Papers from 2015

That Changed My Practice

Jon Sweet, MD, FACP

Carilion Clinic &

Virginia Tech Carilion School of Medicine

Disclosures

• None

Case: VTE

• 64 yo man admitted withan unprovoked pulmonary embolism, his first episode of VTE.No weight loss, cough, or GI complaints

• PMH: HTN and T2DM. No abnormal bleeding

• Meds: Lisinopril, amlodipine, metformin

• Occasional ETOH, non-smoker. Not very active.

• BP 142/80, HR 106, RR 20, afebrile

• You start rivaroxaban 15 mg PO BID

How long should he be

anticoagulated?

A. 3 month

B. 6 months

C. 24 months

D. Indefinitely

• Question: can normal D-dimer levels during and 1 month after cessation of anticoagulation predict a recurrent VTE rate low enough to justify cessation of anticoagulation?

• Prospective cohort study w/ blinded outcome assessment

• 410 adult with first VTE (PE or proximal DVT leg); 13 centers

• Anticoagulation stopped if D-dimer negative and not restarted if remained negative after 1 month

• Outcome: recurrent VTE (average follow-up 2.2 y)

Results: Kearon, et al.

• 78% had 2 negative D-dimers and therefore stopped

anticoagulation

– 2 had recurrence before repeat test

• Recurrence rate for VTE per patient-year

Group % per Patient-Year 95% CI

Overall 6.7 4.8 to 9.0

Men 9.7 6.7 to 13.7

Women 5.4 2.5 to 10.2

Estrogen-

associated

0 0.0 to 3.0

• Randomized, blinded, placebo-controlled trial of

additional 18 months VKA

• 374 adults, 18 centers

• Follow-up planned for 42 months; stopped after

18 by steering committee

• Primary outcome: symptomatic recurrent VTE

or major bleeding

• Patient follow-up: 97%JAMA 2015;314:31-40

PADIS-PE

ACP Journal Club, 11/17/15

Is our patient low risk for

bleeding?• HAS-BLED

– 0 = 1% annual risk of bleeding

• ATRIA

– 0 = 0.76% annual risk of bleeding

In addition to age-appropriate

cancer screenings should patient

undergo CT abdomen & pelvis

A. Yes

B. No

• Question: does extensive testing increase

diagnosis of occult cancer or reduce mortality in

the ~10% of patients who will develop overt

cancer in the 1-2 years after unprovoked VTE

SOME Trial

• 862 adults with first unprovoked VTE; 9 centers

• Age-appropriate screening alone versus with CT

abdo/pelvis

• Primary outcome: Dx of cancer after initial

negative screening

– Secondary: recurrent VTE, cancer mortality,

all-cause mortality

• Patient follow-up: 95%

• Results: No differences in any outcome

Pearls

• Extended anticoagulation is recommended

in those at low risk of bleeding

• In the setting of a first unprovoked VTE,

screening CT abdomen & pelvis is not

helpful and possibly harmful (radiation,

incidental findings, expense)

Case 2: CAP

• 68 yo man admitted with typical symptoms of PNA. No hx of same. No COPD or HIV risk factors.

• PMH: HTN, T2DM, GERD, hx of colon cancer (2007).

• 20 pack-years tobacco, none in 30 years

• Influenza, PPSV23 and PCV13 vaccines UTD

• Meds: lisinopril, metformin, glipizide, omeprazole

• BP 110/74, HR 106, RR 24, T 103.2 F

• Mild distress, findings of consolidation over right posterior middle lung zone. No wheezes, JVD or S3.

• WBC 19,000, BUN 28, Cr 1.2

In addition to ceftriaxone and

azithromycin, you add?

