IDN/CONCO/0319/0012

1
IDN/CONCO/0319/0012
2
Bisoprolol shows a dose-dependent BP
reduction over 24 hours1

• 24 hour post dose, mean reductions in SBP and DBP

from baseline with bisoprolol was significant in
comparison to placebo.1

• Bisoprolol once daily provides a 24 hours

antihypertensive coverage for your patients.1

Bisoprolol showed dose dependent BP reduction vs.

placebo (p<0.01).

5 mg 10 mg 20 mg placebo

SBP (mmHg) 8.6 8.6 10.9 3.3

DBP (mmHg) 6.3 8.8 10.1 1.6

Reference: Davidov ME, et al. Clin Cardiol. 1994;17:263-8.

IDN/CONCO/0319/0012
3
Bisoprolol shows a dose-dependent BP reduction over 24 hours1

• Comparison of raw mean change in

Placebo 5mg 10mg 20mg

sitting DBP at 3 and 24h post dose. 0

Values are mean± SEM. -2

-3
-4
• Three- and 24-h post dose data -3.6
±1.2
±1.0
demonstrated that most of the -6

bisoprolol induced decrease in diastolic -7.4

-8

blood pressure at 3 h post dose was ±1.6

-10
sustained at 24 h post dose.1
-10.5

-12 ±1.4
-12.7 -12.8
-14 ±1.3 ±1.4 -13.4
±1.6
-14.7
-16 ±1.3
Bisoprolol Dose
3h postdose 24h postdose

Adapted from: Davidov ME, et al. 1994.

Reference: Adapted from: Davidov ME, et al. Clin Cardiol. 1994;17:263-8.

IDN/CONCO/0319/0012
4
More effective 24-hour BP control with bisoprolol versus
atenolol after once-daily dosing1,2

• Bisoprolol shows greater reduction in 0

mean 24-h DBP control better than

-2

Decrease in 24-hr average diastolic BP (mmHg)

atenolol.1
-4

• By 24 hour monitoring, bisoprolol

-6
demonstrated a 33% greater reduction
in whole day average diastolic BP than -8

P<0.01
did atenolol (11.6 ± 0.7 mm Hg vs. 8.7 -8.7
-10

± 0.8 mmHg, p<0.01).1

-12 -11.6

-14

Bisoprolol Atenolol
Adapted from: Neutal JM, et al. 1993.

References:
1. Adapted from: Neutel JM, et al. Am J Med. 1993 Feb;94(2):181-7.
2. Cruickshank JM. Shelton, CT: People's Medical Publishing House-USA;2011. IDN/CONCO/0319/0012
5
More effective 24-hour BP control with bisoprolol versus atenolol
after once-daily dosing1,2
Bisoprolol provides greater SBP and DBP reduction vs. atenolol, during the last 4 hours dosing interval.1

SBP DBP
0
Bisoprolol
Mean Change in blood press (mmHg)

-2
Atenolol
-4

-6
SBP
-8 -7.3 Systolic
Blood
-8.9
-10 Pressure

-12 -10.9 DBP

Diastolic
-14 -13.2 Blood Press

P<0.05 P<0.01

Adapted from: Neutal JM, et al. 1993.

References:
1. Adapted from: Neutel JM, et al. Am J Med. 1993 Feb;94(2):181-7.
2. Cruickshank JM. Shelton, CT: People's Medical Publishing House-USA;2011.
IDN/CONCO/0319/0012
6
Concor shows greater antihypertensive effect on ambulatory
BP vs other agents (losartan, amlodipine & HCTZ)1
A pronounced and significant antihypertensive effect on 24-h ambulatory BP vs. other agents*1

24-h ABP responses

Adapted from: Hiltunen TP, et al. 2007.

*Losartan, Amlodipine and Hydrochlorothiazide; ABP: Ambulatory BP

Reference: Adapted from: Hiltunen TP, et al. Am J Hypertens. 2007 Mar;20(3):311-8.
IDN/CONCO/0319/0012
7
Concor shows greater antihypertensive effect on office
BP vs other agents (losartan, amlodipine & HCTZ)1
A pronounced and significant antihypertensive effect on office BP vs. other agents*1

Adapted from: Hiltunen TP, et al. 2007.

