Presentation on theme: "Conflict of Interest Nothig to disclose."— Presentation transcript:
0Preventive Strategies of REnal Insufficiency in Patients with Diabetes Undergoing InterVENTion or Arteriography: The PREVENT trialYoung-Hak Kim, MD, PhDon behalf of the PREVENT investigatorsDepartment of Cardiology, University of Ulsan College of MedicineAsan Medical Center, Seoul, Korea
2Background Contrast-Induced Nephropathy (CIN): - Common cause of hospital acquired renal failure.- Occurs in less than 1% of general population.- Occurs in up to 50% of patients with chronic renal insufficiency, especially if diabetes is present.Diabetic nephropathy and chronic kidney disease are the most common risk factors for the development of CIN.CIN is the 3rd most common cause of hospital acquired renal failureOccurs in less than 1% of general populationOccurs in "only" 5.5% of patients with renal insufficiencyBut, occurs in 50% of patients with both renal insufficiency and diabetes mellitus2
3BackgroundRecent small scale studies suggested that hydration with sodium bicarbonate may be more protective than sodium chloride alone in the prevention of CIN.However, in the recent meta-analysis, the effectiveness of sodium bicarbonate treatment remains uncertain due to the heterogeneity in outcomes across studies.Ann Intern Med. 2009;151:631In particular, there are a few data about its effectiveness for patients with diabetes mellitus.
4ObjectiveTo determine if sodium bicarbonate is superior to sodium chloride for preventing CIN in diabetic patients with mild to moderate chronic kidney dysfunction who are undergoing coronary and/or endovascular intervention or angiography.
5Subjects 3569 Patients screened 423 Eligible 382 Randomized 3146 Excluded423 Eligible41 Denied382 Randomized189 Randomized to Saline193 Randomized to Bicarbonate187 Included in primary contrast-induced nephropathy analysis2 Excluded because did not have laboratory data after angiography189 Included in 30-day clinical FU188 Included in 6-month clinical FU188 Included in primary contrast-induced nephropathy analysis5 Excluded because did not have laboratory data after angiography193 Included in 30-day clinical FU192 Included in 6-month clinical FU
6Study Protocol Before After Preparation Clinical FUto 6 monthsContrast Media ExposureBeforeAfterPreparationSalineCreatinine, GFRBicarbonateElectrolyte12 hrs1 hr6 hrs12 hrs24 hrs48 hrsNACNAC1:1 randomization, open label design9 cardiac centers in KoreaIndependent event committee and data managementSponsored by CardioVascular Research Foundation, Seoul, Korea
7Study ProtocolBicarbonate group: Sodium bicarbonate 154mEq/L: 3 mL/kg for 1 hour prior, decreased to 1 mL/kg/hr during and 6 hours after the procedure.Saline group: Isotonic saline 0.9% NaCl: 1 mL/kg/hr for 12 hours before and 12 hours after.All patients received oral N-acetylcysteine 1200 mg twice daily for 2 days, prior to procedure.If ejection fraction < 45%, hydration rate was reduced to 0.5mL/kg/hr in both arms.
8Study ProtocolSerum creatinine was measured on days 1 and 2 post angiography.For all patients, creatinine levesls were assessed until any increase of renal resolved or reached a new baseline of renal function.All patients who developed CIN were asked to return around 1 month for repeat measurement of creatinine.All study participants received idixanol (Visipaque, 320mg iodine/mL, Amersham), a non-ionic, dimeric iso-osmolar contrast medium.
9Inclusion Criteria Age>18 years, no upper limits, Diabetes treated with insulin or oral hypoglycemic agents,Serum creatinine ≥ 1.1mg/dL, andresting estimated glomerular filtration rate (GFR)< 60 ml/min per 1.73 m2 by Modification of Diet in Renal Disease formula (1.863 x serum creatinine level x age x [0.742 if female])
10Exclusion Criteria Serum creatinine ≥ 8 mg/dL Resting estimated GFR < 15 ml/min/1.73 m2End stage renal disease on hemodialysisMultiple myelomaPulmonary edemaUncontrolled hypertension (systolic BP >160mmHg or diastolic BP>100mmHg)Acute STEMI undergoing primary PCIEmergent coronary angioplasty or angiographyRecent use of contrast agent within 2 daysAllergic reaction to contrastPregnancyAllergic to following medication : theophylline, dopamine, mannitol, fenoldopam, N-acetylcysteine
11Primary Study Endpoint Occurrence of CIN within 48 hours after contrast exposure.CIN was defined as an increase of serum creatinine >25% or absolute increase of serum creatinine 0.5mg/dL within 48 hours after coronary and/or endovascular intervention or angioplasty
12Secondary Endpoints Secondary Endpoint : Death (all-cause) : Myocardial infarction: Stroke: Dialysis including hemofiltrationat 30 days, between 1 month and 6 months, and 6 months after contrast exposure.
13Sample Size Estimation Study sample size was calculated on the basis of a power analysis assuming that 10% of sodium chloride group and 2% of the sodium bicarbonate group would develop contrast induced nephropathy.With a power of 90% and 2-sided α of 0.05, 368 patients with complete data would be required to detect a statistically significant difference.
14Statistical AnalysisThe categorical variables were presented as number (percentage) and were compared using chi-square or Fisher exact test.The continuous variables were presented as median (interquartile range) and were compared using Mann-Whitney U test.To identify independent predictors of CIN, multivariate logistic regression test was performed with fixed 7 covariates.
27Effect of Bicarbonate According to the Contrast Volume
28CIN according to Contrast Volume P=0.93P=0.058(2/137)(8/134)(8/50)(9/54)* HCL, High Contrast Load: >140 mL and > maximal contrast dose (5Xbody weight/creatinine)
29Dialysis according to Contrast Volume P=1.00P=0.37(1/50)(1/54)(1/137)(3/134)* HCL, High Contrast Load: >140 mL and > maximal contrast dose (5Xbody weight/creatinine)
30CIN according to Contrast Volume P=0.61P=0.156/768/784/1119/110
31Dialysis according to Contrast Volume P=1.00P=1.00(1/76)(2/78)(1/110)(2/110)
32Multivariate Predictors of CIN VariablesOdds ratio95% CIPvalueContrast amount (mL)1.0051.002, 1.0090.003LV ejection fraction (%)0.9610.929, 0.9950.026OKFrom 7 covariates including age, sex, contrast amount, procedural type,LV ejection fraction, randomization, and body mass index
34Major Adverse Events at 1 Month P=1.00P=1.00P=1.0011112* MAE: Cumulative major adverse events
35Major Adverse Events between 1 to 6 months P=0.11P=0.45P=0.2525328* MAE: Cumulative major adverse events
36Major Adverse Events at 6 Months P=0.053P=0.45P=0.372614310* MAE: Cumulative major adverse events
37ConclusionIn patients with diabetic nephropathy who received coronary or endovascular angiography or intervention, hydration with sodium bicarbonate before or after contrast exposure was not superior to hydration with sodium chloride for the prevention of CIN.