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 1875. • 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 Don’t talk about J-club. 1st rule of J-Club:
Incidentally… • Happy 157th birthday, Dr. Osler. (a day late)
And now, down to business… N-Acetylcysteine and Contrast-Induced Nephropathy in Primary AngioplastyNEJM 354;26 June 29, 2006Marenzi et al. at the Institute of Cardiology, University of Milan, Italy
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)
Methods • 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 • 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.
Methods • 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 • 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.
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 0.05. 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. Methods
Methods • 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.