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1、Grazie per aver scelto di utilizzare a scopo didattico questo materiale delle Guidelines 2021 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-MORBIDITIESProfessor Peter
2、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 affect the co-morbidity?BETA BLOCKERS AND COPDuGood data for
3、 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 reason why this is the caseBETA-BLOCKERS,COPD AND VASCULAR S
4、URGERYu1205 COPD patients,462 receiving therapy with BB pre-surgeryVan Gestel et al AJRCCM 2021Why COPD is not asthma bronchodilator testing is not helpfulChange in FEV1(L),Post-bronchodilatorSubject GroupPercentSmoker ControlsPercentNon-smoker ContrPercentCOPD Subjects353025201510503530252015105035
5、3025201510500.150.05-0.65-0.55-0.25-0.050.250.350.450.550.650.750.850.951.051.151.251.35-0.45-0.35-0.15THE STATIN STORYCOPD/Low Risk(Steroid Users)Risk Ratio0.00.51.01.52.0Hospitalization for COPDMyocardial InfarctionDeathMyocardial Infarction or Death0.91(.84,.99),p=.02600.86(.78,.96),p=.00560.74(.
6、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 .00010.35(.28,.44),p .00010.82(.73,.92),p=.00080.68(.58,.80),p .00010.64(.55,.75),p .00010.48(.40,.58),p .0001CombinationStatinACE InhibitorARBCombina
7、tionStatinACE InhibitorARBCombinationStatinACE InhibitorARBACE InhibitorARBStatinCombinationCOPD/Low RiskRisk Ratio0.00.51.01.52.0ACE InhibitorARBStatinCombinationACE InhibitorARBStatinCombinationACE InhibitorARBStatinCombinationACE InhibitorARBStatinCombinationHospitalization for COPDMyocardial Inf
8、arctionDeathMyocardial Infarction or Death0.87(.76,1.0),p=.05020.78(.64,.95),p=.0150.65(.55,.78),p .00010.74(.59,.92),p=.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),
9、p=.00110.65(.51,.83),p=.00060.49(.36,.66),p .0001 STATINS AND COPD OUTCOMES IN LOW RISK PATIENTSMancini et al JACC 2006STATINS AND EXACERBATIONSMortenson E et al Respir Res 2021Systemic Effects of COPD:Target Organs Lung Infections Lung CancerWeight lossMuscle weaknessOsteoporosisAngina Acute corona
10、ry syndromesDepressionDiabetesMetabolic syndromeSystemic InflammationOxidatitive StressDepressionPeptic ulceration/refluxDepressionFrom W MacNeeTREATMENT AND COMPLICATIONSuDepression common,often associated with fatigue.Interaction with therapy more likely with systemic treatment.Corticosteroids pos
11、sibly roflumilast unprovenuReflux 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 EFFECTSDiarrhoeaNau
12、sea1 week1 weekto 4 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
13、confined to patients 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
14、.9)p 0.0001Timecourse: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 Resp
15、ir Crit Care Med 2021;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 oc
16、s 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-Traumatic20(1.
17、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%CIHazardRatio5.1%5.1%5.4%6.3%KM Prob a
18、t 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)Ferguson et al Chest 2021Time t
19、o 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 50/5006645434974684242426405387136TIO 1891
20、0TIO 18SFC 50/500TIME TO FIRST PNEUMONIA AE OR SAESin et al Lancet 2021Cardiovascular Events with TiotropiumPlaceboPlaceboTiotropiumTiotropiumRate RatioRate Ratio1 1(95%CI)(95%CI)n nRateRate2 2n nRateRate2 2UPLIFTUPLIFT Composite endpoint2462.892082.250.78(0.65,0.94)Fatal composite1241.42981.040.73(
21、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 UPLIFTSALMFP All-cause mortality a
22、t 3 yearsVertical bars are standard errors181614121086420Time to death(weeks)Probability of death(%)1524153315211534146414871481148713991426141714091293133913161288PlaceboSFCNumberalive01224364860728496108 120 132 144 156Calverley et al.NEJM 2007CARDIOVASCULAR EVENTS AND THERAPYCalverley et al Thora
23、x 2021CVS TREATED COPD AND THERAPYCalverley et al Thorax 2021Time 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 event0.000.020.040306090120150180210240270300330360390Days post-randomisation0.010.03CONCLUSIONSuBetab
24、lockers and other cardiac drugs are safe in COPDuStatins may improve COPD outcomes but proper trial data are neededuOral therapies produce more GI upset,oral corticosteroids long term are hazardousu Inhaled corticosteroids do not seem to accelerate osteoporosis but some may induce pneumoniauLAMA and LABA treatment is safe in COPD anti-inflammatory therapy may improve cardiac outcomesuOn balance our treatments are more friend than foe
HARMACOLOGICAL MANAGEMENT OF COPD IN PATIENTS 慢性阻塞性肺疾病患者的药物治疗