Office BP Responses

*Losartan, Amlodipine and Hydrochlorothiazide IDN/CONCO/0319/0012

8
IDN/CONCO/0319/0012
9
Bisoprolol is more effective in reducing BP and is associated with a stronger
HR reduction as compared to metoprolol over 24 hours dosage interval1

• The residual effects 24 hours after

administration in relation to the
effects 3 hours after administration Bisoprolol 86% 93%

were significantly higher for

bisoprolol (86-93%) than for
metoprolol (53-66%).1
Metoprolol 53% 66%

• Residual effects 24 hours after

administration in relation to the
0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%
effects 3 hours after administration
Lower effect Upper effect

Adapted from: Hasis R, et al. 1987.

Reference: Adapted from: Haasis R, et al. Eur Heart J 1987;8 (Supplement M):103-13.

IDN/CONCO/0319/0012 10
Bisoprolol is more effective in reducing BP and is associated with a
stronger HR reduction as compared to metoprolol over 24 hours
dosage interval1
Mean Change in heart rate (beats/min)

• Bisoprolol is associated with stable HR

reduction for 24 hours1

• In contrast to the findings with 100 mg

10.7
metoprolol o.d., 10 mg bisoprolol o.d.
guarantees a persistent reduction in exercise
18.2
blood pressure and heart rate throughout
the entire dosage interval of 24h.1
P<0.01

24h mean change in heart rate

at 4 weeks vs. baseline

Adapted from: Hasis R, et al. 1987.

HR, Heart Rate

Reference: Adapted from: Haasis R, et al. Eur Heart J 1987;8 (Supplement M):103-13.
IDN/CONCO/0319/0012 11
Concor is associated with a better HR
control vs metoprolol SR over 24 hours
in hypertensive patients1

• Bisoprolol significantly lowered the 24-h mean

ambulatory, mean daytime and mean nighttime HR
over 24 hours in hypertensive patients.1

• The overall adverse event rate was similar between the

bisoprolol treated and metoprolol treated groups.1

• The Yang T, et al., study concluded that bisoprolol

provides better dynamic HR reduction and non-inferior
dynamic BP reduction vs. metoprolol CR/ZOK in
patients with mild-to-moderate hypertension.1

Reference: Yang T, et al. Hypertens Res. 2017 Jan;40(1):79-86. IDN/CONCO/0319/0012

12
Concor is associated with a better HR control vs
metoprolol SR over 24 hours in hypertensive patients1
Mean heart rate in the last 4 hours of the treatment period from baseline

Adapted from: Yang T, et al. 2017.

Reference: Yang T, et al. Hypertens Res. 2017 Jan;40(1):79-86.

IDN/CONCO/0319/0012
13
Bisoprolol is associated with a dose dependent HR
reduction over 24 hours1

• Bisoprolol showed dose Progressive reduction in HR with

increasing dose1
dependent reduction in the heart
12
rate by 5.1, 7.1 and 10.2
10.2
beats/min, respectively vs. 0.9 10
5 mg
with placebo.1

Heart Rate (beats/minute)

8 10 mg
7.1
20 mg
• Response rate with bisoprolol 6
5.1 Placebo

ranged from 47–70%, compared

4
to 18% under placebo.1
2
0.9

0
5 mg 10 mg 20 mg Placebo
Reduction in the heart rate
Adapted from: Davidov ME, et al. 1994.

Reference: Adapted from: Davidov ME, et al. Clin Cardiol. 1994;17:263-8. IDN/CONCO/0319/0012
14
Bisoprolol effectively reduces BP and is
associated with a HR reduction1,2

Antihypertensive effect of bisoprolol (5mg) vs. losartan (50

mg) shows that the heart rate was reduced only in the

Percentage of Patients achieving Target BP (%)

90 86
80
bisoprolol group.2 80

70
• The reduction in heart rate was seen due to reduction
60

of BP (target of <130/80 mmHg) in 30 patients 50

(86%) with bisoprolol vs. 28 patients (80%) in the 40

losartan group.2 30

20

• A significant difference (p < 0.01) was observed 10

between the two treatment groups in favor of bisoprolol 0

for DBP.2
Bisoprolol Losartan

Adapted from: Parrinello G, et al. 2009.

