patrickj$strollo,$jr,$md,$facp,$fccp,$faasm … · outline:$beneﬁts$of$cpap$ • background$ •...

CPAP Benefits for OSA

Patrick J Strollo, Jr, MD, FACP, FCCP, FAASM Professor of Medicine and Clinical and Transla<onal

Science Medical Director, UPMC Sleep Medicine Center

University of Pi.sburgh / CTSI / Clinical + Transla<onal Science Ins<tute

Disclosure: Patrick J Strollo, Jr., MD Research Support •  Federal

–  R01 HL107370 –  RO1 DK096028-‐02 –  RO1 HL120354-‐01A1 –  1UH2HL125103-‐01 –  5UL1TR000005-‐09

•  State –  PA DOH MD-‐02-‐384

•  Industry –  Research Grant Philips-‐Respironics, Inc. –  Research Grant ResMed, Corp. –  Inspire Medical Systems –  Na<onal Football League –  PinMed

•  Founda<on –  American Sleep Medicine Founda<on

Industry advisory: -‐  ResMed -‐  Philips-‐Respironics -‐  Emmi Solu<ons -‐  Jazz Pharmaceu<cals

Outline: Benefits of CPAP

•  Background •  Metabolic / Type II DM •  Neurocogni<ve / Accidents •  Cardiovascular •  Healthcare u<liza<on •  Summary / Conclusions

Untreated OSA Results in Major Economic Cost

4

The Price of Fa<gue, Harvard Medical School, Division of Sleep Medicine, 2010 healthysleep.med.harvard.edu/file/20

Sleep Apnea is Associated with Significant Co-morbidities

Cardiovascular Complications

Metabolic Complications

Neuro-cognitive Complications

* Non-‐propor<onal Venn diagram

Effect of CPAP on Insulin Sensi<vity

•  Subjects 34 m / 6 f •  Age 53.8 + 11.8 •  BMI 32.7 + 6.9 •  No Diabetes •  Insulin sensi<vity measured

by euglycemic clamp

Insulin

Sen

si<v

ity In

dex

Baseline 2 Days 3 Months 0 2 4 6 8 10 12

AJRCCM 2004 169:156-‐62

p < 0.001

p < 0.001 n.s.

Greatest effect on subset BMI < 30

Impact of CPAP on HbA1c: Analysis of UK THIN Database

Diabetes Care 2014;37:1263–1

n = 150 n = 150

CPAP adherence was a mean of 5.8 to 6 1.0 h per night (range 4.0–7.2) for 11 pa<ents*

Associa<on of OSA in REM Sleep With Reduced Glycemic Control in Type 2 DM: Rx Implica<ons

•  Aim: To quan<fy the impact of OSA in REM versus NREM sleep on HbA1C in subjects with type 2 DM

•  Design: Prospec<ve cohort. All par<cipants underwent PSG, and glycemic control was assessed by HbA1C

•  Results: n = 115 (65 women) 55.2 + 9.8 yrs, BMI 34.5 + 7.5 kg/m2. Mul<variate linear regression model, REM AHI was independently associated with increasing levels of HbA1C (P =0.008).

•  Conclusions: OSA during REM sleep may influence long-‐term glycemic control. The metabolic benefits of CPAP therapy may not be achieved with the typical adherence of 4 h per night.

Diabetes Care 2014 37:3555-‐363

Associa<on of OSA in REM Sleep With Reduced Glycemic Control in Type 2 DM: Rx Implica<ons

Diabetes Care 2014 37:3555-‐363 Adjusted for age, sex, race, BMI, years of Type 2 DM, and insulin use

Cumula<ve min of REM and NREM over 8 h of bed<me

Diabetes Care 2014 37:3555-‐363

The Apnea Posi<ve Pressure Long-‐term Efficacy Study (APPLES)

Aim: To assess its efficacy on neurocogni<ve func<on in pa<ents with OSA across a range of disease severity. Design: Prospec<ve randomized, double-‐blind, 2-‐arm, sham-‐controlled, mul<center, long-‐term (6 months) trial of CPAP therapy

Sleep 2012 35:1593

APPLES: No Improvements in Subjec<ve or Objec<ve Sleepiness in Mild to Moderate OSA

