trandolapril and Death--Sudden--Cardiac

The results of the major clinical outcome trials related to the potential antiatherosclerotic effects of the angiotensin convertase (ACE) inhibitors are reviewed after the recently published EUROPA trial results. In the postinfarction clinical situation mortality reduction was revealed in the ISIS-4 (captopril), GISSI-3 (lisinopril), AIRE (ramipril), TRACE (trandolapril), CONSENSUS (enalapril), SAVE (captopril) and in the SOLVD (enalapril) trials. In the HOPE trial performed in a high risk population the preventive antiatherosclerotic, endothel-preserving effects of ramipril resulted in a significant mortality and morbidity reduction. In the EUROPA trial a lower risk population--symptomfree coronary patients--were treated by perindopril, and it was proven also in this cohort, that the long term ACE inhibitor treatment decreased the combined endpoint of cardiovascular mortality, myocardial infarction and resuscitated sudden death. Based on the above data it can be advised, that all coronary patients regardless of left ventricular function and symptoms should receive long term ACE inhibitor treatment besides the other established preventive medications (platelet aggregation inhibitors + statins + beta receptor blockers).

Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Captopril; Clinical Trials as Topic; Coronary Disease; Death, Sudden, Cardiac; Enalapril; Humans; Indoles; Lisinopril; Myocardial Infarction; Perindopril; Ramipril; Treatment Outcome

Although sudden cardiac death (SCD) has been extensively studied in patients with coronary artery disease (CAD) and low ejection fraction, prediction of SCD among individuals with preserved left ventricular systolic function is less well understood. We randomized 8,290 patients with stable CAD with preserved left ventricular systolic function to trandolapril or placebo in a secondary coronary prevention trial, and we used Cox proportional hazards models to identify independent baseline predictors of SCD during 4.8 year follow-up (median). Using a risk scoring algorithm based on simple clinical characteristics, we were able to distinguish individuals at higher risk for SCD. Independent determinants of SCD included age (p <0.001), current angina pectoris (p = 0.002), ejection fraction >40% to <50% (as opposed to >50%) (p <0.001), and diuretic (p <0.001) and digitalis use (p <0.001). Negative predictors included having prior coronary revascularization (p = 0.01) and being female (p = 0.02) or Caucasian (p = 0.006). Trandolapril neither increased nor decreased SCD. Thus, among patients with stable CAD with preserved left ventricular systolic function receiving current standard-of-care including coronary revascularization, clinical characteristics can identify individuals at higher risk for SCD.

Topics: Age Factors; Algorithms; Angina Pectoris; Angiotensin-Converting Enzyme Inhibitors; Cardiotonic Agents; Coronary Artery Disease; Death, Sudden, Cardiac; Digitalis Glycosides; Diuretics; Female; Humans; Indoles; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Myocardial Revascularization; Proportional Hazards Models; Racial Groups; Risk Assessment; Sex Factors; Stroke Volume; Systole; Ventricular Function, Left

Atrial fibrillation (AF) is a common complication in patients with acute myocardial infarction and is associated with an increase in the risk of death. The excess mortality associated with AF complicating acute myocardial infarction has not been studied in detail. Observations indicate that AF facilitates induction of ventricular arrhythmias, which may increase the risk of sudden cardiovascular death (SCD). A close examination of the mode of death could potentially provide useful knowledge to guide further investigations and treatments.. We analysed the relation between AF/atrial flutter (AFL) and modes of death in 5983 consecutive patients discharged alive after an acute myocardial infarction screened in the TRAndolapril Cardiac Evaluation registry. This cohort of patients with an enzyme-verified acute myocardial infarction was admitted to 27 centres in 1990-92. Survival status was obtained 2 years after screening of the last patient. An independent endpoint committee assessed the modes of death. Left ventricular ejection fraction was determined in all the screened patients and information about presence or absence of AF/AFL was prospectively collected. Sustained or paroxysmal AF/AFL was observed in 1149 patients (19%) during hospitalization. During follow-up, 1659 patients (34%) died: 482 (50%) patients with AF/AFL and 1177 (30%) patients without AF/AFL, P<0.001. SCD occurred in 536, non-SCD occurred in 725, and 398 died of non-cardiovascular causes (includes 142 unclassifiable cases). The adjusted risk ratio of AF/AFL for total mortality was 1.33 (95% CI: 1.19-1.49; P<0.0001) and the risk ratio for SCD was 1.31 (95% CI: 1.07-1.60; P<0.009). The adjusted risk ratio of AF/AFL for non-SCD was 1.43 (95% CI: 1.21-1.70; P<0.0001).. The excess mortality observed in patients with AF/AFL following acute myocardial infarction is due to a significant increase in both SCD and non-SCD.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Atrial Fibrillation; Atrial Flutter; Cause of Death; Cohort Studies; Death, Sudden, Cardiac; Female; Humans; Indoles; Male; Middle Aged; Myocardial Infarction; Sweden

