Journal Club Naudia N. Lauder, M.D. Evan J. Lipson, M.D. David T. Majure, M.D., M.P.H.

Hx of the J-Club  Sir William Osler established the first formalized journal club at McGill University in Montreal in  The original purpose of Osler's journal club was "for the purchase and distribution of periodicals to which he could ill afford to subscribe.“ 1 1. The ever-reliable Wikipedia…

Rules of J-club 1 st rule of J-Club: Don’t talk about J-club.

Incidentally…  Happy 157 th birthday, Dr. Osler. (a day late)

N-Acetylcysteine and Contrast-Induced Nephropathy in Primary Angioplasty NEJM 354;26 June 29, 2006 Marenzi et al. at the Institute of Cardiology, University of Milan, Italy And now, down to business…

Background  Patients with acute MI undergoing primary angioplasty are at high risk for contrast induced nephropathy.  NAC is a scavenger of oxygen-derived free radicals and causes endothelium-dependent vasodilation.  Approximately a dozen studies on the prophylactic effect of N-acetylcysteine have been published, with contradictory results.

Background  Research question: Can the antioxidant N- acetylcysteine prevent contrast induced nephropathy in patients undergoing primary angioplasty.** **Primary angioplasty vs. elective PCI (e.g. after positive stress echo)

Study population: Over 2 years, all patients admitted to the CCU at Centro Cardiologico Monzino in Milan for STEMI who would then undergo angioplasty Had to present within 12 hours (18 hours in cases of cardiogenic shock) after the onset of symptoms Exclusion criteria were long-term dialysis and known allergy to N-acetylcysteine The study was approved by the ethics committee, and written informed consent was obtained from all patients Let’s walk through it…  Methods

Methods  Eligible patients were randomly assigned to receive standard dose NAC, double dose NAC or placebo. 

Standard dose: 600mg IV bolus NAC before PCI, then 600mg po bid for 48 hours after PCI Double dose: 1200mg IV bolus NAC before PCI, then 1200mg po bid for 48 hours after PCI Placebo

Methods  After intervention, all patients received Normal Saline at 1ml/kg/hr. (or 0.5ml/kg/hr in cases of overt heart failure) for 12 hours.  The use of intraaortic balloon pumps, inotropic drugs, abciximab, beta-blockers, ACE inhibitors and diuretics was left to the discretion of the CCU/Cath cardiologists  Left ventricular function was evaluated by echocardiography in all patients within 24 hours after admission.  Investigators involved in the procedures and those reading echocardiograms were blinded to the treatment randomization.

 Primary end point: occurrence of contrast induced nephropathy, defined as an increase in serum creatinine by ≥25 percent from baseline value within the 72-hour period after PCI.  The major in-hospital clinical events, including death, were recorded. Methods

Methods   The contrast used was iohexol (omnipaque) which is low-osmolar and non-ionic. (versus Visipaque which is iso-osmolar, non-ionic, more expensive, and less damaging to kidneys)   Bare-metal stents (versus drug eluting) were implanted in all patients. Post-stenting antithrombotic treatment consisted of aspirin and either clopidogrel or ticlopidine at standard dosages.   N-acetylcysteine was purchased by the investigators.

Methods  Study was powered assuming a reduction in the average rate of nephropathy by 50 percent in the treatment arm vs. placebo (e.g. from 30 to 15 percent).  100 patients in each group allowed for a statistical power of 80 percent, with a type I error of  80% chance that you will avoid a false null hypothesis.  5% chance of a obtaining a statistically significant result and rejecting the null hypothesis when it is in fact is true.

 Statistical analysis was done as follows:  Clinical characteristics of the three groups: ANOVA for continuous variables, chi-square test or Fisher's exact test for categorical variables.  Time course of creatinine values among the three groups: ANCOVA  Incidence of complications among the three groups: Wald chi-square test with two degrees of freedom and by the Mantel–Haenszel chi-square test for trend.  A P-value of less than 0.05 was considered to indicate statistical significance. Methods