慢性阻塞性肺疾病患者的药物治疗.ppt

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!,Does having COPD influence the choice of therapy for 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-blockade in congestive heart failure, rate control of AF Longstanding worry that beta-blockade might precipitate bronchospasm So most people avoided beta-blockers in COPD Now we have evidence for safety and a reason why this 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 FEV1 (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 Organs,Lung Infections Lung Cancer,Weight loss Muscle weakness,Osteoporosis,Angina Acute coronary syndromes,Depression,Diabetes Metabolic syndrome,Depression,Peptic ulceration/reflux,Depression,From W MacNee,TREATMENT AND COMPLICATIONS,Depression common, often associated with fatigue. Interaction with therapy more likely with systemic treatment. Corticosteroids possibly roflumilast unproven Reflux GI issues with theophyllines and PDEIV inhibitors Metabolism 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 patient-years of exposure,PHARMACOLOGICALLY PREDICTABLE EFFECTS,Diarrhoea,Nausea,1 week,1 week to 4 weeks,4 weeks to 13 weeks,13 weeks to 26 weeks,26 weeks,1 week,1 week to 4 weeks,4 weeks to 13 weeks,13 weeks to 26 weeks,26 weeks,Events in the category (%),Events in the category,Weight loss,Noted as a self-reported finding more often with roflumilast Not just confined to patients reporting GI intolerance Monitored with regular weight measurement in pivotal one year trials In one 6 month study bioimpedance data were available,Body weight over time in the studies with available data,-4,-2,0,2,4,0,8,16,24,32,40,48,Body Weight kg,placebo,roflumilast 500g, = -2.17 kg (CI 2.4;-1.9) p 0.0001,Timecourse: Mean change in kg Between Treatment Differences least-squares means from ANCOVA,Weeks,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 studies pool (SAF),Mass indices kg/m2,-1,0,0,4,8,12,16,20,24,Weeks,Tiotropium + placebo (FFMI),Tiotropium + Daxas (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,-0.5,FFMI: Fat Free Mass Index; BMI: Body Mass Index,MUSCLES,Loss of muscle bulk vs weakness A marker for more health care expense and mortality but the thresholds may vary A clear relationship of weakness to ocs use long term not seen with ics Anabolic 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 severity,TORCH - Time to First Fracture Safety Population,SFC N=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%),FP N=1552,SAL N=1542,Plc N=1544,Traumatic,5.1%,5.1%,5.4%,6.3%,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,161 162 158 162,87 105 112 118,Number of subjects,72 82 80 95,52 78 65 82,0,48,108,158,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 event prior to wk 104 SFC 9.9% TIO 5.5%,Cox Hazard Ratio 95% CI p-value SFC vs TIO 1.94 (1.19, 3.17) 0.008,Number at Risk,0 13 26 39 52 65 78 91 104,0,1,2,3,4,5,6,7,8,11,12,Probability of Event (%),Time to Event (Weeks),Treatment,656 550 511 491 470 451 426 415 150 SFC 50/500 664 543 497 468 4242 426 405 387 136 TIO 18,9,10,TIME TO FIRST PNEUMONIA AE OR SAE,Sin et al Lancet 2009,Cardiovascular Events with Tiotropium,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,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,Placebo,SFC,Number alive,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 THERAPY,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,Betablockers and other cardiac drugs are safe in COPD Statins may improve COPD outcomes but proper trial data are needed Oral therapies produce