Y HỌC CHỨNG CỨ CỦA THUỐC HẠ ÁP PHỐI HỢP LiỀU CỐ ĐỊNH

Y HỌC CHỨNG CỨ CỦA
THUỐC HẠ ÁP PHỐI HỢP
LiỀU CỐ ĐỊNH
PGS. TS. BS. Trương Quang Bình
BỘ MÔN NỘI – ĐHYD
KHOA TIM MẠCH – BV ĐHYD
JNC 7 Algorithm for Treatment of
Hypertension (2003)
Combination
Combination
Combination therapy is more effective
than increasing the dose of one drug

“Giảm tác dụng phụ”
Beta-blocker Diuretic ACE-I ARBs CCB
Combination therapy is better than monotherapy !

Which Antihypertensive Drug
Combinations Should be Used?
Good Combination?
Bad Combination
Good Combination
JNC 7 Algorithm for Treatment of
Hypertension (2003)
2-drug combination for most
(usually thiazide-type diuretic
and ACEI, or ARB, or BB, or
CCB)
ASCOT- BPLA
So sánh hiệu quả trên NMCT không tử

vong và tử vong của chế độ điều trị
tăng HA chuẩn (betablocker ± diuretic)
với chế độ điều trị mới (CCB ± ACE
inhibitor)
Mục tiêu nghiên cứu chính
NMCT không tử vong + tử vong do BMV
Number at risk
Amlodipine  perindopril 9639 9485 9354 9193 8998 7895

Atenolol  thiazide 9618 9475 9302 9099 8881 7768
0.0 1.0
2.0
3.0
4.0
5.0
Naêm
0.0
1.0
2.0
3.0
4.0
5.0
HR = 0.87 (0.761.00)
p = 0.0458
Atenolol  thiazide
(Soá bieán coá 444)
Amlodipine  perindopril
(Soá bieán coá 390)
%
-5

0
5
10
15
ACE inhibitors
0.2
0.4
0.6
0.8
1.0
1.2
1.4
1.8
2.0
Odds ratio for CHD
PEACE
UKPDS39
PROGRESS
PROGRESSCom
CAPPP
ALLHAT/ACEI
STOP2/ACEI
ANBP2
CAMELOT
EUROPA
HOPE
Hypertension. 2005;46:386-392.
Systolic BP difference between randomised groups (mmHg)
Calcium channel blockers
-5

0
5
10
15
INSIGHT
NICOLE
NORDIL
STOP2/CCB
ACTION
PREVENT
SYST-EUR
SYST-China
CAMELOT
IDNT2
STONE
CONVINCE
VHAS
ALLHAT/CCB
INVEST
NICS
ELSA
SHELL
MIDAS
0.2
0.4
0.6
0.8
1.0
1.2
1.4

1.8
2.0
Odds ratio for stroke
Benefits beyond BP reduction
ACE inhibitors in CHD

CCBs in stroke
Kaplan Meier for Primary Endpoint:
Cardiovascular Mortality and Morbidity
Cumulative event rate
HR (95% CI): 0.80 (0.72, 0.90)
20% Risk Reduction
Time to 1
st
CV morbidity/mortality (days)
p = 0
ACEI / HCTZ

CCB / ACEI

650
526
.0 0 0 2
Mar 08
16
BHS 2011 GUIDELINE
- There is no reason to continue to prefere
diuretics for initial therapy.

- Combination therapy is better than monotherapy.

- Combination therapy with an ACEi and
Amlodipine is superior to diuretic based
combination in reducing CV morbidity and
mortality in high risk patients.


Good Combination
ACEi /ARB
+
CCB
Combination therapy is better than
monotherapy !
Free
or
fixed dose combination ???
20
Branded FDC Products Containing an
ARB and Amlodipine
 COZAAR XQ (Amlodipine Camsylate and Losartan
Potassium)
 EXFORGE (Valsartan and Amlodipine Besylate)
 AZOR (Olmesartan Medoxomil and Amlodipine Besylate)
 TWYNSTA (Telmisartan and Amlodipine Besylate)
ARB = angiotensin receptor blocker; CCB = calcium channel blocker.
21
-15
-9
-3

Mean change (mm Hg)
P < 0.0001
–11.7
–3.2
–3.4
–13.4
P < 0.0001
Losartan + Amlodipine FDC* in Uncontrolled on Losartan 100 mg
Mean Reductions in DBP (Primary Endpoint) and SBP
Mean SBP Reductions
Losartan
100 mg
Mean BP Reductions at 8 weeks (N=142)
Losartan
100 mg
Mean DBP Reductions
Amlo/Losartan FDC
5/100 mg
Amlo/Losartan FDC
5/100 mg
22
*The rate of patients who achieved any of the following predefined targets: 1) systolic BP <140 mm Hg or diastolic BP
<90 mm Hg, 2) a reduction in systolic BP >20 mm Hg from baseline, or 3) a reduction in diastolic BP >10 mm Hg from baseline.
Data on file, MSD
*COZAAR XQ, MSD
Losartan + Amlodipine FDC* in Uncontrolled on Losartan 100 mg
Losartan 100 mg Additional Efficacy Results
90%
Losartan
100 mg

66.7%
Amlo/ Losartan FDC
5/100 mg
Patients, %
Blood Pressure Response Rates*

P < 0.0008
0
20
40
60
80
100
23
*The rate of patients who achieved any of the following predefined targets: 1) systolic BP <140 mm Hg or diastolic BP <90 mm Hg,
2) a reduction in systolic BP >20 mm Hg from baseline, or 3) a reduction in diastolic BP >10 mm Hg from baseline.
89.1%
Amlodipine
10 mg
Patients, %
Blood Pressure Response Rates*

P < 0. 07960
87.9%
Losartan + Amlodipine FDC* in Uncontrolled on Amlodipine 5 mg
Additional Efficacy Results
0
20
40
60

80
100
Kang S-M et al. Clin Ther 2011;33(12):1953-1963.
Amlo/Losartan FDC
5/50 mg
Increased Persistence with Fixed-dose
Combinations Compared with Individual
Component-based Therapy
54%
19%
0% 20% 40% 60% 80%
Fixed-dose
combination
(Valsartan/HCTZ)
(n=8,150)
Free combination
(Valsartan + HCTZ)
(n=561)
Persistence (defined as patients remaining on treatment
for a duration of 12 months)
Jackson et al. Value Health Suppl 2006;9:A363
p<0.0001

†
Defined as the total number of days of therapy for
medication dispensed/365 days of study follow-up
Fixed-dose combination
(amlodipine/benazepril)
(n=2,839)
Free combination

(ACEI + CCB)
(n=3,367)
Medication possession ratio (MPR)
†
Wanovich et al. Am J Hypertens 2004;17:223A (poster)
p<0.0001
Improved Compliance with Fixed-dose Combination Therapy
Compared with Free-combination Therapy
88.0%
69.0%
0% 20% 40% 60% 80% 100%