Funding to Oxford University for MRC/BHF Heart Protection Study

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Funding to Oxford Universityfor MRC/BHF Heart
Protection Study

• Medical Research Council 14M
• British Heart Foundation 2M
• Merck 8M
• Roche Vitamins 8M
• Designed, conducted analysed
• independently of all sources of support

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N-Terminal Pro-B-Type Natriuretic Peptide and
Vascular Disease among 20,536 Patients in the
MRC/BHF Heart Protection Study

• Heart Protection Study Collaborative
  GroupUniversity of Oxford
• UK

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BNP and N-BNP

• Prohormone released in ventricular myocardium,
  cleaved to active peptide (BNP) and inactive
  amino-terminal fragment (N-BNP)
• Stimulus for secretion increased ventricular
  stretch and wall tension
• Biological effects regulation of blood pressure,
  blood volume and sodium balance

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Clinical uses of N-BNP measurement

• Provides a highly sensitive (and reasonably
  specific) test for diagnosis of heart failure and
  pre-clinical ventricular dysfunction
• e.g. differential diagnosis of breathlessness in
  primary care and emergency room

• Indicator of disease severity and prognosis in
  patients with heart failure
• Target for treatment titration in heart failure
• Possible risk prediction for vascular disease

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HPS Randomised controlled trial of simvastatin
40mg daily vs placebo

• 20,536 patients aged 40-80 years at high risk
  of vascular disease
• 13,386 (65) with prior CHD
• 7,150 (35) with no CHD but with other vascular
  disease, diabetes or (men aged over 65 only)
  treated hypertension
• Patients with heart failure were eligible
  provided they were not breathless at rest, but
  diagnosis of heart failure was not recorded at
  baseline

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HPS Effect on major vascular events of reducing
LDL cholesterol by 1 mmol/l
SIMVASTATIN
PLACEBO
Rate ratio 95 CI
Vascular
event
(10269)
(10267)
STATIN better
PLACEBO better
898
1212
Major coronary
444
585
Any stroke
939
1205
Revascularisation
24 SE 3
2033
2585
ANY OF ABOVE
reduction
(19.8)
(25.2)
(2Plt0.00001)
0.4
0.6
0.8
1.0
1.2
1.4
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HPS Effect of simvastatin on major vascular
events subdivided by other treatments
SIMVASTATIN
PLACEBO
Rate ratio 95 CI
Baseline
treatment
(10269)
(10267)
STATIN better
PLACEBO better
Aspirin
Yes
1370
1784
(21.1)
(27.4)
No
663
801
(17.5)
(21.3)
ACE inhibitor
Yes
495
568
(24.9)
(28.5)
No
1538
2017
(18.6)
(24.4)
Beta-blocker
Yes
519
705
(19.5)
(26.9)
No
1514
1880
(19.9)
(24.6)
Calcium antagonist
Yes
788
1023
(24.7)
(31.2)
No
1245
1562
(17.6)
(22.4)
24 SE 3
2033
2585
(19.8)
(25.2)
ALL PATIENTS
reduction
(2Plt0.00001)
0.4
0.6
0.8
1.0
1.2
1.4
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Why measure N-BNP in HPS Do statins have similar
benefits in heart failure as in other patients?

• .The potential adverse effects of statins in
  CHF (heart failure) include reduction in coenzyme
  Q10 and loss of the protection that lipoproteins
  may provide through binding and detoxifying
  endotoxinssufficient uncertainty to merit a
  definitive clinical trial. Krum et al.
  JACC 2002
• CORONA placebo-controlled trial of rosuvastatin
  10mg among 5000 elderly patients with
  symptomatic systolic heart failure of ischaemic
  aetiology

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Aims

• To estimate the effect of simvastatin on risk of
  major vascular events and heart failure
  hospitalisation or death, separately according to
  N-BNP level.
• To examine the epidemiological relationship
  between N-BNP and the risk of major vascular
  events and hospitalisation or death due to heart
  failure.

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HPS Relationship of baseline N-BNP to other
baseline characteristics
N-BNP (fmol/ml) lt60 (n6633) 60-188 (n5400) 188-433 (n4244) 433-954 (n2773) gt954 (n1486)
Mean age (years) 60 64 67 68 70
Mean LDL (mmol/l) 3.4 3.4 3.4 3.4 3.3
Any CHD () 47 65 74 80 81
ACEI () 15 16 18 23 37
ß blocker () 11 23 32 37 32
Diuretic () 17 20 24 30 47
adjusted for age and sex
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HPS N-BNP and vascular disease
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HPS Effect of simvastatin allocation on major
coronary events by baseline N-BNP
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HPS Effect of simvastatin allocation on strokes
by baseline N-BNP
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HPS Effect of simvastatin allocation on major
vascular events by baseline N-BNP
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Effect of simvastatin allocation on heart failure
hospitalisation or death
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HPS Conclusions for heart failure and statins

• In people at risk of vascular events, N-BNP is a
  strong independent predictor not only of heart
  failure, but also of major vascular events
• In patients with high N-BNP levels (consistent
  with heart failure), statins produce clear
  benefits, with no evidence of any significant
  hazard

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Slides will be available at www.hpsinfo.org
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HPS Effect of simvastatin allocation on
vascular mortality by baseline N-BNP
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HPS Effect of simvastatin allocation on
non-vascular mortality by baseline N-BNP