Sodium Bicarbonate for the Prevention of Contrast Induced

Sodium Bicarbonate for the Prevention of Contrast Induced Nephropathy: A Meta-analysis of Published Clinical Trials Vijayalakshmi Kunadian 1, 2, Azfar Zaman 1, Weiliang Qiu 2 Freeman Hospital, Newcastle upon Tyne, United Kingdom; 2 The James Cook University Hospital, Middlesbrough, United Kingdom; 3 Channing Laboratory, Brigham and Women’s Hospital, Boston MA 1 SCAI Annual Scientific Sessions 2009 Las Vegas The authors have nothing to disclose

Background Contrast induced nephropathy (CIN) is a serious but rare complication following contrast based procedures Sodium bicarbonate has been demonstrated to prevent CIN through several mechanisms

Objective To perform a meta-analysis of randomized clinical trials to determine if the administration of Na. HCO 3 is superior to Na. Cl among patients with chronic renal failure undergoing catheterization and interventional procedures in preventing CIN

Study Selection A computerized literature search was performed on Pub. Med using the search terms “contrast nephropathy”, “sodium bicarbonate (Na. HCO 3)”, “sodium chloride” (Na. Cl) and “renal failure”. Seven published randomized clinical trials comparing Na. HCO 3 vs. placebo or Na. Cl during diagnostic and interventional procedures requiring contrast media administration were included.

RCTs Included in the Meta-analysis Study CKD Procedure Sample Trial design Brar Yes CA 353 Na. Cl vs. Na. HCO 3 Maioli Yes CA, PCI 502 Na. Cl vs. Na. HCO 3 Brigouri Yes CA, PCI 326 Na. Cl+NAC vs. Na. Cl+Na. HCO 3 vs. ascorbic acid+NAC Masuda Yes Em. CA and PCI 59 Na. Cl vs. Na. HCO 3 Merten Yes Diagnostic and interventional 119 Na. Cl vs. Na. HCO 3 Ozcan Yes CA, PCI 264 Na. Cl vs. Na. HCO 3 vs. Na. Cl+NAC Recio. Mayoral No Urgent or emergency CA, PCI 111 Na. Cl+NAC vs. Na. Cl+Na. HCO 3 CKD-chronic kidney disease, CA-coronary angiography, PCI-Percutaneous coronary intervention, PApulmonary angiography, NAC-N-acetylcysteine

Outcome Measures The development of CIN following administration of Na. HCO 3 and Na. Cl are provided. For the purpose of this meta-analysis, CIN was defined as reported in each of the individual trials. All studies describe CIN as ≥ 25% decrease in glomerular filtration rate (GFR) or an absolute increase of serum creatinine ≥ 0. 5 mg/dl on days 1 -5 following the procedure. Four trials (Brar, Maioli, Masuda and Recio-Mayoral) also report clinical outcomes on death, dialysis, myocardial infarction and cerebrovascular events. The occurrence of death, congestive heart failure and the need for renal replacement therapy between the two groups were evaluated from these trials.

Statistical Analysis Der. Simonian and Laird’s random effects model was utilized to pool the odds ratios (ORs) from individual trials. Cochran’s Q test was used to evaluate heterogeneity. Light and Pillemer’s funnel plot and Egger et al. ’s regressionbased method were used to assess publication bias. Duval and Tweedie’s trim-and-fill method was used to adjust for any observed publication bias. All analyses were undertaken in statistical software R.

Baseline Characteristics Na. Cl (n=772) Na. HCO 3(n=767) P value Age 70. 12 ± 3. 84 69. 76 ± 3. 73 0. 12 Gender 51 (69. 59%) 53. 52 (69. 88%) 0. 82 Height 1. 68 ± 0. 22 1. 66 ± 0. 22 0. 38 Weight 67. 01 ± 6. 78 67. 97 ± 7. 06 0. 04 BMI 26. 35 ± 2. 02 26. 5 ± 2. 41 0. 47 Prior MI 23. 9 (45. 16%) 33. 04 (51. 16%) 0. 65 Prior CHF 14. 48 (25. 75%) 12. 57 (22. 09%) 0. 54 Prior revasc. 115 (64. 6%) 114 (65. 1%) 0. 92 Diabetes 27. 32 (36. 19%) 25. 98 (35. 72%) 0. 57 Hypertension 71. 74 (71. 96%) 76. 72 (76. 05%) 0. 44 Systolic BP 145. 27 ± 15. 51 143. 64 ± 15. 51 0. 68 Diastolic BP 72. 54 ± 7. 93 71. 66 ± 8. 65 0. 33 LVEF 51. 71 ± 5. 8 52. 5 ± 5. 51 0. 55 Data are presented as weighted mean+/-SD and weighted number of events (%)

