key words: chronic obstructive pulmonary disease, beta agonists, Medicare, health care costs, health care utilization

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1 reserch report Helth Cre Use nd Costs Among Medicre Ptients With Chronic Obstructive Pulmonry Disese Treted With Short-Acting Bet Agonists or Long-Acting Bet Agonists Flvi Ejzykowicz, PhD; 1 Vmsi K Bollu, PhD, MBA; 2 Krithik Rjgopln, PhD; 2 Joel W Hy, PhD 1 ffilitions: 1 University of Southern Cliforni, Los Angeles, CA 2 Sunovion Phrmceuticls Inc., Mrlborough, MA ddress correspondence to: Krithik Rjgopln, PhD Hed of Globl HEOR & Mrket Access Sunovion Phrmceuticls Inc. 84 Wterford Drive Mrlborough, MA Phone: (508) Emil: Krithik.rjgopln@sunovion. com bstrct: Chronic obstructive pulmonry disese (COPD) hs high prevlence mong older dults nd is the third leding cuse of mortlity in the United Sttes. COPD excerbtions cn require hospitliztions, resulting in high morbidity nd economic burden. In this retrospective cohort study, Medicre dministrtive clims dt were used to compre inptient resource use nd direct helth cre costs mong ptients with COPD treted with short-cting bet gonists (SABAs) or long-cting bet gonists (LABAs). Prior to djusting for bckground chrcteristics, LABA ptients (n = 833) were less likely thn SABA ptients (n = 2134) to be hospitlized (16.0% vs 23.0%; P <.001), hd fewer inptient dys (3.2 dys vs 6.4 dys; P <.001), nd hd lower totl helth cre costs ($6928 vs $8806; P <.001). After djusting for covrites, LABA-treted ptients hd n verge of 1.53 fewer inptient dys (P =.043) nd 16% lower totl helth cre costs when compred with SABA-treted ptients (P <.001). Tretment with LABAs for ptients with COPD my reduce hospitliztion dys nd lower helth cre costs. key words: chronic obstructive pulmonry disese, bet gonists, Medicre, helth cre costs, helth cre utiliztion cittion: Journl of Clinicl Pthwys. 2016;2(3): Received Februry 23, 2016; ccepted Mrch 28, Chronic obstructive pulmonry disese (COPD) is the third leding cuse of mortlity in the United Sttes. 1,2 Overll, n estimted 14.8 million US dults hve been dignosed with COPD. 3 Ntionl expenditures relted to COPD re pproximtely $49.9 billion nnully, including $29.5 billion in direct costs nd $20.9 billion in indirect costs. 2 Depending on disese severity, the estimted costs of mnging COPD rnge from $5600 to more thn $21,400 per ptient per yer. 4-6 Thus, COPD represents substntil cost burden. In survey of ptients with COPD between 2006 nd 2010, 34% of COPD ptients were Medicre beneficiries, with the remining ptients hving Medicid or privte insurnce. Overll, 51% of totl medicl costs for COPD were pid by Medicre, 25% by Medicid, nd 18% by privte insurnce in ,4 In generl, excerbtions ccount for 70 90% of the direct helth cre costs ssocited with COPD, stemming primrily from higher rtes of emergency deprtment (ED) use nd hospitliztions. 5,7,8 disclosures: At the time this reserch ws being conducted, Flvi Ejzykowicz ws doctorl fellow nd Joel W Hy ws n employee of the University of Southern Cliforni (USC); Joel W Hy remins n employee of USC. USC received unrestricted funding for this reserch from Sunovion Phrmceuticls Inc, through its doctorl fellowship progrm. Krithik Rjgopln is current employee nd Vmsi K Bollu ws n employee t the time of the reserch of Sunovion Phrmceuticls Inc. cknowledgements: We thnk Mrym Nvie, DrPH, Anne C Beubrun, BA, Leighl H Shrghi, BSN, MPA, nd Ronn Chn, MPH, PhD, ll from Advnce Helth Solutions, LLC, for their support with literture synthesis, nlytic review, nd mnuscript composition. We lso thnk Cludette Knight, PhrmD, nd Alison Wgner, PhD, of Percoltion Communictions LLC for providing medicl editoril ssistnce. Development of this mnuscript ws sponsored by Sunovion Phrmceuticls Inc. April 2016 Journl of Clinicl Pthwys 31

