Safety concerns about digoxin after acute myocardial infarction.

We examined clinical outcomes associated with non-randomised digoxin therapy in a postmyocardial infarction population with clinical heart failure (AIRE study). Our results raise concern about the safety of digoxin in this population.

QT dispersion as a predictor of long-term mortality in patients with acute myocardial infarction and clinical evidence of heart failure.

BACKGROUND: QT interval dispersion is a marker of inhomogeneous ventricular repolarization, and therefore has the potential to predict re-entry arrhythmias. Following acute myocardial infarction, increased QT dispersion has been associated with a higher risk of ventricular arrhythmias. However, whether or not QT dispersion predicts prognosis post-acute myocardial infarction is not clear. We addressed this issue by analysing the AIREX study registry. METHODS: AIREX was a follow-up study of 603 post-acute myocardial infarction patients who exhibited clinical signs of heart failure and were randomly allocated to ramipril or placebo. An interpretable 12-lead ECG obtained between day 0 and day 9 after the index infarction (median time 2 days) was available in 501 patients. We examined whether QT dispersion was a predictor of all-cause mortality in the AIREX study registry (mean follow-up 6 years). RESULTS: QT dispersion measurements were significantly increased in patients who subsequently died (QT dispersion: 92.0 +/- 38.5 ms vs 82.7 +/- 34.3 ins. P=0.005; rate corrected QT dispersion: 105.7 +/- 42.7 ms vs 93.1 +/- 35.9 ms, P<0.001). Univariate analysis showed that QT dispersion as a predictor of all-cause mortality risk (QT dispersion: hazard ratio per l0 ms 1.05, [95% CI 1.02 to 1.09]. P= 0.004; rate corrected QT dispersion: 1-07 [1.03 to 1.10], P<0.001): an increase of 10 ms added a 5-7%, relative risk of death. QT dispersion remained an independent predictor of all-cause mortality risk on multivariate analysis (QT dispersion: 1.05 [1.01 to 1.09], P=0.027; rate corrected QT dispersion: 1.05 [1.01 to 1.09]. P=0.022). CONCLUSION: QT dispersion. measured from Li routine 12-lead ECG following acute myocardial infarction complicated by heart failure provides independent information regarding the probability of long-term survival. However. the low sensitivity of this electrocardiographic marker limits its usefulness for risk stratification if used in isolation.

beta blocker treatment and other prognostic variables in patients with clinical evidence of heart failure after acute myocardial infarction: evidence from the AIRE study.

OBJECTIVES: To examine clinical outcomes associated with optional beta blockade in a population of patients with evidence of heart failure after myocardial infarction. DESIGN AND PATIENTS: Data from the acute infarction ramipril efficacy (AIRE) study were analysed retrospectively. At baseline 22.3% of the patients were receiving a beta blocker. To minimise confounding, beta blocker and diuretic treatments, presence of clinical signs of heart failure, left ventricular ejection fraction, and 16 other baseline clinical variables were simultaneously entered in a multivariate Cox regression model. In addition, the same analysis was repeated separately within a high and a low risk group of patients, as defined according to the need for diuretic treatment. RESULTS: beta Blocker treatment was an independent predictor of reduced risk of total mortality (hazard ratio 0.66, 95% confidence interval (CI) 0. 48 to 0.90) and progression to severe heart failure (0.58, 95% CI 0.40 to 0.83) for the entire study population. There were similar findings in high risk patients requiring diuretics (0.59, 95% CI 0.40 to 0.86; and 0.58, 95% CI 0.38 to 0.89). CONCLUSIONS: beta Blocker treatment is associated with improved outcomes in patients with clinical evidence of mild to moderate heart failure after myocardial infarction. Most importantly, high risk patients with persistent heart failure appear to benefit at least as much as lower risk patients with transient heart failure.

Ramipril reduces QT dispersion in patients with acute myocardial infarction and heart failure.

In a cohort of 67 patients from the Acute Infarction Ramipril Efficacy study, we showed that ramipril therapy was associated with a significant reduction in QT dispersion over a 2-month period after acute myocardial infarction. This reduction of ventricular repolarization inhomogeneity indicates an antiarrhythmic effect and may be an important additional mechanism for the reduced all-cause mortality and sudden death incidence achieved with angiotensin-converting enzyme inhibition after acute myocardial infarction.

Clinical implications for the Acute Infarction Ramipril Efficacy extension (AIREX) Study.

It is now clear that angiotensin-converting enzyme (ACE) inhibitor treatment after myocardial infarction (MI) reduces mortality and morbidity. However, the benefits of ACE inhibition are not homogeneous and are largely confined to high-risk patients who have subjective or objective evidence of left ventricular (LV) dysfunction. How long treatment should continue is a vexed question, which also arises with other agents, for example beta-blocker use after MI. The AIREX study assessed the long-term magnitude and duration of the survival benefits observed with ramipril in patients after MI who have clinically defined heart failure. The mortality status of all 603 patients recruited from the UK centres involved in the AIRE study was verified at an extended 5-year follow-up (3 years after the AIRE study closed). Ramipril assignation was associated with a 36% relative and a 11% absolute mortality risk reduction. These findings strongly support the view to select patients on the basis of impaired LV function and reinforce the previously reported conclusions of the "selective" ACE inhibition post-MI trials. Using this approach, the survival benefit is not only of large magnitude but also sustained over many years. These results also argue for life-long treatment with an ACE inhibitor, once a decision to treat an individual patient after MI has been made.