Transcript Curriculum Vitae • • • • • Nama : Dr. Masrul Syafri SpPD, SpJP (K), FIHA Tempat & Tanggal Lahir : Padang, 14 Oktober 1962 Jabatan : Ketua.

Curriculum Vitae
•
•
•
•
•
Nama : Dr. Masrul Syafri SpPD, SpJP (K), FIHA
Tempat & Tanggal Lahir : Padang, 14 Oktober 1962
Jabatan : Ketua Bagian Kardiologi & Kedokteran Vaskuler FK UNAND Padang
Pendidikan
1.
2.
3.
Dokter Umum : FK UNAND 1982 – 1989
Dokter Spesialis Penyakit Dalam : FK UNAND 1994-1999
Dokter Spesialis Penyakit Jantung dan Pembuluh Darah : FKUI 2003-2006
Pekerjaan
1.
2.
3.
4.
Kepala Puskesmas Matur 1990 - 1993
RSUD Muara Labuh 2000 – 2002
RS PJNHK 2003-2006
RS Dr. M. Djamil Padang 2006 - sekarang
The Use of Single Pill Combination Therapy
as a New Paradigm for the Modern Clinical Management of
Hypertension
Masrul Syafri, MD
RS. M Djamil
Padang
The Use of Single Pill Combination Therapy
as a New Paradigm for the
Modern Clinical Management of Hypertension
Agenda
Introduction & Background
Single Pill Combination Concept & Why ARB+CCB
Telmisartan+Amlodipine Clinical Studies
Summary
Adult Population with
Hypertension
Percentage of Adult Population with Hypertension in
Indonesia
Only 24%
Aware of
Hypertensive
Status
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
44.3
39.8
42.0
Myanmar
(37.7-50.5)
(33.1-46.5)
(37.2-46.8)
42.7
39.2
41.0
Indonesia
(35.3-49.9)
(32.5-46.0)
(35.9-45.8)
36
34.2
35.2
India
(29.7-41.8)
(28.6-39.9)
(30.9-35.2)
37.0
31.6
34.2
Thailand
(31.3-42.5)
(26.0-37.1)
(30.0-38.1)
37.6
35.4
36.6
Asia Tenggara
(32.6-42.4)
(30.9-39.8)
(33.1-39.8)
40.8
36.0
38.4
Global
(37.7-43.7)
(33.3-38.6)
(36.3-40.5)
Krishnan A. Regional Health Forum. Vol 17, Number 1;2013;7-11
Classification of Blood Pressure (JNC 7)
BP category
Normal
SBP
(mmHg)
DBP
(mmHg)
<120
and
<80
Pre-hypertension
120–139
or
80–89
Stage 1
140–159
or
90–99
Stage 2
160
or
100
Chobanian A et al. JAMA 2003. 289:2560-72
2014 Hypertension Guideline Management Algorithm
(JNC 8)
James P et al. JAMA. 2013;289: E1-E14
James P et al. JAMA. 2013;289: E1-E14
The Relationship Between BP and Risk of CVD events
Benefits of Lowering BP
35-40%
Stroke
Incidence
50 %
HF
20-25 %
MI
*Individuals aged 40-70 years, from BP
115/75 mm Hg to 185/115 mmHg.
Chobanian A et al. JAMA 2003. 289:2560-72
Rate of Controlled Patients
28% -------------------------------Unaware of their
hypertension
39% -------------------------------Not Receiving therapy
65% -------------------------------Do not have their BP
controlled to levels below
140/90 mmHg
Chobanian A.. NEJM 2009. 361:878-87
Poor Compliance with Antihypertensive Treatment
24-51%
29-58%
Noncompliant
Nonpersistent
- 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
Barkas F, et al. Hellenic Journal of Atherosclerosis 1 (1):1825
Guidelines worldwide Acknowledge That Most Patients Need
Combination Therapy to Achieve BP Goals
•
JNC 8 ; 20141
Initiate therapy with ≥ 2 drugs simultaneously
•
If SBP is > 20 mmHg above goal and/or DBP is > 10 mmHg
above goal
ESH/ESC 20132
•
Combination of two antihypertensive drugs at fixed doses in a
single tablet may be recommended and favoured, because
reducing the number of daily pills improves adherence, which
is low in patients with hypertension.
ASH/ISH Hypertension Guidelines 20133
•
If the untreated blood pressure is at least 20/10 mmHg above the
target blood pressure, consider starting treatment immediately
with 2 drugs
1. James P et al. JAMA. 2013;289: E1-E14
2. Mancia et al. Jounal of Hypertension 2013. 31:1281-1357
3. Weber M et al. The Journal of Clinical Hypertension. 2013. 1-13
Mancia et al. Jounal of Hypertension 2013. 31:1281-1357
ARB+CCB is one of the preffered
antihypertensive combination
Agenda
Introduction & Background
Single Pill Combination Concept & Why ARB+CCB
Telmisartan+Amlodipine Clinical Studies
Summary
Pros and cons of
Monotherapy and combination therapy
Monotherapy
1.Monotherapy can effectively reduce BP in only a limited number of hypertensive
patients1
Combination Therapy
1.The most patiens 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 thant those offered by a single agent.
(e.g : RAAS + CCB reduces oedema) 1
6.Convinient once-daily administration of a single tablet, with potential compliance
benefits2
7.Effectively lowers BP in patients with an inadequate response to monotherapy2
1.