2 5% ntionl smple of Medicre beneficiries between 1/1/2006 nd 12/31/2008 Ptients with t lest two clims for COPD (ICD-9-CM codes: 491.xx, 492.xx, 494.xx, or 496.xx), N = 219,700 Ptients enrolled in Medicre Prts A nd B, n = 187,651 Fee-for-service ptients, n = 165,893 Ptients with t lest one clim under Medicre Prt D, n = 100,177 Ptients with t lest one clim for oxygen tretment or COPD mediction under Medicre Prts B or D, n = 84,388 Ptients ged 65 yers, n = 69,076 Ptients without sthm, n = 44,937 Medicre beneficiries continuously enrolled for 18 months who hd no COPD therpy during 6 months nd LABA nd/or SABA users during the tretment period, n = 3017 Figure 1. Smple Selection Flow Chrt At lest one clim for SABA or LABA. Abbrevitions: COPD, chronic obstructive pulmonry disese; LABA, long-cting bet gonist; SABA, short-cting bet gonist. The Globl Inititive for Chronic Obstructive Lung Disese (GOLD) guidelines recommend mintennce therpy with long-cting bronchodiltors, including bet gonists nd nticholinergics, for ptients with moderte to severe COPD nd short-cting bronchodiltors for use s rescue medictions or to tret intermittent symptoms for ptients with mild COPD. 9,10 The guidelines lso suggest considering prescribing phrmcotherpy, such s long-cting bronchodiltor therpy, before ptient is dischrged for COPD-relted hospitliztion in order to reduce excerbtions nd dely re-hospitliztion. Long-cting bronchodiltor therpy hs been shown to lower the risks of both initil nd repet hospitliztions in mnged Medicre beneficiries, primrily due to reducing the incidence of COPD excerbtions. 11 In comprison between tretment with the long-cting bet gonist (LABA) nd inhled corticosteroid therpy (fluticsone/slmeterol combintion) nd tretment with nticholinergic therpy (tiotropium, iprtropium, iprtropium/lbuterol combintion), COPD ptients in mnged Medicre popultion treted with fluticsone/slmeterol therpy hd fewer hospitliztions nd ED visits thn ptients receiving nticholinergics. 12 Despite these estblished disese mngement guidelines, 9,10 however, short-cting bet gonists (SABAs) pper to be widely used s mintennce tretment in usul clinicl cre for ptients with COPD of ll severities. 13 Among mnged Medicre beneficiries with COPD, nerly 71% re not prescribed ny mintennce therpy. 13 Although the current COPD literture focuses hevily on vrious helth outcomes, including helth service utiliztion ptterns nd costs, existing studies re lmost exclusively limited to commercil helth plns or mnged Medicre popultions. 7,12-16 A recent nlysis conducted in fee-for-service Medicre popultion in ptients newly inititing COPD therpy reveled tht ptients receiving LABA therpy hd longer time to ll-cuse hospitliztion nd lower risk for hospitliztion thn ptients on SABA therpy, demonstrting tht LABA therpy my provide incresed benefit compred with SABA therpy. 17 The uthors re unwre of ny studies tht hve directly compred the potentil benefits of LABA tretment versus SABA tretment in reltion to number of inptient dys nd totl helth cre costs. The purpose of this study ws to compre differences in inptient resource use nd totl helth cre costs using ntionl smple of Medicre beneficiries with COPD who initited tretment with LABA or SABA medictions. methods Dt Source nd Smple Selection The study proposl ws submitted to the institutionl review bord t the University of Southern Cliforni nd ws grnted wiver prior to initition. A retrospective cohort nlysis ws conducted using dt from 5% ntionl 32 Journl of Clinicl Pthwys April