Baseline Characteristics Na. Cl (n=772) Na. HCO 3(n=767) P value NAC 84 (47. 2%) 80 (45. 7%) 0. 82 β-blocker 55. 5 (76. 96%) 57. 86 (79. 47%) 0. 74 ACE inhibitors 39. 54 (51. 56%) 39. 99 (52. 81%) 0. 89 ARB 21. 01 (23. 47%) 23. 03 (25. 76%) 0. 19 Statin 39. 21 (74. 88%) 31. 23 (71. 28%) 0. 7 Diuretic 33. 41 (37. 57%) 34 (38. 31%) 0. 75 CCB 19. 67 (22. 31%) 26. 94 (29. 29%) 0. 51 CA 55. 08 (43. 05%) 65. 44 (51. 01%) 0. 13 PCI 41. 86 (42. 31%) 34. 59 (38. 35%) 0. 37 CA, ad hoc PCI 30 (27. 02%) 18 (16. 67%) 0. 07 Contrast vol. 157. 39 ± 35. 7 157. 22 ± 41. 4 0. 35 Data are presented as weighted mean+/-SD and weighted number of events (%), ARB-angiotensin receptor blocker, CCB-calcium channel blocker

Development of CIN: All Patients Study Na. HCO 3 Na. Cl Brar 21/158 24/165 Maioli 25/250 29/252 Brigouri 2/108 11/111 Masuda 2/30 10/29 Merten 1/60 8/59 Ozcan 4/88 12/88 Recio-Mayoral 1/56 12/55 Total 750 759 OR 0. 33 (0. 16, 0. 69), P=0. 003 Favours Na. HCO 3 Favours Na. Cl Duval and Tweedie’s trim-and-fill adjustment for publication bias showed there was an attenuated OR of 0. 55 (95% CI 0. 27 -1. 10; P=0. 09) among all patients.

Development of CIN: Renal Failure Patients Study Na. HCO 3 Na. Cl Brar 21/158 24/165 Maioli 25/250 29/252 Brigouri 2/108 11/111 Masuda 2/30 10/29 Merten 1/60 8/59 Ozcan 4/88 12/88 Total 694 704 OR 0. 41 (0. 20, 0. 82), P=0. 01 Favours Na. HCO 3 Favours Na. Cl Duval and Tweedie’s trim-and-fill adjustment for publication bias showed there was an attenuated odds ratio of 0. 70 (95% CI 0. 35 -1. 43; P=0. 33).

Development of CIN: Among Patients Who Received NAC Study Na. HCO 3 Na. Cl Brigouri 2/108 11/111 Recio-Mayoral 1/56 12/55 Total 164 166 OR 0. 12 (0. 04, 0. 42), P=0. 0008 Favours Na. HCO 3 NAC-N-acetylcysteine Favours Na. Cl

Need for Renal Replacement Therapy Study Na. HCO 3 Na. Cl Brar 2/175 4/178 Maioli 1/250 1/252 Brigouri 1/111 Masuda 1/30 3/29 Merten 0/60 0/59 Ozcan 1/88 Recio-Mayoral 1/56 3/55 Total 770. 5 772. 5 OR 0. 56 (0. 22, 1. 41), P=0. 22 Favours Na. HCO 3 Favours Na. Cl

Clinical Endpoint: Death Study Na. HCO 3 Na. Cl Brar 4/175 7/178 Maioli 4/250 3/252 Masuda 0/30 2/29 Recio-Mayoral 1/56 4/55 Total 511 514 OR 0. 60 (0. 26, 1. 41), P=0. 24 Favours Na. HCO 3 Favours Na. Cl

Clinical Endpoint: Heart Failure Study Masuda Na. HCO 3 11/30 Na. Cl 11/29 Recio-Mayoral 1/56 2/55 Total 84 86 OR 0. 85 (0. 32, 2. 24), P=0. 74 Favours Na. HCO 3 Favours Na. Cl

Limitations The results observed here may not be applicable to all patients in clinical practice. The present study remains subject to the inherent caveats of a meta-analysis including publication-bias. Patient level data was not available in this study. The dose of Na. HCO 3 varied across the trials.

Conclusions The present meta-analysis demonstrates that based on currently available randomized trials, the administration of Na. HCO 3 is superior to administration of Na. Cl alone in the prevention of CIN among patients with moderate to severe CKD undergoing diagnostic and interventional procedures requiring contrast media.

Conclusions The use of Na. HCO 3 however, did not result in significant benefit in terms of reductions in death, heart failure and the requirement for renal replacement therapy. The results of this study should be considered in the context of publication bias inherent to meta-analysis. Adequately powered studies are required to determine the beneficial effect of Na. HCO 3 in preventing CIN and improving short-term and long-term clinical outcomes among patients who undergo coronary diagnostic and interventional procedures requiring contrast media.