beta blockers have an ever increasing role in many cardiovascular disorders like heart failure,heart attacks,hypertension & SIHD. With new_generation beta-blockers,their efficacy has increased with fewer side effects.They now have a very important role in heart-failure & CAD,while lesser role in management of hypertension.Their present status in CV disorders according to latest guidelines is highlighted.The so called thierd generation betablockers have shown better efficacy with fewer side-effects though large scale randomized trials are lacking

1. CURRENT STATUS OF BETA-BLOCKER
USE IN CARDIOVASCULAR DISEASES
NOT ALL BETA-BLOCKERS ARE SAME!!
Focus on Bisoprolol
Dr. Deepak Kapila
Director Cardiology

7. –22% –20% –20%
Hanes DS et al. J Clin Hypertens (Greenwich). 2001;3(4):236-243.
Risk Reduction With β-Blockers
in Post-MI Patients
–30%
–40%
–20%
–10%
0%
–33%
Overall
mortality
Sudden
cardiac
death
Non-sudden
death Nonfatal MI
15 Trials (n =18,995)

37. - β blockers are less effective than the other drug
classes for the prevention of stroke.
- β blockers and diuretics lead to a clinically important
increase in the risk of type 2 diabetes.
2012
NICE’s recommendations
BMJ 2012;343:d8078 doi: 10.1136/bmj.d8078

38. Beta Blockers : Not the first choice
•BP reduction not associated with: Significant organ protection or Reduction of events
and mortality
•Side effect profile is not good.. Adverse effects like increased insulin resistance,
dyslipidemia, new onset diabetes, fatigue, and weight gain
Newer non beta blocker drugs are more effective.
Effect of older beta blockers like atenolol which having shorter duration of action
But can we Extrapolate the limitation of Atenolol for all beta blockers?
S.J. Mann / Journal of the American Society of Hypertension 11(1) (2017) 54–65

39. But… All Beta –blockers are NOT SAME…
European Heart Journal
doi:10.1093/eurheartj/ehs092

40. Degradation of beta blocker use in 2018 ESC/ESH hypertension
guidelines
“The limitations of the atenolol (the BB used in
most prior studies) cannot be extrapolated to the
newer BBs, and might bring about premature
curtailment in the use of these agents in general”
BBs constitute one of the most heterogeneous
class of antihypertensive medications.
In conclusion, BBs should also be considered in
Steps 1–2 of the core drug treatment strategy for
uncomplicated hypertension, especially in
younger patients without a diuretic.

41. In younger hypertensives beta-blockers reverse both ECG – and
echocardiographic – LVH. High beta-1 selectivity ensures reversibility
of echocardiographic LVH at least as great as the action of ACE-
inhibitors.
Beta-blocker-induced metabolic disturbance (lipids, blood sugar and
insulin-resistance) stems from beta-2 blockade (and possibly beta-3
blockade). Such disturbances are avoided by high beta-1 selectivity,
beta-2/3 intrinsic sympathomimetic activity or alpha blockade.
In trials involving younger/middle-aged overweight hypertensives
(MRC mild Hypertension, IPPPSH, MAPHY, UKPDS), with relatively
narrow pulse pressures, first-line beta-blockade has been more
effective than placebo and diuretics, and at least as good as ACE-
inhibitors, in preventing coronary events
International Journal of Cardiology 120

42. Wellstein A et al. J Cardiovasc Pharmacol 1986;8(Suppl. 11):36–40
Wellstein A et al. Eur Heart J 1987;8(Suppl. M):3–8
ß1-selectivity
300:1
1:35 1:35
1:75
Increasing β1-selectivity
Increasing β2-selectivity
ICI 118.551
1.8:1
Propranolol
Atenolol Betaxolol
Bisoprolol
No selectivity
Ratio of constants of inhibition
1:20
Metoprolol

43. Beta Blockers
JAPI Suppl; Dec 2009; 57: 7 – 12

44. beta-blocker Propranol Metoprolol Atenolol Carvedilol Bisoprolol
Half Life 2-5 hr 2-5 hr 7-20 hr 7-10 hr 14
Lipid solubility Strong Strong Nil Moderate Moderate
Absorption (%) 90 95 50 ND > 90
Bioavailability (%) 30 50 40 80
Hepatic
metabolism (HM)
HM HM No HM 50%
Renal excretion
(RE)
RE 50% RE
Beta1selectivity* + ++ α, β1β2 ++++
*β1β2 not recommended and may cause postural hypotension
Pharmacologic properties of beta-adrenoceptor blockers

45. Properties of ß-blockers
Lipid solubility
• High lipid solubility  short T½ and high brain penetration
• Low lipid solubility  long T½ and low brain penetration
• The higher the lipid solubility, the easier it is for the liver to clear
the drug, thus the shorter the half-life
• The higher the lipid solubility, the greater the penetration through
the blood brain barrier, thus the greater the central nervous system
effects (depression, migraine headache treatment, sleep disorders
etc…)

46. –30
–20
–10
%
Reduction of
mortality
ß-blockers without ISA
ß1-selective
without ISA
ß-blockers with ISA
non-selective
without ISA
ß1-selective
with ISA
non-selective
with ISA
Yusuf S et al. Progress Cardiovasc Diseases 1985; 5: 335–371
Secondary prevention of myocardial infarction
with different types of ß-blockers

47. Clinical evidences on Different beta blockers:
Focus on Bisoprolol

48. Bisoprolol
Bisoprolol is a cardioselective β1-blocker.
It is used along with other β 1-blockers to treat multiple heart diseases such as
congestive heart failure, without having the unwanted effect of the β2 receptor
blocking, which can affect multiple systems in the body.
Bisoprolol is considered to be one of the selective agents indicated in the
treatment plan of compensated heart failure, along with carvedilol and
metoprolol.
Selective β - blockers are considered the first-line treatment for chronic stable
angina.
It is also FDA approved for the treatment of hypertension, post, or recent
myocardial infarction (MI).
Bazroon AA et al., Treasure Island (FL): StatPearls
Publishing; 2021 Jan-.

