The Moral of the Tale

As long as we reach the objective BP below 140/90 (130/80), it doesn’t matter how we get there

ALLHAT (JAMA 2002)

“The key message from ALLHAT is that what matters most is getting blood pressure controlled’’

A synergy in Mechanism of Action

3Ferrari R. Optimizing the treatment of hypertension and stable coronary artery disease:

clinical evidence for fixed-combination perindopril/amlodipine. Curr Med Res Opin. 2008;24:3543-3557.

ACE Inhibitor

Perindopril

Induction of relaxation

= Vasodilation

CCB

Amlodipine

Prevention of constriction

= Vasodilation

ESHESC Recommendations for Combining BP-lowering Drugs

Mancia et al. European Heart Journal 2013:1-72

PROGRESS

ADVANCE

HYVET

FEVER

ELSA

VALUE

LIFE

SCOPE

ACCOMPLISH

ASCOT

INVEST

“Until now, no outcome study has been

conducted using the combination of

an angiotensin receptor antagonist

with a calcium antagonist.”

ACCOMPLISH: A Novel Hypertension Trial

• Traditional approach to hypertension management:

– Initiate monotherapy then sequentially add medications to achieve target BP

• ACCOMPLISH:

– Initiate single tablet combination therapy in high-risk hypertension

– Specific combinations may confer target organ protection in addition to their BP-lowering effects

Kaplan Meier for Primary EndpointC

um

ula

tive e

vent

rate

HR (95% CI): 0.80 (0.72, 0.90)

20% Risk Reduction

Time to 1st CV morbidity/mortality (days)

p = 0

ACEI / HCTZ

CCB / ACEI650

526

.0002

INTERIM RESULTS Mar 08

B.Dahlof (Co-chair), P.Sever (Co-chair), N. Poulter (Secretary)

H. Wedel (Statistician), G. Beevers, M. Caulfield, R. Collins

S. Kjeldsen, A. Kristinsson, J. Mehlsen, G. McInnes, M. Nieminen

E. O’Brien, J. Östergren, on behalf of the ASCOT Investigators

A randomised controlled trial of the prevention of CHD and other vascular events by BP and cholesterol lowering in a factorial

study design

• Different components of antihypertensive efficacy have an

independent predictive value

1. Ohkubo DT, et al. The Ohasama study. J Hypertens. 2000;18:847–854. 2. Yamamoto Y, et al. Stroke. 1998; 29:570–576.

3. Ohkubo T et al. J Hypertens. 2002;20:2183–2189. 4. Stanton A, et al. Blood Press. 1993;2:289–295. 5. Pedersen OL? et

al. VALUE trial group. J Hypertens. 2007; 25:707–712.

Anti-Hypertensive Efficacy

Antihypertensive

Efficacy

Brachial

BP

Central

BP

BP

Variablilty

Nocturnal

BP

12

Early & Strong BP Reduction

Bahl UK. Fixed dose perindopril and amlodipine in moderate-to-severe hypertension. 14th World Congress of Heart Disease 2008, Toronto, Canada.

Perindopril+Amlodipine

n= 1 250> 160mmHg

n= 161> 180mmHg

• Different components of antihypertensive efficacy have an

independent predictive value

Antihypertensive Efficacy

Antihypertensive

Efficacy

Brachial

BP

Central

BP

BP

Variablilty

Nocturnal

BP

1. Ohkubo DT, et al. The Ohasama study. J Hypertens. 2000;18:847–854. 2. Yamamoto Y, et al. Stroke. 1998; 29:570–576.

3. Ohkubo T et al. J Hypertens. 2002;20:2183–2189. 4. Stanton A, et al. Blood Press. 1993;2:289–295. 5. Pedersen OL? et

al. VALUE trial group. J Hypertens. 2007; 25:707–712.

Perindopril-Amlodipine : Superior night-time SBP control

Better night-time BP control is

related to better survival rates

Dolan E et al; on behalf of the ASCOT Investigators. J Hypertens. 2009,27:876–885.

AMBP

• Different components of antihypertensive efficacy have an

independent predictive value

Antihypertensive Efficacy

Antihypertensive

Efficacy

Brachial

BP

Central

BP

BP

Variablilty

Nocturnal

BP

1. Ohkubo DT, et al. The Ohasama study. J Hypertens. 2000;18:847–854. 2. Yamamoto Y, et al. Stroke. 1998; 29:570–576.

3. Ohkubo T et al. J Hypertens. 2002;20:2183–2189. 4. Stanton A, et al. Blood Press. 1993;2:289–295. 5. Pedersen OL? et

al. VALUE trial group. J Hypertens. 2007; 25:707–712.

Williams B. Circulation. 2006;113:1213-1225.

140

135

130

125

120

(mm

Hg

)

0 1 2 3 4 5 6 Years

Brachial SBP:∆ 0.7 mmHgP=0.07

Central SBP:∆ 4.3 mmHg P<0.0001

Amlodipine/Perindopril (n=1042) -blocker/diuretic (n=1031)

Amlodipine/perindopril combination significantly reduces central blood pressure

115

• Different components of antihypertensive efficacy have an

independent predictive value

1. Ohkubo DT, et al. The Ohasama study. J Hypertens. 2000;18:847–854. 2. Yamamoto Y, et al. Stroke. 1998; 29:570–576.

3. Ohkubo T et al. J Hypertens. 2002;20:2183–2189. 4. Stanton A, et al. Blood Press. 1993;2:289–295. 5. Pedersen OL? et

al. VALUE trial group. J Hypertens. 2007; 25:707–712.

Anti-Hypertensive Efficacy

Antihypertensive

Efficacy

Brachial

BP

Central

BP

BP

Variablilty

Nocturnal

BP

20

Stabilizes blood pressure to avoid excessive BP variability 1,2

BP variability: main cause of CV events.3

1.Rothwell PM et al. Lancet Neurol. 2010;9(5):469-480 2. Rothwell PM et al. Lancet. 2010;375:938-948.

3. Rothwell PM et al. Lancet. 2010;375:895–905.

/Perindopril

Perindopril-Amlodipine provides key organ protection

Perindopril/Amlodipine also

provides :

- a 30% reduction in the

new onset of diabetes and

- a 35% reduction in

peripheral arterial disease.

Dahlöf B et al. Lancet. 2005:366;895-906.