Robert A. Gluckman, MD, FACPRegent, American College of PhysiciansChief Medical Officer- Providence Health

PlansNavy Chapter-American College of

PhysiciansOctober 8,2011

Update in Outpatient Internal Medicine

GoalsUsing evidence to promote accountable care

Practice variation in cardiac careUsing evidence to promote shared decision

makingPSA screening and treatment of early prostate

cancerUsing “consumer” technology to improve chronic

disease managementSystems of care

HypertensionHospital discharge

“Potpourri”New agents for stroke prophylaxis in atrial fibrillationCT screening for lung cancerTreatment choices in COPD

Appropriate Use of PCIMulticenter prospective study of patients within

the National Cardiovascular Data Registry from 7/1/09- 9/30/10

500,154 PCI’s 71.1% acute indications

STEMI, NSSTEMI, unstable angina with high risk features

28.9% non-acute indication17 member expert panel developed

appropriateness criteriaClassified as appropriate, uncertain, inappropriate

Acute interventions 98.6% appropriateInappropriate procedures largely stable patients, >

12 hours from symptom onset

JAMA 2011; 306:53-61

Appropriate Use of PCINon-acute PCI

50.4% appropriate38% uncertain

13.4%% had CCS Class III-IV angina5.1% documented high risk ischemia on non-

invasive testing2.7% > 2 meds (83.5% on 0-1 med)

11.6% inappropriate53.8% no symptoms68.7% documented low risk ischemia on non-

invasive testing42.3% no meds, 53.5% 1 med

Optimal Medical Therapy in Patients Undergoing PCIData collected from National

Cardiovascular Data Registry on 467,211 patients Known CAD, 70% lesion with + stress test or

80% lesion with symptoms Excluded patients with ACS, LM disease or EF

<30%OMT defined as anti-platelet agent, beta

blocker, and statin unless contraindicationsAnalyzed % patients receiving OMT pre and

post publication of the COURAGE Trial.

JAMA 2011;305:1882-1889

Medication Prescription Rates Before PCI

Before COURAGE9/1/2005-3/25/2007

After COURAGE7/1/2007-6/30/2009

OMT 43.5% 44.7%

Anti-platelet agent

88.8% 88.3%

Beta blocker 62.0% 63.1%

Statin 62.4% 63.0%

Medication Prescription Rates After PCI

Before COURAGE9/1/2005-3/25/2007

After COURAGE7/1/2007-6/30/2009

OMT 63.5% 66.0%

Anti-platelet agent

99.0% 99.2%

Beta blocker 74.0% 75.9%

Statin 82.7% 84.7%

ACE/ARB 57.7% 60.7%

Appropriateness of Diagnostic AngiographyRetrospective analysis of 565,504 patients

without previous MI or revascularization from 2005-2008 undergoing elective coronary angiography

JACC 2011;58:801-809

Low CAD RateHospital

High CAD RateHospital

Beta Blocker Use

38% 50%

Low Framingham Risk

33% 21%

High Framingham Risk

14% 21%

Atypical CP 45% 27%

Stable Angina 33% 42%

Positive Stress Test

66% 71%

Mean PCI Volume

562/yr 802/yr

Patients’ and Cardiologists’ Perceptions of the Benefits of PCI in stable CADSurvey of 153 patients undergoing elective

cardiac catheterization with possible PCI and 27 cardiologists at Baystate Medical Center

77% patients had + stress test 65% patients had hx of angina

41% had angina < once per week41% had activity limited by angina

77% who received PCI reported anginaCardiologists’ reported angina in 98% of

these patientsAnnals of Int Med 2010;153:307-313

Reasons for performing and beliefs about PCI.Error bars represent 95% CIs. LV = left ventricular; MI = myocardial infarction; OMT = optimal medical therapy; PCI = percutaneous

coronary intervention.

