enalapril and Death--Sudden--Cardiac

The heart failure is one of the pathologies with major social and economic impact in the western world. The neurohormonal modulation is the only effective pharmacological approach. The increasing use of implantable devices apparently sets against the possibilities of implementing in the patient's treatment scheme. However, the anti-adrenergic therapy, once used at optimal dose, is highly effective on sudden death and on rates of implantable cardioverter defibrillators discharges. CIBIS-III proposes the beta-blocker use as primary approach, even prior to ACE inhibitors. This might be specifically true in the patient whit evidence of autonomic imbalance resulting in sympathetic hyperactivity. CIBIS-III shows that bisoprolol can be used in chronic heart failure patients also in absence of the concomitant enalapril therapy. Using bisoprolol as primary approach allows to reach optimal doses more effective on arrhythmic risk. CIBIS III results propose new strategies to the current international heart failure guidelines's recommendations.

Topics: Adrenergic beta-Antagonists; Aged; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Arrhythmias, Cardiac; Bisoprolol; Death, Sudden, Cardiac; Defibrillators, Implantable; Enalapril; Heart Failure; Humans; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Time Factors

Left ventricular hypertrophy (LVH) is a strong, independent predictor of cardiovascular events and all-cause mortality. Patients with LVH are at increased risk for stroke, coronary heart disease, congestive heart failure, and sudden cardiac death. Hypertension is a major influence on the development of LVH. The prognostic power of LVH is likely multifactorial. LVH represents both a manifestation of the effects of hypertension and other cardiac risk factors over time as well as an intrinsic condition causing pathologic changes in cardiac structure and function. Angiotensin II plays a central role in the development of LVH. Several antihypertensive treatments, especially angiotensin II receptor blockers, can reverse LVH and improve cardiovascular outcomes independent of blood pressure reduction. Further studies are required to determine if these agents should become first-line therapy for all patients with hypertension and LVH.

Topics: Adrenergic Antagonists; Angiotensin II; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzimidazoles; Benzoates; Carbazoles; Carvedilol; Chi-Square Distribution; Cohort Studies; Coronary Disease; Death, Sudden, Cardiac; Diuretics; Drug Therapy, Combination; Echocardiography; Electroencephalography; Enalapril; Female; Follow-Up Studies; Heart Failure; Humans; Hypertension; Hypertrophy, Left Ventricular; Indapamide; Logistic Models; Losartan; Male; Multivariate Analysis; Prognosis; Propanolamines; Prospective Studies; Randomized Controlled Trials as Topic; Risk; Risk Assessment; Risk Factors; Sex Factors; Stroke; Survival Analysis; Telmisartan

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

Topics: Adrenergic beta-Antagonists; Aged; Angiotensin-Converting Enzyme Inhibitors; Carbazoles; Carvedilol; Confidence Intervals; Death, Sudden, Cardiac; Enalapril; Female; Follow-Up Studies; Heart Failure; Hospitalization; Humans; Male; Meta-Analysis as Topic; Middle Aged; Myocardial Infarction; Placebos; Propanolamines; Randomized Controlled Trials as Topic; Recurrence; Risk Factors; Time Factors; Ventricular Dysfunction, Left; Ventricular Function, Left

n 1987 the results of the Consensus study were published, and showed that enalapril, an angiotensin convertor enzyme inhibitor (ACEI), was able to modify the clinical course of the heart failure syndrome thereby reducing mortality. Other ACEI later demonstrated the same effect on the different degrees of symptomatic heart failure, left ventricular dysfunction, myocardial infarction and more recently in diabetic patients. In 1996 studies on the betablockers carvedilol, bisoprolol and metoprolol showed their efficacy in reducing deaths due to progressive heart impairment and sudden death in chronic heart failure. The RALES study showed that small doses of spironolactone also improved the prognosis on this disease. Digital improves the quality of life but not the survival rate. Only amiodarone (among the antiarrhythmics) reduces sudden death. Other drugs and groups of drugs can not be considered for chronic outpatient treatment of heart failure. Multicenter trials make it possible to obtain scientific evidence for establishing rational treatments. Many groups of patients such as women, elderly people and the more severe cases of the disease are often not included in these trials. Occasionally, multicenter trials are badly designed (CIBIS and MCD), which in the case of betablockers, led to a substantial delay in their administration. Other times, as in the ELITE study, the results were badly interpreted. The knowledge obtained from these studies is slow in reaching patients, with few patients taking betablockers. It is known that most patients do not take the doses found to be effective in multicenter trials.

