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2014 (and early 2015)The Year in Review

No conflicts of interest

How to make this talk….

Areas Searched• Medline• ACP Journal Club• Residency Journal Clubs• Faculty Suggestion• Practical, Applicable, Interesting• Whatever is not being covered

elsewhere….

Topics!

1- Diagnostics -Stroke and TIA

2- Imaging2a- Stones2b- Lung screening

3- Therapeutics3a- Soft tissues3b- DAPT duration

TIA and StrokeA 75 year old woman arrives a week after being sent home from the ER after experiencing 2 hours of mild dysarthria. She was diagnosed by neurology with a TIA. Her CTA showed no carotid or vertebral vascular disease, her tele no afib and she had a normal echo. She is on atorvastatin for hyperlipidemia and chlorthalidone for well controlled hypertension. She is on clopidogrel for a coronary stent. You recommend which of the following:

A. Add aspirin to clopidogrelB. Change atorvastatin to rosuvastatinC. Change chlorthalidone to atenololD. Ambulatory cardiac monitoring for one month E. Order carotid ultrasound

A d d a s p

i r i n t o

c l o pi d o

g r el

C h an g e

a t or v a

s t at i n

t o r. . .

C h an g e

c h lo r t

h a li d o

n e t o . .

.

A mb u l

a t or y c

a r di a c

m on . . .

O r de r c

a r ot i d

u l t ra s o

u n d

26%

0%

34%36%

4%

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Burden of Disease - Stroke

- 12 million annual strokes

-3rd leading cause of death in Western World

- 200,000 deaths in U.S. annually

- 15-20% mortality per event

- 18% unable to return to work

- 4% total custodial care

Aprox $60 Billion U.S. annually

AHA, 2012 Heart and Stroke Statistical Update

Match TrialSecondary Prevention: Plavix + Aspirin or

Plavix + Placebo• N=7599 followed for 18 months

• Outcomes: CVA, MI, hospitalization or death– Dual Rx. 596/3793 (15.7%)– Clopidogrel 636/3802 (16.7%)- no asa alone arm….– RRR 6.4% (-4.6-16.3)– Significant increase in bleeding on dual therapy

• Conclusions: Dual Rx no better than clopidogrel alone– VA Neuro- change antiplatelet agent

» Lancet Vol. 364 July, 2004

Hypertension is the biggest strokerisk factor… BUT

American Heart Association, 2002 Heart and Stroke Statistical Update,

Cryptogenic stroke

• Stroke evaluation includes**– 12 lead EKG with 24 hour holter (or tele)– Brain and neurovascular imaging– Echocardiography (+ bubble study)

– AHA Guidelines. Stroke 2013;44

• Cerebrovascular events without a cause after standard evaluation– 20-40% strokes– 50% of TIAs

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-Common disorder, increases with age

-Stroke risk increases:

-17X for valvular afib

-5 times for nonvalvular

-How to RX?Circulation 201: 103:162-182

Rate vs Rhythm Control on StrokeAtrial fibrillation follow-up investigation of rhythm management- AFFIRM

Randomized 4060 patients to cardioversion vs rate control

All received coumadin

-Rate control=rhythm control

--paroxysmal afib=chronic afib

Stroke Prevention in A. Fib-RxMeta-analysis Data – 9874 participants, 16 trials

1. Warfarin vs. Placebo� 62-68% RRR INR 2-3

- Absolute risk bleeding 0.3%/year

- Reduction of all cause mortality 26% (ARR 1.6%/Year)

2. Aspirin vs. Placebo�21-22% RRR ANY Dose

- Absolute risk bleeding 0.2%/Year

- No overall reduction of mortality

Annals of Int. Medicine Vol. 131, No. 7 October 5, 1999

Warfarin Versus Aspirin5Trials with 2837participants and 205strokes over 2 years

Relative risk reduction 36% favoring warfarin

-NNT 167primary prevention

-NNT 14 secondary prevention (includes TIA)

