OPTIMAAL: Optimal Trial In Myocardial Infarction with the Angiotensin Antagonist Losartan

1
OPTIMAAL Optimal Trial In Myocardial Infarction
with the Angiotensin Antagonist Losartan

• Purpose
• To determine whether the angiotensin II receptor
  blocker losartan is superior or inferior to the
  angiotensin converting enzyme (ACE) inhibitor
  captopril in reduction of all-cause mortality in
  high-risk patients after acute MI
• Reference
• Dickstein K, Kjekshus J and the OPTIMAAL
  Steering Committee, for the OPTIMAAL Study Group.
  Effects of losartan and captopril on mortality
  and morbidity in high-risk patients after acute
  myocardial infarction the OPTIMAAL randomised
  trial. Lancet 200236075260.

2
OPTIMAAL Optimal Trial In Myocardial Infarction
with the Angiotensin Antagonist Losartan- TRIAL
DESIGN -

• Design
• Multicenter, multinational, randomized,
  double-blind, parallel-group
• Patients
• 5466 patients aged gt50 years with acute MI and
  evidence of heart failure or left ventricular
  dysfunction (left ventricular ejection fraction
  lt35)
• Follow up and primary endpoint
• Primary endpoint all-cause mortality. Mean 2.7
  years follow up
• Treatment
• Captopril (titrated to target dose 50 mg three
  times daily, as tolerated) or losartan (titrated
  to target 50 mg daily, as tolerated)

3
OPTIMAAL Optimal Trial In Myocardial Infarction
with the Angiotensin Antagonist Losartan- TRIAL
DESIGN continued-

Baseline characteristics
Losartan
All
Captopril
(n2733)
(n5477)
(n2744)
Mean age (years)
67
67
67
Male ()
72
71
71
History
Hypertension ()
36
36
36
Previous MI ()
18
18
18
Mean BP (mmHg)
Systolic
123.0
122.8
122.5
Diastolic
71.5
71.4
71.4
Medications
Thrombolytic ()
54
54
55
Beta-blocker ()
79
79
78
Aspirin ()
95
96
96
Statin ()
30
31
31
Time to randomization (h)
84.9
84.9
85
Dickstein et al. Lancet 2002 36075260.
4
OPTIMAAL Optimal Trial In Myocardial Infarction
with the Angiotensin Antagonist Losartan-
RESULTS -

• All-cause mortality nonsignificantly higher in
  losartan group compared with captopril (18.2 vs.
  16.4, P0.069)
• Mortality curves separated early on and then
  largely remained parallel
• Nonsignificant difference in favor of captopril
  in
• Sudden cardiac death or resuscitated cardiac
  arrest
• Fatal or nonfatal reinfarction
• All-cause hospitalization
• Losartan better tolerated than captopril as
  defined by permanent discontinuation of drug (17
  vs. 23, hazard ratio 0.70, 95 CI 0.620.79,
  Plt0.0001)

5
OPTIMAAL Optimal Trial In Myocardial Infarction
with the Angiotensin Antagonist Losartan-
RESULTS continued -
All-cause mortality
Mortality
25
()
20
15
10
5
0
0
6
12
18
24
30
36
Months after randomization
Dickstein et al. Lancet 2002 36075260.
6
OPTIMAAL Optimal Trial In Myocardial Infarction
with the Angiotensin Antagonist Losartan-
RESULTS continued -
Secondary and tertiary endpoints
Endpoint
15
rate ()
RR 1.19 (95 CI 0.981.43)
Sudden cardiac death or cardiac arrest
10
P 0.072
5
0
15
RR 1.03 (95 CI 0.891.18)
Reinfarction
10
P 0.72
5
Captopril
0
Losartan
0
6
12
18
24
30
36
Months after randomization
Dickstein et al. Lancet 2002 36075260.
7
OPTIMAAL Optimal Trial In Myocardial Infarction
with the Angiotensin Antagonist Losartan-
RESULTS continued -
The three major endpoints
Losartan
Captopril
Relative risk
P
(n2744)
(n2733)
(95 CI)
No.
()
No.
()
All-cause mortality
1.13 (0.991.28)
0.069
499
(18.2)
447
(16.4)
Sudden cardiac death or
1.19 (0.991.43)
0.072
239
(8.7)
203
(7.4)
resuscitated cardiac arrest
Myocardial reinfarction
1.03 (0.891.18)
0.722
384
(14)
379
(13.9)
(fatal or nonfatal)
Dickstein et al. Lancet 2002 36075260.
8
OPTIMAAL Optimal Trial In Myocardial Infarction
with the Angiotensin Antagonist Losartan-
RESULTS continued -
All-cause hospitalization
Hospitalization
80
()
60
40
20
0
0
6
12
18
24
30
36
Months after randomization
Dickstein et al. Lancet 2002 36075260.
9
OPTIMAAL Optimal Trial In Myocardial Infarction
with the Angiotensin Antagonist Losartan-
SUMMARY -

• In patients with acute MI and evidence of heart
  failure or left ventricular dysfunction, losartan
  50 mg daily
• Conferred no benefit in comparison with captopril
• Was better tolerated than captopril
• ACE inhibitors therefore remain the first-choice
  therapy in this group