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
Reference Bart BA, MD et al. Ultrafiltration in Decompensated Heart Failure with Cardiorenal Syndrome. NEJM. Nov. 6, 2012. 5
Article Conclusion The use of stepped pharmacologictherapy (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? 7
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. 8
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 9
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. 10
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). 11
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) 12
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 13
What are the Results? 1 Endpoint Pharm Ultrafiltration P Value Cr change 0.04 0.23 0.003 Wt 5.5kg 5.7kg 0.58 change (12.1 lb) (12.6 lb) 14
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) Serious Adverse Events Mortality @ 60 d Pharm UF P value 57% 72% 0.03 13% 17% 0.47 16
What are the results? Calculations: Adverse Events ARI RRI NNH 57%-72% = 15%/57% = 1/.15 15% 26% 6.7 If you treat 7 people with ultrafiltration 1 additional person will have a serious adverse event compared to diuretic tx. 17
What are the results? How precise were the results? No confidence intervals Probably not due to small sample size 18
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 20
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 21
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) 22
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 26