3 Index dte for first SABA or LABA prescription fill Ptients must be on no prior therpy for COPD for t lest 6 months Ptients must meet ll inclusion criteri Evlution of tretment choice: SABA (group 1) LABA (group 2) SABA + LABA (group 2) Estimtions of helth service utiliztion pttern nd costs Bseline Period (minimum 6 months) Tretment Period (6 months) Follow-up Period (6 months) Figure 2. Study Design Included ptients who: (1) hd t lest 2 clims for COPD; (2) were enrolled in Medicre Prts A nd B; (3) were under fee-for-service Medicre pln; (4) hd t lest one clim under Medicre Prt D; (5) hd t lest one clim for COPD mediction under Medicre Prts B or D or oxygen tretment; (6) were 65 yers of ge or older; (7) hd no dignosis or indiction of sthm; nd (8) hd no COPD therpy during 6 months prior to tretment with SABA nd/or LABA. Abbrevitions: COPD, chronic obstructive pulmonry disese; LABA, long-cting bet gonist; SABA, short-cting bet gonist. smple of Medicre beneficiries 18 between Jnury 1, 2006, nd December 31, The dtbse contined informtion on inptient nd outptient dignoses bsed on the Interntionl Clssifiction of Diseses 9th Revision-Clinicl Modifiction (ICD-9-CM), long with ll procedure codes nd medictions dispensed to the ptient. The dtbse included inptient fcility clims (Prt A), outptient medicl service clims (Prt B), nd prescription drug clims (Prt D). The nlysis ws restricted to ptients who hd feefor-service Medicre pln nd did not include beneficiries enrolled in the Medicre Advntge supplementl insurnce (Prt C). Additionlly, ptients were included if they hd two clims for primry COPD dignosis (ICD codes 491.xx, 492.xx, 494.xx, 496.xx), enrolled in Medicre Prts A nd B, nd hd t lest one clim under Medicre Prt D. The finl smple selection followed the ppliction of sequentil inclusion criteri s delineted in Figure 1. Study Design Three time periods (bseline, tretment, nd follow-up) were determined for ech ptient in the dtbse (Figure 2). First, n index dte ws determined bsed on the first prescription fill dte for SABA (metered-dose inhler or nebulizer) or LABA (metered-dose inhler, dry powder inhler, or nebulizer) tretment using Medicre Prts B nd D clims. The bseline period ws determined to be minimum period of 6 months before the index dte. New users of COPD medictions were identified s ptients who did not receive ny SABA or LABA tretment during the bseline period. Ptients were ctegorized s SABA-treted ptients or LABA-treted ptients bsed on the COPD tretments received during the 6-month tretment period following the index dte. Ptients who received LABA mintennce therpy on the index dte were ctegorized s LABA-treted ptients. Ptients who received SABA on the index dte nd did not hve ny LABA prescription during the follow-up period were ctegorized s SABAtreted. Ptients clssified s LABA-treted could hve been treted with SABA therpy during the follow-up period. In the bsence of informtion on COPD disese severity mong ptients who were newly prescribed COPD phrmcotherpies, 6-month tretment period ws selected to permit sufficient lpsed time from which cliniclly meningful results could be ttributed to LABA or SABA therpy, while controlling for potentil underlying differences between the groups. Ptients were then followed for n dditionl 6 months, during which inptient dmissions nd totl helth cre costs were evluted. Independent nd Dependent Vribles Multiple bckground vribles were nlyzed. Demogrphic chrcteristics included ge, sex, nd rce/ethnicity. Clinicl indictors included primry dignosis (ie, COPD); number nd type of comorbid conditions (such s depression, April 2016 Journl of Clinicl Pthwys 33

4 Tble 1. Demogrphic Chrcteristics, Comorbidities, Helth Service Utiliztion Ptterns, nd Helth Cre Costs of the Study Popultion During the 6-Month Tretment Period Demogrphic chrcteristics SABA-Treted (n = 2134) LABA-Treted (n = 883) P-vlue Femle, n (%) 1429 (67.0) 570 (64.5).205 White, non-hispnic, n (%) 1888 (88.5) 791 (89.6) <.001 Age, yers, men (SD) 78.5 (8.2) 77.0 (7.2) <.001 Top five comorbidities Depression, n (%) 1764 (83.0) 710 (80.4).145 Vsculr disese, n (%) 1220 (57.2) 560 (63.0).002 Congestive hert filure, n (%) 794 (37.2) 264 (29.9) <.001 Hypertension uncomplicted, n (%) 786 (36.8) 234 (26.5) <.001 Hyperlipidemi, n (%) 708 (33.2) 225 (25.5) <.001 Helth service use Spirometry, n (%) 83 (4.0) 52 (6.0).028 Orl corticosteroid use, n (%) 401 (19.0) 171 (19.0).280 Specilist visit, n (%) 102 (5.0) 93 (10.5) <.001 Physicin visit, n (%) 1591 (74.0) 820 (93.0) <.001 Emergency deprtment visit, n (%) 497 (23.0) 158 (18.0) <.001 Hospitliztion, n (%) 809 (38.0) 266 (30.0) <.001 Inptient dys, men (SD) 11.0 (28.0) 5.4 (15.0) <.001 Helth cre costs Phrmcy, men (SD) 9204 (1221) 1005 (1182).078 Medicl, b men (SD) 9333 (15044) 6637 (11836) <.001 Totl, men (SD) (15225) 7642 (11957) <.001 Defined s peripherl vsculr disese, unspecified (ICD-9-CM 443.9) b Includes ll physicin visits, outptient visits, nd hospitliztions. Abbrevitions: LABA, long-cting bet gonist; SABA, short-cting bet gonist; SD, stndrd devition. vsculr disese, congestive hert filure, hypertension, nd hyperlipidemi); number of spirometry tests; nd prescription (ie, SABA, LABA, nd orl corticosteroid [OCS]). Helth service utiliztion vribles included physicin office visits, outptient visits, ED visits, nd hospitliztions. Dependent vribles relted to helth cre resource use nd costs were exmined, including the following: (1) percentge of ptients with one or more hospitliztions; (2) number of inptient dys, defined s the sum of ll hospitl sty dys during the entire follow-up period for ny reson; (3) ll-cuse helth cre resource use; nd (4) ll-cuse totl helth cre costs. The cost estimtes were derived from clims pid by Medicre Prts A, B, nd D during the 6-month follow-up period for phrmcy services nd medicl cre specific to physicin nd outptient visits, ED visits, nd hospitliztions. Sttisticl Anlysis Descriptive sttistics, bivrite comprisons, nd multivrite regression nlyses using ordinry lest-squres (OLS) modeling techniques were performed using SAS version 9.2 (SAS Institute, Cry, NC). Differences in men number of inptient dys nd helth cre costs were ssessed using Student t tests. The following vribles from both the bseline nd tretment periods were included in the regression models: number of spirometry tests, number of physicin visits, log of totl helth cre costs, number of dys on OCS, nd totl number of inptient dys. Two OLS regression models were fitted for the follow-up period: one with the log of totl helth cre costs without regrd to dignosis (ie, s ll cuse ) s the outcome vrible, nd one with number of inptient dys s the outcome vrible. For the cost model, the log of totl helth 34 Journl of Clinicl Pthwys April

5 SABA Treted LABA Treted P < % Percentge of Ptients P =.02 15% 14% P = % P =.33 P < % 16% 10 0 p = % 8% 3% 0.5% 0.1% 7% Spirometry OCS Use Specilist Visit Physicin Visit ED Visit Hospitliztion Helth Service Indictors Figure 3. Comprison of Helth Service Utiliztion Ptterns Between Ptients With Chronic Obstructive Pulmonry Disese on SABA Versus LABA Tretment t 6-Month Follow-up After the Initil Observtion Period (6 Months) Represents undjusted results. Abbrevitions: ED, emergency deprtment; LABA, long-cting bet gonist; OCS, orl corticosteroid; SABA, short-cting bet gonist. cre costs ws exmined s function of LABA or SABA tretment while djusting for the forementioned confounding vribles (number of inptient dys not included). Log of totl costs ws used due to the skewness to the right in the distribution of cost dt. For the inptient dys model, the number of inptient dys ws exmined s function of LABA or SABA tretment while djusting for potentil confounders (costs not included). In ddition, both models djusted for ge, sex, rce/ethnicity, nd Chrlson Comorbidity Index score. 