References:
1. Cruickshank JM. Shelton, CT: People's Medical Publishing House-USA;2011
2. Adapted From: Parrinello G , et al. Clin Drug Invest 2009;29(9):591-600. IDN/CONCO/0319/0012
15
Bisoprolol has shown a better efficacy than
amlodipine, doxazosin, lisinopril,
bendrofluazide in middle-aged hypertensive
patients (ADLIB study)1

• Bisoprolol 5 mg proved to have better efficacy than

amlodipine 5 mg, doxazosin, lisinopril 2.5-10 mg,
bendrofluazide 2.5 mg and placebo OD in middle-aged
hypertensive patients.1

• Bisoprolol proved to be significantly better (p=0.004),

suggesting that β-blockade resulted in a lower heart
rate than all other drugs studied, providing evidence of
potent β1-receptor blockade.1

Reference: Cruickshank JM. Shelton, CT: People's Medical Publishing House-USA;2011.

IDN/CONCO/0319/0012 16
IDN/CONCO/0319/0012
17
Beta1-blockade may be particularly beneficial in hypertensive patients
with central obesity/type 2 diabetes*/insulin resistance1

Increased Reducing the damage

Release of leptin by Renin release and Reduces the risk of
Central obesity or Insulin resistance sympathetic outflow to the cardiac
adipocytes + Insulin angiotensin II ventricular arrhythmias
diabetes high insulin levels and norepinephrine myocytes and
release production & vasoconstriction
release coronary arteries

*Bisoprolol must be used with caution in patients with: Diabetes mellitus Selective β1-blockade reduces
showing large fluctuations in blood glucose values. Symptoms of
hypoglycemia can be masked.2

Reference: 1. Cruickshank JM. Shelton, CT: People's Medical Publishing House-USA;2011. 2.

Concor®/Concor® COR. Product information (abbreviated prescribing information shortened for visual)..
IDN/CONCO/0319/0012 18
Beta1-blockade may be particularly beneficial in hypertensive
patients with central obesity/type 2 diabetes*/insulin resistance1
Selective β1-
blockade

Effects of chronic β1-stimulation

The risk of
ventricular

β1-mediated vasoconstriction and damage to

the cardiac myocytes and coronary arteries
arrhythmias

The β1-mediated release

of renin from the
*Bisoprolol must be used with caution in patients with: Diabetes mellitus showing large juxtaglomerular
fluctuations in blood glucose values. Symptoms of hypoglycemia can be masked.
apparatus Reduction.

Reference: 1. Cruickshank JM. Shelton, CT: People's Medical Publishing House-USA;2011. 2. Concor®/Concor® COR. Product
information (abbreviated prescribing information shortened for visual). IDN/CONCO/0319/0012
19
Importance of β1 selectivity1 Effects of β-1 and β-2 stimulation and
blockade upon myocardial apoptosis/necrosis
• Certainly, β1 blockade in humans prevent cardiac
necrosis and specific β-2 blockade has been
Catecholamine cardiac stimulation
observed to induce a marked negative inotropic
effect in isolated myocytes from failing human
hearts.1

β1 β2
• Stimulation of the β-1 receptor induces myocardial Apoptosis
Apoptosis
myocyte apoptosis or necrosis via a C-AMP
dependent process; whereas stimulation of the β-2
receptor inhibits myocardial apoptosis/ necrosis via a
Gi-coupled pathway. The implication is that β-2 Apoptosis Apoptosis

blockade would be potentially harmful.1

Most β-blocker-related adverse reactions are associated with β-2

blockade and alpha-blockade (e.g. labetalol and carvedilol).1
Adapted from: Cruickshank JM. 2010.

Reference: Adapted from: Cruickshank JM. Indian Heart J. 2010;62:101-110.

IDN/CONCO/0319/0012
20
Bisoprolol is a second generation β-blocker with a remarkably
high β1-selectivity1
Bisoprolol was found to have the highest selectivity for the beta1 receptor, displaying a beta2/beta1
ratio of 19.6 fold.1

25

19.6
~20-fold
20
Greater selectivity for
β1 than β2 receptors

15

10
7.5
6 5.7
5

0.6 0.3
0
Bisoprolol Betaxolol Metoprolol Atenolol Carvedilol Propranolol

Adapted from: Smith C, et al. 1999.

Reference: Adapted from: Smith C, et al. Cardiovasc Drugs Ther. 1999;13(2):123-126.