Rothberg M B et al. Ann Intern Med 2010;153:307-313

©2010 by American College of Physicians

Cardiac Procedures per 1000 Members by Top 6 Regions in 1 Large Employer Group

Opportunity cost: state Opportunity cost: state governmentgovernmentState expenditures (all states), 2006State expenditures (all states), 2006

0%

5%

10%

15%

20%

25%

Medicaid K-12 HigherEd Transport Corrections

Nat’l Assoc of State Budget Officers, Nat’l Assoc of State Budget Officers, 20072007

Practice Variation in the Use of Cardiac Procedures- SummaryThe ACC is leading the way for specialty society

efforts to reduce inappropriate proceduresGeneral internists should be active

collaborators rather than passive observers in engaging with specialty colleagues in reducing practice variationMedical staff involvementCollegial physician-physician communication

Increased transparency of local and regional utilization patterns is coming and can potentially reduce ineffective or marginally effective utilization

Eplerenone in Patients with CHF and Mild Symptoms2737 patients with NYHA Class II CHF and EF ≤

35%Hospitalized within the last 6 months or increased

BNPRandomized to eplerenone titrated to 50 mg qd

vs. placeboStarted 25 mg qd and increased to 50 mg qd at 4

weeksIf CrCl 30-49 ml/min started 25 mg qod and titrated

to qd if K+ ≤ 5.0Dose decreased if K+ 5.5-5.9Drug stopped for K+ ≥ 6.0, remeasured after 72

hours and restarted if K+ < 5.0

NEJM 2011 ;364:11-21

Eplerenone in Mild CHFEplerenone Placebo

CV death or CHF Hospitalization

18.3% 25.9%

Overall mortality or CHFHospitalization

19.8% 27.4%

Hospitalization for worsening renal function

0.7% 0.6%

Aldosterone Antagonists in CHFObservational analysis of 43,625 patients

admitted with CHF and discharged home242 hospitals participating in the Get With The

Guidelines-HF Program12,565 patient eligible for aldosterone antagonist

therapyEF ≤ 35%Serum potassium ≤ 5.0 mEq/LSerum creatinine ≤ 2.5 mg/dl in menSerum creatinine ≤ 2.0 mg/dl in women

34.5% eligible patients received aldosterone antagonist

10.55% inappropriate or potentially inappropriate use

JAMA 2009 302;1658-1665

Aldosterone Antagonists in CHFPatients admitted for CHF may have

multiple medication changesClinician concern about initiating multiple

interventions may be a barrier to initiating treatment

Dose intensification of multiple medications is generally needed in CHF patients

Clinical inertia may be a barrier to optimal care in CHF

Need for specialty/PCP role clarification

Population Based Prostate Cancer Screening Trial- Goteberg Trial20,000 age 50-64 randomized to PSA every

2 years vs. no screeningScreening discontinued at age 69Elevated PSA, defined as 2.5-3, offered DRE,

ultrasound and biopsyMen with negative evaluation re-screened

every 2 years and biopsied for repeat PSA elevation

Primary endpoint- prostate cancer specific mortality

Median follow-up 14 years

Lancet Oncol. 2010 Aug;11(8):725-32

Control Invited to screen

Attendees

Non-attendees

Prostate CAdiagnosed

7.2% 11.4% 13.8% 3.9%

Low risk 2.0% 6.1% 7.8% 0.6%

Moderate risk

2.5% 3.6% 4.5% 1.0%

High Risk 1.3% 1.0% 1.0% 0.8%

Advanced 0.9% 0.3% 0.2% 0.5%

Low risk: T1, Gleason score ≤ 6, PSA <10Moderate risk: T1-2, Gleason score ≤ 7, PSA <20High risk: T1-4, Gleason score ≥ 8, PSA <100

# invited to screen to prevent one death= 293# diagnosed to prevent one death= 12

Co-Morbidity and Mortality Results From the PLCO Trial

J Clin Oncol 2010 29:355-61

Men with minimal or no

Significant co-morbidity examples: CAD, MI, DM, HTN, CVA, BMI > 30, COPD, chronic bronchitis

Men with ≥ 1 significant co-morbidity

Determinants and Outcome of Watchful Waiting in Men with Prostate CancerHealth Professionals Follow-up Study

Cohort 51,529 men3331 diagnosed with prostate cancer 1986-2007342 chose watchful waiting

51% remained untreated after 7.7 yearsTreatment delayed average of 3.9 years in

those undergoing treatmentNo difference in prostate cancer death or

metastatic disease (about 10 per 1000 pt-years)

