betablockers in copd

8/8/2019 BetaBlockers in COPD

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Journal Club, July 23rd, 2010

James Gray, MD

Donna Windish, MD, MPH


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COPD is estimated to be the ______most common cause of death in the

Western world by 2020.

1. 1st

2. 3rd

3. 5th

4. 10th


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0%

0%

Do beta-blockers (selective and non-

selective) increase the frequency of

COPD exacerbations?

1. Yes

2. No


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0%

0%

Do you avoid using beta-blockers in

patients with COPD?

1. Yes

2. No


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ARCH INTERN MED/ VOL 170 (NO. 10), MAY 24, 2010


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Background


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Background

Traditional dogma states that -blockers

are contraindicated in patients with COPD

because of their presumed

bronchoconstrictive properties andcompetition with 2-agonists


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Background

Traditional dogma states that -blockers

are contraindicated in patients with COPD

because of their presumed

bronchoconstrictive properties andcompetition with 2-agonists

Many physicians avoid prescribing -blockers in patients with COPD


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Background - COPD

COPD is characterized by systemic

inflammation


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Background - COPD


inflammation

This inflammation promotes atherosclerotic

disease progression independent of age,

smoking, or other cardiovascular risk factors


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Background - COPD


inflammation

This inflammation promotes atherosclerotic

disease progression independent of age,

smoking, or other cardiovascular risk factors

Therefore, patients with COPD are more

prone to develop cardiovascular diseases,which account for most deaths in these

patients


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Background -blockers

Known to improve survival of patients within

a large spectrum of cardiovascular disease


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Known to improve survival of patients within

a large spectrum of cardiovascular disease

Theoretical benefit in COPD patients by

tempering sympathetic nervous system or

by reducing ischemic burden


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Meta-analysis have shown that -blockers

are well-tolerated in patients with COPD

y No real effect on FEV1

y No significant change in 2-agonist response

y No change in inhaler use or symptoms

[Salpeter SS et al. Cardioselective beta-blockers for chronic obstructive

pulmonary disease. Cochrane Database Syst. Rev. 2002]


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Article Overview

What journal published the article?


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Article Overview


y Archives of Internal Medicine

Is it a reputable source?


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Article Overview




yYes


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Article Overview




yYes

When did the study take place?


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Article Overview




yYes


y Jan 1, 1995 through December 31, 2005


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Article Overview




yYes


y Jan 1, 1995 through December 31, 2005

When was the article published?

y May, 2010


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Article Overview

Is the information current and up to date?


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Article Overview


y Yes


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Article Overview


y Yes

Where does the study take place?

yWithin the Utrecht General Practitioners (GPs) Networkdatabase, a network of 35 collaborating GPs, working in 23

practices in the vicinity of Utrecht, the Netherlands


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Article Overview


y Yes


yWithin the Utrecht General Practitioners (GPs) Networkdatabase, a network of 35 collaborating GPs, working in 23


Who sponsored the study?

y No financial disclosures


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Article Overview


y Yes


y

Within the Utrecht General Practitioners (GPs) Networkdatabase, a network of 35 collaborating GPs, working in 23




Any potential conflicts of interest?


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Article Overview


y Yes


y

Within the Utrecht General Practitioners (GPs) Networkdatabase, a network of 35 collaborating GPs, working in 23




Any potential conflicts of interest?y Doesnt appear to be


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Study Question and Study Design

What is the main study question (primary outcome of

interest)?


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interest)?

y In patients with COPD, what effects do beta-blockers have on

all-cause mortality or the first exacerbation of COPD?


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interest)?



What is the study design?


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interest)?



What is the study design?

y Observational cohort study


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What other outcomes are being assessed in the study


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y No other real outcomes other than all-cause mortality or first

exacerbation of COPD are mentioned. However, the

researches break the study cohort into various subgroups:


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y No other real outcomes other than all-cause mortality or first

exacerbation of COPD are mentioned. However, the

researches break the study cohort into various subgroups:

Patients who use 2 or more pulmonary medications Patients who use inhaled -agonists

Patients who inhaled anticholinergic agents

Patients who were referred to a pulmonologist

(Incident cases of COPD)


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Study Population

Who was included in this study?