Sleep 2012 35:1593

PAP n = 551 Sham n = 535

APPLES: No Improvements in Neurocognitive function with OSA Rx

•  No significant changes in –  Agen<on and Psychomotor Func<on

(Pathfinder Number Test) –  Verbal Learning and Memory (Buschke

Selec<ve Reminding Test Sum Recall) –  Execu<ve and Frontal Lobe Func<on

(Sustained Working Memory Test)

•  No differences by severity of OSA •  Only transient improvements in

Execu<ve and Frontal Lobe Func<on at 2 mo seen in pa<ents with severe OSA and did not persist at 6 mo

Sleep 2012 35:1593 n = 1098

CPAP Treatment of Sleepy Pa<ents with Milder OSA: Results of the CATNAP Randomized Clinical Trial

•  Sleepy pa<ents with mild and moderately severe OSA had greater func<onal improvement aier 8 weeks of CPAP therapy compared to sham CPAP.

•  Compared to placebo, CPAP treatment also produced clinically meaningful changes in mood and self-‐reported day<me sleepiness.

•  As a mul<site study conducted at large and smaller clinical prac<ce sites, the results are highly generalizable and indicate the efficacy of this therapy in trea<ng sleepy pa<ents with less severe OSA. AJRCCM 2012 186:677-‐83

*

Incidence of motor vehicle accidents (MVAs) per 1,000 individuals per year before and aier CPAP

SLEEP 2015;38(3):341–349

Sleep 2008 31:1071-78

Sleep Disordered Breathing and Mortality: Eighteen-Year Follow-up of the Wisconsin Sleep Cohort (n = 1396)

•  SDB, irrespec<ve of EDS, was associated with increased mortality. •  The striking high CV mortality risk in untreated severe SDB, suggests that SDB Rx should not be con<ngent on day<me sleepiness symptoms

Cumula<

ve In

cide

nce of Fatal CV Even

ts

Cumula<

ve In

cide

nce of Non

-‐fatal CV Even

ts

AIM: Observa<onal study to compare incidence of fatal and non-‐fatal cardiovascular events in simple snorers, pa<ents with untreated OSA, pa<ents treated with CPAP, and healthy men recruited from the general popula<on. Design: Prospec<ve observa<onal cohort. 264 healthy men, 377 simple snorers, 403 with untreated mild-‐moderate OSA (AHI 5-‐30), 235 with untreated severe OSA (AHI > 30), and 372 with OSA and treated with CPAP

Lancet 2005 365: 1046–53

Months Months

.

Conclusion: In men, severe OSA significantly increases the risk of fatal and non-‐fatal cardiovascular events. CPAP treatment reduces this risk.

Long-‐term cardiovascular outcomes in men with OSA

OSA is associated with CV Mortality in Women & Treatment Modifies This Risk

Conclusion: Severe OSA is associated with cardiovascular death in women, and adequate CPAP treatment may reduce this risk.

Ann Intern Med. 2012;156:115-‐122.

n = 1116

24 Hour BP Before and Aier 1 Month of CPAP, Therapeu<c Versus Sub-‐therapeu<c

Mean bloo

d pressure (m

mHg

)

Time from wake and sleep onset (hours)

Mean bloo

d pressure (m

mHg

)

Time from wake and sleep onset (hours)

Before Treatment Aier Treatment

Lancet 2002 359:204 -‐10

Effect of CPAP on 24-‐h mean blood pressure in OSA

Treatment with CPAP promoted significantly but small reduc<ons in blood pressure in individuals with OSA. Further studies should be performed to evaluate the effects of long-‐term CPAP and the impact on cardiovascular risk.

Journal of Hypertension 2014, 32:1762–1773

Mean change in 24-‐h DBP from RCTs in Resistant HTN

•  The pooled es<mate shows a favorable reduc<on of BP with CPAP treatment in pa<ents with resistant hypertension and OSA.

•  The effect sizes are larger than those previously reported in pa<ents with OSA without resistant hypertension

J Hypertens 2014 32:2341–2350

Hospital Stays: Men Physician Claims: Men

SLEEP 1999 22:740-‐47 SLEEP 2006 29:1307-‐11.