Topics: Adrenergic alpha-Antagonists; Adrenergic beta-Antagonists; Amiodarone; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Antihypertensive Agents; Calcium Channel Blockers; Carbazoles; Cardiotonic Agents; Carvedilol; Clinical Trials as Topic; Death, Sudden, Cardiac; Diuretics; Enalapril; Heart Failure; Humans; Middle Aged; Multicenter Studies as Topic; Prognosis; Propanolamines; Quality of Life; Risk Factors; Time Factors; Vasodilator Agents

Topics: Age Factors; Aged; Angiotensin I; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Antihypertensive Agents; Benzimidazoles; Biphenyl Compounds; Captopril; Clinical Trials as Topic; Death, Sudden, Cardiac; Enalapril; Heart Failure; Humans; Losartan; Prodrugs; Prognosis; Randomized Controlled Trials as Topic; Risk Factors; Tetrazoles; Time Factors

The failure of encainide and flecainide to reduce mortality after infarction in the Cardiac Arrhythmia Suppression Trial and the failure of low-dose amiodarone to prevent sudden cardiac death in patients with a low left ventricular ejection fraction has shifted attention to other strategies, such as beta-adrenergic blocking agents, to prevent sudden cardiac death. Evidence suggesting that beta-adrenergic blocking agents might be useful, especially in patients with low left ventricular ejection fraction, is accumulating. Previous data from studies using beta-adrenergic blocking agents and the mechanisms by which beta-adrenergic blocking agents might be of value in preventing sudden cardiac death are reviewed. These considerations and the availability of new investigational beta-adrenergic blocking agents with vasodilator properties provide a new opportunity to test the hypothesis that beta-adrenergic blocking agents are useful in preventing sudden cardiac death, especially in patients with a low left ventricular ejection fraction.

Topics: Adrenergic beta-Antagonists; Arrhythmias, Cardiac; Cardiac Output, Low; Cardiomyopathy, Dilated; Catecholamines; Clinical Trials as Topic; Coronary Disease; Death, Sudden, Cardiac; Diuretics; Enalapril; Heart Ventricles; Humans; Magnesium; Myocardial Infarction

Compared to heart failure patients with higher systolic blood pressure (SBP), those with lower SBP have a worse prognosis. To make matters worse, the latter patients often do not receive treatment with life-saving therapies that might lower blood pressure further. We examined the association between SBP and outcomes in the Prospective Comparison of angiotensin receptor-neprilysin inhibitor (ARNI) with an angiotensin-converting enzyme (ACE) inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure trial (PARADIGM-HF), as well as the effect of sacubitril/valsartan, compared with enalapril, according to baseline SBP.. We analysed the effect of treatment on SBP and on the primary composite outcome (cardiovascular death or heart failure hospitalization), its components and all-cause death. We examined baseline SBP as a categorical (<110, 110 to < 120, 120 to < 130, 130 to < 140 and ≥140 mmHg) and continuous variable, as well as average in-trial SBP and time-updated SBP.. All-cause and cardiovascular mortality rates were highest in patients with the lowest SBP whereas there was a U-shaped relationship between SBP and the rate of heart failure hospitalization. The benefit of sacubitril/valsartan over enalapril was consistent across all baseline SBP categories for all outcomes. For example, the sacubitril/valsartan versus enalapril hazard ratio for the primary endpoint was 0.88 (95%CI 0.74-1.06) in patients with a baseline SBP <110 mmHg and 0.81 (0.65-1.02) for those with a SBP ≥140 mmHg (P for interaction = 0.55). Symptomatic hypotension, study drug dose-reduction and discontinuation were more frequent in patients with a lower SBP.. In PARADIGM-HF, patients with lower SBP at randomization, notably after tolerating full doses of both study drugs during a run-in period, were at higher risk but generally tolerated sacubitril/valsartan and had the same relative benefit over enalapril as patients with higher baseline SBP.

