HARMACOLOGICALMANAGEMENTOFCOPDINPATIENTS慢性阻塞性肺疾病患者的藥物治療課件

1、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.HARMACOLOGICALMANAGEMENTOFCOPDINPATIENTS慢性阻塞性肺疾病患者的藥物治療PHARMACOLOGICAL MANAGEMENT OF COPD

2、IN PATIENTS WITH CHRONIC CO-MORBIDITIESProfessor Peter CalverleyUniversity Hospital AintreeLiverpoolUKA 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 affec

3、t the co-morbidity?BETA BLOCKERS AND COPDuGood data for the benefits of selective beta-blockade in congestive heart failure, rate control of AFuLongstanding worry that beta-blockade might precipitate bronchospasmuSo most people avoided beta-blockers in COPDuNow we have evidence for safety and a reas

4、on why this is the caseBETA-BLOCKERS, COPD AND VASCULAR SURGERYu1205 COPD patients, 462 receiving therapy with BB pre-surgeryVan Gestel et al AJRCCM 2008Why COPD is not asthma bronchodilator testing is not helpfulChange in FEV1 (L), Post-bronchodilatorSubject GroupPercentSmoker ControlsPercentNon-sm

5、oker ContrPercentCOPD Subjects3530252015105035302520151050353025201510500.150.05-0.65-0.55-0.25-0.050.250.350.450.550.650.750.850.951.051.151.251.35-0.45-0.35-0.15HARMACOLOGICALMANAGEMENTOFCOPDINPATIENTS慢性阻塞性肺疾病患者的藥物治療THE STATIN STORYCOPD/Low Risk(Steroid Users)Risk Ratio0.00.51.01.52.0Hospitalizati

6、on for COPDMyocardial InfarctionDeathMyocardial Infarction or Death0.91 (.84, .99), p = .02600.86 (.78, .96), p = .00560.74 (.67, .81), p .00010.70 (.62, .80), p .00011.17 (.90, 1.52)1.10 (.79, 1.54)0.85 (.61, 1.18)1.27 (.90, 1.78)0.73 (.65, .83), p .00010.55 (.46, .66), p .00010.51 (.43, .62), p .0

7、0010.35 (.28, .44), p .00010.82 (.73, .92), p = .00080.68 (.58, .80), p .00010.64 (.55, .75), p .00010.48 (.40, .58), p .0001CombinationStatinACE InhibitorARBCombinationStatinACE InhibitorARBCombinationStatinACE InhibitorARBACE InhibitorARBStatinCombinationCOPD/Low RiskRisk Ratio0.00.51.01.52.0ACE I

8、nhibitorARBStatinCombinationACE InhibitorARBStatinCombinationACE InhibitorARBStatinCombinationACE InhibitorARBStatinCombinationHospitalization for COPDMyocardial InfarctionDeathMyocardial Infarction or Death0.87 (.76, 1.0), p = .05020.78 (.64, .95), p = .0150.65 (.55, .78), p .00010.74 (.59, .92), p

9、 = .00620.97 (.63, 1.50)0.96 (.53, 1.73)0.87 (.51, 1.49)0.87 (.49, 1.54)0.60 (.49, .73), p .00010.52 (.38, .72), p .00010.56 (.42, .74), p .00010.38 (.27, .54), p .00010.71 (.59, .85), p = .00020.64 (.49, .84), p = .00110.65 (.51, .83), p = .00060.49 (.36, .66), p .0001 STATINS AND COPD OUTCOMES IN

10、LOW RISK PATIENTSMancini et al JACC 2006STATINS AND EXACERBATIONSMortenson E et al Respir Res 2009Systemic Effects of COPD: Target Organs Lung Infections Lung CancerWeight lossMuscle weaknessOsteoporosisAngina Acute coronary syndromesDepressionDiabetesMetabolic syndromeSystemic InflammationOxidatiti

11、ve StressDepressionPeptic ulceration/refluxDepressionFrom W MacNeeHARMACOLOGICALMANAGEMENTOFCOPDINPATIENTS慢性阻塞性肺疾病患者的藥物治療TREATMENT AND COMPLICATIONSuDepression common, often associated with fatigue. Interaction with therapy more likely with systemic treatment. Corticosteroids possibly roflumilast un