Physician claims: Women Ambulatory clinic visits: Women

Healthcare U<liza<on with OSA 2 Years Aier Diagnosis and Treatment

Diagnosis

Diagnosis

Diagnosis

Diagnosis

Summary

•  Observa<onal data demonstrate a posi<ve treatment effect on: – Metabolic risk – Insulin sensi<vity / HbA1c

– Neurocogni<ve risk – FOSQ / MVA – Cardiovascular risk – Fatal and Nonfatal MI – Healthcare U<liza<on

•  Randomized Control Trials – Cardiovascular risk – Blood pressure / Cardiac remodeling

– Mortality / Morbidity?

OSA RCTs: CV Outcomes (Secondary Preven<on)

Study Popula<on Interven<on n Recruitment Status

CANPAP Systolic HF CPAP vs UC 258 Complete

RICCADSA Revascularized CAD

CPAP vs UC* * Four groups

400 Complete

SAVE CAD CPAP vs UC 2717 Complete

SERVE-‐HF Systolic HF ASV vs UC ~1200 Complete

ADVENT -‐HF

Systolic HF ASV vs UC 860 Ac<ve

UC = Usual Care

CPAP Therapy and Adherence PAP therapy when used consistently results in decreased day<me sleepiness*, improved HRQOL, and decreased vascular risk. Recent studies of CPAP therapy inves<gated adherence:

•  APPLES Study – largest RCT in sleep medicine to date (1,516 subjects enrolled) and CPAP adherence rate was 39% at 6-‐months use of CPAP therapy (174 of 443)

• Home PAP Study – Evalua<on of standard OSA care vs. home-‐base diagnos<cs and <tra<on. Results of 3-‐month follow-‐up: CPAP adherence was 39% (Lab <tra<on); CPAP adherence was 50% (Home <tra<on)

Conclusion: •  CPAP is first-‐line therapy and effec<ve when consistently used by OSA pa<ents.

•  Alterna<ve therapy op<ons for moderate or severe OSA pa<ents who are nonadherent to PAP are desirable

0

5

10

15

20

25

30

0 10 20 30 40 50 60 70 80 90 100

Epw

orth

Sle

epin

ess

Scal

e

Apnea – Hypopnea Index

The Relationship of Self Reported Sleepiness to Sleep Apnea

n = 4653

Non-Sleepy Sleep Apnea

Sleepy Sleep Apnea

J Clin Sleep Med 2010 6:196-204

Future Research & Management

•  Diagnos<c classifica<on –  Clinical phenotypes –  Sleepy vs Non-‐Sleepy Endotypes

•  Management – U<lity of Advanced Posi<ve Pressure Devices – Op<mal treatment dura<on*

•  Impact of co-‐morbid condi<ons –  Cardiac compromise (R & L* Heart Failure) –  Insomnia –  Insufficient sleep (independent of sleep fragmenta<on) – Obesity

NATURE 2010 463: 258-259

Thank You


Physiologic Phenotyping in OSA

•  Upper Airway Anatomy/Collapsibility: –  Posi<ve Airway Pressure, Dental appliances, Upper Airway Surgery.

•  The Upper Airway Response: –  Unilateral Hypoglossal Nerve S<mula<on

•  Arousal Threshold to a Respiratory S<mulus: –  Hypno<cs (eszopiclone and trazodone)

•  Loop Gain (Ven<latory Control Instability): –  Both oxygen and acetazolamide can lower loop gain.

Semin Respir Crit Care Med 2014;35:621–628

Obstruc<ve Sleep Apnea and Type II Diabetes

•  Up to 40% of people with OSA have diabetes, the incidence of new diabetes in people with OSA is not known.1

•  In people who have diabetes, the prevalence of OSA may be up to 23%2

•  The prevalence of some form of sleep disordered breathing may be as high as 58%.3

•  Overweight and obesity may play a role, recent studies show an associa<on between the two condi<ons that is independent of overweight/ obesity.

•  OSA may have effects on glycemic control in people with type 2 diabetes.

