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Trial Overview

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Trial Overview

  1. 1. Western Norway B-vitamin Intervention Trial Presented at the European Society of Cardiology Congress 2007 Presented by: Dr Marta Ebbing Department of Heart Disease, Haukeland University Hospital, Bergen The WENBIT Study Group WENBIT Trial
  2. 2. WENBIT Trial: Background and Objectives <ul><li>Background </li></ul><ul><li>Homocysteine-hypothesis of vascular disease </li></ul><ul><li>Vitamin B 6 status cardiovascular risk modifier </li></ul><ul><li>Objectives </li></ul><ul><li>To study the effect of homocysteine-lowering therapy with folic acid + vitamin B 12 , and the separate effect of vitamin B6 therapy, on mortality and cardiovascular events in patients undergoing coronary angiography. </li></ul>ESC 2007
  3. 3. Study Population <ul><li>3090 patients with stable angina (84%), ACS (15%), or aortic valve stenosis (1%), undergoing coronary angiography at Bergen or Stavanger University Hospitals, 1999-2004 </li></ul>ESC 2007
  4. 4. Sample Size Calculation <ul><li>Sample size N = 3088 to give 80% power to detect 20% difference if: </li></ul><ul><li>Follow-up 4 years </li></ul><ul><li>4-year total event rate 22% </li></ul><ul><li>Drop-outs ≤ 20% </li></ul><ul><li>At a 5% significance level </li></ul>ESC 2007
  5. 5. Intervention Groups ESC 2007 Placebo N = 779 Folic acid (0.8 mg) +B 12 (0.4 mg) N = 769 Non-vitamin B 6 B 6 (40 mg) N = 771 Folic acid (0.8 mg) +B 12 (0.4 mg) +B 6 (40 mg) N=771 Vitamin B 6 Non-folic acid Folic acid + vitamin B 12
  6. 6. Primary End Point <ul><li>A composite of: </li></ul><ul><li>Death (all cause) </li></ul><ul><li>Non-fatal acute myocardial infarction </li></ul><ul><li>Acute hospitalization for unstable angina </li></ul><ul><ul><li>With ECG signs of acute ischemia and/or </li></ul></ul><ul><ul><li>With angiographically verified progression </li></ul></ul><ul><li>Non-fatal thromboembolic stroke </li></ul>ESC 2007
  7. 7. WENBIT Trial: Baseline Characteristics 1 ESC 2007 59.2 60.7 58.6 58.2 Prior chol. ≥ 6.5 mmol/L (%) 5.1 ± 1.2 5.1 ± 1.2 5.1 ± 1.3 5.1 ± 1.1 Cholesterol (mmol/L  SD) 27.6 30.9 26.4 28.4 Current smoker (%) 14.4 15.6 13.9 14.9 Reduced LVEF ≤ 0.5 (%) 47.8 45.7 46.3 45.4 Hypertension (%) 76.5 80.2 80.4 81.2 Male (%) 62.0 ± 9.9 61.4 ± 9.7 61.3  10.0 61.7  10.3 Age (yrs  SD) Placebo B 6 Folic Acid +B 12 Folic Acid +B 12 +B 6 Characteristic
  8. 8. WENBIT Trial: Baseline Characteristics 2 ESC 2007 22.2 24.3 25.7 23.0 CABG at baseline % 42.5 43.5 45.5 44.6 PCI at baseline % 32.0 31.9 33.2 33.1 3-vessel disease % 27.5 25.7 26.7 27.0 2-vessel disease % 29.3 31.3 29.5 29.1 1-vessel disease % 13.6 14.1 11.3 14.7 Prior CABG % 21.4 21.0 20.4 19.7 Prior PCI % 42.9 43.1 42.0 37.9 Prior MI % Placebo B 6 Folic Acid +B 12 Folic Acid +B 12 +B 6 Characteristic
  9. 9. WENBIT Trial: Baseline Characteristics 3 ESC 2007 12.7 10.2 9.1 11.5 AT II Antagonists % 22.3 21.0 23.4 18.8 ACE inhibitors % 76.5 78.9 80.0 77.3 Beta-blockers % 88.6 89.8 87.0 88.1 Statins % 24.1 26.7 25.5 23.6 Clopidogrel % 90.9 90.0 90.8 89.0 Acetylsalisylic Acid % Placebo B 6 Folic Acid +B 12 Folic Acid +B 12 +B 6 Characteristic
  10. 10. Baseline Vitamin Status <ul><li>No mandatory folic acid fortification of foods in Norway </li></ul><ul><li>19% used B-vitamin supplements containing small doses of folic acid </li></ul><ul><li>Supplement users had somewhat lower total homocysteine levels (10.6 µ mol/L) than non-users (10.8 µ mol/L), p= 0.02 </li></ul>ESC 2007
  11. 11. Follow Up <ul><li>Study visits at 1 month, 12 months, and final after median follow-up time 38 months </li></ul><ul><li>18% drop-outs, no significant differences in drop-out rates </li></ul><ul><li>Intervention terminated ahead of schedule for 22% of participants October 2005 </li></ul><ul><li>422 participants (13.7%) with events classified as the primary end point (intention to treat). </li></ul>ESC 2007
  12. 12. Folate Levels ESC 2007
  13. 13. Homocysteine-Lowering ESC 2007
  14. 14. Events in Primary End Point* *Numbers ESC 2007 422 97 106 126 93 Total 56 16 15 16 9 Stroke 87 22 20 27 18 Unstable angina 162 34 43 50 35 Non-fatal AMI 117 25 28 33 31 All cause death Total Placebo B 6 Folic Acid +B 12 Folic Acid +B 12 +B 6
  15. 15. Primary End Point – 422 Events ESC 2007
  16. 16. Norwegian Secondary Prevention Trials with Identical B-vitamin Intervention Bonaa et al. New Engl J Med 2006
  17. 17. WENBIT <ul><li>Large B-vitamin intervention trial in population with mainly stable angina and 2 or 3 vessel CAD, without folic acid fortification of foods. </li></ul><ul><li>Homocysteine-lowering effect as expected </li></ul><ul><li>No significant difference in primary end point (death and cardiovascular events) between folate and non-folate or B 6 and non-B 6 groups. </li></ul>ESC 2007
  18. 18. WENBIT Organization <ul><li>Steering Committee </li></ul><ul><li>Prof. Jan Erik Nordrehaug 1,2 </li></ul><ul><li>Prof. Per Magne Ueland 2 </li></ul><ul><li>Prof. Stein Emil Vollset 3 </li></ul><ul><li>Prof. Helga Refsum 4 </li></ul><ul><li>Prof. Dennis Nilsen 5 </li></ul><ul><li>Prof. Ottar Nygard 1,2 </li></ul><ul><li>End Points Committee </li></ul><ul><li>Prof. Per Lund-Johansen 2 </li></ul><ul><li>MD Leik Woie 5 </li></ul><ul><li>MD Marta Ebbing 1,2 </li></ul><ul><li>Safety Committee </li></ul><ul><li>Prof. Rolv T Lie 3 </li></ul><ul><li>Prof. Terje R Pedersen 6 </li></ul>1 Department of Heart Disease, Haukeland University Hospital, Bergen; 2 Institute of Medicine; 3 Department of Public Health and Primary Health Care, University of Bergen; 4 Institute of Basic Medical Science, Department of Nutrition, University of Oslo; 5 Department of Cardiology, Stavanger University Hospital, Stavanger; 6 Centre for Preventive Medicine, Ulleval University Hospital, Oslo; Norway Western Norway B-Vitamin Intervention Trial ESC 2007

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