Age, tumor size, Gleason score, PSA level predicted future treatment

PSA ≤ 10, Gleason <7 Stage 1 and 2

PSA 10.1-20 or Gleason 7, Stage 1 or 2

PSA > 20 or Gleason >7, or Stage 3

Radical Prostatectomy vs. Watchful Waiting in Early Prostate Cancer695 men age < 75, life expectancy > 10 years,

T1 or T2 tumor randomized to RP or WWOnly 12% non-palpable T1c tumors at enrollment5% diagnosed by screening≈ 75% T2 tumors> 45% with PSA >10

RP patients received hormonal therapy for recurrence

WW patients underwent TURP for obstructive symptoms

Median follow-up 12.8 years

NEJM 2011 364:1708-117

NCCN GuidelinesActive surveillance reasonable option for

men withStage T1-2a, Gleason score ≤ 6, PSA < 10

Active surveillancePSA at least every 6 monthsDRE at least every 12 monthsBiopsy 6 months if initial bx. < 10 coresBiopsy 18 months if initial bx. ≥ 10 cores

www.nccn.org accessed 10/29/10

Prostate Cancer Screening-ConclusionsPSA screening may provide small survival benefit

Pre-screening, contamination, biopsy threshold and treatment differences limits data interpretation

Survival curves start to diverge at about 10 yearsSignificant benefit may take longer

Overdiagnosis is a serious health hazardOver 1 million treatedSide effects immediateImpact of overdiagnosis could be dramatically

reduced if active surveillance was initial treatment strategy in appropriate patients

Shared decision making should emphasize delayed benefit, short term risk, baseline health and option for delayed curative treatment

Collaboration with urology community to determine treatment options is essential

USPTF Grade D recommendation

Mobile Diabetes Intervention StudyRandomly assigned 26 primary care

practices to 4 study groups No academic affiliation > 10% patients had diabetesEnrolled 163 commercially insured patients,

HgBA1C ≥ 7.5%No mental health diagnoses, substance abuse, must

have internet accessInterventions

Usual CareCoachCoach + Patient PortalCoach + Portal +Decision Support

Diabetes Care published online 7/25/2011

Mobile Diabetes Intervention Study

Usual Care

Coaching CoachingPortal

CoachingPortalDecision Support

BaselineHgBA1C

9.2% 9.3% 9.0% 9.9%

12 monthHgBA1C

8.5% 7.7% 7.9% 7.9%

Mean change

- 0.7% - 1.6% 1.2% 1.9%

Txt2stop Trial: Smoking Cessation Support via Mobile Phone Text Messaging5800 patients aged ≥ 16 willing to attempt

to quit smoking within 1 monthParticipants socioeconomically diverse, 44%

left school ≤ age 16Participants responded to ads via text or

onlineAll participants allowed to participate in any

other smoking cessation program and all provided helpline numbers

Lancet 2011:378:49-55

Txt2stop Trial: Smoking Cessation Support via Mobile Phone Text MessagingIntervention group received 5 texts daily x 5

weeks, then 3 texts weekly for 26 weeksCore program of 186 standard messages and 713

personalized messagesMessages selected from algorithm based on

patient specific dataMessages provided motivation and behavior

change techniquesControl group received text message every 2

weeks thanking them for study participationBiochemically verified 6 month quit rate 10.7%

vs. 4.9%

Randomized Trial of DepressionFollow-Up Care by On Line Messaging208 patients with newly prescribed antidepressant

depression in 9 primary clinics in Group Health CooperativePatients already enrolled in on line messagingExcluded patients with anti-depressant within 270 days, with

bi-polar disorder or any previous mood stabilizer, anti-psychotic

Randomized to usual care in primary care setting (including psychotherapy, medication, online messaging) vs. usual care plus nurse based outreach via online messagingOutreach included PHQ-9, medication adherence, side effects,

facilitated visits, referral as needed3 contacts plus additional patient initiated contactScripted response and algorithm based on questionnaire,

tight coordination with PCPReview with supervising psychiatrist, did not provide direct

care

JGIM 2011 26(7):698-704

Randomized Trial of DepressionFollow-Up Care by On Line Messaging

Intervention Control

Adherence 81% 61%

Second medication 22% 16%

Mental health specialistvisit

32% 31%

50% improvement indepression score

55% 41%

Very satisfied with depression treatment

53% 33%

Care Transitions Intervention (CTI)Quasi-experimental prospective cohort

study of FFS Medicare patients in 6 Rhode Island hospitalsAssess generalizability of previous RCT