-AR major bleeding 0.2%/year increasewith warfarinAnnals of Internal Medicine Vol. 131, No. 7

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CHADS2 Prediction RuleAFI, SPAF - 2 large prediction rule trials

- don’t always agree

- Framingham hard to use

C – CHF in last 100 days

H – Hypertension

A – Age >75 Years

D – Diabetes

S2 – x2 previous Stroke or TIAGage et al. JAMA June 13, 2001

Score 0=1%1=2.5%/year 4=8%2=4% 5=12%3=6% 6=18%

Cardiac Monitoring Cryptogenic Stroke

• 2 large RCTs of 30 day monitor vs. 24 hours– Outcome: Incident atrial fibrillation (> 30 sec)

• Embrace Trial– 572 patients, age 73, 89% white– 30 day event triggered recorder vs. standard– New afib >30 seconds

• Crystal-AF Trial– 441 patients, age 62, 87% white– Implantable loop recorder

• NEJM 370;26 June 26, 2014

Gladstone DJ et al. N Engl J Med 2014;370:2467-2477.

EMBRACE TRIAL

Gladstone DJ et al. N Engl J Med 2014;370:2467-2477.

Atrial fibrillation 6 of 277 (3.2%) 6 of 277 (3.2%) 6 of 277 (3.2%) 6 of 277 (3.2%) controls

33

21

3542/284

NNS=9/30 days

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Cryptogenic Stroke Conclusions

• Limitations:– Primary Outcome- > 30secs afib– Not designed to show reduced stroke

• Implications:– Cryptogenic stroke patients should receive 30

days of cardiac monitoring for atrial fibrillation– Anticoagulation decisions based on results

Case Outcome

• 75 year old woman post TIA- 30 day monitor patch-discovered to have afib and started on coumadin

Case #240 year AA old man with difficult to control ulcerative colitis and chronic diarrhea presents with 12 hours of worsening flank pain that radiates to his right testicle. He has microscopic hematuria on dipstick urine. You suspect nephrolithiasis. Your initial evaluation should include:

A. Home to push fluidsB. Ultrasound for stone evaluationC. Non-contrast CT scan

D. 24 hour urine collectionE. A and D

H o me t o

p u sh f l

u i ds

U l t ra s o

u n d f o r

s t on e

e v a. . .

N o n- c o n

t r a st C T

s c an

2 4 ho u r

u r in e c

o l l ec t i o

nA a

n d D

7%

28%

17%

2%

47%

Nephrolithiasis• Common: 2.5 million visits/year• $2 billion per year in US• 16% men and 8% women will have at

least one symptomatic stone by the age of 70 years

• 80 percent calcium oxalate• Recurrence:

15 percent at one year, 40 percent at five years, and 50 percent at 10 years

• Goal: Avoid high risk complications– Sepsis, Obstruction, Renal Failure,

Hospitalization

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Stone Evaluation• 2 Evaluations: Conservative vs. Aggressive

– Conservative-• First time without other risks• UA, Culture, stone analysis• No immediate imaging

– Aggressive-• Diabetes, chronic diarrhea, AA,

gout, elderly, CKDz• UA, Culture, stone analysis• Imaging- Helical CT scan

–Radiation exposure..

CT Scan Cancer Risk

NNH one cancer in 40 year old man = 1002

Smith-Bindman Arch Intern Med. 2009;169(22):2078-2086

Imaging for Nephrolithiasis

• RCT 2759 patients in ER (40yo, 40% white, 24% AA, 24% Hispanic)

• POC Ultrasound (908)

• Radiology US (893)

• Non-Con Helical CT (958)

• 1 outcome- Immediately life threatening

• 2 outcome- Serious adverse events– Smith-Bindman N Engl J Med 2014; 371:1100-1110

Results:

• High Risk Diagnosis- 0.4% overall p=0.3

• Radiation Exposure- 10mSv vs. 17mSv p<0.001

• Secondary Outcomes:– Serious adverse events: 11% p=0.5– Return ER visits: 10% one week p=0.43– Hospital admit: 3% one week p=0.21– Pain score: 2.0 one week p-0.80

