The REACH Registry study found that beta-blockers do not reduce the risk of cardiovascular events like death, heart attack, or stroke in stable outpatients with or without coronary artery disease. However, beta-blockers were found to lower the risk of secondary outcomes in patients who had a heart attack within the past year. The study followed over 45,000 patients for 4 years on average and compared outcomes in patients taking beta-blockers to those not taking them.

1. Beta Blocker Use in Stable
Outpatients with/ Without
Coronary Artery Disease
Dr R Barik,MD,DNB.
NIMS,Hyderabd
A 250 Year search and experience – Beta Blocker
A 250 Year search and experience – Beta Blocker
saves life in Chronic Stable Angina ??!!!!!
saves life in Chronic Stable Angina ??!!!!!

4. ANGINA PECTORIS
ANGINA PECTORIS
50% OF CAD
50% OF CAD
MOST COMMON SYMPTOM EVEN AFTER
MOST COMMON SYMPTOM EVEN AFTER
REVASCULARISATION IN CAD
REVASCULARISATION IN CAD
50% ↑ IN NEXT THREE DECADES
50% ↑ IN NEXT THREE DECADES
1 OUT OF 5 DEATH IN 1 YR WITH ISCHEMIA
1 OUT OF 5 DEATH IN 1 YR WITH ISCHEMIA
4/100 PATIENT YRS DEATH IN CAD(CAG+)
4/100 PATIENT YRS DEATH IN CAD(CAG+)

5. ARTHEROSCLEROSIS IS AN INTERPLAY BETWEEN LIPID AND THROMBUS.
IS STATIN AND ANTIPLATLETS ENOUGH ?
Thrombosis
Thrombosis
UA
ACS
MI
Ischemic
stroke/TIA
Vascular death
Stable angina
Stable angina

6. DETERMINANT OF MYOCARDIAL ISCHEMIA
DETERMINANT OF MYOCARDIAL ISCHEMIA
HR EFFORT ANGINA-S/D
CONTRACTILITY
WALL STRESS
VASOSPASTIC-SUPPLY
SBP MIXED(COLD)-S/D
LV VOLUME WALK THROUGH-
WALL THICKNESS
AO2 SUPPLY
CORONARY BF LINKED -?(to Acid
PERFUSION PRESSURE/TIME
CAD-DEGREE OF STENOSIS
peptic disease)
CORONARY VASCULAR SYNDROME X-SUPPLY
RESISTANCE
CS SINUS PRESSURE
LVEDP Then we cannot ignore
COLLATERAL BLOOD FLOW beta blocker for symptom

9. DECREASE CARDIOVASCUALR RELIEVE ANGINA
EVENT
CSA
CSA
ANTIPLATLETS BB
LL DRUGS NTG
ACEI CCB
BETA BLOCKER NICORANDIL
HTN CONTROL
TRIMETAZIDINE
DM CONTROL
FOLATE RANOLAZINE
RX OF DEPRESSION IVABRADINE
SMOKING STOP OMIPATRILAT
WT REDUCTION FASUDIL

10. BETA ±ALPHA BLOCKER IN CSA –ACC/AHA
BETA ±ALPHA BLOCKER IN CSA –ACC/AHA
PATIENT WITH PRIOR MI NEEDS
PATIENT WITH PRIOR MI NEEDS
BB IS -CLASS I/A
BB IS -CLASS I/A
DOES IT NEED REVISION?
DOES IT NEED REVISION?
ATTENTION OF THE EVENNING

11. Year of reference comments
observation
1994 The Atenolol Silent Atenolol -Reduced risk for adverse outcome in
Ischemia Study (ASIST)- asymptomatic and mildly symptomatic patients
compared with placebo.
1999 Comparison of safety and Carvedilol is better in reducing angina
efficacy
carvedilol and metoprolol i
n stable angina pectoris,
AJCC
2005 Abrams J et al, Therapy of β-Blockers - improve survival/reduce
stabIe angina hospitalization HF(LVEF ≤40% )/in survivors of
pectoris( Circulation) acute MI and 1st line in CSA+ reduced LVSF,
provided that such patients are on background
treatment with ACEI.Practice guidelines
recommend that β-blockers are the first choice of
therapy for uncomplicated CSA.
2007 COURAGE TRIAL Medical Rx =revascularization
2012 ACCF/AHA/ACP/AATS/PCN Beta blockers are first-line therapy in the control
A/SCAI/STS Guideline of symptoms in patients with chronic stable
angina, particularly effort-induced angina

