Interven'ons that Improve Outcomes of COPD

Interven'ons that Improve Outcomes of COPD Sidney S. Braman MD FCCP Professor of Medicine The Ichan School of Medicine at Mount Sinai New York, NY

Disclosures Consultant Sunovion, BI, Forest, Meda Reference to studies of drugs not approved for COPD exacerba'on

Interven'ons that Improve Outcomes of COPD Objec'ves: 1. Recognize the COPD risk factors that lead to hospital admission 2. Discuss the evidence- based hospital protocols to improve symptoms and other outcomes of the COPD exacerba'on 3. Iden'fy the high risk co- morbidi'es of COPD that may lead to a COPD readmission 4. List the reasons for poor adherence to therapy and how to improve low adherence rates

Interven'ons that Improve Outcomes of COPD 1. Iden'fy the High Risk Pa'ent

Interven'ons that Improve Outcomes of COPD: 1. Iden'fy the High Risk Pa'ent Severity of airway obstruction (FEV1 impairment) Chronic bronchial mucous hypersecretion (productive cough) Poor health-related quality of life Increased age and duration of COPD Prior use of medications for COPD, especially PO steroids Bacterial colonization Comorbid conditions (e.g., cardiovascular disease) Antibiotic or systemic corticosteroid use in the past year Pulmonary Artery to Aorta ratio (PA:A) > 1 Failure to use Oxygen (LTOC) when needed Poor Adherence to medication

Interven'ons that Improve Outcomes of COPD 1. Iden'fy the High Risk Pa'ent 2. Use evidence- based hospital protocols

Which of the following has been shown to reduce the risk re- exacerba'on within 30 days? a. b. c. d. Course of prednisone for 2 weeks Dietary protein supplementa'on Home- based pulmonary rehabilita'on Nocturnal BiPAP ven'la'on

Evidence- Based Hospital Protocols Assess severity of symptoms, blood gases, chest radiograph Give supplemental O2 therapy; obtain serial ABG measurements Give Bronchodilators Add oral or intravenous cor'costeroids Consider an'bio'cs (oral or occasionally intravenous) when signs of Consider noninvasive mechanical ven'la'on At all 'mes: Monitor ﬂuid balance and nutri'on Consider subcutaneous heparin or low molecular weight heparin Iden'fy and treat associated condi'ons (e.g., heart failure, arrhythmias) Closely monitor condi'on of the pa'ent (GOLD) 2013. http//www.goldcopd.org

Evidence- Based Hospital Protocols Short- ac'ng inhaled beta2- agonists with or without short- ac'ng an'cholinergics are usually the preferred bronchodilators- Evidence C (no controlled trials) No diﬀerence MDI + spacer vs. nebulizers Methyl Xanthines-?? Evidence B Cor'costeroids Evidence A An'bio'cs Three cardinal symptoms (Evidence B); Two cardinal symptoms with purulent sputum (Evidence C) Mechanical ven'la'on (invasive or noninvasive) (Evidence B) Length of an'bio'c therapy is usually 5-10 days (Evidence D).

IV Corticosteroids for Treatment of Exacerbations- 1999 Niewoehner DE, et al. N Engl J Med. 1999;340:1941-1947

Outpa'ent Cor'costeroids to Prevent Relapse of Exacerba'ons Probability of Remaining Relapse Free (%) 40 mg Prednisone vs PBO: Probability of Remaining Relapse Free for 30 Days 100 90 80 Prednisone 70 PBO 60 50 40 0 0 5 P=.04 by the log-rank test. 10 15 Days After ED Treatment Aaron SD, et al. N Engl J Med. 2003;348:2618-2625. 20 25 30

Short- term vs Conven'onal Glucocor'coid Therapy in Exacerba'ons: the REDUCE Study Percent with Exacerbation within 180 Days P=0.006 for non-inferiority Leuppi JD, et al. JAMA. 2013;309:2223-2231.

Cor'costeroids for COPD Exacerba'ons for ICU Pa'ents Group I (2/3) Group II (1/3) > 240 mg/day 240 mg/day Common Dosage: 125 mg methyl-prednisolone Q 6 hours Common Dosage: 60 mg methylprednisolone Q 6 hours Kiser TH et al. AJRCCM 2014;189:1052-1064

Cor'costeroids for COPD Exacerba'ons for ICU Pa'ents Low Dose vs. High Dose: No diﬀerence in mortality With Low Dose Cor'costeroids: Reduced ICU length of stay P<0.01 Reduced Hospital length of stay P<0.01 Reduced Hospital costs P=0.01 Reduced 'me of the ven'lator P=0.01 Reduced insulin need P<0.01 Reduced fungal infec'ons (an'fungal treatment) P<0.01 Kiser TH et al. AJRCCM 2014;189:1052-1064