– Smith-Bindman N Engl J Med 2014; 371:1100-1110

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Imaging in Nephrolithiasis

• Ultrasound (either radiology or POC) good initial screen

• Radiation lower

POC Rad US Non-con

• Sn= 85 84 86• Sp= 50 53 53

• Smith-Bindman N Engl J Med 2014; 371:1100-1110

Case #3A 60 year old man, never-smoker, arrives requesting screening for lung cancer. He had a 1mm LLL nodule without spiculations on CXR. He is an economist and asks societal costs. You decide:

A. Lung cancer screening costs more than dialysisB. Lung cancer specific mortality is not improved

with screeningC. It is cheaper to screen older patients for lung

cancerD. Costs depend dramatically according to lung

cancer risk profileE. I only screen in non-smokers if they are litigating

lawyers

L u ng c a

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r e en i n

g c o. . .

L u ng c a

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I t i s c h e

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s c re e n

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C o st s d

e p en d

d r am a

t i c al l . . .

I o nl y s

c r ee n i

n no n -

s m o. . .

2%

15%10%

61%

12%

Lung Cancer Screening

• NSLT – National Lung Screening Trial– 53K patients CXR vs. helical CT x3– 20% reduction in lung cancer mortality– 18 vs. 21/1000 pts died over 6.5 years– NNS 333 to save one life from lung cancer

• Aberle et al. NEJM 2011;307

• USPT grade B (benefit moderate-significant)

• Private insurance must cover..

CT Scan Cancer Risk

NNH one cancer in 60 year old man = 2080

Smith-Bindman Arch Intern Med. 2009;169(22):2078-2086

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Cost by Subgroups

Women

Age 60-69

Current Smokers

Highest Quintiles of risk

Black et al. NEJM 371:19 Nov. 6 2014, Risk Calcul ator- NEJM 2013; 368:728-736 http://reference.medscape.com/calculator/solitary-pulmonary-nodule-risk

http://reference.medscape.com/calculator/solitary-pulmonary-nodule-risk

Lung cancer screening

Follow USPTF recs: “now recommends annual screening for lung cancer with low-dose CT in people 55 through 80 years old with a 30 or more pack year history of smoking who are currently smoking or have quit within the past 15 years.”

Stay tuned for sharpening tool for screening as more data comes through!

Risk Calculator- N Engl J Med 2013; 368:728-736

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Case 430 yo woman presents to clinic with a 5cm abscess with surrounding cellulitis. After I&D you choose to prescribe her which of the following.

A. Cephalexin

B. Clindamycin

C. TMP/SMXD. Cephalexin and TMP/SMX

E. B or C C e ph a l e

x i nC l i n

d a my c i n

T MP / S

M X

C e ph a l e

x i n a n d

T MP / S

M X B o r C

20%

14%

34%

16%16%

IDSA 2014 Skin and Soft Tissue Infection Guidelines

Clin Infect Dis. 2014;cid.ciu296

SSTI RCT• RCT 524 patients • Abscess >5cm (30%), cellulitis

(54%), both (16%)• Age=27, 39% pediatrics• 52% M, 50% AA, 24% hispanic• DM, immunosuppressed, fever

> 38.5, BMI> 40, CrCl<30

• Clinda 300mg tid x10 days• TMP/SMX 2 SS bid x10 days

• Miller NEJM. 2015;371:1093-‐1103.

Results!!

• Primary outcome Cure 7 days

• Secondary outcome

Cure one month, SEs, complications

• Abscess- 56% MRSA, 13% MSSA, 12% clindaresistance

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SSTI Treatment- summary

• Drainage only for small abscesses <3-4cm

• Cellulitis, abscess > 5cm

• TMP/SMX

• Clindamycin or

• Doxycycline

• Careful with dual therapy- count on close follow up- remember resistance…

Case 568 yo man arrives in your office 14 months after receiving a single DES in his LAD after an NSTEMI. He has been asymptomatic since then. He is on chlorthalidone, metoprolol, atorvastatin, omeprazole, aspirin and clopidogrel. He asks if he is on the right medications. You advise.