Intervention consisted of health coachingVisit in hospital before dischargeHome visit within 3 daysTelephone call within 7-10 daysFinal telephone call by day 30

Coaches worked 18-24 hours per week and carried case loads of 12-15 patients

Arch Int Medicine 2011;171:1232-37

InterventionEnsure medications taken matched those prescribed

and patients can describe which meds to take and how often

Identify health conditions and maintain a personal health record

Discuss/practice how to schedule a follow-up appointmentPatients make their own appointments

Help the patient recognize “red flags” that should prompt a telephone call or urgent appointment with provider

Enrolled patients in state-wide HIEDiscussed and encouraged completion of advanced

directive

Readmission Rates

Intervention Group 12.7%

External Control (eligible for CTI not approached)

20%

Internal Control (declined CTI or lost to follow up before home visit)

18.6%

Decline 18.6%

Lost to follow up 18.7%

Simplified approach to treat HTN

45 Canadian family practices able to enroll 30 patients with uncontrolled hypertension randomized to algorithm or guideline based care

Uncontrolled HTN define as ≥ 140/90 or diabetics ≥ 130/80

Mean age 61, 15% diabeticsAlgorithm consisted of:

Step 1- fixed dose ACE/diuretic or ARB diuretic with up titrationi.e. lisinopril 10/12.5 HCTZ; max dose 20/25

Step 2 calcium channel blocker with up titrationStep 3 add α blocker, β blocker, or spironolactone

BP Control at 6 months:

Algorithm 64.7%

Guideline 52.7%

Effectiveness of Home BP Monitoring, Web Based Communication, and Pharmacist Care on BP Control

778 patients with uncontrolled hypertension randomized to Usual careHome BP monitoring and Web servicesHome BP monitoring, Web services,

pharmacist care management Outcomes were changes in BP and %

patients controlled 12 month follow-upGoal BP 135/85

JAMA 2008;299:2857-67

Effectiveness of Home BP Monitoring, Web Based Communication, and Pharmacist Care on BP Control

Usual Care

Home BP +Web

Home BP +pharmacist

Systolic BP drop

-5.3 mm -8.2 mm -14.2 mm

Diastolic BP

-3.5 mm -4.4 mm -7.2 mm

% control 31% 36% 56%

# E-Mail contacts

2.4 3.3 22.3

# BP meds 1.69 1.94 2.16No difference in primary care visitsModest decline in specialist visits

Intensive Blood Pressure Control in Diabetic Patients- ACCORD BP 4733 patients with HgBA1C ≥ 7.5%

Age ≥ 40-79 with CVDAge ≥ 55-79 at high risk for CVDSystolic BP 130-180 taking ≤ 3 BP drugsCreatinine ≤ 1.5 mg/dl or < 1 gm proteinuria

Intensive treatment- Goal BP ≤ 120 mm Hg monthly visits x4, then q2mo

Control group- Goal BP ≤ 140 mm Hg visits month 1 and 4, then q4mo

1° outcome- non-fatal MI, CVA, CV deathMean follow-up 4.7 years

NEJM 2010 362: 1575-85

2.1 meds

3.4 meds

Similar use of ACEI/ARB, thiazides, beta blocker, calcium channel blocker

ACCORD BP TrialIntensive TherapyEvents %/yr

Standard TherapyEvents %/yr

Primary Outcome 1.87 2.09 (NS)

CVA 0.32 0.53 (NNT x 5 yr 89)

Non-fatal MI 1.13 1.28

Death 1.28 1.19

ACCORD BP TrialIntensive Therapy Standard Therapy

Serious adverse events

3.3% 1.27%

Dizziness on standing

44.3% 40.3%

Macroalbuminuria(protein excretion ≥ 300 mg/d

6.6% 8.7%

Consider periodic monitoring urinary protein for overt nephropathy

INVEST TrialObservational secondary analysis involving

6400 diabetic patients with HTN and CADPatients randomized to calcium channel

blocker vs. beta blocker strategy to achieve BP <130/85Added ACEI and thiazide

Patients categorizedTight control systolic BP <130Usual control systolic BP 130-139Uncontrolled systolic BP ≥ 140

