Dr James Young

1
BNP for CHF

• Dr James Young
• Head, Section of Heart Failure and
• Cardiac Transplant Medicine
• Cleveland Clinic Foundation
• Cleveland, OH

2
BNP for CHF
B-type natriuretic peptide

• 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.

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BNP for CHF
VMAC trial

• 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

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BNP for CHF
VMAC design
3-hourplacebo-controlled period
Active-controlledtreatment period
randomization
nitroglycerin (n60)
nitroglycerin (n92)
stratification
catheterized(n246)
placebo (n62)
nesiritide fixed-dose (n62)
nesiritide fixed-dose (n92)
nesiritide adjustable-dose (n62)
nesiritide adjustable-dose (n62)
eligiblepatient(n489)
non- catheterized(n243)
nitroglycerin (n124)
nitroglycerin (n83)
placebo (n80)
nesiritide fixed-dose (n80)
nesiritide fixed-dose (n119)
3 hours
time zero
end ofstudydrug
6 months
Time
5
BNP for CHF
VMAC findings
Primary endpoint PCWP through 3 hours
NTG
Nesiritide
Placebo
30
29
28
27
26
25


24

23



22

21
20
19
18
Time
p lt0.05 versus placebo
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BNP for CHF
Mortality

• VMAC not designed to answer mortality question
• No statistically significant difference at 30
  day, 90 day, 150 day marks.

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BNP for CHF
Costs

• 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.

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BNP for CHF
FDA approval

• 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.

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BNP for CHF
3 of 4
Specificity and sensitivity
100 patients presenting to the ER with signs or
symptoms of congestive heart failure (eg,
dyspnea, edema, weight gain)
Dao and colleagues, 49th Annual Scientific
Session ofthe American College of Cardiology
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BNP for CHF
2 of 4
Marker for CHF

• 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, plt0.001)

Koon and colleagues, 49th Annual Scientific
Session ofthe American College of Cardiology
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BNP for CHF
The future?

• I think its 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