2.
Beta blockers are not recommended as initial treatment of
uncomplicated hypertension
beta-blockers had a reduced ability to protect against stroke,
though being equally effective for protection from coronary
events and mortality
Administration of beta-blockers is beneficial in patients with
angina pectoris, heart failure and a recent myocardial
infarction
3.
In a meta-analysis of over 24,000 hypertensive patients aged
52-70 years, atenolol was found
inferior to other anti-
hypertensive drugs with higher total mortality (RR 1.13, 1.021.25), cardiovascular mortality (RR 1.16, 1.00-1.34) and
stroke (RR1.30, 1.12-1.50) in patients on atenolol
Carlberg B, Samuelsson O, Lindholm LH. Atenolol in hypertension : is it a wise choice? Lancet 2004; 364: 1684-89.
4.
A recent Cochrane review of over 95,000 hypertensive patients in
13 trials showed that beta-blockers do not reduce mortality and are
inferior to other antihypertensive drugs suggesting that they should
not be initiating drugs in hypertension
Wiysonge CS, Bradley HA, Volmink J, Mayosi BM, Mbewu A, Opie LH. Beta-blockers for hypertension. Cochrane
Database Syst Rev. 2012; 11: CD002003.
5.
The inferiority of beta-blockers compared with that of other
antihypertensive agents was established by the LIFE study
and the ASCOT study
They showed superiority of an ACE inhibitor and, a calcium
antagonist over therapy initiated by a b-blocker as far as stroke
(LIFE) or stroke and mortality (ASCOT) were concerned
6.
In the LIFE study 9000 hypertensive patients with left
ventricular hypertrophy were randomized to either losarten or
atenolol
Similar reduction in systolic and diastolic BP were achieved
with both drugs
Despite similar BP reduction atenolol was associated with
25% higher incidence of stroke but not with higher incidence
of MI
7.
There was 25% lower incidence of new onset diabetes in the
losartan group
In the subgroup of patients with diabetes the 24% reduction in
primary endpoint was linked with reduction in cardiovascular
and total mortality
8.
9.
ASCOT trial Suggested that BP in the central aorta might be
an explanation for increase stroke in beta blocker group
In this trial atenolol based regimen was less efficacious in
reducing central aortic pressure than amlodipine based
regimen
Williams Bet al: differential impact of blood pressure lowering drugs on central aortic pressure and clinicaL
outcomes CAFÉ study . CIRCULATION 113:1213,2006
10.
The difference in central aortic pressure is largely explained
by heart rate lowering effect of beta blockers
Slowing heart rate will increase central augmentation index
and in turn diminish central BP lowering effect of beta
blockers
Williams B, Lacy PS. Impact of heart rate on central aortic pressures and
hemodynamics: analysis from the CAFE (Conduit Artery Function Evaluation)
study: CAFE-Heart Rate. J Am Coll Cardiol 2009;54:705–713.
11.
These findings cannot be directly extrapolated to other
β-blockers, such as nebivolol and carvedilol, which have
vasodilating effect in the peripheral circulation and less
heart-rate–slowing effect in the heart
Impact of Heart Rate on Central Hemodynamics and Stroke: A Meta-Analysis of β-Blocker Trials
Feng-Hua Ding1, Yan Li1, Li-Hua Li1, Ji-Guang Wang1 American Journal of Hypertension 26(1)
January 2013
12.
In a recent meta analysis of 9 trials (n = 754),
β-blockers were less efficacious in reducing
cAI than all the other classes of drugs (8.6%,
P < 0.001).
Baseline-adjusted difference in HR between
randomized groups was associated with cAI
(7.0% increase for each 10 bpm decrease in
HR, P = 0.02), which was associated with cSBP
(1.2 mm Hg increase for each 1% increase in
cAI, P = 0.009)
13.
Beta blockers does not reduce cental aortic
pressure equally
They reduces heart rate and increase
peripheral resistance so that the arterial wave
reflection from the periphery returns during
systole rather than during diastole
This leads to systolic augmentation of BP
Williams Bet al: differential impact of blood pressure lowering drugs on central aortic pressure and
clinicaL outcomes CAFÉ study . CIRCULATION 113:1213,2006
14.
1.
2.
3.
4.
5.
6.
7.
Beta-blockers are not a preferred initial therapy
for uncomplicated hypertension.
Beta-blockers may be considered in
Angina pectoris
Post-myocardial infarction
Heart failure
Supraventricular tachycardia
Glaucoma
Pregnancy
with evidence of increased sympathetic drive.
15.
Beta blockers increase the incidence of diabetes
through a decrease in insulin sensitivity secondary
to reduce skeletal muscle perfusion from
peripheral vasoconstriction
If therapy is initiated with a beta-blocker and a
second drug is required, add a calcium-channel
blocker rather than a thiazide-like diuretic to
reduce the person’s risk of developing diabetes.
17.
Beta blockers have been one of the mainstays of
treatment because of their ability to reverse the
neurohumoral effects of the sustained sympathetic
nervous system activation with prognostic and
symptomatic benefits
Although there are potential benefits of blocking
all three adrenergic receptors ,most of the
deleterious effects are mediated by beta1 receptors
18.