Primary outcome- mortality, non-fatal MI, CVA

JAMA 2010:304;61-68

INVEST TRIALBP < 130 BP 130-139 BP ≥ 140

Primary Outcome

12.7% 12.6% 19.8%

Total Mortality 11.0% 10.2% 15.4%

Non-fatal MI 1.3% 1.7% 3.1%

Non-fatal CVA 1.0% 1.3% 2.4%

Amer J Med 2010 123:719-726

INVEST TRIAL- BP Control in CAD

HypertensionA simple algorithm may improve BP control3-4 drugs may be necessaryPatients with uncontrolled hypertension

require therapeutic intensification and efforts to improve adherence

Team based care and frequent patient/provider contact increases BP control

Carefully consider target BP based on patient characteristics

Apixiban for Atrial Fibrillation-ARISTOTLE Trial18,201 patients with atrial fibrillation and one

additional risk factor for strokeRandomized to a apixiban (Direct Factor Xa

inhibitor) 5 mg po bid vs. warfarinDose reduced to 2.5 mg if 2 of the following

Age ≥ 80Weight ≤ 60 kgCreatinine ≤ 1.5 mg/dl

Median duration of follow-up 1.8 yearsPrimary outcome ischemic/hemorrhagic stroke

or systemic embolismSecondary outcome major bleeding, death

NEJM 2011;365:981-92

ApixibanEvent Rate%/year

WarfarinEvent Rate%/year

Hazard Ratio

CVA or Systemic embolism

1.27 1.60 0.79

Hemorrhagic CVA

0.24 0.47 0.51

Total Mortality 3.52 3.94 0.89

CVA, MI, systemicEmbolism or death

4.85 5.45 0.88

CVA, systemicEmbolism, death, or major bleeding

6.13 7.20 0.85

INR median time in therapeutic range 66%ARR for any bleeding 7.7%/year

New Anticoagulants in Atrial Fibrillation- SummaryApixiban, dabigitran, and rivoroxaban all reduce

hemorrhagic stroke, major bleedingDabigitran only drug to reduce ischemic strokeApixiban reduces rate of major bleeding and total

mortalityCost an issue, especially for Medicare patients or

other coverage with greater cost share for drugsPatients well controlled on warfarin may not require

med changeBeneficial when difficult to control or monitor in

adherent patients. Cannot extrapolate to non-adherent patients due to

shorter half life

The National Lung Screening Trial53,454 patients age 55-74 with ≥ 30 pack year

smoking history, current smoker or quit within 15 years

Randomized to yearly low dose chest CT vs. CXR for 3 years

Median follow-up 6.5 years18,146 positive tests in CT group

96.4% false positive 5,043 positive tests in CXR group

94.5% false positiveMost diagnostic evaluations were f/u imaging4% CT group underwent a surgical procedure

NEJM 2011;365:395-409

CT Group

Radiology Group

Major complication after diagnostic evaluation

11.6%N=75

8.6%N=95

Intermediate complication after diagnostic evaluation

14.6%N=24

12.5%N=35

309/100,000Patient-years

247/100,000Patient-years

6.7% reduction in total mortality

Conclusions- CT screening for lung cancerIn this trial, CT screening resulted in a 20%

reduction in lung cancer death and 6.7% reduction in overall mortality

Complications uncommon but higher in screened group

Areas of uncertaintyOverdiagnosis rateImpact of newer technology (i.e. greater mortality

reduction vs. more false positives)Cost-effectivenessDuration and interval of screeningTarget patient population

Authors recommended policy makers wait for additional data

Tiotropium vs. Salmeterol to prevent COPD Exacerbation7376 patients with moderate to very severe COPD

90% Stage II-III Gold CriteriaPatients continued other medications

>50% used inhaled corticosteroids, short acting bronchodilators

Primary outcome- time to first exacerbationSecondary outcomes

Risk of severe exacerbationsExacerbations requiring inhaled steroids and/or

antibioticsDiscontinuation due to adverse effects

Follow-up 1 year

NEJM 2011;364:1093-1103

Probability of COPD exacerbation

Time to first exacerbation decreased by 42 days

Probability of severe COPD exacerbation