1Eur Respir J 22(1): 156-‐160, 2003 2Thorax 61(11): 945-‐950, 2006 3Diabetes Care 26(3): 702-‐709, 2003

OSA and Cardiovascular Disease

•  Primary HTN: 35% prevalence •  Drug-‐resistant HTN: 65 to 80% prevalence

– Most common secondary cause

•  Coronary Artery Disease: 30% prevalence •  Heart failure: 21-‐37% prevalence •  Atrial Fibrilla<on: OSA present 5 X more likely •  Stroke: 60% prevalence

Circula<on 2012;126:1495-‐1510

Interven<onal RCTs

•  No published large scale interven<onal RCTs on benefit of OSA treatment on CVD/Mortality

•  RICCADSA: Randomized Interven<on with CPAP in Coronary Artery Disease and Sleep Apnoea –  400 CAD ppts: 100 each to 1) non-‐sleepy OSA/CPAP, 2) non-‐sleepy OSA/no CPAP, 3) sleepy OSA/CPAP, 4) CAD but no OSA

–  Follow-‐up for 3 years for CVD morbidity and mortality

Scand Cardiovasc J. 2009 Feb;43(1):24-‐31

Sleep Apnea Cardiovascular Endpoints Study

•  Mul<na<onal randomized, controlled trial to determine the

effects of nasal con<nuous posi<ve airway pressure (CPAP) in preven<ng cardiovascular (CV) disease in high risk pa<ents with moderate-‐severe obstruc<ve sleep apnea (OSA)

•  Par<cipants randomized to CPAP or Op<mal medical care •  Follow-‐up for 3-‐5 years (avg 4 yrs) •  2717 randomized by Dec 2013 •  Sites (n = 89) in China, Australia, New Zealand, India, USA,

Spain and Brazil •  Primary Endpoint: Composite of CV death, MI, HF, and

ischemic stroke (hospitaliza<on)

Jointly funded by Philips Respironics (unrestricted grant) and the Australian Na<onal Health and Research Council. Equipment Grants from ResMed & Compumedics NCT00738179

Aim: Demonstrate that ASV therapy over minimum two years can improve morbidly and mortality in HF patients with predominately CSA Design: RCT with n = > 1300 (78 centers)

•  Control arm: Optimal medical care

•  Active arm: Optimal medical care plus ASV

Status: Enrolment complete (2013)

Funded by ResMed NCT00733343

HF patients ≥ 18 yrs of age with LVEF ≤ 45% on optimal HF therapy, undergo a sleep study

ADAPTIVE-‐SERVO VENTILATION FOR TREATMENT OF OSA AND CSA IN HEART FAILURE

AHI ≥ 15 (≥ 50% obstructive = OSA, >50% central = CSA)

Randomization

Control – no ASV, n = 430 ASV – titrated on sleep study to eliminate OSA and/or CSA, n = 430

Baseline QOL, NT-pro-BNP, 6MWT, LVEF, LVEDV and LV mass

•  1 month clinic visit, sleep study and QOL •  3 month clinic visit •  6 month clinic visit, QOL, NT-pro-BNP, 6MWT, LVEF, LVEDV and LV mass •  6 monthly clinic visits and QOL until end of trial at 60 months •  Primary outcome is the composite endpoint of deaths, and CV hospitalizations over the follow-up period •  Endpoint is 540 primary events which we estimate will require a 3-year accrual time with minimum and maximum follow up times of 2 and 5 years •  2 interim analyses after 50% (n=270) and 75% (n=405) of the predicted number of primary events have occurred

Jointly funded by CIHR and an unrestricted grant fro PHILIPS/RESPIRONICS NCT01128816

Effects of Con<nuous Posi<ve Airway Pressure on Cardiac Remodeling

A-‐D, Serial improvement in RAVI (A), RVEDD (B), RVEDVI (C), and LVMI (D) by either transthoracic echocardiography (A, B) or cardiac MRI (C, D)

LVMI = lem ventricular mass index; RAVI = right atrial volume index; RVEDD = right ventricular enddiastolic diameter; RVEDVI = right ventricular end-‐diastolic volume index CHEST 2012; 141(3):674–681