Beta blockers are indicated in symptomatic and
asymptomatic HF and a depressed EF<40%
Three
beta blockers have been shown to be
effective in reducing the risk of death in patients
with chronic HF bisoprolol, sustained release
metoprolol succinate and carvedilol
Beta blockers reduces mortality from both SCD and
progressive pump faliure in both ischemic and non
ischemic patients
19.
Carvedilol is superior to metoprolol in maintaining a
favorable glycemic profile in patients with diabetes,
improved insulin sensitivity, and decreased progression
to microalbuminuria, all of which have been shown to
have cardioprotective effects
Bakris GL, Fonseca V, Katholi RE, McGill JB, Messerli F, Phillips RA, et al, for the GEMINI Investigators. Metabolic
effects of carvedilol vs metoprolol in patients with type 2 diabetes mellitus and hypertension: a randomized
controlled trial. JAMA 2004;292:2227-36
20.
The first trial that showed mortality benefit of beta
blockers was MERIT-HF trial
In this trial metoprolol succinate provided a
significant 34% reduction in mortality in subjects
with moderate to severe systolic dysfunction
Subsequently CBIS trial with bisoprolol established
beta blockers in heart failure
21.
CBIS 3 trial found that initial treatment strategy
using the beta blocker was non inferior to using
ACE inhibitor first in newly diagnosed mild to
moderate heart failure
COPERNICUS study of carvedilol enroll more
advanced heart failure patients with EF<25% when
compared with placebo carvedilol reduced the
mortality risk at 12 month by 38% and the relative
risk of death or heart failure hospitalization by 31%
22.
23.
24.
25.
In a recent meta analysis of 8,680 patients with HF,
and 1,677 of them had AF (19%; mean 68 years of
age; 30% women); there were 842 patients treated
with beta-blocker, and 835 with placebo.
In AF patients, beta blockade did not reduce
mortality (odds ratio [OR]: 0.86 [95% confidence
interval (CI): 0.66 to 1.13]; p ¼ 0.28)
While in sinus rhythm patients, there was a
significant reduction (OR: 0.63 [95% CI: 0.54 to
0.73]; p < 0.0001).
26.
In patients with sinus rhythm with HF lower heart
rate is associated with a better outcome and
reduction of HR plays an important role in the
beneficial effect of these drugs
In patients with AF with or without HF, lower heart
rate, however, is not associated with a better
outcome
Van Gelder IC, Groenveld HF, Crijns HJ, et al. Lenient versus strict rate control in patients with atrial
fibrillation. N Engl J Med 2010;362:1363–73
27.
Loss of the atrial kick and irregularity in ventricular
response during AF patients with AF may need a
higher heart rate to maintain a similar cardiac
output
Low heart rate in patients with AF may be an
expression of an underlying conduction disorder,
which may be associated with impaired outcome
Itself
AF in patients with HF may be a marker of a poorer
clinical condition leading to a worse outcome, less
modifiable by beta-blocker treatment
28.
During sinus rhythm beta-blockers exert their
heart rate lowering effect by targeting the sinus
node, whereas during AF their main site of action is
the AV node.
Heart rates were measured only at rest. HR
reduction during exercise may have been different
between AF and sinus rhythm patients
29.
Other drugs for HF ACE inhibitors, ARB and
mineralocorticoid antagonists have been shown to
be as effective in patients with AF as they are in
patients with sinus rhythm
Swedberg K, Olsson LG, Charlesworth A, et al. Prognostic relevance of atrial fibrillation in patients
with chronic heart failure on long-term treatment with beta-blockers: results from COMET. Eur Heart J
2005; 26:1303–8
31.
Meta analysis of trials from prethrombolytic era
involving more than 24000 patients who received
beta blockers in doses sufficient to blunt the heart
rate response to stress or exercise after STEMI have
shown a 23% reduction in long term mortality
Much of the impact of beta blockers in preventing
mortality occurs in the first weeks so treatment
should be started early
32.
The latest ECS guidelines, however, have
downgraded the recommendation to class Iia for all
patients with ST-segment elevation MI with normal
LV function and no heart failure
ESC guidelines for the management of acute myocardial infarction in patients presenting with
ST-segment elevation: the Task Force on the Management of ST-Segment Elevation Acute Myocardial
Infarction of the European Society of Cardiology (ESC). Eur. Heart J. 33, 2569–2619 (2012)
33.
In French national reimbursement database on a
population of 11,604 patients hospitalized for MI
in 2006, and who were alive after 6 months. Longterm adherence to their treatment in patients who
had been prescribed β-blockers at discharge was
not associated with a reduced risk of death or
readmission for acute coronary syndromes at 30
months
Tuppin, P. et al. Evidence-based pharmacotherapy after myocardial infarction in France: adherenceassociated factors and relationship with 30-month mortality and rehospitalization. Arch. Cardiovasc. Dis. 103,
363–375 (2010).
34.
FAST-MI 2005 registry cohort of patients with STsegment elevation MI who were given β-blockers at
discharge from hospital, 5-year survival was
similar whether β-blocker treatment was stopped
or on-going at 1 year