13. 1ST GENERATION(NON 2ND GENERATION(SELECTIVE) 3RD
SELECTIVE) GENERATION(+VASODILATOR
Y/OTHER)
I
Propranolol S
Metoprolol Labetalol
Atenolol Carvedilol
Timolol Acebutolol Celiprolol
Bisoprolol Nebivolol
Sotalol Esmolol
Pindolol

14. 2009

16. Blockers remain the standard of care after a
Blockers remain the standard of care after a
myocardial infarction (MI).
myocardial infarction (MI).
Benefit of -blocker use in remote MI?
Benefit of -blocker use in remote MI?
-- Coronary artery disease only?
Coronary artery disease only?
-Risk factors for CAD only?
-Risk factors for CAD only?
symptom control or survival or both
symptom control or survival or both

17. Participation in REACH Registry:
4-year follow-up study
10.0%
32.3%
34.6% 7.8% 11.2%
1.0%
North America
Latin America 3.0%
Western Europe
Eastern Europe
Middle East
Asia
•• 45,227 patients enrolled at 3,647 centers in 29 countries provided the outcome
45,227 patients enrolled at 3,647 centers in 29 countries provided the outcome
data for this 4-year follow-up
data for this 4-year follow-up

18. Design, Setting, and Patients
Longitudinal, observational study
3 cohorts:
CAD+ MI (n=14 043),
CAD ONLY (n=12 012),
CAD risk factors only (n=18 653).
 Propensity score matching to avoid bias
Last F/U - April 2009.

19. Participation in REACH Registry:
4-year follow-up study
10.0%
32.3%
34.6% 7.8% 11.2%
1.0%
North America
Latin America 3.0%
Western Europe
Eastern Europe
Middle East
Asia
•• 45,227 patients enrolled at 3,647 centers in 29 countries provided the outcome
45,227 patients enrolled at 3,647 centers in 29 countries provided the outcome
data for this 4-year follow-up.STARTED 2003 AND ENDED IN 2009.
data for this 4-year follow-up.STARTED 2003 AND ENDED IN 2009.

20. Global REACH Registry Inclusion Criteria
1. Documented
cerebrovascular disease
Must include:
Ischemic stroke or TIA 1. Male aged ≥65 years
(CVD) or female aged ≥70 years
Signed
written 2. Current smoking
2. Documented >15 cigarettes/day
informed
coronary disease
consent 3. Type 1 or 2
Angina, MI, angioplasty/
stent/bypass diabetes
Patients aged 4. Hypercholesterolemia
(CAD)
≥45 years
5. Diabetic nephropathy
3. Documented historical 6. Hypertension
or current intermittent 7. ABI <0.9 in either
claudication associated
leg at rest
with ABI <0.9
(PAD) 8. Asymptomatic carotid
stenosis ≥70%
At least
At least 9. Presence of at least
1 of four
criteria
3 atherothrombotic
risk factors
one carotid plaque
.

22. Main Outcome
 The primary:
composite of cardiovascular death,nonfatal MI,or
non fatal stroke.
The secondary:
The primary outcome plus hospitalization for
atherothrombotic events or a revascularization
procedure.

23. Primary End Point- composite of cardiovascular
death, nonfatal MI, or nonfatal stroke.

27. Secondary end points
Secondary end points
BB vs no BB
BB vs no BB

28. BB vs no BB TERTIARY OUTCOMES-repeated hospitalization, stroke.
TERTIARY OUTCOMES-repeated hospitalization, stroke.
 Hospitalization-870 [24.17%] vs 773 [21.48%]; OR, 1.17
 Hospitalization-870 [24.17%] vs 773 [21.48%]; OR, 1.17
[95% CI, 1.04-1.30];P=.01:No difference
[95% CI, 1.04-1.30];P=.01:No difference
Stroke-210 [6.55%] vs 168 [5.12%]; HR, 1.22 [95% CI,
Stroke-210 [6.55%] vs 168 [5.12%]; HR, 1.22 [95% CI,
0.99-1.52]; P=.06:No difference.
0.99-1.52]; P=.06:No difference.

29. However, in those with recent MI (1 year), -blocker use
However, in those with recent MI (1 year), -blocker use
was associated with a lower incidence of the secondary
was associated with a lower incidence of the secondary
outcome (OR, 0.77 [95% CI, 0.64-0.92]).
outcome (OR, 0.77 [95% CI, 0.64-0.92]).

