Comparison of baseline data, initial course, and management: losartan versus captopril following acute myocardial infarction (the OPTIMAAL trial)☆

The impact on prognosis of alcohol use in patients with coronary artery disease remains uncertain. We related alcohol use to all-cause mortality, cardiovascular (CV)-mortality and hospitalization in patients following a complicated myocardial infarction (MI).

In the OPTIMAAL trial, 5477 patients from 7 Western European countries with heart failure and/or evidence of left ventricular dysfunction following MI were recruited. Following randomization median 3 days, patients were asked to assess their average alcohol consumption prior to the index infarction. Patients were stratified by the frequency of the use of alcohol into either non-users (n = 2160), moderate users (1–7 drinks/week, n = 2753) and heavy users (> 7 drinks/week, n = 545) and related to prespecified clinical outcomes in the groups.

A total of 5477 patients were included in the trial. During the follow-up period of 2.7 years 946 deaths were reported. Adjusted for age and smoking status, patients with moderate use of alcohol had 24% lower risk of all-cause death (p < 0.001), 26% lower risk of CV-death (p < 0.000) and 8% lower risk for hospitalization (p = 0.030) than abstainers. There was no significant difference between non-drinkers and heavy drinkers with regard to survival following adjustment for age and smoking status.

Our results demonstrate a strong positive association between moderate alcohol use and survival in a cohort of patients following complicated MI. Both heavy drinkers and abstainers had poorer prognosis, with no significance difference between those 2 groups.

The presence or onset of bundle branch block (BBB) is associated with increased mortality in patients after acute myocardial infarction (AMI). The risk increases with age. We assessed the prognostic power of BBB patterns for predicting clinical outcomes in patients after high-risk AMI. In the OPTIMAAL trial, the effects of losartan versus captopril were compared in 5,477 patients with heart failure and/or evidence of left ventricular dysfunction after MI. The association between clinical outcomes and the presence of left or right BBB at randomization (median 3 days after AMI) or occurring during follow-up (mean 2.7 years) was assessed using Cox regression models. At randomization, 8% of patients (n = 438) showed BBB patterns; 3.7% (n = 203) showed left BBB and 4.3% (n = 235) showed right BBB patterns. In patients with left BBB, there was an increased risk of all-cause death and cardiovascular death. In patients with right BBB, there was increased risk of sudden cardiac death/resuscitated cardiac arrest. During follow-up, another 4.9% (n = 272) developed BBB patterns; 2.8% (n = 153) developed left BBB and 2.17% (n = 119) developed right BBB. Left BBB was associated with increased risk for all-cause death, cardiovascular death, and sudden cardiac death/resuscitated cardiac arrest, whereas right BBB was related to increased risk of sudden cardiac death/resuscitated cardiac arrest. In conclusion, our results confirm and quantify previous observations showing substantially increased mortality in patients with BBB patterns at baseline or occurring soon after AMI.

This study examined the effect of statin therapy on vascular markers of inflammation and echocardiographic findings in patients with nonischemic forms of cardiomyopathy.

Despite advances in therapy, morbidity and mortality from heart failure (HF) remain high. We wished to determine whether treatment with atorvastatin affects left ventricular (LV) systolic function and markers of inflammation in patients with nonischemic HF.

A total of 108 patients with nonischemic HF and a left ventricular ejection fraction (LVEF) ≤35% were randomized to either atorvastatin 20 mg/day or placebo in a double-blinded fashion for a 12-month period. The LVEF and LV end-diastolic diameter (LVEDD) and left ventricular end-systolic diameter (LVESD) were determined by echocardiography. Serum markers of inflammation and oxidation were also measured.

The LVEF increased from 0.33 ± 0.05 to 0.37 ± 0.04 (p = 0.01) in the atorvastatin group over the 12-month follow-up period, whereas those patients in the placebo group experienced a decline in ejection fraction during the same time period. In addition, LVEDD was reduced from 57.1 ± 5.9 mm to 53.4 ± 5.1 mm (p = 0.007) and LVESD was reduced from 42.4 ± 3.8 mm to 39.1 ± 3.8 mm (p = 0.02) in the cohort of patients treated with atorvastatin; these dimensions increased in the placebo group. There was an increase in erythrocyte superoxide dismutase (E-SOD) activity, and there were significant reductions in serum levels of high sensitivity C-reactive protein, interleukin-6 (IL-6), and tumor necrosis factor-alpha receptor II (TNF-α RII) in the atorvastatin group.

