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

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

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.


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

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