A. Nothing

B. Nebulized albuterol and ipratropium every

4 hours while awake

C. Prednisone PO daily

D. Methylprednisolone IV every 6 hours

E. Vancomycin

• 802 adults, mean age 74, 62% men

• 7 tertiary care hospitals

• Prednisone 50 mg QD x 7 days

• Primary outcome: clinical stability x 24 h

– T <37.8, HR <100, RR <24, SBP >90 (>100 if

Hx HTN), Sat >90% RA, baseline mental

status, oral intake

• 13 RCTs

• 2005 patients

• Variety of different steroids and regimens

compared to placebo

Siemieniuk et al

All-cause

mortality

RR 0.67 95% CI, 0.45 to 1.01

Need for

mechanical

ventilation

RR 0.45 0.26 to 0.79

ARDS RR 0.24 0.10 to 0.56

Time to clinical

stability

-1.22 d -2.08 to -0.35

LOS -1.00 d -1.79 to -0.21

Hyperglycemia

requiring

treatment

RR 1.49 1.01 to 2.19

Pearl

• Treatment of CAP with prednisone leads to

reduction in time to clinical stability,

decreased LOS, decreased duration of IV

ABX, decreased ARDS and need for

mechanical ventilation with an increase

in hyperglycemia requiring insulin

Case 3: Stroke

• 72 yo R-handed woman evaluated2 hrs after the sudden onset ofexpressive aphasia and right armweakness

• PMH: HTN, osteoporosis

• Meds: HCTZ, amlodipine, alendronate, calcium, vitamin D

• BP 172/82, HR 78, RR 18, afebrile

• Dense expressive aphasia and 2/5 RUE weakness

• CBC, CMP, PT INR unremarkable

What is the best approach to

this patient?

A. Aspirin

B. Aspirin plus clopidrogrel

C. Alteplase

D. Endovascular treatment

E. Alteplase followed by endovascular

treatment

Endovascular Management of

Acute Ischemic Stroke• Earlier trials with earlier-generation devices

(Merci, Penumbra) did not help

– 2013: MR RESCUE, IMS III, SYNTHESIS Expansion

• Newer-generation stent-retrievers are safer and

more effective

– Inclusion criteria differed slightly

– Intracranial ICA or proximal MCA

– Functionally independent before stroke

– Intervention feasible within 6 hours

– Most patients received TPA

Modified Rankin ScaleScore Description

0 No symptoms

1 No significant disability; can do all duties & activities

2 Slightly disability; can’t do all previous activities but CAN handle affairs without assistance

3 Moderate disability; needs some help but can WALK WITHOUT ASSISTANCE

4 Moderately severe disability; needs help with ADLs; CAN’T WALK without assistance

5 Severe disability, bedridden, incontinent, constant nursing care

6 Dead

• mRS 0 – 2 = Functional Independence

mRS 0 – 2 at 90 Days

Trial Stent-Retriever (%) Standard Care (%)

MR CLEAN 33 19

EXTEND-IA 71 40

ESCAPE 53 29

SWIFT PRIME 60 35

REVASCAT 44 28

• Mortality was lowered in only one trial

• AHA/ASA have updated their guidelines (Class I, level A

if eligible for at least 2 of the trials above)

• Challenge: delivering endovascular intervention in a

timely fashion (groin puncture <6 h)

Pearl

• Mechanical thrombectomy following thrombolysis

improves functional outcomes at 90 days

compared to thrombolysis alone and is the

treatment of choice for suitable candidates with

severe strokes (NIHSS >6) and large vessel

occlusions (ICA or M1)

• 42 yo nurse is your office c/o the sudden onset of palpitations 30 minutes ago, mild dyspnea and apprehension. This has happened before, but has always resolved within minutes without treatment

• PMH: hypothyroidism

• Meds: levothyroxine

• HR 200 (regular), BP 94/50, RR 20, afebrile

The best initial approach would be?

A. Valsalva maneuver

B. Modified valsalva maneuver

C. Check D-dimer, TSH, electrolytes

D. Adenosine 6 mg IV x 1

E. Transfer to Emergency Department

• Valsalva is effect only 5%-20% of time

• Adenosine is not well-tolerated

• Question: would a modified valsalva which

increases relaxation phase venous return and

vagal stimulation be more effective?