Which of the following has been shown to reduce the risk of a re- exacerba'on within 30 days? a. b. c. d. Course of prednisone for 2 weeks Dietary protein supplementa'on Home- based pulmonary rehabilita'on Nocturnal BiPAP ven'la'on

Checklist for Time of Discharge Assurance of eﬀec've home maintenance pharmacotherapy regimen Reassessment of inhaler technique Educa'on regarding role of maintenance regimen Instruc'on regarding comple'on of steroid therapy and an'bio'cs, if prescribed Assess need for long- term oxygen therapy Assure follow- up visit in 4-6 weeks? 7 days Provide a management plan for comorbidi'es and their follow- up. (GOLD) 2013. http//www.goldcopd.org

High- Risk Period for Recurrent Exacerba'on Was 8 Weeks A\er First Exacerba'on Weibull function Exponential function Exacerbation intervals >1 year Number of Exacerbations 150 75 0 0 26 52 >1 year Inter-exacerbation Interval (weeks) 633 exacerbations between weeks 3 and 8; 103 (19.4%) more than predicted (P=0.040) Donaldson GC, et al. Thorax. 2002;57:847-852

The most common reason for a 30 day readmission a\er an admission for a COPD exacerba'on is: a. b. c. d. Pneumonia Acute myocardial infarc'on Conges've heart failure COPD exacerba'on

Most Frequent Medical Reasons for Rehospitaliza'on, According to Condi'on at Index Discharge (Medicare Claims Data) Condition at Index" Discharge" 30-Day" Rehospitalization Rate (%)" Reasons for Rehospitalization (%)" Most Frequen t" 2nd Most Frequent" 3rd Most Frequent" 4th Most Frequent" 5th to 10th Most Frequent" All" 21.0" Heart failure (8.6)" Pneumonia (7.3)" Psychoses (4.3)" COPD (3.9)" GI problems, nutrition-related or metabolic issues, septicemia, GI bleeding, renal failure, urinary tract infection (17.0)" Heart failure" 26.9" Heart failure (37.0)" Pneumonia (5.1)" Renal failure (3.9)" Nutrition-related or metabolic" issues (3.1)" Acute MI, COPD, arrhythmias, circulatory disorders, GI bleeding, GI problems (14.0)" Pneumonia" 20.1" Pneumonia (29.1)" Heart failure (7.4)" COPD (6.1)" Septicemia (3.6)" Nutrition-related or metabolic issues, GI problems, respiratory or ventilation problems, pulmonary edema, GI bleeding, urinary tract infection (14.9)" 22.6" COPD (36.2)" Pneumonia (11.4)" Heart failure (5.7)" Pulmonary edema" (3.9)" Respiratory or ventilation problems, GI problems, nutrition-related or metabolic issues, arrhythmias, GI bleeding, acute MI (12.5)" Psychoses" 24.6" Psychoses (67.3)" Drug toxicity (1.9)" Drug or alcohol" misuse (1.6)" Pneumonia (1.6)" Chest pain, nutrition-related or metabolic issues, depression, GI problems, COPD, organic mental conditions (7.0)" GI problems" 19.2" GI problems (21.1)" Nutrition-related or metabolic" issues (4.9)" Pneumonia (4.3)" Heart failure (4.2)" Major bowel surgery, urinary tract infection, septicemia, GI bleeding, COPD, chest pain (13.4)" COPD" COPD = chronic obstruc've pulmonary disease; GI = gastrointes'nal; MI = myocardial infarc'on Jencks SF, et al. New Eng J Med. 2009;360:1418-19.

The most common reason for a 30 day readmission a\er an admission for a COPD exacerba'on is: a. b. c. d. Pneumonia Acute myocardial infarc'on Conges've heart failure COPD exacerba'on

Interven'ons that Improve Outcomes of COPD 1. Iden'fy the High Risk Pa'ent 2. Use evidence- based hospital protocols 3. Consider assessment of high risk co- morbidi'es 1. 2. 3. 4. 5. Pneumonia Heart Failure Myocardial infarc'on Arrhythmias GI bleed

Interven'ons that Improve Outcomes of COPD 1. Iden'fy the High Risk Pa'ent 2. Use evidence- based hospital protocols 3. Consider assessment of high risk co- morbidi'es 4. Assess for poor adherence to therapy

Which of the following is the most common reason for poor adherence with COPD medica'on? a. b. c. d. Can t aﬀord the medica'on Adverse side eﬀects Felt good and decided not to dose Confusion about proper dose

Underu'liza'on of Long term Oxygen Therapy is Associated with Higher Risk of Hospitaliza'on In a mul'variate model, under use of O2 when indicated was associated with: v Three or more COPD admissions in the previous year, (OR 6.21 P=0.008) v Underprescription of LTOT has a higher risk of admission for a COPD exacerbation (OR 22.64) P=0.007 Garcia-Aymerich J, et al Am J Respir Crit Care Med 2000;164:1002-7

Persistence with All Commonly Used COPD Medica'ons is Poor N=3436. Jung E, et al. Respir Med. 2009;103:525-534.