Topics: Aged; Aminobutyrates; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Biphenyl Compounds; Blood Pressure; Chronic Disease; Death, Sudden, Cardiac; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Drug Therapy, Combination; Enalapril; Female; Heart Failure; Hospitalization; Humans; Hypotension; Male; Neprilysin; Stroke Volume; Tetrazoles; Treatment Outcome; Valsartan

Mode of death in chronic heart failure (CHF) may be of relevance to choice of therapy for this condition. Sudden death is particularly common in patients with early and/or mild/moderate CHF. β-Blockade may provide better protection against sudden death than ACE inhibition (ACEI) in this setting.. We randomized 1010 patients with mild or moderate, stable CHF and left ventricular ejection fraction ≤35%, without ACEI, β-blocker or angiotensin-receptor-blocker therapy, to either bisoprolol (n = 505) or enalapril (n = 505) for 6 months, followed by their combination for 6-24 months. The two strategies were blindly compared regarding adjudicated mode of death, including sudden death and progressive pump failure death.. During the monotherapy phase, 8 of 23 deaths in the bisoprolol-first group were sudden, compared to 16 of 32 in the enalapril-first group: hazard ratio (HR) for sudden death 0.50; 95% confidence interval (CI) 0.21-1.16; P= 0.107. At 1 year, 16 of 42 versus 29 of 60 deaths were sudden: HR 0.54; 95% CI 0.29-1.00; P= 0.049. At study end, 29 of 65 versus 34 of 73 deaths were sudden: HR 0.84; 95% CI 0.51-1.38; P= 0.487. Comparable figures for pump failure death were: monotherapy, 7 of 23 deaths versus 2 of 32: HR 3.43; 95% CI 0.71-16.53; P= 0.124, at 1 year, 13 of 42 versus 5 of 60: HR 2.57; 95% CI 0.92-7.20; P= 0.073, at study end, 17 of 65 versus 7 of 73: HR 2.39; 95% CI 0.99-5.75; P= 0.053. There were no significant between-group differences in any other fatal events.. Initiating therapy with bisoprolol compared to enalapril decreased the risk of sudden death during the first year in this mild systolic CHF cohort. This was somewhat offset by an increase in pump failure deaths in the bisoprolol-first cohort.

Topics: Adrenergic beta-Antagonists; Aged; Angiotensin-Converting Enzyme Inhibitors; Bisoprolol; Chronic Disease; Death, Sudden, Cardiac; Drug Therapy, Combination; Enalapril; Female; Heart Failure; Hospitalization; Humans; Male

To determine the efficacy of long-term enalapril administration in delaying the onset of congestive heart failure (CHF).. Placebo-controlled, double-blind, multicenter, randomized trial.. 124 dogs with compensated mitral valve regurgitation (MR).. Dogs randomly assigned to receive enalapril or placebo were monitored for the primary endpoint of onset of CHF for < or = 58 months. Secondary endpoints included time from study entry to the combined endpoint of CHF-all-cause death; number of dogs free of CHF at 500, 1,000, and 1,500 days; and mean number of CHF-free days.. Kaplan-Meier estimates of the effect of enalapril on the primary endpoint did not reveal a significant treatment benefit. Chronic enalapril administration did have a significant benefit on the combined endpoint of CHF-all-cause death (benefit was 317 days [10.6 months]). Dogs receiving enalapril remained free of CHF for a significantly longer time than those receiving placebo and were significantly more likely to be free of CHF at day 500 and at study end.. Chronic enalapril treatment of dogs with naturally occurring, moderate to severe MR significantly delayed onset of CHF, compared with placebo, on the basis of number of CHF-free days, number of dogs free of CHF at days 500 and study end, and increased time to a combined secondary endpoint of CHF-all-cause death. Improvement in the primary endpoint, CHF-free survival, was not significant. Results suggest that enalapril modestly delays the onset of CHF in dogs with moderate to severe MR.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Death, Sudden, Cardiac; Disease Progression; Disease-Free Survival; Dog Diseases; Dogs; Double-Blind Method; Enalapril; Female; Heart Failure; Kaplan-Meier Estimate; Male; Mitral Valve Insufficiency; Severity of Illness Index; Time Factors; Treatment Outcome