IDN/CONCO/0319/0012 21
Bisoprolol is a highly beta1-selective beta-blocker
that was chosen for clinical development because
of its excellent pharmacological and
pharmacokinetic properties1-3
• The drug does not have any partial agonistic nor membrane
stabilizing activity.1

• Absolute oral bioavailability of 90%, with virtually no first-

pass effect (10 %)2

• Terminal elimination half-life of 10-11 hours, enabling once-

daily dosing with a clearance of approximately 16 L/hour.2

• Low plasma protein binding (30%) minimizes the risk of

drug interactions and a balanced clearance via renal and
hepatic routes ensures that bisoprolol is suitable for use in
patients with renal or hepatic insufficiency.2,3

References:
1. Leopold G, et al. Rev Contemp Pharmacother. 1997;8:35-43.
2. Leopold G, et al. J Clin Pharmacol. 1986;26:616-621.
3. Leopold G. J Cardiovasc Pharmacol. 1986;8(Suppl 11):16-20.
IDN/CONCO/0319/0012 22
IDN/CONCO/0319/0012
23
Bisoprolol offers a consistent
pharmacokinetic profile with a balanced
clearance of renal elimination (~50%)
and hepatic metabolism (~50%).1-3
• Long plasma-elimination half-life (10-11h) allows a once-a-day
(OD) dose regimen, because of low plasma protein-binding,
kinetics and is insensitive to protein-binding interactions.1

• Less than 2% of the dose was recovered from the feces.2

• Not subject to stereo-selectivity or genetic polymorphism.

Therefore, no interaction with other drugs and can be co-
administered in patients with other diseases.3

• No relevant food interactions.3

References:
1. Leopold G, et al. Rev Contemp Pharmacother. 1997;8:35-43.
2. Leopold G, et al. J Clin Pharmacol. 1986;26:616-621.
3. Leopold G. J Cardiovasc Pharmacol. 1986;8(Suppl 11):16-20. IDN/CONCO/0319/0012
24
In contrast to metoprolol, bisoprolol offers a reliable pharmacokinetic
profile regardless of the patient´s metabolic phenotype.1-4
• The plasma metoprolol profile differed significantly Cmax value for bisoprolol vs. metoprolol

(p<0.05) from the bisoprolol profile regarding time to

maximum concentration, mean residence time, the P<0.01
ratio of peak concentration (Cmax) to the area under
the curve (AUC) and the plateau time as estimated
from the half-value duration.1 Bisoprolol
30%
• The average drug plasma concentration observed 24
h after administration still accounted for 54% of the
Cmax value for the metoprolol controlled release
Metoprolol
tablet, but only 23% with the bisoprolol normal 70%

release tablet.1

Adapted from: Deroubaix X , et al. 1996.

References:
1. Adapted from: Deroubaix X , et al. Int J Clin Pharmacol Ther. 1996;34:61-70.
2. Leopold G, et al. Rev Contemp Pharmacother. 1997;8:35-43.
3. Leopold G, et al. J Clin Pharmacol. 1986;26:616-621. IDN/CONCO/0319/0012
4. Leopold G. J Cardiovasc Pharmacol. 1986;8(Suppl 11):16-20. 25
Bisoprolol: Beta1-selectivity results in minimal effects on lung function in
coronary patients with chronic obstructive lung* disease1,2
• After 24 hours, the significant reduction in HR from
baseline was still evident with bisoprolol (p<0.01), but Reduction in patients with COPD and angina.

not with atenolol, indicating sustained beta1-blockade.2 100

91.25
90

• Although cardioselective (beta1) beta-blockers may 80

have less effect on lung function than nonselective P<0.01 68.54
beta-blockers, as with all beta-blockers, these should 70

Reduction in BP (%)
be avoided in patients with obstructive airways 60
diseases, unless there are compelling clinical reasons
50
for their use.3
40

• Bisoprolol is contra-indicated in patients with severe 30

bronchial asthma.3 23.13

20

10

β1-selective Lower risk of 0

Non-selective Category 1
β-blockers1 bronchoconstriction In
patients with COPD
β-blockers1 Placebo Atenolol Bisoprolol

Adapted from: Dorow P, et al. 1986.

References:
1. Cruickshank JM. Shelton, CT: People's Medical Publishing House-USA;2011.
2. Adapted from: Dorow P, et al. Eur J Clin Pharmacol. 1986;31:143–7.
3. Concor®/Concor® COR. Product information (abbreviated prescribing information shortened for visual).
26
IDN/CONCO/0319/0012
 Bisoprolol results in minimal effects on lung* function1,2
• Bisoprolol did not increase the airways resistance Significant increase in AWR with atenolol vs. placebo
when compared to atenolol and placebo, suggesting (p < 0.05) and bisoprolol (p < 0.05)2
that risk of bronchoconstriction decreases with
increasing β1-selectivity.2
AWR (n=11)

