Definition COPD def- A disease state characterized by

air flow limitation that is not fully reversible It is expected to be the 3rd leading cause of

death by 2020Approximately 14 million Indians are

currently suffering form COPD

The Indian J Chest Dis & Allied Sciences 2001; 43:139-47

The airflow limitation is usually progressive and is associated with an abnormal inflammatory response of the lungs to noxious particles or gases, primarily caused by cigarette smoking.

RISK FACTORSSmoke from home cooking and heating fuelOccupational dust and chemicalsGender: More common in men. M:F ratio is

5%:2.7% (in India)Increasing ageOthers: Infection, nutrition and deficiency of

1 antitrypsin

PATHOPHYSIOLOGY Increased mucus production and reduced

mucociliary clearance - cough and sputum production

Loss of elastic recoil - airway collapse Increase smooth muscle tone Pulmonary hyperinflation Gas exchange abnormalities - hypoxemia

and/or hypercapnia

PATHOGENESIS

Classification

TREATMENTStable COPDAcute COPD

STABLE COPDSmoking cessationOxygen therapyBronchodilators- anticholinergics,beta

agonists, inhaled steroids, xanthines

Pharmacotherapy for Stable COPD

Bronchodilators Short-acting 2-

agonist – Salbutamol Long-acting 2-

agonist - Salmeterol and Formoterol

Anticholinergics – Ipratropium, Tiotropium

Methylxanthines - Theophylline

Steroids Oral – Prednisolone

Inhaled - Fluticasone, Budesonide

ACUTE EXACERBATIONBronchodilatorsAntibioticsGlucocorticoidsOxygen Ventilatory support

Management based on GOLD

JAMA sept 2008;300(12):1439-49.Sonal Singh, Yoon k, Curt D

Need for this meta analysisCOPD – 4TH leading cause of chronic

morbidity and mortality.

CV disease is an important cause of morbidity and mortality.

Need for this meta analysisGOLD guidance-small increase in

cardiovascular adverse events with anticholinergics

US FDA-possible increased risk of stroke(8/1000/yr vs 6/1000/yr)

No risk( chest 2006;130(6):1695-1703)

OBJECTIVEAscertain cardiovascular risks with long term

use of inhaled anticholinergics compared with control therapies in patients with COPD in RCTs.

ELIGIBLITY CRITERIAMore than 30 days of follow up

Diagnosis of COPD of any severity

Inhaled anticholinergics vs placebo or inhaled beta agonists and/or steroids

Cardiovascular events reported

STUDY SELECTION703 reports17 RCTs- 12 tiotropium,5 ipratropium5 long term trials(48weeks-5yrs)12 short term(6weeks-26weeks)

RESULTSPrimary outcome-increased risk of

MI(1.2%vs0.2%) Significantly increased risk of cardiovascular

death(0.9%vs0.5%) No significant increase in risk of

stroke(0.5%vs0.4%)

Secondary outcome- no significant increase in all cause mortality

Long term trials- increased risk of cardio vascular events(2.9%vs1.8%)

Short term trials-no statistically significant increase in cardiovascular event

NUMBER NEEDED TO HARMFor MI-174/yr (baseline event 10.9/1000)

For cardiovascular mortality-40/yr(31.9/1000)

MECHANISMCOPD- inflammatory cytokines

Inhaled tiotropium increases interleukin 8-destabilizes existing atherosclerotic plaques

CONCLUSSIONInhales anticholinergics used for >30 days

significantly increases the risk of cardiovascular events by approx.58%- long term trials

Then Why to use it?Number needed to treat for tiotropium to

prevent one COPD exacerbation is 21Versus number needed to harm -40 for

cardiovascular deaths and 174 for MITreatment modalities are limitedBaseline cardiovascular risks should be

evaluated.