Peripheral arterial disease (PAD) and diabetes are both associated with a high risk of ischemic events, but the role of intensive blood pressure control in PAD has not been established.. The Appropriate Blood Pressure Control in Diabetes study followed 950 subjects with type 2 diabetes for 5 years; 480 of the subjects were normotensive (baseline diastolic blood pressure of 80 to 89 mm Hg). Patients randomized to placebo (moderate blood pressure control) had a mean blood pressure of 137+/-0.7/81+/-0.3 mm Hg over the last 4 years of treatment. In contrast, patients randomized to intensive treatment with enalapril or nisoldipine had a mean 4-year blood pressure of 128+/-0.8/75+/-0.3 mm Hg (P<0.0001 compared with moderate control). PAD, which is defined as an ankle-brachial index <0.90 at the baseline visit, was diagnosed in 53 patients. In patients with PAD, there were 3 cardiovascular events (13.6%) on intensive treatment compared with 12 events (38.7%) on moderate treatment (P=0.046). After adjustment for multiple cardiovascular risk factors, an inverse relationship between ankle-brachial index and cardiovascular events was observed with moderate treatment (P=0.009), but not with intensive treatment (P=0.91). Thus, with intensive blood pressure control, the risk of an event was not increased, even at the lowest ankle-brachial index values, and was the same as in a patient without PAD.. In PAD patients with diabetes, intensive blood pressure lowering to a mean of 128/75 mm Hg resulted in a marked reduction in cardiovascular events.

Topics: Antihypertensive Agents; Blood Pressure; Cardiovascular Diseases; Cohort Studies; Comorbidity; Death, Sudden, Cardiac; Diabetes Mellitus, Type 2; Enalapril; Female; Follow-Up Studies; Humans; Hypertension; Male; Middle Aged; Myocardial Infarction; Nisoldipine; Odds Ratio; Peripheral Vascular Diseases; Risk Assessment; Stroke; Treatment Outcome

This study sought to evaluate the relation between antiplatelet agent (APA) use and survival and morbidity from cardiac disease in patients with left ventricular (LV) systolic dysfunction.. APAs play an important role in the prevention and treatment of coronary disease. Their effects in patients with LV systolic dysfunction are unknown.. We reviewed data on APA use in 6,797 patients enrolled in the Studies of Left Ventricular Dysfunction (SOLVD) trial and analyzed the relation between their use and all-cause mortality as well as the combined end point of death or hospital admission for heart failure (HF). We used Cox regression to adjust for differences in baseline characteristics and to test for the interaction between APA use and selected patient variables in relation to outcome.. APA use (46.3% of patients) was associated with significantly reduced mortality from all causes (adjusted hazard ratio [HR] 0.82, 95% confidence interval [CI] 0.73 to 0.92, p = 0.0005) and reduced risk of death or hospital admission for HF (adjusted HR 0.81, 95% CI 0.74 to 0.89, p < 0.0001) but was not influenced by trial assignment, gender, LV ejection fraction, New York Heart Association class or etiology. A strong interaction was observed among APA use, randomization group and all-cause mortality. The association between APA use and survival was not observed in the enalapril group, nor was an enalapril benefit on survival detectable in patients receiving APAs at baseline. However, randomization to enalapril therapy significantly reduced the combined end point of death or hospital admission for HF in APA users.. In patients with LV systolic dysfunction, use of APAs is associated with improved survival and reduced morbidity. This association is retained after adjustment for baseline characteristics. APA use is associated with retained but reduced benefit from enalapril.

Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Cardiac Output, Low; Cause of Death; Cohort Studies; Confidence Intervals; Coronary Disease; Death, Sudden, Cardiac; Double-Blind Method; Enalapril; Female; Follow-Up Studies; Humans; Male; Middle Aged; Odds Ratio; Patient Admission; Placebos; Platelet Aggregation Inhibitors; Regression Analysis; Risk Factors; Sex Factors; Stroke Volume; Survival Analysis; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Function, Left

