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 saves life in Chronic Stable Angina ??!!!!!A 250 Year search and experience – Beta Blocker saves life in Chronic Stable Angina ??!!!!!

ANGINA PECTORIS ANGINA PECTORIS

50% OF CADMOST COMMON SYMPTOM EVEN AFTER REVASCULARISATION IN CAD50% ↑ IN NEXT THREE DECADES1 OUT OF 5 DEATH IN 1 YR WITH ISCHEMIA4/100 PATIENT YRS DEATH IN CAD(CAG+)

50% OF CADMOST COMMON SYMPTOM EVEN AFTER REVASCULARISATION IN CAD50% ↑ IN NEXT THREE DECADES1 OUT OF 5 DEATH IN 1 YR WITH ISCHEMIA4/100 PATIENT YRS DEATH IN CAD(CAG+)

Stable anginaStable angina

ThrombosisThrombosis

UA MI

Ischemic stroke/TIA

Vascular death

ACS

ARTHEROSCLEROSIS IS AN INTERPLAY BETWEEN LIPID AND THROMBUS.IS STATIN AND ANTIPLATLETS ENOUGH ?

DETERMINANT OF MYOCARDIAL ISCHEMIADETERMINANT OF MYOCARDIAL ISCHEMIA

HRCONTRACTILITYWALL STRESSSBPLV VOLUMEWALL THICKNESSAO2CORONARY BFPERFUSION PRESSURE/TIMECAD-DEGREE OF STENOSISCORONARY VASCULAR RESISTANCECS SINUS PRESSURELVEDPCOLLATERAL BLOOD FLOW

EFFORT ANGINA-S/DVASOSPASTIC-SUPPLYMIXED(COLD)-S/DWALK THROUGH-SUPPLYLINKED -?(to Acid peptic disease)SYNDROME X-SUPPLY

Then we cannot ignore beta blocker for symptom

CSACSA

DECREASE CARDIOVASCUALR EVENT

RELIEVE ANGINA

ANTIPLATLETSLL DRUGSACEIBETA BLOCKERHTN CONTROLDM CONTROLFOLATERX OF DEPRESSIONSMOKING STOPWT REDUCTIONREGULAR EXERCISE

BBNTGCCBNICORANDILTRIMETAZIDINERANOLAZINEIVABRADINEOMIPATRILATFASUDIL

BETA ±ALPHA BLOCKER IN CSA –ACC/AHABETA ±ALPHA BLOCKER IN CSA –ACC/AHA

PATIENT WITH PRIOR MI NEEDS BB IS -CLASS I/ADOES IT NEED REVISION?

PATIENT WITH PRIOR MI NEEDS BB IS -CLASS I/ADOES IT NEED REVISION?

ATTENTION OF THE EVENNING

Year of observation

reference comments

1994 The Atenolol Silent Ischemia Study (ASIST)-

Atenolol -Reduced risk for adverse outcome in asymptomatic and mildly symptomatic patients compared with placebo.

1999 Comparison of safety and efficacy carvedilol and metoprolol in stable angina pectoris, AJCC

Carvedilol is better in reducing angina

2005 Abrams J et al, Therapy of stabIe angina pectoris( Circulation)

β-Blockers - improve survival/reduce hospitalization HF(LVEF ≤40% )/in survivors of 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/PCNA/SCAI/STS Guideline

Beta blockers are first-line therapy in the control of symptoms in patients with chronic stable angina, particularly effort-induced angina

2012 OCT REACH RESISTRY IN DISCUSSION NOW

1ST GENERATION(NON SELECTIVE)

2ND GENERATION(SELECTIVE) 3RD GENERATION(+VASODILATORY/OTHER)

Propranolol Timolol

Sotalol

Pindolol

Metoprolol Atenolol Acebutolol Bisoprolol Esmolol

Labetalol Carvedilol Celiprolol Nebivolol

IS

2009

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

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

Participation in REACH Registry: 4-year follow-up study

North America

Latin America

Western Europe

Eastern Europe

Middle East

Asia

• 45,227 patients enrolled at 3,647 centers in 29 countries provided the outcome data for this 4-year follow-up

• 45,227 patients enrolled at 3,647 centers in 29 countries provided the outcome data for this 4-year follow-up

34.6%

3.0%

32.3%

10.0%

7.8%1.0% 11.2%

Longitudinal, observational study3 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.

Design, Setting, and Patients

Participation in REACH Registry: 4-year follow-up study

North America

Latin America

Western Europe

Eastern Europe

Middle East

Asia

• 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.