• 433 adults randomized (1:1), 10 U.K. EDs

– No Afib/Flutter

• Primary outcome: NSR at 1 minute

Modified Valsalva Technique

• 15 s, 40 mm Hg semi-recumbent Valsalva

strain then immediate supine position

with passive leg raise (45° x 15 s)

– “Lying down with leg lift Valsalva”

– Or blow into 10 mL syringe enough to

move the plunger

• Repeat x 1 PRN

• For home: written instructions, 10 mL

syringe, website

Modified Valsalva in SVT

Outcome Event Rates NNT (CI)

Modified Standard

Sinus rhythm

at 1 min

43 17 4 (3 to 7)

Adenosine in

ED

50 59 6 (4 to 12)

Any

antiarrhythmi

c

57 80 5 (3 to 8)

• No differences in time in ED, discharge to

home, or adverse effects

Pearl

• A simple modification to the Valsalva

maneuver dramatically increases its

effectiveness in terminating SVT and

decreases the need for adenosine

Case: HTN

• 42 yo man with resistanthypertension on HCTZ25 mg, lisinopril 40 mgand amlodipine 10 mgdaily

• No tobacco, drugs, NSAIDS, or pseudoephredrine. Occasional ETOH

• STOP-BANG score = 2 (HTN, male)

• BP 152/88, HR 70, BMI 26, Cr 1.2

Which of the following is the

most appropriate?

A. Add clonidine

B. Add doxazosin

C. Add hydralazine

D. Add metoprolol

E. Add spironolactone

F. Change HCTZ to furosemide

• Resistant HTN is common and treatment

approach is undefined

• Many patients might have sodium retention

or aldosteronism

• 335 adults (ages 18-79) with resistant HTN

• 14 sites in UK

PATHWAY-2

• Double-blind, placebo-controlled, cross-

over trial in random 12 wk blocks

– Spironolactone 25 mg 50 mg

– Bisoprolol 5 mg 10 mg

– Doxazosin 4 mg 8 mg

– Placebo

– Dose doubled after 6 weeks

• Analysis by intention to treat

Spironolactone is most effective

• 2.1% of patients on spirono had a single K >6.0

Pearl

• Spironolactone is the most effective 4th-line

medication by far for patients with resistant

hypertension

Case:

Urolithiasis

• 44 yo man with a 4 mm leftureteral stone withouthydronephrosis, AKI,infection or sepsis

• No prior history of urolithiasis

• Meds: none

• Adequate analgesia in the ED with ketorolac IV x 1

• Vital signs and physical examination are unremarkable

In addition to NSAIDs, increasing

fluids, decreasing soft drinks, and

straining urine, you recommend?

A. Nothing

B. Doxazosin

C. Hydrochlorothiazide

D. Nifedipine

E. Tamsulosin

• Guidelines often recommend medical expulsive

therapy

• Based on small, single-center, lower-quality trials

and meta-analyses of same

• Placebo-controlled RCT, 1167 adults; 24 U.K.

sites

• Tamsulosin 0.4 mg, nifedipine 30 mg, or placebo

(1:1:1) daily for up to 4 weeks

• Primary outcome: spontaneous passage at 4 wk

Pickard et al

Outcome Tamsulosin Nifedipine Placebo

Stone passage 81% 80% 80%

# Days of pain

medication (mean)

11.6 10.7 10.5

# Days to stone

passage (mean)

16.5 16.2 15.9

• No difference regardless of stone size (<5

mm or >5 mm) or location (upper, middle,

lower)

• No differences in health status (SF-36)

Pearl

• In patients with ureteral colic and small

stones, tamsulosin and nifedipine do not

appear to be effective at decreasing the

need for further treatment to achieve stone

clearance in 4 weeks

Summary:Papers that changed my practice

• In CAP, steroids decrease LOS, IV ABX, ARDS and need

for mechanical ventilation

• Mechanical thrombectomy with stent-retrievers improves

functional outcomes in stroke due to large vessel

occlusions (ICA, M1 segment)

• Spironolactone is the most effective add-on medication in

resistant HTN

• Medical expulsive therapy is not effective for small

ureteral stones <5 mm

• Patients with SVT should undergo a modified valsalva

maneuver