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.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Death, Sudden, Cardiac; Double-Blind Method; Europe; Female; Heart Failure; Humans; Indoles; Male; Middle Aged; Myocardial Infarction; Ventricular Dysfunction, Left

The TRACE (TRAndolapril Cardiac Evaluation) study was designed to determine whether long-term treatment with an ACE inhibitor is beneficial in patients with early post-myocardial infarction cardiac failure. A total 6,676 consecutive patients with 7,001 myocardial infarctions were included; 2,606 patients had echocardiographic signes of left ventricular dysfunction (ejection fraction < 35%), 3 to 7 days after myocardial infarction; 1,749 patients were randomised and given either oral trandolapril (876 patients) or placebo (873 patients). Follow-up ranged from 24 to 50 months. Three hundred and four patients (34.7%) in the trandolapril group died, compared with 369 (42.3%) in the placebo group (p = 0.001). The relative risk of death in the trandolapril group compared with the placebo group was 0.78. Trandolapril was also associated with a statistically significantly lower risk of cardiovascular death and of sudden death. Progression to severe cardiac failure was also less frequent in the treatment group. On the other hand, the risk of recurrent myocardial infarction was not significantly reduced. In conclusion, long-term treatment with trandolapril in patients with early post-infarction left ventricular dysfunction significantly reduced the risk of cardiovascular mortality, sudden death and progression to severe cardiac failure.

Topics: Angiotensin-Converting Enzyme Inhibitors; Death, Sudden, Cardiac; Double-Blind Method; Female; Follow-Up Studies; Heart Failure; Humans; Indoles; Male; Myocardial Infarction; Recurrence; Risk Factors; Survival Analysis; Ventricular Dysfunction, Left

To study the prognostic information of congestive heart failure (CHF) and left ventricular systolic dysfunction regarding sudden and non-sudden cardiovascular death (SCD and non-SCD) in patients with acute myocardial infarction (MI), as this may indicate the potential benefit of implantable defibrillators.. Data from consecutive patients with acute MI screened in 1990-92 for the TRAndolapril Cardiac Evaluation (TRACE) study were entered into a registry. A total of 5502 patients were alive 30 days after the MI and were followed for up to 4 years with respect to cause of death. SCD was defined as cardiovascular death within 1 h of onset of symptoms. An echocardiography was performed 1-6 days after the admission and evaluated centrally using the wall motion index (WMI).. Half of the patients had CHF and 17% of the patients had WMI < or =1.0 (corresponding to an ejection fraction < or =0.30). During follow-up 431 patients died from SCD and 606 from non-SCD. The risk ratios for SCD and non-SCD associated with WMI < or =1.0 were 3.17 and 2.95, transient CHF 2.01 and 1.46, and permanent CHF 3.71 and 4.42, respectively. No risk factor was a specific marker of SCD or non-SCD. The 3-year probability of SCD was 7.9% for patients with transient CHF, 13.3% for permanent CHF, and 15.5% for WMI < or =1.0.. CHF and low WMI identify a relevant proportion of patients with MI who are at high absolute risk of SCD. This study indicates the relevance of defibrillators in consecutive post-MI patients with left ventricular dysfunction or clinical signs of heart failure.

Topics: Aged; Aged, 80 and over; Antihypertensive Agents; Death, Sudden, Cardiac; Denmark; Echocardiography; Female; Follow-Up Studies; Heart Failure; Humans; Indoles; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Odds Ratio; Proportional Hazards Models; Randomized Controlled Trials as Topic; Registries; Risk Factors; Systole; Ventricular Dysfunction, Left