19 Sttisticl significnce ws set t P <.05. results Descriptive Findings The finl smple included 3017 ptients with COPD newly inititing tretment: 2134 ctegorized s SABA-treted ptients, nd 883 ctegorized s LABA-treted ptients. SABA-treted ptients were slightly older thn the LABAtreted ptients (P <.001) nd were more likely to hve comorbid congestive hert filure (P <.001), uncomplicted hypertension (P <.001), nd hyperlipidemi (P <.001; Tble 1). However, significntly higher percentge of LABA-treted ptients hd comorbid vsculr disese compred with SABA-treted ptients (P =.002). During the tretment period, there were significnt differences between the study groups in helth service utiliztion nd ssocited costs (Tble 1). SABA-treted ptients hd significntly more COPD-relted ED visits (23% vs 18%; P <.001), hospitliztions (38% vs 30%; P <.001), nd inptient dys (28% vs 15%; P <.001) thn LABA-treted ptients, wheres LABA-treted ptients hd significntly more COPD-relted outptient visits to physicins (93% vs 74%; P <.001) nd specilists (10.5% vs 5%; P <.001) thn SABA-treted ptients. Along with the greter inptient service use, SABA-treted ptients lso hd significntly higher medicl costs ($9333 vs $6637; P <.001) nd totl helth cre costs ($10,253 vs $7642; P <.001) during the tretment period thn LABA-treted ptients. Helth Service Utiliztion nd Costs During the Follow-up Period Undjusted comprisons during the 6-month follow-up period reveled tht SABA-treted ptients were significntly more likely to hve used OCS (15% vs 14%; P =.02) nd were significntly more likely to hve greter number of hospitliztions compred with LABA-treted ptients (23% vs 16%; P <.001; Figure 3). However, LABA-treted April 2016 Journl of Clinicl Pthwys 35

6 10, SABA-Treted LABA-Treted P = P = Helth Cre Costs (USD) P = Phrmcy Medicl Totl Helth Cre Ctegories Figure 4. Comprison of Averge Helth Cre Costs Between Ptients With Chronic Obstructive Pulmonry Disese on SABA Versus LABA Tretment t 6-Month Follow-up After the Initil Observtion Period (6 Months),b Amounts rounded to the nerest dollr. Medicl costs included ll physicin visits, outptient visits, nd hospitliztions. b Represents undjusted results. Abbrevitions: LABA, long-cting bet gonist, SABA, short-cting bet gonist. ptients were more likely to hve hd greter number of physicin visits (85% vs 65%; P <.001), including specilist visits (6% vs 3%; P <.002), thn SABA-treted ptients. Additionlly, LABA-treted ptients hd significntly lower verge medicl costs ($6094 vs $8020; P =.012) s well s lower verge totl helth cre costs from ll cuses compred with SABA-treted ptients ($6928 vs $8806; P =.001; Figure 4). After djusting for potentil confounders, the regression models reveled tht LABA-treted ptients hd fewer inptient dys nd lower overll totl helth cre costs thn SABA-treted ptients. LABA-treted ptients hd 1.53 fewer inptient dys thn SABA-treted ptients (P =.043) during the 6-month follow-up period. In ddition, LABAtreted ptients hd 16% lower reltive totl helth cre costs thn SABA-treted ptients (P <.001). discussion COPD is chronic, progressive disese in which mny ptients experience episodic worsening of symptoms or excerbtions. 9,10 On verge, ptient with COPD experiences between fewer thn one nd three excerbtions per yer Excerbtions my increse ptients risk of hospitliztion up to 70% nd result in substntil economic burden. 8,23 To mitigte the risk of preventble hospitliztions secondry to COPD excerbtions, globl tretment guidelines for best prctices recommend the use of long-cting bronchodiltors, such s LABA, for mintennce tretment, nd recommend its initition prior to hospitl dischrge. 9,10 The findings from this rel-world nlysis lend support to these guidelines by showing tht, mong Medicre beneficiries with COPD, tretment with LABA resulted in fewer inptient dys nd 16% lower totl helth cre costs thn tretment with SABA. The findings from this nlysis re consistent with reserch in other smller subpopultions of Medicre beneficiries demonstrting the benefits of LABA mintennce therpy. Simoni-Wstil et l 12 reported tht mnged Medicre ptients with COPD who were treted with inhled corticosteroids nd LABA combintion therpy hd n 18% lower reltive risk of COPD-relted hospitliztion nd ED visit compred with ptients treted with lterntive therpies. Lower costs re ssocited with lower helth cre utiliztion subsequent to fewer incidents of COPDrelted excerbtions. 14 Similrly, Sturt et l 11 found tht ptients receiving mintennce therpy tht included 36 Journl of Clinicl Pthwys April