Observational trials in untreated OSA is associated with

•  Prevalent1 and incident2,3 hypertension •  Prevalent and incident CAD4 and CHF5

•  Cardiac arrhythmias6 and sudden death7 •  Stroke8 •  Pulmonary HTN9

1JAMA 2000 283(14): 1829-1836 2 AJRCCM 2009 179:1159-1164 3JAMA. 2012 307(20):2169 4Circ 2010 122:325-60 5AJRCCM 2001 163:19-25 6AJRCCM 2006 170:910-16 7NEJM 2005 352:1206-14 8AJRCCM 2010 182: 269-77 9Prog Cardiovasc Dis 2009 51:369-70

Progress in ADVENT-‐HF

•  33 ac<ve sites ini<ated in: –  Canada, –  USA –  Spain, –  Germany –  UK –  Italy –  Brazil

•  271 pa<ents randomized as of August 26, 2014 (about 50% of predicted rate)

Conclusions •  Substan<al progress has been made in the past 25-‐30 years in our understanding of the OSA/CVD rela<onship

•  Accumula<ng evidence implicates SDB as an independent risk factor for hypertension, CHD and Stroke

•  Risk may not be the same for all segments of the popula<on

•  Treatment appears to mi<gate the risk in some clinical popula<ons

•  Unclear whether treatment is beneficial in pa<ents without symptoms

Sleep Apnea / Hypopnea

Clin Chest Med 2003 24:307–313

Differential susceptibility to daytime sleepiness

Differential susceptibility to vascular risk

The variable effect of OSA on physiologic outcomes

Impact of CPAP CVD

•  Hypertension –  Does treatment of OSA reduce incident hypertension? –  In whom does treatment of OSA significantly lower BP?

•  Coronary Heart Disease/CHF/Stroke –  Does treatment of OSA decrease risk of CHD/CHF/Stroke? – What treatments will be effec<ve?

•  Mortality –  Does treatment of OSA decrease mortality risk?

CPAP Might Prevent HTN or CVD in Non-Sleepy OSA Patients

• Pa<ents with mostly severe OSA recruited • Benefits seen only if adherent to CPAP

Barbe F, et al. JAMA 2012: 307:2161.

© 2015 American Academy of Sleep Medicine 11

CPAP Might Improve Blood Pressure in Non-Sleepy OSA Patients with Hypertension

• Pa<ents with mostly severe OSA recruited • Benefits seen only poten<ally seen if adherent to CPAP (>5.65h/night)

Barbe F, et al. JAMA 2012: 307:2161.

© 2015 American Academy of Sleep Medicine 12

OSA is only associated with mortality in those with severe OSA

Sleep Heart Health Study

Amer adjustments for age, race, BMI, smoking status, blood pressure, prevalent hypertension, diabetes, and CVD.

© 2015 American Academy of Sleep Medicine

Wisconsin Cohort

Table 6 —Mortality Risk* With Untreated Sleep-Disordered Breathing (n = 1396)** Baseline AHI All-cause Cardiovascular category mortality mortality Hazard Ratio Hazard Ratio

(95% CI) (95% CI) None: 0 - < 5 Reference Reference

Mild: 5 - < 15 1.4 (0.7, 2.6) 1.3 (0.4, 4.1) Moderate: 15 - < 30 1.7 (0.7, 4.1) 1.5 (0.3, 7.3) Σεϖερε: 30 3 8 (1 6 9 0) 5 2 (1 4 9 2) P trend = 0.004 P-trend = 0.03

*Hazard ratios adjusted for age, age2, sex, body mass index, and body mass index2

**126 persons who reported usual use of continuous positive air πρ σσυρε Χ Α Π) 4 νιγη σ περ ω εε ερε εξχλυδεδ φροµ σ µπλε AHI denotes number of apnea and hypopnea events per hour of σλεεπ ΧΙ δενοτ σ χον ιδνχε ιντ ρϖαλ

Punjabi NM, et al. PLoS Medicine 2009; Young TB, et al. Sleep 2008; 31: 1071.

14

Factors Affec<ng CPAP Adherence

•  Snoring history. •  Apnea / hypopnea index ( > 30). •  Epworth sleepiness score ( > 10).

