Not

All CCBs are EQUAL

Because Your 24 Hours Protection Very
Important

Dadang Hendrawan
 Hypertension :
Prevalence & Complication
q Prevalence :
q 1 Bio in the World and
q 25.8% in Indonesia1,2

q Common condition leading to :

q myocardial infarction
q stroke &
q kidney failure
q death if not detected early and
treated appropriately.3

1. WHO News Release April 2013. ; 2. RISKESDAS 2013 Depkes RI ; 3. James PA et al. JAMA 2014;311:507–20 2
Hypertension:
A Risk Factor for Cardiovascular Disease
Coronary Peripheral artery Cardiac
Stroke
disease disease failure
50
45.5
45
40

Biennial age-adjusted rate

35 Normotensive

per 1,000 subjects 30 Hypertensive

25 22.7
21.3
20
15 13.9
12.4
9.5 9.9
10 7.3
6.2 6.3
5.0
5 3.3 2.4 3.5
2.0 2.1
0
Ratio Man Woman Man Woman Man Woman Man Woman
Risk: 2.0 2.2 3.8 2.6 2.0 3.7 4.0 3.0

Kannel WB. JAMA 1996;275:1571-1576 3

Target in Hypertension Management

JNC-8 2014
ESH/ESC 2013
• BP target for general population <140/90
mmHg.1,2

• Consider BPV Control as a goal.1

• Reduces morbidity & mortality cardiovascular

and kidney.2
1. James PA et al. JAMA 2014;311:507–20; 2. Mancia et al. ESH/ESC Guidelines July 2013, Journal of Hypertension : Vol. 31:
Nu.7;1285-1357

4
 JNC-8, 2014 guidelines on initial antihypertension treatment

• Antihypertension treatment that recommended for general population:

• Diuretik,
• Calcium Channel Blocker (CCB),
• Angiotensin-Converting Enzyme Inhibitor (ACEI),
• Angiotensin Receptor Blocker (ARB).

β-blockers (BB) not recommended for initial BP treatment because of a higher rate of the primary composite
outcome of CV death, MI, or stroke compared with the use of an ARB

5
Antihypertension treatment of choice
Patient needs antihypertension that can provides :
Effective reduction BP, Has good BPV and has cardiovascular and renal protection.

Reduction BP Antihypertension
as recomended treatment that :
• can reduction BP as
Which
Consider BPV recommended
antihypertension
control • can control BPV
Treatment to
as a goal better
choose ?
• Has Cardiovascular
Benefit for and Renal
Cardiovascular Protection
and Renal

• There are a lot of class of antihypertension, which one can provide the
patient needs and can reach a goals as antihypertension treatment ?

6
Early SBP control leads to improved outcomes

VALUE Study demonstrated that a long-acting CCB is superior in reducing BP

compared with an ARB. Long-acting CCBs can therefore be considered an
appropriate choice for first-line therapy for BP control, in particular SBP control, which
is strongly related to preventing CV complications
Julius S, Kjeldsen S, Weber M, et al. Outcomes in hypertensive patients at high cardiovascular risk treated
with regimens based on valsartan or amlodipine: the VALUE randomised trial. Lancet 2004;363:2022–31
CCBs+ Mechanism of Action
CCBs are recommended in JNC 8 and ESC/ESH for treating hypertension

Ca++

Ca++ antagonist

Decreased contraction

+ Nifedipine and Amlodipine

“ inhibit calcium ion entry into cardiac smooth muscle cell & vascular through
‘voltage-dependent Ca2+’ channel leading to relaxation “
Doyle AE: Calcium antagonists. In Handbook of Hypertension, Vol. 11, Clinical Pharmacology of Antihypertensive Drugs 8
(Eds. BirkenhBger WH, Reid JL, Doyle AE). Elsevier Science Publishers, Amsterdam (1988) 424
Not All CCBs are EQUAL
Not All Nifedipine are the SAME
Nifedipine GITS/OROS has more optimal T/P Ratio in CCB Class
The optimal of T/P ratio shown that the BP fluctuation more stable/minimal, minimal BP Fluctuation can reduce the
risk of organ damage.

Nifedipine GITS/ OROS has more optimal T/P Ratio

Agent T/P Ratio

Adalat OROS (Nifedipine

0.81 – 1.07
GITS)

Amlodipine 0.66

Nifedipine Standard 0.40 – 0.60

IIMS Therapeutic Focus, 1996

Can reduce the

High T/P Ratio Smooth BP
Not Increase BPV risk of organ
≥ 0.50 Variability
damage

J Hypertens Suppl. 1995 Aug; 13(2)-5109-12.Pracyical relevance of the 24-hour trough peak ratio of antihypertensive drugs

10
Nifedipine GITS/OROS different with other Nifedipine
Nifedipine GITS/OROS have a smooth and gradual mechanism of action with Oral Osmotic Delivery System, has better concentration profile than other Nifedipine

Drug concentration profiles

Nifedipine GITS/OROS* enables 24-h

drug availability with once-daily
dosing unlike older/other
formulations

*Nifedipine OROS/ Nifedipine Long-Acting / Nifedipine GITS

Nifedipine IR = Capsule; Nifedipine SR = Retard.

