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 2002;360:752–60.
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 >50 years with acute MI and evidence of heart failure or left ventricular dysfunction (left ventricular ejection fraction <35%)
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)
OPTIMAAL: Optimal Trial In Myocardial Infarction with the Angiotensin Antagonist Losartan - TRIAL DESIGN continued-
Mean age (years)
Male (%)
History
Mean BP (mmHg)
Medications
Time to randomization (h)
Hypertension (%)
Previous MI (%)
Systolic
Diastolic
Thrombolytic (%)
Beta-blocker (%)
Aspirin (%)
Statin (%)
Baseline characteristics
67
123.0
71.5
84.9
72
36
18
54
79
95
30
Losartan
(n=2733)
67
122.8
71.4
84.9
71
36
18
54
79
96
31
All
(n=5477)
67
122.5
71.4
85
71
36
18
55
78
96
31
Captopril
(n=2744)
Dickstein et al. Lancet 2002; 360:752–60.
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%, P=0.069)
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 0.62–0.79, P<0.0001)
OPTIMAAL: Optimal Trial In Myocardial Infarction with the Angiotensin Antagonist Losartan - RESULTS continued -
Months after randomization
Mortality
(%)
0
0
6
12
18
24
30
36
5
10
15
20
25
All-cause mortality
Dickstein et al. Lancet 2002; 360:752–60.
OPTIMAAL: Optimal Trial In Myocardial Infarction with the Angiotensin Antagonist Losartan - RESULTS continued -
Months after randomization
Endpoint
rate (%)
0
0
6
12
18
24
30
36
Secondary and tertiary endpoints
Dickstein et al. Lancet 2002; 360:752–60.
RR 1.19
(95% CI 0.98–1.43)
P = 0.072
Captopril
Losartan
0
5
10
15
5
10
15
Sudden cardiac death or cardiac arrest
RR 1.03
(95% CI 0.89–1.18)
P = 0.72
Reinfarction
OPTIMAAL: Optimal Trial In Myocardial Infarction with the Angiotensin Antagonist Losartan - RESULTS continued -
P
All-cause mortality
Sudden cardiac death or
resuscitated cardiac arrest
Myocardial reinfarction
(fatal or nonfatal)
1.13 (0.99–1.28)
1.19 (0.99–1.43)
1.03 (0.89–1.18)
0.069
0.072
0.722
The three major endpoints
499
239
384
No.
(18.2)
(8.7)
(14)
(%)
Losartan
(n=2744)
447
203
379
No.
(16.4)
(7.4)
(13.9)
(%)
Captopril
(n=2733)
Relative risk
(95% CI)
Dickstein et al. Lancet 2002; 360:752–60.
OPTIMAAL: Optimal Trial In Myocardial Infarction with the Angiotensin Antagonist Losartan - RESULTS continued -
Months after randomization
Hospitalization
(%)
0
0
6
12
18
24
30
36
20
40
60
80
All-cause hospitalization
Dickstein et al. Lancet 2002; 360:752–60.
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