50. CIBIS–ELD
2011

51. Bisoprolol vs carvedilol

52. Carvedilol, Bisoprolol, and Metoprolol Use in Patients With Coexistent Heart Failure and
Chronic Obstructive Pulmonary Disease
n=11,558 subjects
Mean follow-up period: 4.07 years.
3 beta-blockers proven to be beneficial to HF (carvedilol, bisoprolol, and
metoprolol) during the study period were extracted.
Primary endpoint was distinct survival effects of the three b-blockers
recommended in the guidelines for HF (carvedilol, bisoprolol, and
metoprolol) in patients with coexistent HF and COPD.
Results: Bisoprolol use showed a dose–response survival benefit, whereas no
survival difference was observed for carvedilol or
metoprolol.
Patients with coexisting HF and COPD, this study demonstrated a dose–
response survival benefit of bisoprolol use, but not of carvedilol or metoprolol
use.
Medicine Volume 95, Number 5, February 2016

53. Respiratory effect of beta-blockers in people with asthma and
cardiovascular disease: population-based nested case control
study
-35,502 people identified with active asthma and CVD
- Cardioselective beta-blocker exposure consisted mainly of atenolol (7.9%) and
bisoprolol (5.4%), whilst non-selective beta-blocker exposure consisted mainly of
sotalol (0.6%) and carvedilol (0.4%)
- Cardioselective beta-blocker use was not associated with a significantly increased
risk of moderate or severe asthma exacerbations. But non-selective beta-blockers
were associated with a significantly increased risk of moderate asthma
exacerbations when initiated at low to moderate doses and both moderate and
severe exacerbations when prescribed chronically at high dose
- Cardioselective beta-blocker use was not associated with a significantly
increased risk of moderate or severe asthma exacerbations.
Morales et al. BMC Medicine (2017) 15:18

54. –16.5
–12.4
–14.2
–9.9
–12.2
–10.9
–13.2
–8.9
p = 0.03
0
–5
–10
–15
–20
day
(6 a.m. – 10 p.m.) (6 a.m. – noon)
night
(10 p.m. – 6 a.m.)
last 4 hours
of dosing interval
(6 a.m. – 10 a.m.)
p = 0.03
p = 0.54
p <0.05
mean
change
in
systolic
blood
pressure
(mm
Hg)
Atenolol (n = 96)
Bisoprolol (n = 107)
S± SEM
BISOPROLOL Vs ATENOLOL
Neutel JM et al. Am J Med 1993; 94:181–187
ABPM technique were used to compare between the bisoprolol (10 to 20
mg OD) and atenolol (50 to 100 mg) for blood pressure reduction
n=203

55. p<0.001
p<0.01
0
–2
–4
–6
–8
–10
–12
–14
–16
–12.8
–8.9
–11.5
–7.7
–9.6
–8.5
–10.9
–7.3
p=0.41
p<0.01
mean
change
in
diastolic
blood
pressure
(mm
Hg)
day
(6 a.m. – 10 p.m.) (6 a.m. – noon)
night
(10 p.m. – 6 a.m.)
last 4 hours
of dosing interval
(6 a.m. – 10 a.m.)
Atenolol (n = 96)
Bisoprolol (n = 107)
S± SEM
Neutel JM et al. Am J Med 1993; 94:181–187
BISOPROLOL Vs ATENOLOL

56. Haasis R et al. Eur Heart J 1987; 8 (Suppl M): 103–113
0
20
40
60
80
100
90%
SBP HR RPP
66%
93%
54%
92%
60%
%
Bisoprolol: 24 H Efficacy In Comparison To Metoprolol
(BISOMET Study)
The effects of the beta blockers on systolic blood pressure, heart rate and rate-
pressure product during exercise, 24 h and 3h at rest after administration (p.a.) were
compared with the values obtained in the baseline exercise test (El)
Bisoprolol 10 mg
Metoprolol
n = 87
Under Exercise Conditions

57. Beta blockers in Post operative stroke
A retrospective cohort study to evaluate the association of β-blocker selectivity with
the risk of postoperative acute stroke.
Total 44,092 consecutive patients with age 50 yr or more having noncardiac,
nonneurologic surgery were involved
The primary outcome was stroke within 7 days of surgery. The secondary outcome
was a composite of all-cause mortality, postoperative myocardial injury, and stroke.
Metoprolol: ------ blue;
Atenolol: ----- green
Bisoprolol : ------ red.
The use of metoprolol and
atenolol is associated with
increased risks of post-
operative stroke, compared
with bisoprolol.
Anesthesiology 2013; 119:777-87