y All patients 45 with an incident or prevalent diagnosis of COPD

within the study time-frame (roughly 10 years)

y Diagnosis of COPD based on symptoms (dyspnea, cough,

sputum production for at least 3 months in 2 years) andpulmonary rhonchi with exacerbations; preferably with

spirometric evidence of obstruction


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Statistical Methods

Cox proportional hazards regression analysis used to calculate

crude (unadjusted) and adjusted hazard ratios (HR) and their 95%

CI for the risk of all-cause death and COPD exacerbation

associated with the use of beta-blockers


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Statistical Methods

Cox proportional hazards regression analysis used to calculate

crude (unadjusted) and adjusted hazard ratios (HR) and their 95%

CI for the risk of all-cause death and COPD exacerbation

associated with the use of beta-blockers

Adjusted HR were calculated after correction for the following(potentially confounding) variables:

y Age

y Sex

y Current and former smoking

y History of CAD (angina, MI, CABG, PCI, a-fib, CHF, PVD, stroke)

y Hypertension

y Diabetes

y Pulmonary drug use

y Referral to pulmonologist


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Statistical Methods

The study basically is looking at three different hazard

ratios:


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Statistical Methods


ratios:

y Crude, unadjusted HR

y Adjusted HR (based on multivariate CP hazard model)

y Adjusted HR conditional on a propensity score (PS):


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Statistical Methods


ratios:




PS calculated as a continuous variable and is derived from a logistic

regression model, with beta-blocker use as the dichotomous dependent

variable

Used covariates known from the literature to be associated with beta-blocker

prescriptions (HTN, angina, CAD, etc)

Adjusted HRs for beta-blocker use calculated by including PS as the only

covariate in the Cox analysis


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Statistical Methods


ratios:




PS calculated as a continuous variable and is derived from a logistic

regression model, with beta-blocker use as the dichotomous dependent

variable

Used covariates known from the literature to be associated with beta-blocker

prescriptions (HTN, angina, CAD, etc)

Adjusted HRs for beta-blocker use calculated by including PS as the only

covariate in the Cox analysis


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Subgourp analysis

Patients with COPD but no overt CAD

Patients with COPD who used 2 or more pulmonary

drugs

Patients with COPD who inhaled beta-agonists Patients with COPD who inhaled anticholinergic agents

Patients with COPD who were referred to a

pulmonologist


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Results

Total of 2230 patients 45 years and older with diagnosis of COPD

were included


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Results


were included

560 patients (25%) had prevalent COPD at the start of the study


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Results


were included


1670 patients (75%) developed COPD during the follow-up period

(incident COPD)


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Results


were included



(incident COPD) Mean age 64.8 years, 53% were male


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Results


were included





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Results


were included




In total, 686 patients died

y 27.2% used a beta-blocker

y 32.3% did not use a beta-blocker


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Results


were included




In total, 686 patients died

y 27.2% used a beta-blocker


1055 patients had at least one COPD exacerbationy 42.7% used a beta-blocker



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Results

Total of 2230 patients 45 years and older with diagnosis of COPDwere included


1670 patients (75%) developed COPD during the follow-up period(incident COPD)

Mean age 64.8 years, 53% were male

In total, 686 patients diedy 27.2% used a beta-blocker


1055 patients had at least one COPD exacerbation

y 42.7% used a beta-blockery 49.3% did not use a beta-blocker

In total, 44.9% of patients with COPD had cardiovascular co-morbidities


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Results


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Results


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Results


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Results


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Discussion

This is the first observational study that shows that long-term

treatment with beta-blockers may improve survival and reduce the

risk of an exacerbation of COPD in the broad spectrum of patients

with COPD (with or without CAD)


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Discussion





Some other important points:


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Discussion





Some other important points:y Previous studies in COPD patients showed similar benefits with ACE/ARBs on

all-cause mortality. This study was unable to show such similar benefit.


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Discussion





Some other important points:y Previous studies in COPD patients showed similar benefits with ACE/ARBs on

all-cause mortality. This study was unable to show such similar benefit.

y Statins had a nonsignificant beneficial trend for survival


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Limitations?


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Discussion Talking Points

How close is the link between COPD and CAD?

Are there any special considerations using beta-

blockers in COPD patients who use inhaled beta-agonists or other pulmonary meds?

What effect, in general, might beta-blockers have on 2

receptors in the lungs


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The Big Question

Now, what will you say when your hear, hey! you cant

put that patient on a beta-blocker! He has COPD!?

betablockers in copd

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