慢性阻塞性肺疾病患者的藥物治療

1、Grazie per aver scelto di utilizzare a scopo didattico questo materiale delle Guidelines 2011 libra.Le ricordiamo che questo materiale è di proprietà dell’autore e fornito come supporto didattico per uso perso

2、nale.,PHARMACOLOGICAL MANAGEMENT OF COPD IN PATIENTS WITH CHRONIC CO-MORBIDITIES,Professor Peter CalverleyUniversity Hospital AintreeLiverpoolUK,A RUMSFELD MOMENT!,Does having COPD influence the choice of therapy for

3、a co-morbidity?Does taking a treatment for a co-morbidity improve the outcome in COPD?Does taking a treatment for COPD affect the co-morbidity?,BETA –BLOCKERS AND COPD,Good data for the benefits of selective beta-blo

4、ckade in congestive heart failure, rate control of AFLongstanding worry that beta-blockade might precipitate bronchospasmSo most people avoided beta-blockers in COPDNow we have evidence for safety and a reason why thi

5、s is the case,BETA-BLOCKERS, COPD AND VASCULAR SURGERY,1205 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 F

6、EV1 (L), Post-bronchodilator,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

7、Organs,Lung Infections Lung Cancer,Weight lossMuscle weakness,Osteoporosis,Angina Acute coronary syndromes,Depression,DiabetesMetabolic syndrome,Depression,,,Peptic ulceration/reflux,Depression,,,,,,,From W MacNe

8、e,TREATMENT AND COMPLICATIONS,Depression –common, often associated with fatigue. Interaction with therapy more likely with systemic treatment. Corticosteroids possibly –roflumilast unprovenReflux – GI issues with theoph

9、yllines and PDEIV inhibitorsMetabolism and diabetes –ocs associated with hyperglycaemia but this is a feature of acute exacerbations. More data from roflumilast Muscles,,,Most frequently reported AEs,ET=number of patie

10、nt-years of exposure,PHARMACOLOGICALLY PREDICTABLE EFFECTS,Diarrhoea,Nausea,<1 week,≥1 weekto <4 weeks,≥4 weeksto <13 weeks,≥13 weeksto <26 weeks,≥26 weeks,<1 week,≥1 weekto <4 weeks,≥4 weeksto <

11、;13 weeks,≥13 weeksto <26 weeks,≥26 weeks,Events in the category (%),Events in the category,Weight loss,Noted as a self-reported finding more often with roflumilastNot just confined to patients reporting GI intolera

12、nceMonitored with regular weight measurement in pivotal one year trialsIn one 6 month study bioimpedance data were available,,,Body weight over time in the studies with available data,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,-4

13、,-2,0,2,4,0,8,16,24,32,40,48,Body Weight [kg],placebo,roflumilast 500µg,,,,? = -2.17 kg(CI –2.4;-1.9)p < 0.0001,Timecourse: Mean change in kgBetween Treatment Differences least-squares means from ANCOVA,Weeks,

14、,Weight change by BMI,N =,127,134,605,572,462,475,316,317,Underweight,Normal,Overweight,Obese,,,Mean Change (%),Placebo,Rof500,Percent weight change from baseline to end of treatment by BMI at baseline: pivotal COPD stud

15、ies pool (SAF),Mass indices [kg/m2],,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,-1,0,0,4,8,12,16,20,24,Weeks,Tiotropium + placebo(FFMI),Tiotropium + Daxas&#

16、174;(FFMI),Tiotropium + placebo(BMI),Tiotropium + Daxas®(BMI),Wouters EFM, Teichmann P, Brose M, et al. Am J Respir Crit Care Med 2010;181:A4473.,Weight loss associated with roflumilast was primarily fat mass,-0.

17、5,,FFMI: Fat Free Mass Index; BMI: Body Mass Index,MUSCLES,Loss of muscle bulk vs weaknessA marker for more health care expense and mortality but the thresholds may varyA clear relationship of weakness to ocs use lon

18、g term –not seen with icsAnabolic steroids reverse this process but only in people taking oral corticosteroids (Kreutzberg E et al),BONES AND INHALED CORTICSTEROIDS,Database associations but confounded by disease sever

19、ity,TORCH - Time to First FractureSafety Population,SFCN=1546,Non-Traumatic,,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=1552,SALN=1542,PlcN=1544,Traumatic,5.1%,5.1%,5.4%,6.3%

20、,KM Prob at 3 years,Prevalence of Osteoporosis & Osteopenia at Baseline,SFC,US Safety sub-study : percent change in total hip BMD,Vertical bars are standard errors,161162158162,87105112118,Numberof subjects,7

21、2828095,52786582,,,,,,,,0,48,108,158,,,,,,,,,,Placebo,SAL,FP,,,,,,,,,,,,,,,–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 eve

22、nt prior to wk 104 SFC 9.9%TIO 5.5%,Cox Hazard Ratio95% CIp-valueSFC vs TIO1.94(1.19, 3.17)0.008,Numberat Risk,013263952657891104,0,1,2,3,4,5,6,7,8,11,12,Probability of Event (%),Time to Event (Weeks),Tr

23、eatment,656550511491470451426415150SFC 50/5006645434974684242426405387136TIO 18,9,10,TIME TO FIRST PNEUMONIA AE OR SAE,Sin et al Lancet 2009,Cardiovascular Events with Tiotropium,1 rate ratio tio vs.

24、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* Use

25、d by Singh et al applied to UPLIFT,,,All-cause mortality at 3 years,Vertical bars are standard errors,181614121086420,Time to death (weeks),Probability of death (%),1524153315211534,1464148714811487,13991

26、42614171409,1293133913161288,,Placebo,,SFC,Numberalive,0,12,24,36,48,60,72,84,96,108,120,132,144,156,Calverley et al. NEJM 2007,CARDIOVASCULAR EVENTS AND THERAPY,Calverley et al Thorax 2010,CVS TREATED COPD AND THE

27、RAPY,Calverley et al Thorax 2010,Time to onset of first major adverse CV event (MACE*),MACE : CV death, non-fatal MI, non-fatal stroke,CONCLUSIONS,Beta–blockers and other cardiac drugs are safe in COPDStatins may improv

28、e COPD outcomes but proper trial data are neededOral therapies produce more GI upset, oral corticosteroids long term are hazardous Inhaled corticosteroids do not seem to accelerate osteoporosis but some may induce pneu