12、provenuReflux GI issues with theophyllines and PDEIV inhibitorsuMetabolism and diabetes ocs associated with hyperglycaemia but this is a feature of acute exacerbations. More data from roflumilast uMusclesMost frequently reported AEsPHARMACOLOGICALLY PREDICTABLE EFFECTSDiarrhoeaNausea1 week1 weekto 4

13、 weeks4 weeksto 13 weeks13 weeksto 26 weeks26 weeks1 week 1 weekto 4 weeks4 weeksto 13 weeks13 weeksto 26 weeks26 weeksplacebo (n=5491)rof 500 mcg (n=5766Events in the category (%)Events in the categoryWeight lossuNoted as a self-reported finding more often with roflumilastuNot just confined to pati

14、ents reporting GI intoleranceuMonitored with regular weight measurement in pivotal one year trialsuIn one 6 month study bioimpedance data were availableBody weight over time in the studies with available data-4-2024081624324048Body Weight kgplaceboroflumilast 500g = -2.17 kg(CI 2.4;-1.9)p 0.0001Time

15、course: Mean change in kgBetween Treatment Differences least-squares means from ANCOVAWeeksWeight change by BMI Mass indices kg/m2-1004812162024WeeksTiotropium + placebo(FFMI)Tiotropium + Daxas(FFMI)Tiotropium + placebo(BMI)Tiotropium + Daxas(BMI)Wouters EFM, Teichmann P, Brose M, et al. Am J Respir

16、 Crit Care Med 2010;181:A4473. Weight loss associated with roflumilast was primarily fat mass-0.5FFMI: Fat Free Mass Index; BMI: Body Mass IndexMUSCLESuLoss of muscle bulk vs weaknessuA marker for more health care expense and mortality but the thresholds may varyuA clear relationship of weakness to

17、ocs use long term not seen with icsuAnabolic steroids reverse this process but only in people taking oral corticosteroids (Kreutzberg E et al)BONES AND INHALED CORTICSTEROIDSuDatabase associations but confounded by disease severityTORCH - Time to First FractureSafety PopulationSFCN=1546Non-Traumatic

18、20 (1.3%)29 (1.9%) 21 (1.4%) 21 (1.4%)39 (2.5%)37 (2.4%) 45 (2.9%) 58 (3.8%)FPN=1552SALN=1542PlcN=1544Traumatic SFC vs Placebo1.22(0.87, 1.72)0.248SFC vs SAL 1.23(0.88, 1.72)0.229SFC vs FP 1.16(0.83, 1.61)0.382SAL vs Placebo 1.00(0.69, 1.43)0.977FP vs Placebo1.06(0.74, 1.51)0.765p95% CIHazardRatio5.

19、1%5.1%5.4%6.3%KM Prob at 3 years Prevalence of Osteoporosis & Osteopenia at BaselineSFCUS Safety sub-study : percent change in total hip BMDVertical bars are standard errors16116215816287105112118Numberof subjects7282809552786582048108158PlaceboSALFP5432101Adjusted mean change BMD hipTime (weeks

20、)Ferguson et al Chest 2009Time to First Pneumonia AEProbability of event prior to wk 104 SFC 9.9%TIO 5.5%Cox Hazard Ratio95% CIp-valueSFC vs TIO1.94(1.19, 3.17)0.008Numberat Risk0132639526578911040123456781112Probability of Event (%)Time to Event (Weeks)Treatment656550511491470451426415150SFC 50/500

21、6645434974684242426405387136TIO 18910TIO 18SFC 50/500TIME TO FIRST PNEUMONIA AE OR SAESin et al Lancet 2009Cardiovascular Events with TiotropiumPlaceboPlaceboTiotropiumTiotropiumRate RatioRate Ratio1 1 (95 % CI) (95 % CI)n nRateRate2 2n nRateRate2 2UPLIFTUPLIFT Composite endpoint2462.892082.250.78 (

22、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 b

23、y Singh et al applied to UPLIFTSALMFP All-cause mortality at 3 yearsVertical bars are standard errors181614121086420Time to death (weeks)Probability of death (%)1524153315211534146414871481148713991426141714091293133913161288PlaceboSFCNumberalive01224364860728496108 120 132 144 156Calverley et al. NEJM 2007CARDIOVASCULAR EVENTS AND THER