To test the long-term effect of enalapril maleate treatment on progression of clinical signs of heart disease in dogs with moderate or severe naturally acquired heart failure associated with chronic degenerative mitral valvular disease (mitral regurgitation [MR]) or dilated cardiomyopathy (DCM).. Prospective multicenter study.. 110 dogs enrolled at 15 locations in the United States.. All dogs enrolled in this study were maintained on their randomly allocated treatment regimen until death, treatment failure (deterioration of condition requiring additional medication), or termination of the study. All dogs entered in the study received standard heart failure treatment (furosemide with or without digoxin). Statistical analysis (log-rank test) was performed to compare the distribution of number of days in the study between dogs that received placebo tablets and dogs that received enalapril tablets.. When dogs with MR and DCM were grouped together, mean number of days until treatment failure was significantly different between those receiving enalapril and those given placebo tablets (157.5 and 77.0 days, respectively). For dogs with MR, mean number of days until treatment failure was significantly different between those receiving enalapril and placebo tablets (159.5 and 86.6 days, respectively). Mean number of days until treatment failure among dogs with DCM receiving enalapril and placebo tablets was 142.8 and 56.5, respectively.. Use of enalapril in combination with standard treatment (diuretics with or without digoxin) appears to be beneficial over an extended period, compared with standard treatment alone.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Cardiomyopathy, Dilated; Cardiotonic Agents; Death, Sudden, Cardiac; Digoxin; Disease Progression; Diuretics; Dog Diseases; Dogs; Double-Blind Method; Drug Therapy, Combination; Enalapril; Female; Furosemide; Heart Failure; Male; Mitral Valve Insufficiency; Prospective Studies; Uremia

To investigate the actions of beta-blocker (atenolol) and ACE inhibitor (enalapril) for the secondary prevention of the main cardiac complications after acute myocardial infarction (AMI).. 1106 cases of AMI from 7 hospitals in the Beijing area were collected and were divided randomly into three groups: control (group C), atenolol (group A), and enalapril (group E). Drugs for investigation were administered 2-4 weeks after the onset of AMI, and the subjects were followed up for a median period of 19 months. All patients were given aspirin 50 mg/day. The end points of observation were cardiac events and non-cardiac events. Cardiac events included sudden cardiac death (SCD), heart failure death, total cardiac deaths, and myocardial re-infarction.. The clinical conditions of the three groups were compatible. Sixty-six cardiac events (6.0%) occurred. Comparing with group C, the rate of SCD decreased significantly by 68% in group A after atenolol treatment for 28 months. Both atenolol and enalapril significantly increased left ventricular ejection fraction (LVEF), whereas in group C the LVEF did not change during the follow-up period. There was obvious decreasing tendency of the survival curve in group C, compared with the other two groups. Totally drugs decrease one cardiac death 0/00/month. But the rate of myocardial re-infarction was the same in the three groups. No serious side effects on blood pressure or heart rate were observed.. Both atenolol and enalapril (domestic products) are beneficial to the secondary prevention of SCD and heart failure death after AMI, but not to re-infarction. Both drugs should be continued for a prolonged period to be effective. Drugs given 2-4 weeks after acute stage are also effective, with no serious side effects.

Topics: Adrenergic beta-Antagonists; Aged; Angiotensin-Converting Enzyme Inhibitors; Atenolol; Cardiac Output, Low; Death, Sudden, Cardiac; Enalapril; Follow-Up Studies; Humans; Myocardial Infarction

The Vasodilator-Heart Failure Trial (V-HeFT) data base provides information on the mechanism of death of male veterans entered into two trials that evaluated the effect of vasodilator therapy on survival in heart failure.. Men aged 18-75 years with heart failure were recruited at 13 Department of Veterans Affairs Medical Centers. In V-HeFT I, 283 of 642 patients (44%) died during follow-up (average, 2.3 years), and in V-HeFT II, 285 of 804 randomized patients (35.5%) died during follow-up (average, 2.5 years). Mechanism of death was established centrally using a standardized classification. In V-HeFT I, 124 of the 283 deaths (43.8%) were sudden with no worsening of symptoms; in V-HeFT II, 104 of the 285 deaths (36.5%) were sudden. An average of 31.5% of the deaths (31.4% and 31.6%, respectively) in the two trials was due to pump failure. The proportion of sudden deaths that occurred without worsening of symptoms was similar in patients with and without ischemic heart failure. Sudden deaths tended to occur earlier and pump failure deaths later in both V-HeFT studies. There was a trend for a lower percentage of cardiac deaths from pump failure and a higher percentage from sudden death in subgroups with higher peak exercise oxygen consumption (VO2), higher ejection fraction, and lower plasma norepinephrine levels. The proportion of deaths that occurred suddenly was similar in placebo, prazosin, and hydralazine plus isosorbide dinitrate treatment groups but was significantly lower in the enalapril treatment group. In V-HeFT I, measures of cardiac function and VO2 predicted pump failure death and sudden death. In V-HeFT II, VO2 and cardiothoracic ratio were independent predictors of all-cause deaths and pump failure deaths; only ejection fraction was an independent predictor of both pump failure and sudden death.. Although mechanistically distinct terminal events can be identified in patients with heart failure and physiological measurements can provide some insight into the risk of these disparate events, sudden death and pump failure death both appear largely to be linked to the severity of cardiac dysfunction and symptoms. Strategies to identify individuals for selective preventive therapy are not yet practical.