• Bisoprolol proved to have minimal effects on lung 1.5

function, even in patients with COPD and suitable for 1.18

hypertension therapy.2
1

• Although cardioselective (beta1) beta-blockers may

have less effect on lung function than nonselective 0.5

beta-blockers, as with all beta-blockers, these should

be avoided in patients with obstructive airways 0

diseases, unless there are compelling clinical reasons

for their use.3 -0.5
-0.245
-0.35

P<0.05
• Bisoprolol is contra-indicated in patients with severe n.s.p>0.05
-1
bronchial asthma.3 P<0.05

Placebo Bisoprolol Atenolol

Adapted from: Dorow P, et al. 1986.

References:
1. Cruickshank JM. Shelton, CT: People's Medical Publishing House-USA;2011.
2. Adapted from: Dorow P, et al. Eur J Clin Pharmacol. 1986;31:143–7.
3. Concor®/Concor® COR. Product information (abbreviated prescribing information shortened for visual).

IDN/CONCO/0319/0012 27
Bisoprolol has minimal effects on glucose*1-3
Course of the blood glucose before and after 12, 24, and 36 months of treatment3

*Bisoprolol must be used with caution in patients with: Diabetes mellitus showing large fluctuations in blood glucose values.
Symptoms of hypoglycemia can be masked.4

Adapted from: Giesecke HG. and Bushner-Moil D. 1990.

References:
1. Cruickshank JM. Shelton, CT: People's Medical Publishing House-USA;2011. Doc ID.
2. Janka HU, et al. J Cardiovasc Pharmacol. 1986;8(Suppl 11):S96–9.
3. Adapted from: Giesecke HG. and Bushner-Moil D. J Cardiovasc Pharmacol 1990;16(Suppl 5): S175-8.
4. Concor®/Concor® COR. Product information (abbreviated prescribing information shortened for visual).
IDN/CONCO/0319/0012 28
Bisoprolol has minimal effects on lipids1-3
Course of the triglycerides before and after 12, 24, and 36 months of treatment3

*Bisoprolol may cause undesirable side effects in rare conditions like increased triglycerides, increased liver enzymes (ALAT, ASAT).4

Adapted from: Giesecke HG. and Bushner-Moil D. 1990.

References:
1. Cruickshank JM. Shelton, CT: People's Medical Publishing House-USA;2011. Doc ID.
2. Janka HU, et al. J Cardiovasc Pharmacol. 1986;8(Suppl 11):S96–9.
3. Adapted from: Giesecke HG. and Bushner-Moil D. J Cardiovasc Pharmacol 1990;16(Suppl 5): S175-8.
4. Concor®/Concor® COR. Product information (abbreviated prescribing information shortened for visual).
IDN/CONCO/0319/0012 29
Bisoprolol has minimal effects on lipids1-3
Course of the cholesterol before and after 12, 24, and 36 months of treatment3

Adapted from: Giesecke HG. and Bushner-Moil D. 1990.

References:
1. Cruickshank JM. Shelton, CT: People's Medical Publishing House-USA;2011. Doc ID.
2. Janka HU, et al. J Cardiovasc Pharmacol. 1986;8(Suppl 11):S96–9.
3. Adapted from: Giesecke HG. and Bushner-Moil D. J Cardiovasc Pharmacol 1990;16(Suppl 5): S175-8.
IDN/CONCO/0319/0012 30
Safety profile and tolerability of bisoprolol1-10
Although cardioselective (beta1) beta- Lung* function
β1-selectivity of bisoprolol results in minimal
blockers may have less effect on lung effects on lung function in patients with
chronic obstructive lung diseases1,2
function than nonselective beta-
blockers, as with all beta-blockers, Peripheral circulation
Bisoprolol has minimal effect on peripheral
these should be avoided in patients circulation3-6
with obstructive airways diseases,
unless there are compelling clinical Male sexual function
Bisoprolol has minimal effect on male sexual
reasons for their use. Bisoprolol is
function7
contra-indicated in patients with severe
bronchial asthma.11 Renal clearance and hepatic
metabolism
Bisoprolol shows a consistent
pharmacokinetic profile with a clearance
which is balanced between renal
elimination (~50%) and hepatic
metabolism (~50%)8-10