Prospective evaluation of CPAP use (n = 1,211)

Adherence at 5 yrs (68%): 3 month use predictive

AJRCCM 1999 159:1108-‐14

CPAP is not op<mal treatment for some

•  Restric<ve to sleep for some pa<ents •  Side effects can include sore throat, facial soreness, claustrophobia and disrupted sleep

Mean Nightly CPAP Use: Consistent vs. Intermittent Users

Sleep 1997 20:278-83

Consistent CPAP Users (n=17)

Intermittent CPAP users (n=15)

Days of Therapy

CPAP Use (hrs)

Targeted interven<ons using objec<ve measurement can improve adherence

•  Increased Adherence to CPAP With a Group Cogni<ve Behavioral Treatment Interven<on: A Randomized Trial (n = 100) •  A higher adherence to CPAP therapy was found in the CBT group (2.9 hours

difference) rela<ve to treatment as usual (P < 0.001) at 28 days. •  Long-‐term Compliance Rates to CPAP in OSA* A Popula<on-‐Based Study (n =296)

•  A popula<on-‐based CPAP program consis<ng of consistent follow-‐up, “troubleshoo<ng,” and regular feedback to both pa<ents and physicians can achieve CPAP compliance rates of > 85% over 6 months (> 3.5 hrs/d).

•  Interven<ons to improve compliance in sleep apnea pa<ents previously non-‐compliant with CPAP (n = 204) •  A two phase interven<on program, first employing standard interven<ons,

followed by a change to flexible bilevel airway pressure, can achieve improved compliance in pa<ents previously non compliant with CPAP

SLEEP 2007; 30(5):635-640 CHEST 2002; 121:430–435 JCSM 2007; 3:706-12

An approach to poor compliance with CPAP

Sleep Med Rev 2007 11:195-207

Rhinitis

Leaks Skin lesions Conjunctivitis Noise

Dry Mouth

Lack of Improvement

Involuntary removal asleep

Anxiety / Phobia

Negative social aspects

Thoracic pain, Expiration difficulties, Aerophagia, Cold and pressure sensation

Tooth problems, Sinus problems Ear problems

Review steps 1-4

CBT, Desensitization

Nasal sprays

Mask re-fit

Avoid leaks Humidification Chinstrap FFM

Suboptimal pressure Non-pulmonary sleep disorder

Frequently transient

ENT /OMF

1

2

3

4

5

6

7

8

9

n = 115 n = 116

CHEST 2001; 120:1923–1929

Prevalence of Insomnia Symptoms in Patients with OSA

Persistent Sleepiness in OSA treated with CPAP

Sleep Med Rev 2007 11:195-207

Ensure duration of sleep is adequate

Confirm Dx of OSA

Confirm adequate CPAP titration

Data management software: Adherence Control of SDB Leaks Variability*

Exclude co-morbid condition causing EDS: Depression Narcolepsy RLS Poor sleep hygiene

Re-examine treatment goals

Modafinil as an Adjunc<ve Rx to CPAP

Baseline Week 4

Mea

n Sl

eep

Late

ncy

(min

)

8.6 7.2 7.5 7.4

•  Population (n = 177) •  Randomized placebo controlled •  Intervention => 400 mg Modafinil •  Outcome measures ESS CPAP adherence MSLT

AJRCCM 2001 164: 1675-81

Conclusions

•  Obstruc<ve sleep apnea is commonly encountered in the outpa<ent clinic

•  It is rela<vely easily diagnosed •  It is associated with significant co-‐morbidi<es •  Effec<ve treatment is available, but requires chronic disease

management •  Input from sleep specialists can be helpful in difficult to treat

cases –  Poor adherence posi<ve pressure –  Co-‐morbid sleep disorders (i.e. insomnia, restless legs, etc)

