Presentation on theme: "Young-Hak Kim, MD, PhD on behalf of the PREVENT investigators Preventive Strategies of REnal Insufficiency in Patients with Diabetes Undergoing InterVENTion."— Presentation transcript:
Young-Hak Kim, MD, PhD on behalf of the PREVENT investigators Preventive Strategies of REnal Insufficiency in Patients with Diabetes Undergoing InterVENTion or Arteriography: The PREVENT trial Department of Cardiology, University of Ulsan College of Medicine Asan Medical Center, Seoul, Korea
Conflict of Interest Nothig to disclose
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. Background
Recent 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;151:631 In particular, there are a few data about its effectiveness for patients with diabetes mellitus. Background
To 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. Objective
187 Included in primary contrast-induced nephropathy analysis 2 Excluded because did not have laboratory data after angiography 189 Included in 30-day clinical FU 188 Included in 6-month clinical FU 188 Included in primary contrast-induced nephropathy analysis 5 Excluded because did not have laboratory data after angiography 193 Included in 30-day clinical FU 192 Included in 6-month clinical FU Subjects 3569 Patients screened 189 Randomized to Saline193 Randomized to Bicarbonate 3146 Excluded 423 Eligible 41 Denied 382 Randomized
12 hrs Preparation BeforeAfter 48 hrs24 hrs Contrast Media Exposure 1:1 randomization, open label design 9 cardiac centers in Korea Independent event committee and data management Sponsored by CardioVascular Research Foundation, Seoul, Korea 1:1 randomization, open label design 9 cardiac centers in Korea Independent event committee and data management Sponsored by CardioVascular Research Foundation, Seoul, Korea Saline Creatinine, GFR Electrolyte Study Protocol NAC 12 hrs NAC 6 hrs Bicarbonate 1 hr Clinical FU to 6 months
Study Protocol Bicarbonate 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.
Study Protocol Serum 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.
Age>18 years, no upper limits, Diabetes treated with insulin or oral hypoglycemic agents, Serum creatinine 1.1mg/dL, and resting estimated glomerular filtration rate (GFR) < 60 ml/min per 1.73 m 2 by Modification of Diet in Renal Disease formula ( x serum creatinine level x age x [0.742 if female]) Inclusion Criteria
Serum creatinine 8 mg/dL Resting estimated GFR < 15 ml/min/1.73 m 2 End stage renal disease on hemodialysis Multiple myeloma Pulmonary edema Uncontrolled hypertension (systolic BP >160mmHg or diastolic BP>100mmHg) Acute STEMI undergoing primary PCI Emergent coronary angioplasty or angiography Recent use of contrast agent within 2 days Allergic reaction to contrast Pregnancy Allergic to following medication : theophylline, dopamine, mannitol, fenoldopam, N-acetylcysteine Exclusion Criteria
Primary 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
Secondary Endpoints Secondary Endpoint : Death (all-cause) : Myocardial infarction : Stroke : Dialysis including hemofiltration at 30 days, between 1 month and 6 months, and 6 months after contrast exposure.
Sample 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.
Statistical Analysis The 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.
Measures Before Contrast After Contrast P value* Sodium Chloride group Serum Creatinine, mg/dL <0.001 Estimated GFR, mL/min/1.73m Sodium Bicarbonate group Serum Creatinine, mg/dL Estimated GFR, mL/min/1.73m Changes in Renal Function * Wilcoxon signed rank test
Effect of Bicarbonate
Primary End Point - Occurrence of CIN - % 10/187 P= /188 % %
Difference in Serum Creatinine mg/dL P=0.49 P=0.18 Mann-Whitney U test
Difference in Estimated GFR mL/min/1.73 P=0.18 P=0.48 Mann-Whitney U test
Rates of Dialysis % 2/187 P=0.69 4/188
Effect of Bicarbonate According to the Contrast Volume
P=0.93 P=0.058 (8/50) CIN according to Contrast Volume (9/54) (2/137)(8/134) * HCL, High Contrast Load: >140 mL and > maximal contrast dose (5Xbody weight/creatinine)
P=1.00 P=0.37 (1/50) Dialysis according to Contrast Volume (1/54) (1/137) (3/134) * HCL, High Contrast Load: >140 mL and > maximal contrast dose (5Xbody weight/creatinine)
P=0.61P=0.15 6/76 CIN according to Contrast Volume 8/78 4/111 9/110
P=1.00 (1/76) Dialysis according to Contrast Volume (2/78) (1/110) (2/110)
Variables Odds ratio 95% CI P value Contrast amount (mL) , LV ejection fraction (%) , Multivariate Predictors of CIN From 7 covariates including age, sex, contrast amount, procedural type, LV ejection fraction, randomization, and body mass index
P= * MAE: Cumulative major adverse events Major Adverse Events at 1 Month P=
5 * MAE: Cumulative major adverse events 8 P=0.45 Major Adverse Events between 1 to 6 months 2 P= P=0.25
6 * MAE: Cumulative major adverse events 10 P= P= Major Adverse Events at 6 Months P=
In 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. Conclusion