7 LABA use hd verge nnul Medicre expenditures of pproximtely $3916 less thn those for ptients receiving no mintennce therpy. Those uthors concluded tht Medicre beneficiries with COPD who filed to tke the recommended mintennce medictions for COPD were t incresed risk for hospitliztions nd corresponding increses in Medicre expenditures. While there re numerous studies evluting outcomes with LABA therpy, the mjority hve ssessed redmission risk or ptient outcomes fter hospitl dischrge. To the best of our knowledge, our study is currently the only nlysis tht evlutes the impct of LABA nd SABA therpy on hospitl dys nd costs nd in fee-for-service Medicre popultion. Overll, the results of our study demonstrte tht the use of LABA therpy provides vlue to Medicre in terms of helth cre cost svings compred with SABA therpy. Previous nlyses hve evluted the economic impct of COPD, including hospitliztions, on the Medicre system; however, the cost estimtes vry. The verge nnul per-ptient tretment costs for Medicre COPD beneficiry hve been estimted t $21,409 (excluding phrmcy costs). 6 A prior report exmining only the costs ttributble to COPD estimted the verge nnul costs mong Medicre enrollees t $ Dll et l 16 reported COPDrelted costs of $7544 for hospitliztion of Medicre ptients with simple dmissions; however, when excerbtions require intensive cre unit dmission nd intubtion, costs incresed to $45,607 per hospitliztion. Estimtes of cost burden to the Medicre system vry cross studies due to methodologicl differences, such s the yer in which expenditures were incurred; COPD disese severity; Medicre smpling strtegy (mnged cre, fee-for-service, or both); services included in cost computtions; the durtion of follow-up to cpture costs; nd fctors used in djusting costs to chieve comprbility mong study popultions. Notwithstnding the vritions in estimtes of cost burden, the consistent messge from the evidence-bsed literture is tht reducing COPD excerbtion frequency nd severity reduces the incidence of first-time nd repeted COPD-relted hospitliztions, resulting in considerble cost svings. Given tht Medicre spending is projected to grow from $512 billion in 2014 to $858 billion in 2024, the implictions of improved chronic disese mngement for conditions such s COPD, which rnks mong the most costly to the Medicre system, re substntil. 25,26 As is the cse with ll reserch, the results of the present study must be interpreted in light of certin limittions. First, findings from these retrospective clims of Medicre beneficiries my not be generlizble to other ptient popultions with COPD. Second, retrospective dtbse reviews re dependent on informtion recorded in medicl records nd my be subject to coding errors or dt omissions. Third, the nlysis did not control for use of inhled steroids, clss of mediction tht hs been shown to positively impct the prmeters evluted in this study (including COPD excerbtions nd hospitliztions). Fourth, potentil residul confounding could hve risen from fctors such s COPD disese severity, current or pst smoking sttus, nd relevnt clinicl lb vlues (eg, spirometry test results, pek inspirtory flow rte), which were not vilble for exmintion. 27 To mitigte the potentil effects of such unmesured confounders, multivrite nlyses included severl proxies of disese severity such s OCS use nd number of physicin visits. Fifth, the specific detils of ptients tretment persistence or dherence were not vilble, nd poor ptient tretment dherence hs been ssocited with incresed COPD excerbtions, excessive helth service use, nd incresed COPD-relted tretment costs. 