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

Combination therapy is more effective than increasing the dose of one drug... Beta-blocker Combination therapy is better than monotherapy!. †Defined as the total number of days of therap

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

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

2-drug combination for most (usually thiazide-type diuretic and ACEI, or ARB, or BB, or

CCB)

NMCT không tử vong + tử vong do BMV

HR = 0.87 (0.761.00)

p = 0.0458

Atenolol  thiazide (Soá bieán coá 444)

Amlodipine  perindopril

(Soá bieán coá 390)

%

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

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

Benefits beyond BP reduction

ACE inhibitors in CHD CCBs in stroke

Kaplan Meier for Primary Endpoint:

Cardiovascular Mortality and Morbidity

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

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

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

Losartan + Amlodipine FDC* in Uncontrolled on Losartan 100 mg

Mean Reductions in DBP (Primary Endpoint) and SBP

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

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

Losartan + Amlodipine FDC* in Uncontrolled on Amlodipine 5 mg

Additional Efficacy Results

Increased Persistence with Fixed-dose

Combinations Compared with Individual

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%

*p<0.0001

Number of concomitant drugs

Gerbino & Shoheiber Am J Health System Pharm 2007;64:1279–83

Viên phối hợp gia tăng tuân trị

bất kể số thuốc dùng kèm

Taylor et al Congest Heart Fail 2003;9:324–32

A large managed care database analysis (n=5,732)

44 39

36 30

27

1–19 20–39 40–59 60–79 80–100

Breekveldt-Postma et al Curr Med Res Opin 2008;24:121–7

 77,193 new users of antihypertensive treatment were identified in the

PHARMO record linkage system

CI = confidence interval; IR = incidence rate; MI = myocardial infarction; PY = person-years; RR = relative risk

*adjusted for gender, age, type of prescriber, use of cardiovascular co-medication, initial antihypertensive therapy, number of different

antihypertensive classes during the first 2 years of therapy

Kiên trị tốt điều trị THA làm giảm nguy cơ nhập viện do nhồi máu cơ tim và đột qụy

1,120 3,179

0 2,000

Dickson & Plauschinat Am J Cardiovasc Drugs 2008;8:45–50

*Lower doses generally used in fixed-dose combinations

+ = potential advantage

Advantages of Fixed Versus Free Combinations

of Two Antihypertensive Drugs

The 2012 CHEP Recommendations

VỀ PHỐI HỢP THUỐC

* Điều trị BN tăng HA kèm bệnh tim thiếu máu cục bộ

Trên những BN nguy cơ cao này, nếu cần phối hợp thuốc thì UCMC + dihydropyridine CCB được ưa chuộng hơn UCMC + lợi tiểu

* BN tăng HA kèm đái tháo đường

Trên BN có chỉ định sử dụng UCMC hoặc UCTT, phối hợp với

dihydropyridine CCB được khuyên sử dụng hơn là phối hợp với lợi tiểu thiazide hoặc giống thiazide (thiazide – like)

* Sự tuân thủ điều trị tăng HA có thể được cải thiện khi sử dụng tiếp cận đa mục tiêu bao gồm….thay thế việc phối hợp các viên thuốc rời bằng 1 viên phối hợp

KẾT LUẬN

• Phối hợp thuốc đóng vai trò tối quan trọng

trong việc kiểm soát HA

• Công thức phối hợp hiện nay:

• ACEi/ARB + Amlodipine

• Viên phối hợp liều cố định có lợi hơn phối hợp

tự do