References: 1. Dorow P et al. Eur J Clin Pharmacol (1986) 31: 143-7. 2. Cruickshank JM. The Modern Role of Beta-blockers in Cardiovascular Medicine. Shelton,
CT: People's Medical Publishing House-USA;2011. Doc ID. 3. Chang PC, et al. J Cardiovasc Pharmacol. 1988;12:317-22. 4. Chang PC, et al. J Cardiovasc
Pharmacol. 1986;8(Suppl 11):S58-60. 5. Bailliart O, et al. Eur Heart J. 1987;8(Suppl M):87-93. 6. Asmar RG, et al. Am J Cardiol. 1991;68(1):61-4. 7. Prisant
LM, et al. J Clin Hypertens (Greenwich). 1999;1(1):22-6. 8. Leopold G. J Cardiovasc Pharmacol. 1986;8(Suppl 11):16-20. 9. Leopold G, et al. Rev Contemp
Pharmacother. 1997;8:35-43. 10. Leopold G, et al. J Clin Pharmacol. 1986;26:616-21. 11. Concor®/Concor® COR. Product information (abbreviated prescribing
information shortened for visual). IDN/CONCO/0319/0012
31
IDN/CONCO/0319/0012
32
 Bisoprolol has well established safety profile1-20

• Efficacy: • β1-Selectivity:

• Greater SBP & DBP reduction vs. atenolol1, • Bisoprolol is a third generation beta-blocker
as well as other antihypertensive agents with a remarkably high beta1-selectivity.7
such as losartan, amlodipine and
hydrochlorothiazide.2 • Safety profile:

• Better heart rate reduction vs. metoprolol,3 • Minimal effects on blood glucose*, and
carvedilol and nebivolol.4 lipids8-10, as well as lung function**8,11,
peripheral circulation12-15, and male sexual
• More effective than nifedipine SR in reducing function.16
the total ischemic burden and risk of
coronary events in CHD.5 • Consistent pharmacokinetic profile with a
balanced renal clearance and hepatic
• Reduces morbidity and mortality in CHF.6 metabolism. 17-19

*Bisoprolol must be used with caution in patients with: Diabetes mellitus showing large fluctuations in blood glucose values. Symptoms
of hypoglycemia can be masked.

**Although cardioselective (beta1) beta-blockers may have less effect on lung function than nonselective beta-blockers, as with all
beta-blockers, these should be avoided in patients with obstructive airways diseases, unless there are compelling clinical reasons for
their use. Bisoprolol is contra-indicated in patients with severe bronchial asthma.20

References: 1. Neutel JM, et al. Am J Med. 1993 Feb;94(2):181-7. 2. Hiltunen TP, et al. Am J Hypertens. 2007 Mar;20(3):311-8. 3. Yang T, et al. Hypertens Res. 2017 Jan;40(1):79-86. 4. Stoschitzky K
et al., Cardiology 2006;106:199-206. 5. von Arnim Th, et al. J Am Coll Cardiol. 1995;25:231–8. 6. CIBIS II Investigators and Committees. Lancet 1999;353:913. 7. Smith C, et al. Cardiovasc Drugs
Ther. 1999;13(2):123-126. 8. Cruickshank JM. Shelton, CT: People's Medical Publishing House-USA;2011. Doc ID. 9. Janka HU, et al. J Cardiovasc Pharmacol. 1986;8(Suppl 11):S96–9. 10. Giesecke HG.
and Bushner-Moil D. J Cardiovasc Pharmacol 1990;16(Suppl 5): S175-8. 11. Dorow P et al. Eur J Clin Pharmacol (1986) 31: 143-7. 12. Chang PC, et al. J Cardiovasc Pharmacol. 1988;12:317-22.13.
Chang PC, et al. J Cardiovasc Pharmacol. 1986;8(Suppl 11):S58-60. 14. Bailliart O, et al. Eur Heart J. 1987;8(Suppl M):87-93. 15. Asmar RG, et al. Am J Cardiol. 1991;68(1):61-4. 16. Prisant LM, et al. J
Clin Hypertens (Greenwich). 1999;1(1):22-6. 17. Leopold G. J Cardiovasc Pharmacol. 1986;8(Suppl 11):16-20. 18. Leopold G, et al. Rev Contemp Pharmacother. 1997;8:35-43. 19. Leopold G, et al. J
Clin Pharmacol. 1986;26:616-21. 20. Concor®/Concor® COR. Product information (abbreviated prescribing information shortened for visual).
IDN/CONCO/0319/0012
IDN/CONCO/0319/0012 34
THANKS FOR YOUR ATTENTION

IDN/CONCO/0319/0012 35