A. Stop omeprazole due to risk of C. DifB. Change atorva to rosuvastatinC. Change chlorthalidone to hydrochlorothiazide

D. Obtain a stress thalium testE. Discuss stopping clopidogrel

S t op o

m ep r a

z o l e d u

e t o r . . .

C h an g e

a t or v a

t o r o s

u v as . . .

C h an g e

c h lo r t

h a li d o

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O b ta i n

a st r e s

s t ha l i u

m te s t

D i sc u s

s s to p p

i n g c l o

p i do g r

e l

13%

0%

75%

8%4%

Drug-eluting Stents

• Millions of patients get stents

• DES stents fewer thrombotic events c/w BMS

• AHA/ACA guidelines – Dual antiplatelet therapy 6-12 post stent

• Observational studies– Possible antiplatelet/CV benefit– Possible bleeding dangers

• True duration of therapy unknown

12 vs. 30 mos DAPT for DES

• 10K compliant patients post 1 year of DAPT

• Randomized 18 moscontinued DAPT vsplacebo

• 62 yo, 25% women, 88% white

Mauri L et al. N Engl J Med 2014;371:2155-2166.

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Good News

NNT=100over 18 months prevent one stent thrombosis

Mauri L et al. N Engl J Med 2014;371:2155-2166.

More Good News

NNT=62.5over 18 months prevent CV/CVA event

Mauri L et al. N Engl J M 2014;371:2155-2166.

Cause for ConcernNNT - 100 stent thrombosis- 62.5 events- 50 MI

NNH- 200 death*Cancer deaths 31 vs. 14 p=0.02

- 104 bleedingBleeding deaths 11 vs. 3 P=0.06

Outcome of cardiac death or MI short-term (3 mos) DAPT compared with extended DAPT (12 mos).- No difference in primary outcomeEl-Hayek The American Journal of Cardiology, Volume 114, Issue 2, 2014, 236 - 242

Meta-Analysis of Randomized Clinical Trials Comparin g Short-Term Versus Long-Term Dual Antiplatelet Therapy Following Drug- Eluting Stents

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Outcome of major bleeding in patients treated with short-term (3 mos) DAPT compared with extended DAPT (12 mos). -59% RRR bleeding shorter durationEl-Hayek The American Journal of Cardiology, Volume 114, Issue 2, 2014, 236 - 242

Meta-Analysis of Randomized Clinical Trials Comparin g Short-Term Versus Long-Term Dual Antiplatelet Therapy Following Drug- Eluting Stents

NNH=240

ISAR-TRIPLE Trial

• 614 coumadin + ASA post DES stent

• 307 6-weeks clopidogrel, 307 6-months

• Death, MI, stent thrombosis, stroke

• Primary Outcome: (No Difference)

• 30 patients (9.8%) 6-week group • 27 patients (8.8%) 6-month group

• hazard ratio [HR]: 1.14 p = 0.63 – JACC Volume 65, Issue 16, 28 April 2015

ISAR-Triple Trial- Cumulative >BARC 3 Bleeding

BARC 3-5- Actionable

bleeding- Death

BARC Score http://circ.ahajournals.org/content/123/23/2736.fullJACC Volume 65, Issue 16, 28 April 2015, Pages 1619–1629

60% increase in BARC 3 bleeding in 6 months group

DAPT Therapy

• Bottom Line:Shared decision making: balance of CV risks vs. possible harm, ongoing PPI use and patient preference.- Engage your cardiologists- 6-12 months seems safe with simple stents- 6 weeks for triple therapy- Biggest risk in first 3 mos stopping DAPT- Future antiplatelet tapers? Individualized Tx?

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Thanks for your attention!!