LIPID: Longterm Intervention with Pravastatin in Ischemic Disease

1
LIPID Long-term Intervention with Pravastatin
in Ischemic Disease

• Purpose
• To determine whether pravastatin will reduce
  coronary mortality and morbidity in patients with
  AMI or unstable angina pectoris and broad range
  of initial cholesterol levels
• Reference
• LIPID Study Group. Prevention of cardiovascular
  events and death with pravastatin in patients
  with coronary heart disease and a broad range of
  initial cholesterol levels. N Engl J Med
  1998339134957.

2
LIPID Long-term Intervention with Pravastatin in
Ischemic Disease- TRIAL DESIGN -

• Design
• Randomized, double-blind, placebo-controlled
• Patients
• 9014 patients with AMI or hospitalization 336
  months previously for unstable angina pectoris
  baseline cholesterol 155-271 mg/dL (47 mmol/L)
• Follow up and primary endpoint
• Follow up mean 6.1 years. Primary endpoint death
  from CHD
• Treatment
• Pravastatin 40 mg daily or placebo. Dietary
  counseling for both groups

3
LIPID Long-term Intervention with Pravastatin in
Ischemic Disease - RESULTS -

• Significant reduction in overall mortality, death
  from CHD and all other pre-specified
  cardiovascular events
• Total plasma cholesterol 21 lower than in
  placebo group at 6 months, falling to 13 at 6.1
  years due to discontinuation of treatment in
  pravastatin group and commencement of open-label
  therapy in placebo group
• Pravastatin well tolerated no significant
  differences in cancers, accidents, violence,
  suicide (11 vs. 6 deaths due to trauma or
  suicide) or myopathy (8 vs. 10 cases) in
  pravastatin group compared with placebo

4
LIPID Long-term Intervention with Pravastatin in
Ischemic Disease - RESULTS continued -

Death from all causes and CHD
20
Death
Death
Death
Placebo
from all
due to
from all
Pravastatin
causes
CHD
causes
10
Death
due to
Pravastatin
6.4
11.0
CHD
( of patients)
5
Placebo
8.3
14.1
( of patients)
Relative reduction in
24
22
risk ()
0
0
3
6
9
12
16
18
21
95 CI
12
35
13

31
Years after randomization
P
lt0.001
lt0.001
LIPID Study Group.
N Engl J Med
1998
339
1349

57.
5
LIPID Long-term Intervention with Pravastatin in
Ischemic Disease - RESULTS continued -

Relative reduction in risk of cardiovascular
outcomes
Placebo
Pravastatin
Relative reduction in risk
n4502
n4512
Outcome
with pravastatin ()
()
()
CHD mortality
8.3
6.4
Overall mortality
14.1
11.0
10.3
MI
7.4
15.9
Non-fatal MI or death due to CHD
12.3
Stroke
4.5
3.7
Coronary revascularization
15.7
13.0
95 CI, Plt0.001 for all except stroke (P
0.048)
LIPID Study Group.
N Engl J Med
1998
339
1349

57.
6
LIPID Long-term Intervention with Pravastatin in
Ischemic Disease - SUMMARY -

• As seen in other studies, cholesterol-lowering
  therapy significantly reduced all major
  cardiovascular events however, study also
  specifically demonstrated that pravastatin
• reduced both mortality due to CHD and overall
  mortality
• had benefit for patients with unstable angina
• On basis of differences in proportions of
  patients with an event, for every 1000 patients
  assigned pravastatin
• death from any cause avoided in 30 patients
• death due to CHD avoided in 19
• non-fatal MI/death due to CHD avoided in 35
• death due to stroke avoided in 8