9,10,28,29 Sixth, the smple size ws insufficient to restrict the nlysis to specific mode of tretment delivery nd formultion (eg, comprison of nebulized LABA with nebulized SABA). Seventh, the study s findings re bsed on reltively short follow-up period of 6 months; therefore, the true long-term impct of tretment with LABA, either lone or in combintion therpy, remins uncler. Finlly, the nlysis exmined the costs reimbursed by Medicre for services, which did not include out-of-pocket expenses or cost shring by ptients for services not covered by Medicre; therefore, it my underestimte the per-ptient burden of COPD. Despite these limittions, the results of this study exmining the effects of recommended mintennce therpy with LABA on inptient dys nd helth cre costs in the broder Medicre popultion ultimtely provide two importnt dditions to the literture. First, pst studies hve limited generlizbility becuse they hve primrily focused on Medicre mnged cre popultions tht constitute specific popultion of only 30% of ll Medicre enrollees. 30 By contrst, the results presented in the current study re more generlizble to Medicre beneficiries; pproximtely 70% of Medicre ptients receive trditionl fee-for-service benefits. 30 Second, these results my guide improved clinicl decision-mking to the betterment of cre for ptients with COPD nd with importnt implictions for potentil cost svings. conclusion Findings from the present study suggest tht inititing mintennce tretment for COPD with LABA insted of SABA is ssocited with reduction in inptient dys nd reduction in totl helth cre costs. These findings my hve significnt implictions for helth cre cost svings with LABA tretment. The findings highlight the potentil need for mjor eductionl effort to disseminte evidence-bsed guidelines to helth cre providers nd their ptients on the long-term benefits of mintennce therpy for COPD mngement. In order to dvnce COPD April 2016 Journl of Clinicl Pthwys 37

8 reserch tht cn enhnce clinicl decision-mking specific to phrmcologic pproches to disese mngement, future studies on longer-term outcomes nd differences in the modes of tretment delivery (eg, nebulizer vs dry-powder inhler) for LABA versus SABA would be vluble. Additionlly, studies compring numerous timefrmes nd longer follow-up might lso be vluble. REFERENCES 1. Kochnek K, Murphy SL, Jiqun JX, Aris E. Mortlity in the United Sttes, NCHS Dt Brief. 2014;178. Accessed Mrch 25, Americn Lung Assocition. Trends in COPD (Chronic Bronchitis nd Emphysem): Morbidity nd Mortlity. Published Mrch Accessed Mrch 25, US Deprtment of Helth nd Humn Services. Ntionl Hert Lung nd Blood Institute. Morbidity nd mortlity: 2012 chrtbook on crdiovsculr, lung, nd blood diseses. pdf. Published Februry Accessed Mrch 25, Ford ES, Murphy LB, Khvjou O, Giles WH, Holt JB, Croft JB. Totl nd sttespecific medicl nd bsenteeism costs of COPD mong dults ged >/= 18 yers in the United Sttes for 2010 nd projections through Chest. 2015;147(1): Hlpern MT, Stnford RH, Borker R. The burden of COPD in the USA: results from the Confronting COPD survey. Respir Med. 2003;97(supp C):S Schneider KM, O Donnell BE, Den D. Prevlence of multiple chronic conditions in the United Sttes Medicre popultion. Helth Qul Life Outcomes. 2009;7: Dll AA, Christensen L, Liu F, Riedel AA. Direct costs of chronic obstructive pulmonry disese mong mnged cre ptients. Int J Chron Obstruct Pulmon Dis. 2010;5: Toy EL, Gllgher KF, Stnley EL, Swensen AR, Duh MS. The economic impct of excerbtions of chronic obstructive pulmonry disese nd excerbtion definition: review. COPD. 2010;7(3): Globl Inititive for Chronic Obstructive Lung Disese (GOLD). Globl Strtegy for the Dignosis, Mngement nd Prevention of Chronic Obstructive Pulmonry Disese. 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