11
Meredith PA, et al. J Hypertens 2004;22:1641-8.
Nifedipine GITS/OROS different with other Nifedipine
Nifedipine GITS/OROS have a smooth and gradual mechanism of action with Oral Osmotic Delivery System, has better BPV control than other Nifedipine

BP reduction profile
Nifedipine GITS/Adalat OROS resulting
in smooth onset and a sustained anti-
hypertensive effect over a 24-hour
period …

*Nifedipine OROS/ Nifedipine Long-Acting / Nifedipine GITS

Nifedipine IR = Capsule; Nifedipine SR = Retard.

Meredith PA, et al. J Hypertens 2004;22:1641-8. 12
Nifedipine GITS/OROS different with other Nifedipine
Nifedipine GITS/OROS have a smooth and gradual mechanism of action with Oral Osmotic Delivery System, has than other Nifedipine

Heart Rate Response

(Placebo corrected)

… without cardio-acceleration

*Nifedipine OROS/ Nifedipine Long-Acting / Nifedipine GITS

Nifedipine IR = Capsule; Nifedipine SR = Retard.

Meredith PA, et al. J Hypertens 2004;22:1641-8.
13
Nifedipine GITS/OROS vs Amlodipine
Compared with amlodipine, Nifedipine GITS/OROS provides better BP reduction

Hypertens Res Vol. 29, No 10 (2006); dr Rich.J.Bauer

14
Nifedipine GITS/OROS vs Amlodipine
Nifedipine GITS/OROS provides minimal side effect than Amlodipine

Decreased SA
Pedal
Overall Headache Dizziness GI Flushing &/or AV Hypotension
Oedema
Conduction
Nifedipine ≈ 10 + + + + 0 + +
GITS
Amlodipine ≈ 15 2+ + + + 0 + 2+

0 = No Report; + = Rare; 2+ = Occasional; 3+ = Frequent

GI = Gastrointestinal; SA = Sinoatrial Node, AV = Atrioventricular Node
GITS = Gastrointestinal Therapeutic System

Frishman WH and Sonnenblick EH, Cardiovascular Pharmacotherapeutics, 1997

15
Nifedipine GITS/OROS
Nifedipine GITS/OROS 60 mg has a better efficacy vs Valsartan 160 mg and has the same effectiveness in
reducing BP vs combination Nifedipine GITS/OROS 30 mg + Valsartan 80 mg.

-5

-10
SBP Reduction

N30+V80
-15
N60

V160
-20

-25

-30
8 weeks

• Focus Study

16
Benefit of Nifedipine GITS/OROS
in Cardivascular protection
Nifedipine GITS/OROS reduces CV risk

INSIGHT Nifedipine ACTION

GITS/OROS

CV Risk Lumen Diameter

(50%)1 (88%)3
Death Risk & CV Event
(13%)2

1. Brown MJ. et al. European Hear Journal Supplement. 2001;3(Supplement B) B20-B26 2. Sierra C, et al. Expert Rev Cardiovasc Ther 18
2008 Sep;6(8): 1055-62 3. ENCORE Investigators. Circulation 2003;107:422–8.
Nifedipine GITS/OROS benefit in Cardiovascular
Insight Study : Nifedipine GITS/OROS significantly reduces the risk of stroke, coronary disease, All cardiovascular events, Cardiovascular Death

All
Coronary Cardiovascular Cardiovascular
Stroke Disease Death
Events
0

Reduced of Risk (%)

-5

-10
-13%
-15

-20
-23%
-25
-26%
-30
-30%

-35
Brown MJ. et al. European Hear Journal Supplement. 2001;3(Supplement B) B20-B26

19
Nifedipine GITS/OROS benefit in Cardiovascular
ACTION Study
Nifedipine GITS/OROS significantly reduces the risk of adverse outcomes in hypertensive patients
Risk reduction: 38% new-overt heart failure, 33% stroke, 16% angiography

Hypertensive patients (BP ≥140/90 mmHg; n=3977) and normotensive patients (n=3684) treated with nifedipine GITS 30-60 mg/day or placebo.
Rate in number of events/100 patient-years of follow-up ‘at risk’.
Lubsen J, et al. J Hypertens 2005;23:641-8.

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Antiatherosclerotic Effects of Nifedipine
Carotid Arteries:

Lumen

Vesel

Change

Coronary Arteries:
Endothelial
Function Study
Nifedipine GITS/OROS benefit in endothelial
ENCORE Study :
Nifedipine GITS/OROS improves coronary endothelial function

Difference in mean lumen

diameter change** (%)
Improvement
20
88% p = 0.04
18.8
15

10
10.0
0
5
Placebo Nifedipine GITS/OROS
Difference between % change at baseline and % change at month 6; Highest dose of acetylcholine administered at baseline and
at month 6; p-value vs placebo

Lüscher: ENCORE results, American Heart Association, 2000

Benefit of Nifedipine GITS/OROS
in Renal protection
Nifedipine GITS/OROS benefit in Renal Function
Nifedipine GITS/OROS significantly impaired GFR (glomerular filtration rate) and renal plasma flow in patients with
renal dysfunction.

Brown et al: Lancet 2000: 56: 366-72

24
Conclusion
o Nifedipine GITS/OROS has minimal BPV better than other CCBs (Amlodipine and
Nifedipine standard) that can reduce the risk of organ damage.
o Nifedipine GITS/OROS has stable drug release than Nifedipine standard with Once
Daily dose.
o Nifedipine GITS/OROS has better efficacy in reduction BP with minimum SNS
activation than amlodipine.
o Nifedipine GITS/OROS has well-established safety and tolerability profile
o Nifedipine GITS/OROS provide benefit in Cardiovascular and Renal Protection

25
Thank you!