ASCOTLLA: AngloScandinavian Cardiac Outcomes Trial Lipid Lowering Arm

1
ASCOT-LLA Anglo-Scandinavian Cardiac Outcomes
Trial Lipid Lowering Arm

• Purpose
• To determine whether cholesterol lowering with
  atorvastatin reduces coronary heart disease (CHD)
  in hypertensive patients with average or
  lower-than-average cholesterol concentrations
• Reference
• Sever PS, Dahlöf B, Poulter NR et al. for the
  ASCOT Investigators. Prevention of coronary and
  stroke events with atorvastatin in hypertensive
  patients who have average or lower-than-average
  cholesterol concentrations, in the
  Anglo-Scandinavian Cardiac Outcomes Trial Lipid
  Lowering Arm (ASCOT-LLA) a multicentre
  randomised controlled trial. Lancet
  2003361114958.

2
ASCOT-LLA Anglo-Scandinavian Cardiac Outcomes
Trial Lipid Lowering Arm- TRIAL DESIGN -

• Design
• Multicenter, multinational, randomized,
  double-blind, placebo-controlled
• Patients
• 10,305 patients aged 4079 years who had
  hypertension, with total cholesterol lt250 mg/dL
  (lt6.5 mmol/L) and gt3 risk factors for
  cardiovascular disease. Patients currently
  receiving a statin or who had a recent
  cerebrovascular event, previous MI or heart
  failure were excluded.
• Follow up and primary endpoint
• Primary endpoint nonfatal MI and fatal CHD.
  Median 3.3 years follow up.
• Treatment
• Atorvastatin 10 mg once daily or placebo

3
ASCOT-LLA Anglo-Scandinavian Cardiac Outcomes
Trial Lipid Lowering Arm- TRIAL DESIGN
continued-
Baseline characteristics
Placebo
(n5137)
a
Age (years)
63
Female ()
19
a
BP (mmHg)
Systolic
164
Diastolic
95
2
a
Body mass index (kg/m
)
29
Previous antihypertensive treatments ()
None
19
1
44
gt2
36
Lipid-lowering treatment
1
Aspirin use
17
a
Mean
Sever et al.
Lancet
2003
361
1149

58.
4
ASCOT-LLA Anglo-Scandinavian Cardiac Outcomes
Trial Lipid Lowering Arm- RESULTS -

• Trial stopped early at median 3.3 years because,
  compared with placebo, atorvastatin group had
  significantly reduced
• primary endpoint of nonfatal MI and fatal CHD
  (1.9 vs. 3.0, hazard ratio 0.64, P0.0005)
• combined endpoint of fatal and nonfatal stroke
• coronary events
• Benefit of atorvastatin emerged in first year of
  follow up and for primary endpoint was similar
  for all subgroups over 3.3 years
• All-cause mortality not significantly reduced in
  atorvastatin group but trend was towards
  reduction
• Compared with placebo, atorvastatin lowered total
  cholesterol by 24 (50 mg/dL, 1.3 mmol/L) at 12
  months and 19 (43 mg/dL, 1.1 mmol/L) at 3 years
• Drug well tolerated as defined by similar
  withdrawal rate in both groups

5
ASCOT-LLA Anglo-Scandinavian Cardiac Outcomes
Trial Lipid Lowering Arm- RESULTS continued -
Nonfatal MI and fatal CHD
Proportion of
4
patients
()
3
2
HR0.64
(95 CI0.500.83)
P0.0005
1
Placebo
Atorvastatin
0
0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
Years after randomization
Sever et al.
Lancet
2003
361
1149

58.
6
ASCOT-LLA Anglo-Scandinavian Cardiac Outcomes
Trial Lipid Lowering Arm- RESULTS continued -
Primary and selected secondary outcomes
Unadjusted
Placebo
Atorvastatin
hazard ratio
(n5137)
(n5168)
P
a
a
No.
()
Rate
No.
()
Rate
(95 CI)
Primary endpoint
(3.0)
Secondary endpoints
Sever et al.
Lancet
2003
361
1149

58.
7
ASCOT-LLA Anglo-Scandinavian Cardiac Outcomes
Trial Lipid Lowering Arm - SUMMARY -

• In patients with hypertension and risk factors
  for CHD, with average or lower-than-average
  cholesterol, atorvastatin
• Reduced primary endpoint of nonfatal MI and fatal
  CHD, in all subgroups
• Reduced fatal/nonfatal stroke
• Reduced coronary events
• Conferred no change in all-cause mortality