCB :
1. Synergistic mechanism of action
2. Vascular protective effects due to the improvement in endothelial dysfunction
3. A neutral metabolic profile4. Nephroprotective effect due to its capacity to dilate the renal arterioles
5. Reduced incidence of oedema secondary to the use of CCBs
6. Greater capacity to reduce morbidity/mortality rates in high-risk hypertensive patients than the
RASI-diuretic combination
Natriuresis
Vasodilation
CCB ARB RAS inhibition
↓RAS ↓SNS
Attenuates peripheral oedema
↑RAS ↑SNS
Peripheral Oedema
ArterialArterial +
Venous
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Effects of CCB & RAS
on Capillary Pressure and Oedema Formation
Sierra. Journal of Human Hypertension 2009. 23:503-511
CCB monotherapy
• Selective vasodilation of the
arteriolar side of the circulation
• Increased pressure within the
capillary bed, leading to fluidtransudation and oedema
formation
ARB + CCB (Telmisartan+Amlodipine)
• Cause both arteriolar and venous
vasodilation• Reduces the pressure within the
capillary bed, thereby ameliorating
the oedema
Increased
capillary
pressure
Capillarypressure
lower than
in A
a
b
CCB monotherapy
Arteriolar vasodilationVenous resistance
unchanged
Arteriolar vasodilation Venous vasodilation
RAS inhibitor + CCB
Oedema formation
Oedema formation
reduced
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Telmisartan has Unique Pharmacology among ARBs
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Telmisartan : No Posology Adjustment is Required for
Patients with Renal Impairment,
including those on Haemodialysis
DrugElimination
(feces/urine)
Telmisartan >98% fecal
Losartan 60/35
Valsartan 83/13
Irbesartan 80/20
Candesartan 67/33
Eprosartan 90/10
Olmesartan 35-49% urinary recovery rate*
1. Local Product Information of Micardis, 20142. Adapted from Verdecchia., et al. Expert Rev. Clin. Pharmacol. 4(2). 151-161 (2011)
*For Intravenous olmesartan
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Amlodipine – The longest Half-life in Class
Abernethy et al. The new England Journal of Medicine 1999. 341(9):1447-57
P l a s m a e l i m i n
a t i o n h a l f - l i f e ( h )
2 2
8
12
16
50
0
5
10
15
20
25
30
35
Nifedipine Nimodipine Nicardipine Nisoldipine Felodipine Amlodipine
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Telmisartan + Amlodipine Clinical Studies
Single Pill Combination Concept & Why ARB + CCB
Summary
Introduction & Background
Agenda
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Telmisartan + Amlodipine: Provides consistent BP
Reductions across hypertension severities1,2
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Telmisartan + Amlodipine: Consistently High BP reductions
in added-risk Hypertensive Patients1
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Telmisartan + Amlodipine: Provides Significant Greater BP
Reductions Compared to Amlodipine monotherapy after 1
week
Neutel et al. The Journal of Clinical Hypertension 2012; 14:206-215
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Telmisartan + Amlodipine
Provides 80% of its Maximum Effect After Just 2 Weeks of
Treatment
Neutel J et al. The Journal of Clinical Hypertension. April 2012
A5 and T80/A5 for the first 2 weeks, then forced-titration to A10 and T80/A10, respectively;
baseline BP = 185.4/103.2 mmHg
* Percentage of effect achieved after 2 weeks of treatment compared with
end of study (Week 8)
M e a n S B P ( m m H g )
Mean SBP reduction (mmHg)
185.4
137.9Week 8
80%*
Week 2147.5
Baseline
–47.5 mmHg
T80/A10(n =379)
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Twynsta®: The BP reductions needed
to get hypertensive patients to goal1
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Incidence of peripheral oedema in hypertensive patients
treated for 8 weeks
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Telmisartan + Amlodipine Clinical Studies
Single Pill Combination Concept & Why ARB + CCB
Summary
Introduction & Background
Agenda
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Summary
• Hypertension is the single most important risk factor for mortality in South-East Asia (SEA) region1
• Guidelines on hypertension have consistently recommended early diagnosis and treatment ofhypertension in order to reduce cardiovascular morbidity and mortality2,3,4
• Single Pill Combination simplify treatment regimen, enhanced patient adherence and provide
superior BP-lowering efficacy and improved tolerability profile5
Why Telmisartan + Amlodipine, because:
• Telmisartan has the longest plasma half-life, and long duration of action, higher binding affinity
and longer blockade AT1 receptor, high lipophilicity and large volume distribution6
• Amlodipine has the longest half life in class7
• Twynsta reduces incidence of peripheral oedema in hypertensive patients up to 90%8
• Telmisartan + Amlodipine are well tolerated and provide the combined benefits of powerful BP
reduction and CV protection for difficult-to-manage patients with additional risk factors6
1. Krishnan A. Regional Health Forum. Vol 17, Number 1;2013;7-112. James P et al. JAMA. 2013;289: E1-E143. Mancia et al. Jounal of Hypertension 2013. 31:1281-13574. Weber M et al. The Journal of Clinical Hypertension. 2013. 1-13
5. Suarez C. Drugs 2011. 71(17):2295-23056. Adapted from Verdecchia., et al. Expert Rev. Clin. Pharmacol. 4(2). 151-161 (2011)