The use of atorvastatin in patients with nonischemic HF improves LVEF and attenuates adverse LV remodeling. The effects on soluble levels of several inflammatory markers with atorvastatin suggest, in part, mechanisms by which statins might exert their beneficial effects in nonischemic HF.

We wished to determine whether the addition of statins affect cardiovascular events and markers of inflammation in patients with heart failure.

A total of 446 patients with heart failure and ejection fraction ≤35% were followed in a prospective, nonrandomized fashion and were classified according to treatment with a statin. We determined all-cause mortality, cardiovascular morbidity, and serum markers of inflammation over a 24-month period. Statin therapy in patients with heart failure was associated with decreased all-cause mortality at 2 years compared with those not on statin therapy (15% versus 33%, P < .005) as well as hospitalizations for heart failure (22% versus 38%, P = .001) and nonfatal myocardial infarction (11% versus 15%, P < .001). In addition, statin therapy was associated with a decrease in serum levels of C-reactive protein (1.12 ± 0.13 versus 1.47 ± 0.11 mg/dL, P = .001), interleukin-6 (13.3 ± 0.8 versus 17.3 ± 1.4 ng/dL, P = .001), and tumor necrosis factor-alpha receptor II (24.3 ± 1.0 versus 34.5 ± 3.0 ng/dL, P = .001).

The use of statin therapy in this nonrandomized trial was associated with a significant reduction in all-cause mortality and cardiac morbidity. In addition, the improvement in levels of several serum inflammatory markers with statin therapy suggests in part possible mechanisms by which these agents may exert their benefits.

According to several reports, patients who smoke paradoxically have favorable outcomes after acute myocardial infarctions (AMIs) compared with nonsmokers. The Optimal Trial in Myocardial Infarction With the Angiotensin II Antagonist Losartan evaluated 5,477 high-risk patients after AMIs. Patients with a history of smoking had a 17% smaller risk for death (hazard ratio 0.83, p = 0.005) compared with nonsmokers. After adjustment for age only, without correction for other co-morbidities or risk factors, the lower all-cause mortality in smoker population was explained by the smokers' generally younger age, with better prognoses due to their age.

ACE inhibitors attenuate the detrimental effects of angiotensin II, and improve survival and reduce morbidity in patients with acute myocardial infarction and evidence of heart failure or left-ventricular dysfunction. Selective antagonism of the angiotensin type 1 receptor represents an alternative approach to inhibition of the renin-angiotensin system. We did a multicentre, randomised trial to test the hypothesis that the angiotensin II antagonist losartan would be superior or non-inferior to the ACE inhibitor captopril in decreasing all-cause mortality in high-risk patients after acute myocardial infarction.

5477 patients 50 years of age or older (mean age 67·4 years [SD 9·8]), with confirmed acute myocardial infarction and heart failure during the acute phase or a new Q-wave anterior infarction or reinfarction, were recruited from 329 centres in seven European countries. Patients were randomly assigned and titrated to a target dose of losartan (50 mg once daily) or captopril (50 mg three times daily) as tolerated. The primary endpoint was all-cause mortality. Analysis was by intention to treat.

There were 946 deaths during a mean follow-up of 2·7 (0·9) years: 499 (18%) in the losartan group and 447 (16%) in the captopril group (relative risk 1·13 [95% CI 0·99–1·28], p=0·07). The results for the secondary and tertiary endpoints were as follows: sudden cardiac death or resuscitated cardiac arrest 239 (9%) versus 203 (7%), 1·19 (0·98–1·43), p=0·07, and fatal or non-fatal reinfarction 384 (14%) versus 379 (14%), 1·03 (0·89–1·18), p=0·72. The allcause hospital admission rates were 1806 (66%) versus 1774 (65%), 1·03 (0·97–1·10), p=0·37. Losartan was significantly better tolerated than captopril, with fewer patients discontinuing study medication (458 [17%] vs 624 [23%], 0·70 [0·62–0·79], p<0·0001).

Since we saw a non-significant difference in total mortality in favour of captopril, ACE inhibitors should remain first-choice treatment in patients after complicated acute myocardial infarction. Losartan cannot be generally recommended in this population. However, it was better tolerated than captopril, and was associated with significantly fewer discontinuations. Although the role of losartan in patients intolerant of ACE inhibition is not clearly defined, it can be considered in such patients.

Published online September 1, 2002 http://image.thelancet.com/extras/02art6111web.pdf