1. BNP for CHF Dr James Young Head, Section of Heart Failure and Cardiac Transplant Medicine Cleveland Clinic Foundation Cleveland, OH

2. B-type natriuretic peptide BNP for CHF nesiritide (B-type natriuretic peptide) Hormone produced by the left ventricle in response to increase in volume and pressure in the left ventricle. A potent vasodilator, acts to counteract other hormones that are associated with heart failure.

3. VMAC trial BNP for CHF Vasodilation in the Management of Acute CHF 498 patients in a multicenter (55 US sites ) trial Randomization stratified by use of right heart catheter Placebo- and nitroglycerin-controlled

4. VMAC: design BNP for CHF 6 months eligible patient (n=489) stratification catheterized (n=246) non- catheterized (n=243) randomization 3-hour placebo-controlled period Active-controlled treatment period nitroglycerin (n=60) placebo (n=62) nesiritide fixed-dose (n=62) nesiritide adjustable-dose (n=62) nitroglycerin (n=92) nesiritide fixed-dose (n=92) nesiritide adjustable-dose (n=62) nitroglycerin (n=83) placebo (n=80) nesiritide fixed-dose (n=80) nitroglycerin (n=124) nesiritide fixed-dose (n=119) time zero 3 hours end of study drug Time

5. VMAC: findings BNP for CHF NTG Nesiritide Placebo 18 19 20 21 22 23 24 25 26 27 28 29 30 Time # *# * *p <0.05 versus placebo # *# * # *# * # # * Primary endpoint: PCWP through 3 hours

6. Mortality BNP for CHF VMAC not designed to answer mortality question No statistically significant difference at 30 day, 90 day, 150 day marks.

7. Costs BNP for CHF Yet to be approved for general use as treatment by the FDA. Pharmacoeconomic studies have not been done. Hope to see it competitively priced with some of the inotropic agents used today. Added value possible if it aids treatment by keeping people out of ICU or out of hospital.

8. FDA approval BNP for CHF Cardio-renal advisory panel of FDA voted 5- 4 in January 1999 for the drug. VMAC was designed to answer some additional questions the FDA had.

9. SpecificitySensitivity Jugular venous pressure92%34% Third heart sound90%26% Rales81%57% BNP (cutoff value of 100 pg/mL)98%100% 100 patients presenting to the ER with signs or symptoms of congestive heart failure (eg, dyspnea, edema, weight gain) 3 of 4 Dao and colleagues, 49th Annual Scientific Session of the American College of Cardiology BNP for CHF Specificity and sensitivity

10. BNP levels identified individuals with: normal heart function (BNP = 38  4 pg/mL) normal ejection fraction but wall motion abnormalities (BNP = 177  20 pg/mL) impaired ejection fraction (BNP = 523  50 pg/mL, p<0.001) 2 of 4 Koon and colleagues, 49th Annual Scientific Session of the American College of Cardiology Marker for CHF BNP for CHF

11. The future? BNP for CHF “I think it’s going to be an elegant way of being able to track patients with heart failure and seeing where exactly they are. It may become, if my hunch is right […] the complete blood count measurement to see where a patient is at with this heart failure syndrome at any given time.” Dr James Young Head, Section of Heart Failure and Cardiac Transplant Medicine Cleveland Clinic Foundation Cleveland, OH