The Most Common Reason for Nonadherence in COPD Pa'ents Is Lack of Symptoms Family problems interfered Insufficient funds to purchase medications Confused over schedule and decided not to dose Socially inconvenient Believed medication was not effective or did not Believed immune to medication: decided not to dose Ran out of medicine Side effects Change in normal routine: unexpected Change in normal routine: planned Interrupted prior to doing and forgot Absorbed in activity and forgot Felt good and forgot to dose Felt good and decided not to dose Restrepo RD, et al. Int J Chron Obstruct Pulmon Dis. 2008;3(3):371-384..

What therapies are eﬀec've to prevent exacerba'ons?

Non- Pharmacologic Evidence- Based Measures That Reduce COPD Exacerba'ons Smoking cessa'on Immuniza'ons Pulmonary rehabilita'on 29 Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease 2011. Global Initiative for Chronic Obstructive Lung Disease. www.goldcopd.org. Accessed March 30, 2012."

Reduce Exacerba'on Risk Factors: Inﬂuenza Vaccina'on Evidence from randomized clinical trials indicates that inac'vated inﬂuenza vaccine reduces exacerba'on rates in COPD pa'ents The magnitude of this beneﬁt is similar to that seen in large observa'onal studies and was due to a reduc'on in late exacerba'ons occurring 3 or more weeks aner vaccina'on and due to inﬂuenza A mild increase in transient local adverse eﬀects with vaccina'on is observed, but there was no evidence of an increase in exacerba'ons occurring within 2 weeks of vaccina'on Poole PJ, et al. Cochrane Database Syst Rev. 2006;CD002733. " 30

Reduce Exacerba'on Risk Factors: Pulmonary Rehabilita'on Study (n for rehabilitation/ n for usual care group)" Behnke (14/12)" Length of follow-up" Risk ratio (95% CI)" 18 months" 0.29 (0.10-0.82)" 37%" Man (20/21)" 3 months" 0.17 (0.04-0.69)" 44%" Murphy (13/13)" 6 months" 0.40 (0.09-1.70)" 19%" Overall (47/46)" 0.26 (0.12 to 0.54) Chi-Squared 0.70, P=0.71".25" Favors rehabilitation" Puhan MA, et al. Respir Res. 2005;6:54-60." 31 Weight (%)".5".75" 1" 1.5" Favors usual care" Risk of unplanned hospital admission"

ICS Decrease COPD Exacerba'on Risk * P=0.026 versus placebo Annual Exacerbation Rate 1.4 1.2 1.0 1.32 * 0.99 0.8 0.6 0.4 0.2 0 Fluticasone Burge PS, et al. BMJ. 2000;320:1297-1303. Placebo

TORCH STUDY Lower Exacerbation Rate With LABA Plus ICS 1.2 1.13 * 0.97 Annual Rate 1 Placebo (N=1524) * P<0.05 versus placebo * 0.93 Salmeterol (N=1521) * 0.85 0.8 Fluticasone (N=1534) 0.8 Combination Therapy (N=1533) * 0.64 0.6 * 0.52 * 0.46 0.4 * * 0.19 0.16 0.17 0.16 0.2 0 Moderate or Severe Requiring Systemic Requiring Hospitalization Steroids Calverley PM, et al. N Engl J Med. 2007;356:775-789.

UPLIFT Study Eﬀects on Exacerba'ons 0.85/yr Probability of exacerbation (%) 80 Control 60 Tiotropium 40 Hazard ratio = 0.86, (95% CI = 0.81, 0.91) P<0.0001 (log-rank test) 20 0.73/yr; P<0.001 (14% reduction) 0 0 6 12 18 24 30 36 42 48 Months Tashkin DP, et al. N Engl J Med. 2008;359:1543-1554. 34

Macrolides Prevent COPD Exacerba'ons Median time to exacerbation 266 Azithro 174 Placebo Median 'me to 1st exacerba'on 271 days Macrolide; 89 days Placebo Seemungal TAR, et al. AJRCCM 2008 Proportion of Participants Free from Acute Exacerbations of COPD for 1 Year Albert RK et al NEJM 2011

Reduc'on in Moderate or Severe Exacerba'ons- Roﬂumilast Mean Rate of Exacerbations Per Patient Per Year" Trials 5 & 6 (Pooled Data)" " = -17%" (P<0.0003)" Placebo" DALIRESP" (N=1554)" (N=1537)" Calverley PMA, et al. Lancet. 2009;374:685-94."

Higher Adherence to Therapy Lowers Risk for Hospitaliza'on in COPD Rate of Hospitalisation (per patient year) P<0.05* * based on 95% CI for relative risk Percent of Days Covered with Prescribed Medication Simoni- Was'la, et al. Am J Geriatr Pharmacother. 2012;10:201-210.

Thanks for your agen'on!