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Angiotensin-converting enzyme inhibition after myocardial infarction: the Trandolapril Cardiac Evaluation Study
C Torp-Pedersen1, L Køber, J Carlsen
1Department of Cardiology, Gentofte University Hospital, Hellermp, Denmark.
Insights
Trandolapril significantly reduced mortality and heart failure progression in post-myocardial infarction patients with reduced ejection fraction. This angiotensin-converting enzyme (ACE) inhibitor offers substantial benefits for cardiac recovery and survival.
Area of Science:
- Cardiology
- Pharmacology
- Clinical Trials
Background:
- Reduced left ventricular systolic function post-myocardial infarction (MI) is associated with increased mortality.
- Angiotensin-converting enzyme (ACE) inhibitors are crucial in managing post-MI patients.
- The Trandolapril Cardiac Evaluation study investigated the efficacy of ACE inhibitors in this specific patient population.
Purpose of the Study:
- To assess the impact of trandolapril, an ACE inhibitor, on mortality and morbidity in patients with reduced left ventricular systolic function following an MI.
- To determine the long-term benefits of early ACE inhibitor treatment in post-MI patients.
Main Methods:
- A randomized, placebo-controlled trial involving 1749 patients with ejection fraction <= 35% after MI.
- Patients received oral trandolapril or placebo starting 3-7 days post-MI, with a follow-up of 2-4 years.
- Echocardiographic assessment of left ventricular dysfunction was used for patient selection.
Main Results:
- Trandolapril significantly reduced all-cause mortality (RR 0.78, p=0.0013) and cardiovascular death (RR 0.75, p=0.001).
- The treatment also decreased sudden death (RR 0.76, p=0.03) and progression to severe heart failure (RR 0.71, p=0.003).
- No significant reduction was observed in recurrent myocardial infarction (RR 0.86, p=0.29).
Conclusions:
- Long-term trandolapril treatment significantly improves survival and reduces morbidity in patients with reduced left ventricular function post-MI.
- The observed benefits are likely transferable to clinical practice due to high patient randomization and moderate discontinuation rates.
- Early initiation of ACE inhibitor therapy is vital for improving outcomes after myocardial infarction.
Abstract:
To study the importance of giving an angiotensin-converting enzyme (ACE) inhibitor to patients with reduced systolic function after an infarction, the Trandodolapril Cardiac Evaluation study was designed to include the majority of patients with echocardiographic signs of left ventricular dysfunction among consecutively screened patients with infarctions. A total of 2606 consecutive patients with left ventricular systolic dysfunction corresponding to an ejection fraction < or = 35% were identified. Of these patients, 1749 (67%) were randomly assigned to receive oral trandolapril or placebo beginning on day 3 to 7 after the infarction. The follow-up period was 2 to 4 years. Trandolapril reduced all-cause mortality, with a relative risk reduction associated with trandolapril treatment of 0.78 (p = 0.0013). Benefit was seen within 1 month of treatment. Trandolapril also reduced cardiovascular death (relative risk 0.75, p = 0.001), sudden death (relative risk 0.76, p = 0.03), and progression to severe/ resistant heart failure (relative risk 0.71, p = 0.003). Recurrent myocardial infarction (fatal or nonfatal) was not significantly reduced (relative risk 0.86, p = 0.29). More than 80% of patients in both treatment groups reached the target dose of 4 mg trandolapril or placebo at the end of dose titration. Nearly half of the patients in both treatment groups discontinued taking study medication before death or trial closure. The need for open-label ACE inhibition was the reason for discontinuation for 48 and 75 patients in the trandolapril and placebo groups, respectively. In conclusion, long-term treatment with trandolapril in patients with reduced left ventricular function shortly after myocardial infarction significantly reduced mortality and morbidity. Most patients received the target dose of 4 mg trandolapril daily. The benefit observed is likely to reflect the benefit in clinical practice because the majority of eligible patients were randomized and the difference in patients leaving the trial to receive open-label ACE inhibition was moderate.