33. CONCLUSIONS
 CAD risk factors only
 CAD risk factors only
 known prior MI
 known prior MI
 known CAD without MI,
 known CAD without MI,
β-blockers was not associated with a
β-blockers was not associated with a
lower risk of composite cardiovascular
lower risk of composite cardiovascular
events.
events.

34. Limitations
Limitations
Not have data on the type of -blocker, the medication
Not have data on the type of -blocker, the medication
dosage, or the reason patients were without –blocker use.
dosage, or the reason patients were without –blocker use.
Not have data on type of MI or prior -blocker use.
Not have data on type of MI or prior -blocker use.
No data for anginal status/Hx of CHF were controlled OR
No data for anginal status/Hx of CHF were controlled OR
not,
not,
Ejection fraction was not recorded
Ejection fraction was not recorded
Propensity score matching adjusts for known
Propensity score matching adjusts for known
confounders, other unmeasured confounders cannot be
confounders, other unmeasured confounders cannot be
accounted for and the possibility of residual confounding by
accounted for and the possibility of residual confounding by
indication can-not be completely ruled out.
indication can-not be completely ruled out.
Limited by the lack of nonrandomized design,
Limited by the lack of nonrandomized design,
Other drug use was associated with a significant reduction
Other drug use was associated with a significant reduction
in the risk of events (HR, 0.73 [95% CI, 0.69-0.77]; P.001),
in the risk of events (HR, 0.73 [95% CI, 0.69-0.77]; P.001),
providing another internal validation of the data set.
providing another internal validation of the data set.

35. REACH Registry Investigators
Bangalore S, Steg PHG, Deedwania P, et al. Beta
blocker use and clinical outcomes in stable
outpatients with and without coronary artery
disease. JAMA 2012; 308:1340-1349. Available at:
http://jama.jamanetwork.com/journal.aspx.

36. Take-Home Points
Take-Home Points
OLD IS GOLD-Concept fades because of evidence lack as many of
OLD IS GOLD-Concept fades because of evidence lack as many of
those studies were carried out in pre-TLT,some in TLT but none of them
those studies were carried out in pre-TLT,some in TLT but none of them
in intervention era.
in intervention era.
REACH Registry --that beta-blockers do not reduce the composite
REACH Registry that beta-blockers do not reduce the composite
event rate of cardiovascular death/MI/stroke (at a mean follow-up time
event rate of cardiovascular death/MI/stroke (at a mean follow-up time
of 4.5 years) in patients with:
of 4.5 years) in patients with:
a. Prior MI (9 months after an ACS event)
a. Prior MI (9 months after an ACS event)
b. Known CAD/ischemia on stress testing but no LVD.
b. Known CAD/ischemia on stress testing but no LVD.
c. ONLY Risk factors for CAD
c. ONLY Risk factors for CAD
BACKGROUND- statins/aspirin/ anti-platelet/ revascularization share
BACKGROUND- statins/aspirin/ anti-platelet/ revascularization share
the outcome.
the outcome.
STRONGLY INDICATED- acute MI/systolic LVD/HF
STRONGLY INDICATED- acute MI/systolic LVD/HF
ALTERNATIVE INDICATIONS- migraine /afib/CSA( symptom relief
ALTERNATIVE INDICATIONS- migraine /afib/CSA( symptom relief
only).
only).
))FINAL DECISION –related to the index case till BB is studied in larger
 FINAL DECISION –related to the index case till BB is studied in larger
randomized trial with Cox regression model avoiding background
randomized trial with Cox regression model avoiding background

37. WHAT TURNED UPSIDE DOWN
WHAT TURNED UPSIDE DOWN
The editorial comment
“Beta blockers of no use in stable CAD patients”
Bangalore S, Steg PHG, Deedwania P, et al. Beta blocker use and clinical outcomes in stable
Bangalore S, Steg PHG, Deedwania P, et al. Beta blocker use and clinical outcomes in stable
outpatients with and without coronary artery disease. JAMA 2012-Oct; 308:1340-
outpatients with and without coronary artery disease. JAMA 2012-Oct; 308:1340-
1349.
1349.
BUT
CLASS I (A):Fresh Myocardial Infarction for First 12
months , systolic left ventricular dysfunction.
stamped as “COMPELLING” indication in JNC-7/ESC/AHA
other CVS uses CLASS II A/B.