Journal Club

PowerPoint Template

A Question of Therapy

RCT

1

EBM Process

• Ask a well built (focused) clinical

question

• Search for the best evidence to answer

the question

• Critically appraise the evidence

• Apply the evidence to the patient

2

Case Presentation

• 61y F w HTN, HFpEF, DM, CKD 4

presented to ED after labs in clinic

revealed acute on chronic renal failure

and hyperkalemia. Pt c/o SOB related to

recent CAP for which she had just

completed Abx. Pt treated for several

days with kayexylate, and high dose IV

lasix with minimal response and

worsening renal function 3

Search Strategy

• Why you chose your article – article

given to me by renal colleagues as

evidence our plan of ultrafiltration was a

bad idea

• Describe your search strategy –

– Cochrane for ‘heart failure ultrafiltration’

• Results of your search

– 5 studies were found which compared UF

with diuretics 4

• Bart BA, MD et al. Ultrafiltration in

Decompensated Heart Failure with

Cardiorenal Syndrome. NEJM. Nov. 6,

2012.

Reference

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Article Conclusion

• The use of stepped pharmacologic-

therapy (diuretics) was superior to

ultrafiltration in preservation of renal

function with similar weight loss at 96

hours. Ultrafiltration was associated

with a higher rate of adverse events.

6

Critically Appraise the

Evidence

• Are the Results Valid?

• What are the results?

• Do the Results Apply to my patient and

the patients in my practice?

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Are the results valid?

• Were the patients randomized? Yes

• Was randomization concealed? Yes

– Study design: Automated Web-based

system, patients were randomly assigned

in 1:1 ratio. Permuted block, stratification in

clinical sites.

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Are the Results Valid?

• Were patients similar at baseline with respect

to prognostic factors? Probably

– Table 1: Some differences as expected with small

sample size of 188 pts.

– Ultrafiltration: older, lower wt, EF. More ischemia,

A-fib, on ACE, ↑ BNP, Bblockers,ACE,

– Pharm: More chf hosp in last year, DM, ↑BUN, ↑Cr

– All quartile ranges overlap

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Are the Results Valid?

• Were all 5 groups blinded (pt, clinicians, data

collectors, outcome assessors, data

analystist)? No – this would be impossible to

do

• Discussion/limitations: Treatment

assignments not blinded, biases of

investigators may have effected treatment.

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Are the Results Valid?

• How complete was follow-up? Fairly

complete

– 2 patients in ultrafiltration group not

included in 1°endpoint due to lack of

baseline Cr (1) and lack of all post baseline

Cr levels (1).

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Are the Results Valid?

• Was the trial stopped early for benefit?

No.

– The study was stopped early for worse

outcomes and higher adverse event rate in

the ultrafiltration group.

– Stopped at 188 pt (planned 200 pt)

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Are the Results Valid?

• Were patients analyzed in the groups to

which they were randomized (Intention

to treat)? Yes

• No difference in cross over

– 18% in Pharm

– 23% in UF

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What are the Results?

1°Endpoint

Pharm Ultra-

filtration

P Value

Cr

change

↓ 0.04 ↑0.23 0.003

Wt

change

↓5.5kg

(12.1 lb)

↓ 5.7kg

(12.6 lb)

0.58

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What are the results?

2°Endpoints • No diff in worsening condition @ 7

days: (Definition of Composite Endpoint of “Worsening Condition”: death, dialysis, adverse events, persistent CHF.

• No sig difference rehospitalizations for HR, or any.

• No sig difference in dyspnea or global well-being (96 hr, 7 d, discharge)

15

What are the Results?

Adverse Events: kidney failure, bleeding, IV catheter

complications including infection (all: HF,CV problems, anemia, lytes)

Pharm UF P value

Serious

Adverse

Events

57% 72% 0.03

Mortality

@ 60 d

13% 17% 0.47

16

What are the results?

Calculations: Adverse Events

• If you treat 7 people with ultrafiltration 1

additional person will have a serious

adverse event compared to diuretic tx.

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ARI RRI NNH

│57%-72%│= 15%/57% = 1/.15

↑15% ↑26% 6.7

What are the results?

• How precise were the results?

– No confidence intervals

– Probably not due to small sample size

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Applicability

• Were the study patients similar to my

patient? No.

– The study would not have included this

particular patient

– But, many of our CHF patients would be

included

19

Applicability

• Was duration of follow-up adequate?

– Yes – days 1,2,3,4,7,30, and 60

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Applicability

• Were all clinically important outcomes

considered?

• 1°outcomes: weight and serum creatinine

• 2°outcomes: – worsened condition during treatment, crossover, death,

rehospitalization, ED or acute clinic visits

– 96hr changes in: clinical decongestion, Na, Hgb, BNP, BUN,

GFR, Pt score of well-being, Pt SOB, Total net fluid loss

– Change in furosemide-equivalent dose from preadmission to

discharge

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Applicability

• Are the benefits worth the costs and

potential risks? No.

• Study showed that the UF group had

more adverse events without

significantly better outcomes

• This was different from other 4 studies

in lit. (N = 200, 100, 30, 19)

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GRADE: Quality of Evidence

RCTs start high • 5 limitations can lower confidence

– Biases in design and execution • Concealment, blinding, ITT, loss to follow up

– Indirectness • Surrogate or physiologic outcomes

– Inconsistency • Variability in results (heterogeneity)

– Imprecision • Small numbers, low power, wide confidence intervals

– Reporting or publication bias • Funnel plot

Grading Recommendations:

• Strong recommendations

– Strong Methods

– Large precise effect

– Few downsides of therapy

• Weak recommendations

– Weak methods

– Imprecise estimate

– Small effect

– Substantial downsides

Strength of Recommendation

• STRONG or WEAK

• STRONG:

– Benefits clearly outweigh risks/hassles/cost

– Risk/hassles/costs clearly outweigh

benefits

• WEAK

– There is a close or uncertain balance

between benefits and risks/hassles/costs

– Based on low quality evidence

Conclusion

• Will I change my practice based on this

evidence?

– No

– In this case, Cardiology proceeded with

ultrafiltration (she is now on dialysis)

– Renal advised against ultrafiltration

– The FM team wanted dialysis from the start

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