ASCOT and Steno-2: Aggressive risk reduction benefits two different patient populations

1
ASCOT and Steno-2 Aggressive risk reduction
benefits two different patient populations
Steno-2
ASCOT-LLA

• Steno-2
• Diabetes microalbuminuria
• Intensive target-driven reduction of BP, total-C,
  TG, A1C vs usual care
• 7.8 years
• ASCOT-LLA
• Hypertension 3 CV risk factors, total-C 250
  mg/dL
• Amlodipine/perindopril atorvastatin vs placebo
• 3.5 years

Relative risk reduction ()


Composite of CV death, nonfatal MI or stroke,
revascularization, and amputation, P lt
0.001 Fatal CHD and nonfatal MI (including
silent MI), P lt 0.0001
Gaede P et al. N Engl J. Med. 2003348383-93. Sev
er PS et al. Circulation. 2005112(suppl
II)II-134. Abstract 730.
2
ASCOT Patients had hypertension and 3 other
risk factors, fitting a common clinical profile
Hypertension Aged 55 years Male Microalbuminuria/
proteinuria Smoker Family history of CHD Plasma
total-CHDL-C 6 Type 2 diabetes Certain ECG
abnormalities LVH Prior cerebrovascular
events Peripheral vascular disease
0
10
20
30
40
50
60
70
80
90
100
Patients with risk factor ()
Sever PS et al. J Hypertens. 2001191139-47.Seve
r PS et al. Lancet. 20033611149-58.
LVH left ventricular hypertrophy
3
ASCOT-BPLA Reduction in primary outcome
(nonfatal MI and fatal CHD)
10
8
RRR 10 HR 0.90 (95 CI, 0.791.02) P
0.1052
6
Proportionof events ()
4
Atenolol-based regimen
2
Amlodipine-based regimen
0
1
2
3
4
5
6
0
Time since randomization (years)
Atenolol 50100 mg bendroflumethiazide
1.252.5 mg Amlodipine 510 mg perindopril
48 mg
Dahlöf B et al. Lancet. 2005366895-906.
4
ASCOT Risk reductions with the
amlodipine/perindopril regimen
Rate/1000 patient-years
Amlodipine-based(n 9639)
Atenolol-based (n 9618)
lt0.05 lt0.01 lt0.0001 lt0.05 0.001
lt0.001 NS lt0.0001 lt0.05
Secondary endpoints Nonfatal MI (excluding
silent) 7.4 8.5 fatal CHD Total coronary
endpoint 14.6 16.8 Total CV events and
procedures 27.4 32.8 All-cause
mortality 13.9 15.5 CV mortality 4.9 6.5
Fatal/nonfatal stroke 6.2 8.1
Fatal/nonfatal HF 2.5 3.0 Tertiary
endpoints Development of diabetes 11.0 15.9
Development of renal impairment 7.7 9.1
Amlodipine-based better
Atenolol-based better
P
0.50
0.75
1.00
1.50
2.00
Unadjusted hazard ratio
Amlodipine 510 mg perindopril 48
mg Atenolol 50100 mg bendroflumethiazide
1.252.5 mg
Dahlöf B et al. Lancet. 2005366895-906.
5
CAFE asked whether newer vs older BP treatments
have differing effects on central aortic BP
N 2199 5 UK ASCOT centers
n 126Excluded HR irregularity Poor waveforms
N 2073Evaluable for tonometry
n 1042Amlodipine perindopril
n 1031Atenolol bendroflumethiazide
n 1042 Intent-to-treatn 1038 Complete
information
n 1031 Intent-to-treatn 1030 Complete
information
Newer antihypertensive regimen Older
antihypertensive regimen
CAFE Investigators. Circulation. 20061131213-25.
6
CAFE Central aortic pressure is lower with the
amlodipine/perindopril regimen
140
Brachial SBP
135
130
Central aortic SBP
mm Hg
125
120
115
0
0.5
1
1.5
2
2.5
3
3.5
4
4.5
5
5.5
6
Time (years)
Amlodipine perindoprilAtenolol
bendroflumethiazide
CAFE Investigators. Circulation. 20061131213-25.
7
CAFE Lesser ability of ß-blockers to reduce
augmentation wave
P lt 0.0001
Atenolol bendroflumethiazide
Amlodipine perindopril
CAFE Investigators. Circulation. 20061131213-25.
8
ASCOT Lipid lowering is beneficial regardless of
baseline cholesterol level
Sever PS et al. Lancet. 20033611149-58.
9
ASCOT Greater gain with statin CCB/ACE
inhibitor vs statin ß-blocker/diuretic
Fatal CHD and nonfatal MI
NS
P lt 0.0001
NS
10
9.8
9
9
8
7
7.5
Events/1000patient-years
6
5
4
3
4.6
2
- Atorvastatin ( placebo)
1
0
Atorvastatin (10 mg)
P (interaction between lipid and BP lowering)
0.025
Atenolol

Amlodipine
Sever PS et al. Circulation. 2005112(suppl
II)II-134. Abstract 730. Sever PS et al. AHA
Scientific Sessions. Nov 2005.
Atenolol bendroflumethiazideAmlodipine
perindopril