management of copd in patients 慢性阻塞性肺疾病患者的药物治疗课件

Grazie per aver scelto di utilizzare a scopo didattico questo materiale delle Guidelines 2011 libra. Le ricordiamo che questo materiale di propriet dellautore e fornito come supporto didattico per uso personale. PHARMACOLOGICAL MANAGEMENT OF COPD IN PATIENTS WITH CHRONIC CO-MORBIDITIES Professor Peter Calverley University Hospital Aintree Liverpool UK A RUMSFELD MOMENT! uDoes having COPD influence the choice of therapy for a co-morbidity? uDoes taking a treatment for a co-morbidity improve the outcome in COPD? uDoes taking a treatment for COPD affect the co- morbidity? BETA BLOCKERS AND COPD uGood data for the benefits of selective beta- blockade in congestive heart failure, rate control of AF uLongstanding worry that beta-blockade might precipitate bronchospasm uSo most people avoided beta-blockers in COPD uNow we have evidence for safety and a reason why this is the case BETA-BLOCKERS, COPD AND VASCULAR SURGERY u1205 COPD patients, 462 receiving therapy with BB pre- surgery Van Gestel et al AJRCCM 2008 Why COPD is not asthma bronchodilator testing is not helpful Change in FEV1 (L), Post-bronchodilator Subject Group Percent Smoker Controls Percent Non-smoker Contr Percent COPD Subjects 35 30 25 20 15 10 5 0 35 30 25 20 15 10 5 0 35 30 25 20 15 10 5 0 0.150.05-0.65-0.55-0.25-0.050.250.350.450.550.650.750.850.951.051.151.251.35-0.45-0.35-0.15 THE STATIN STORY STATINS AND COPD OUTCOMES IN LOW RISK PATIENTS Mancini et al JACC 2006 STATINS AND EXACERBATIONS Mortenson E et al Respir Res 2009 Systemic Effects of COPD: Target Organs Lung Infections Lung Cancer Weight loss Muscle weakness Osteoporosis Angina Acute coronary syndromes Depression Diabetes Metabolic syndrome Systemic Inflammation Oxidatitive Stress Depression Peptic ulceration/reflux Depression From W MacNee TREATMENT AND COMPLICATIONS uDepression common, often associated with fatigue. Interaction with therapy more likely with systemic treatment. Corticosteroids possibly roflumilast unproven uReflux GI issues with theophyllines and PDEIV inhibitors uMetabolism and diabetes ocs associated with hyperglycaemia but this is a feature of acute exacerbations. More data from roflumilast uMuscles COPD safety poolCOPD safety pool placeboplacebo (N=5,491)(N=5,491) (%)(%) rof500rof500 (N=5,766)(N=5,766) (%)(%) Most frequently reported AEs All AEsAll AEs62.862.867.267.2 COPD exacerbationsCOPD exacerbations23.123.119.819.8 Diarrhoea Diarrhoea 2.62.610.110.1 Weight decreasedWeight decreased1.81.86.86.8 Nasopharyngitis Nasopharyngitis 6.36.36.36.3 Nausea Nausea 1.41.45.25.2 Headache Headache 2.02.04.64.6 Upper respiratory tract infectionUpper respiratory tract infection4.34.33.83.8 Bronchitis Bronchitis 3.53.53.13.1 Back painBack pain2.12.13.13.1 InsomniaInsomnia0.90.92.62.6 Influenza Influenza 2.42.42.52.5 DizzinessDizziness1.21.22.42.4 Decreased appetite Decreased appetite 0.40.42.22.2 PneumoniaPneumonia2.02.01.81.8 ET=number ET=number of patient-years of exposureof patient-years of exposure PHARMACOLOGICALLY PREDICTABLE EFFECTS DiarrhoeaNausea -2.5 for hip or spine: osteopaenia T score -2.5 for hip or spine: osteopaenia T score -2.5 for hip or spine: osteoporosis T score -2.5 for hip or spine: osteoporosis % patients% patients SFC US Safety sub-study : percent change in total hip BMD Vertical bars are standard errors 161 162 158 162 87 105 112 118 Number of subjects 72 82 80 95 52 78 65 82 048108158 PlaceboSALFP 5 4 3 2 1 0 1 Adjusted mean change BMD hip Time (weeks) Ferguson et al Chest 2009 Time to First Pneumonia AE Probability of event prior to wk 104 SFC 9.9%TIO 5.5% Cox Hazard Ratio95% CIp-value SFC vs TIO1.94(1.19, 3.17)0.008 Number at Risk 013263952657891104 0 1 2 3 4 5 6 7 8 11 12 Probability of Event (%) Time to Event (Weeks) Treatment 656550511491470451426415150SFC 50/500 6645434974684242426405387136TIO 18 9 10 TIO 18 SFC 50/500 TIME TO FIRST PNEUMONIA AE OR SAE Sin et al Lancet 2009 Cardiovascular Events with Tiotropium PlaceboTiotropiumRate Ratio1 (95 % CI) nRate2nRate2 UPLIFT Composite endpoint2462.892082.250.78 (0.65, 0.94) Fatal composite1241.42981.040.73 (0.56, 0.95) 1 rate ratio tio vs. placebo; 2per 100 person-years of time at risk to tiotropium or placebo *SOC cardiac (fatal), SOC vascular (fatal), MI (fatal+nonfatal), stroke (fatal+nonfatal), sudden death, sudden cardiac death Composite Endpoint* Used by Singh et al applied to UPLIFT SALMFP All-cause mortality at 3 years Vertical bars are standard errors 18 16 14 12 10 8 6 4 2 0 Time to death (weeks) Probability of death (%) 1524 1533 1521 1534 1464 1487 1481 1487 1399 1426 1417 1409 1293 1339 1316 1288 PlaceboSFC Number alive 01224364860728496108 120 132 144 156 Calverley et al. NEJM 2007 CARDIOVASCULAR EVENTS AND THERAPY Calverley et al Thorax 2010 CVS TREATED COPD AND THERAPY Calverley et al Thorax 2010 Time to onset of first major adverse CV event (MACE*) roflumilast 500 mcg, od, p.o. + roflumilast 250 mcg, od p.o. placebo, od, p.o. Probability of event 0.00 0.02 0.04 0306090120150180210240270300330360390 Days post-randomisation 0.01 0.03 MACE : MACE : CV death, non-fatal MI, non-fatal strokeCV death, non-fatal MI, non-fatal stroke CONCLUSIONS uBetablockers and other cardiac drugs are safe in COPD uStatins may improve COPD outcomes but proper trial data are needed uOral therapies produce more GI upset, oral cor