Mancia et al. Jounal of Hypertension 2013. 31:1281-1357
2. Drugs The Perspect 2011;Vol.27. No. 5
Loose Combination or
Single-pill Combination ?
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
1.
Mancia et al. Jounal of Hypertension 2013. 31:1281-1357
2. Suarez C. Drugs 2011. 71(17):2295-2305
3. Drugs The Perspect 2011;Vol.27. No. 5
Benefits of Single Pill Combination Concept
Single Pill Combination
Good levels of compliance
More rapid and sustained BP control
Reduce cardiovascular morbidity & mortality
1.
Mancia et al. Jounal of Hypertension 2013. 31:1281-1357
2. Suarez C. Drugs 2011. 71(17):2295-2305
3. Volpe M, et al. European Journal of Cardiovascular Medicine 2012, 2:1:90-97
Fixed-dose Combinations Provide a Strong
Armamentarium in Chronic Disease Management
Non-compliance
to medication
regimens is
reduced by
24-26%
with fixed-dose
combinations
regimens
Effect of fixed-dose combination vs free-drug combination on the risk of medication non-compliance in
cohort with hypertension
Bangalore S et al. The American Journal of Medicine (2007) 120, 713-719
Why ARB + CCB ???
Natriuresis
Vasodilation
Arterial
Arterial +
Venous
CCB
ARB  RAS inhibition
↑RAS ↑SNS
Peripheral Oedema
↓RAS ↓SNS
Attenuates peripheral oedema
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 profile
4.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
Suarez C. Drugs 2011. 71(17):2295-2305
CCB + ARB :
The Synergies of Counter-Regulation
CCB
 Vasodilation of the arterioles
 Activating the SNS
BP
ARB
 Attenuates peripheral oedema
Synergistic
BP reduction
Complementary
clinical benefits
ARB
 RAS blockade
 CHF and renal
benefits
CCB
 RAS activation
 No renal or CHF
benefits
Suarez C. Drugs 2011. 71(17):2295-2305
Telmisartan : No Posology Adjustment is Required for
Patients with Renal Impairment, including those on
Haemodialysis
Drug
Elimination
(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*
*For Intravenous olmesartan
1. Local Product Information of Micardis, 2014
2. Adapted from Verdecchia., et al. Expert Rev. Clin. Pharmacol. 4(2). 151-161 (2011)
Plasma elimination half-life (h)
Amlodipine – The longest Half-life in Class
35
50
30
25
20
16
15
12
8
10
5
2
2
0
Nifedipine Nimodipine Nicardipine Nisoldipine Felodipine Amlodipine
Abernethy et al. The new England Journal of Medicine 1999. 341(9):1447-57
Effects of CCB & RAS
on Capillary Pressure and Oedema Formation
a
CCB monotherapy
Arteriolar vasodilation
Venous resistance unchanged
Increased
capillary
pressure
Oedema formation
b RAS inhibitor + CCB
Arteriolar vasodilation
Venous vasodilation
Capillary
pressure
lower than
in A
CCB monotherapy
-Selective vasodilation of the
arteriolar side of the circulation
-Increased pressure within the
capillary bed, leading to fluid
transudation and oedema formation
ARB + CCB
(Telmisartan+Amlodipine)
-Cause both arteriolar and venous
vasodilation
-Reduces the pressure within the
capillary bed, thereby ameliorating
the oedema
Oedema formation reduced
Sierra. Journal of Human Hypertension 2009. 23:503-511
Agenda
Introduction & Background
Single Pill Combination Concept & Why ARB+CCB
Telmisartan+Amlodipine Clinical Studies
Summary
PLEASE INSERT Presentation title
07 November 2015
27
PLEASE INSERT Presentation title
07 November 2015
28
Neutel et al. The Journal of Clinical Hypertension 2012; 14:206-215
Telmisartan + Amlodipine
Provides 80% of its Maximum Effect After Just 2 Weeks of Treatment
Mean SBP reduction (mmHg)
T80/A10
Mean SBP (mmHg)
185.4
(n =379)
Baseline
80%*
Week 2
147.5
–47.5 mmHg
137.9
Week 8
* Percentage of effect achieved after 2 weeks of treatment compared with
end of study (Week 8)
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
Neutel J et al. The Journal of Clinical Hypertension. April 2012
30
PLEASE INSERT Presentation title
07 November 2015
31
-
PLEASE INSERT Presentation title
07 November 2015
32
Agenda
Introduction & Background
Single Pill Combination Concept & Why ARB+CCB
Telmisartan+Amlodipine Clinical Studies
Summary
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 of
hypertension 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 distribution 6
•
Amlodipine has the longest half life in class 7
•
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
•
, reduced CV risk
1. Krishnan A. Regional Health Forum. Vol 17, Number 1;2013;7-11
2. James P et al. JAMA. 2013;289: E1-E14
3. Mancia et al. Jounal of Hypertension 2013. 31:1281-1357
4. Weber M et al. The Journal of Clinical Hypertension. 2013. 1-13
5. Suarez C. Drugs 2011. 71(17):2295-2305
6. Adapted from Verdecchia., et al. Expert Rev. Clin. Pharmacol. 4(2). 151-161 (2011)
7. Abernethy et al. The new England Journal of Medicine 2009. 341:1447-57
8. Little john et al. J. Clin. Hyp 2009: 11:207-213
Thank You