–  Residual day<me sleepiness

Focusing the treatment on the primary patient complaint

Obstructive Sleep Apnea / Hypopnea

Trial of positive Pressure

Primary concern: snoring

Primary concern: Vascular risk

Primary concern: Daytime Sleepiness

Intolerant of Positive Pressure

Clin Chest Med 2003 24:307–313

The Future: P4 Medicine

Gene<cs, Genomics, & Proteomics

ü  Predic<ve ü  Personalized ü  Preventa<ve ü  Par<cipatory

Systems Biology

Modern Compu<ng Technology

Molecular Oncology 2009 3(1):9-‐17

NATURE 2010 463: 258-259

Thank You


PAP Adherence: Benefit of Specialty Care

Pearson χ2 p= 0.01

Using PAP

D/C’ed PAP

MD + Center + (n=307)

95% 5%

MD or Center + (n=99)

93% 7%

MD – Center – (n=38)

79% 21%

•  Factors associated with discon<nua<on •  Lack of MD cer<fica<on or center accredita<on*

•  Nasal conges<on severity

•  Factors associated with con<nua<on •  Pa<ent educa<on of health risk of OSA

JCSM 2006 2:133-‐142 MD + = Cer<fied in Sleep Medicine Center + = Accredited AASM Center

CHEST 2012; 141(1):51–57

Conclusions: A be?er understanding of predictors of CPAP adherence may be useful in idenKfying paKents who may benefit from a sleep specialist consultaKon prior to ordering a diagnosKc PSG.

Results: A sleep specialist consultaKon prior to the diagnosKc PSG was associated with 58.2 min more per day ( P = .002)

Fully adjusted OR: Diagnos<c group OR (95% CI) Snoring Untreated Mild-‐moderate OSA Untreated severe OSA CPAP

1.03 (0.31 -‐ 1.84) 1.15 (0.34 -‐ 2.69)

2.87 (1.17 -‐ 7.51)

1.05 (0.39 -‐ 2.21) Model adjusted for age, diagnos<c group, presence of cardiovascular disease,

hypertension, diabetes, lipid disorders, smoking status, alcohol use, systolic and diastolic blood pressure, blood glucose, total cholesterol, triglycerides, and current use of an<hypertensive, lipid-‐lowering, and an<diabe<c drugs. Variables included in the part adjusted model were those included in the fully adjusted model except hypertension and presence of cardiovascular disease

Marin JM, et al. Lancet 2005; 365: 1046.

OSA is only associated with CVD in those with severe OSA

•  BestAIR: Best Apnea Interven<ons In Research –  Prepares for Phase 3 study

•  Sham vs CMT as control arms •  CBT-‐guided CPAP adherence vs RT-‐guided adherence •  Control vs Ac<ve PAP – 24 BP, cardiac func<on, biomarkers

•  ABC: Apnea, Bariatric Surgery, and CPAP Trial –  Bariatric surgery as a first line treatment (vs CPAP)

•  COMET: Compara<ve Effec<veness CPAP Management

–  Oral Appliances vs CPAP in women with OSA

♣ Aim: Demonstrate that MV ASV therapy over minimum two years can improve morbidity and mortality in patients with predominant central sleep apnea and heart

failure (HF) ♣ Design: randomized controlled trial with >1300 evaluable subjects

- Control arm: optimal medical care - Active arm: optimal medical care plus ASV ♣ Status: Enrolment completed in May 2013

♣ Progress: Currently enrolled over 1300 patients in 78 centers ♣ Main sub-study: Demonstrate that MV ASV therapy improves heart failure outcomes such

as left ventricular ejection fraction and quality of life metrics (n=300)

♣ CAT-HF: Cardiovascular improvements with MV ASV therapy in HF ♣ Randomized controlled trial of acute decompensated HF followed for 6 months ♣ n = 200 hospitalized HFrEF and HFpEF with SDB (OSA or CSA) ♣ Endpoint: Primary - survival free from CV hospitalization and improvement in 6MWD ♣ Goal: Incorporation of MV ASV therapy into the ACC/AHA HF guidelines with

SERVE-HF ♣ Randomized controlled study of MV ASV in patients with HF - The confirmatory trial of

efficacy on cardiac function SAVIOR

♣ Scheduled completion Fall 2014 ♣ Study jointly undertaken with our Japanese distributor ♣ Retrospective and prospective components ♣ n = 300* HF “All-comers”

patrickj$strollo,$jr,$md,$facp,$fccp,$faasm … · outline:$beneﬁts$of$cpap$ • background$ •...

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