• 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.

34.6%

3.0%

32.3%

10.0%

7.8%1.0% 11.2%

Must include:

Signedwritten

informedconsent

Patients aged≥45 years

At least of four criteria1

1. Documented cerebrovascular diseaseIschemic stroke or TIA

(CVD)

2. Documentedcoronary diseaseAngina, MI, angioplasty/stent/bypass

(CAD)

3. Documented historicalor current intermittentclaudication associatedwith ABI <0.9

(PAD)

At least atherothrombotic risk factors3

1. Male aged ≥65 yearsor female aged ≥70 years

2. Current smoking>15 cigarettes/day

3. Type 1 or 2diabetes

4. Hypercholesterolemia

5. Diabetic nephropathy

6. Hypertension

7. ABI <0.9 in eitherleg at rest

8. Asymptomatic carotidstenosis ≥70%

9. Presence of at leastone carotid plaque

Global REACH Registry Inclusion Criteria

.

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.

Main Outcome

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

Secondary end pointsSecondary end pointsBB vs no BBBB vs no BB

Hospitalization-870 [24.17%] vs 773 [21.48%]; OR, 1.17 [95% CI, 1.04-1.30];P=.01:No differenceStroke-210 [6.55%] vs 168 [5.12%]; HR, 1.22 [95% CI, 0.99-1.52]; P=.06:No difference.

Hospitalization-870 [24.17%] vs 773 [21.48%]; OR, 1.17 [95% CI, 1.04-1.30];P=.01:No differenceStroke-210 [6.55%] vs 168 [5.12%]; HR, 1.22 [95% CI, 0.99-1.52]; P=.06:No difference.

TERTIARY OUTCOMES-repeated hospitalization, stroke.TERTIARY OUTCOMES-repeated hospitalization, stroke.BB vs no BB

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

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

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

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

CONCLUSIONS

Not have data on the type of -blocker, the medication dosage, or the reason patients were without –blocker use.Not have data on type of MI or prior -blocker use.No data for anginal status/Hx of CHF were controlled OR not,Ejection fraction was not recordedPropensity score matching adjusts for known confounders, other unmeasured confounders cannot be accounted for and the possibility of residual confounding by indication can-not be completely ruled out. Limited by the lack of nonrandomized design,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), providing another internal validation of the data set.

Not have data on the type of -blocker, the medication dosage, or the reason patients were without –blocker use.Not have data on type of MI or prior -blocker use.No data for anginal status/Hx of CHF were controlled OR not,Ejection fraction was not recordedPropensity score matching adjusts for known confounders, other unmeasured confounders cannot be accounted for and the possibility of residual confounding by indication can-not be completely ruled out. Limited by the lack of nonrandomized design,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), providing another internal validation of the data set.

LimitationsLimitations

REACH Registry InvestigatorsBangalore 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.

Take-Home Points 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 in intervention era.REACH Registry - that beta-blockers do not reduce the composite event rate of cardiovascular death/MI/stroke (at a mean follow-up time of 4.5 years) in patients with: a. Prior MI (9 months after an ACS event) b. Known CAD/ischemia on stress testing but no LVD. c. ONLY Risk factors for CADBACKGROUND- statins/aspirin/ anti-platelet/ revascularization share the outcome.STRONGLY INDICATED- acute MI/systolic LVD/HF

ALTERNATIVE INDICATIONS- migraine /afib/CSA( symptom relief only).) FINAL DECISION –related to the index case till BB is studied in larger randomized trial with Cox regression model avoiding background effects of alliance Rx.

Take-Home Points 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 in intervention era.REACH Registry - that beta-blockers do not reduce the composite event rate of cardiovascular death/MI/stroke (at a mean follow-up time of 4.5 years) in patients with: a. Prior MI (9 months after an ACS event) b. Known CAD/ischemia on stress testing but no LVD. c. ONLY Risk factors for CADBACKGROUND- statins/aspirin/ anti-platelet/ revascularization share the outcome.STRONGLY INDICATED- acute MI/systolic LVD/HF

ALTERNATIVE INDICATIONS- migraine /afib/CSA( symptom relief only).) FINAL DECISION –related to the index case till BB is studied in larger randomized trial with Cox regression model avoiding background effects of alliance Rx.

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.

BUT

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; 308:1340-1349.

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; 308:1340-1349.

The editorial comment

“Beta blockers of no use in stable CAD patients”

WHAT TURNED UPSIDE DOWNWHAT TURNED UPSIDE DOWN