Topics: Cause of Death; Death, Sudden, Cardiac; Drug Therapy, Combination; Enalapril; Heart Failure; Humans; Hydralazine; Isosorbide Dinitrate; Male; Middle Aged; Prazosin; Risk Factors; Survival Analysis

Patients with heart failure have a high prevalence of serious arrhythmias and sudden cardiac-death.. Male patients aged 18-75 years with chronic heart failure were randomized to enalapril or hydralazine-isosorbide dinitrate. Short-term (4-hour to 8-hour) Holter tape recordings were performed before randomization, at 3 months, at 1 year, and yearly thereafter. Of 804 patients randomized to therapy, 715 had Holters at baseline. Couplets were noted in 56% versus 60% and ventricular tachycardia (VT) (three or more consecutive ventricular premature beats) in 27% versus 29% of patients randomized to enalapril versus hydralazine-isosorbide dinitrate, respectively. The presence of VT at 3 months, 1 year, and 2 years predicted significantly higher mortality during the subsequent year (p < 0.0001, p < 0.001, and p < 0.037, respectively). In the enalapril group, VT prevalence decreased by 27% at 1 year (p < 0.02). A decrease in prevalence of VT was not seen in the hydralazine-isosorbide dinitrate group. New VT was seen in 11% of enalapril patients versus 24% of hydralazine-isosorbide dinitrate patients at 1 year (p < 0.002). When compared with hydralazine-isosorbide dinitrate at 1 and 2 years, there was a 52% and 49% reduction, respectively, in sudden deaths in the enalapril group. Thus, at 1 and 2 years, the decrease in sudden deaths in the enalapril group coincided with the decrease in VT prevalence and the decrease in new VT emergence.. In patients with heart failure, VT and couplets predict increased mortality. When compared with hydralazine-isosorbide dinitrate, enalapril decreases both the persistence of baseline VT at 3 months and the emergence of new VT at 1 and 2 years. The reduction in VT prevalence parallels a reduction in sudden death. The effect of enalapril on survival over hydralazine-isosorbide dinitrate may be related to its ability to reduce prevalence of ventricular arrhythmia.

Topics: Death, Sudden, Cardiac; Drug Therapy, Combination; Electrocardiography, Ambulatory; Enalapril; Heart Failure; Humans; Hydralazine; Isosorbide Dinitrate; Male; Middle Aged; Prevalence; Risk Factors; Tachycardia, Ventricular

An association between raised renin levels and myocardial infarction has been reported. We studied the effects of enalapril, an angiotensin-converting enzyme (ACE) inhibitor, on the development of myocardial infarction and unstable angina in 6797 patients with ejection fractions < or = 0.35 enrolled into the two Studies of Left Ventricular Dysfunction (SOLVD) trials. Patients were randomly assigned to placebo (n = 3401) or enalapril (n = 3396) at doses of 2.5-20 mg per day in two concurrent double-blind trials with the same protocol. Patients with heart failure entered the treatment trial (n = 2569) and those without heart failure entered the prevention trial (n = 4228). Follow-up averaged 40 months. In each trial there were significant reductions in the number of patients developing myocardial infarction (treatment trial: 158 placebo vs 127 enalapril, p < 0.02; prevention trial: 204 vs 161 p < 0.01) or unstable angina (240 vs 187 p < 0.001; 355 vs 312, p < 0.05). Combined, there were 362 placebo group patients with myocardial infarction compared with 288 in the enalapril group (risk reduction 23%, 95% CI 11-34%; p < 0.001). 595 placebo group patients developed unstable angina compared with 499 in the enalapril group (risk reduction 20%, 95% CI 9-29%, p < 0.001). There was also a reduction in cardiac deaths (711 placebo, 615 enalapril; p < 0.003), so that the reduction in the combined endpoint of deaths, myocardial infarction, and unstable angina was highly significant (20% risk reduction, 95% CI 14-26%; p < 0.0001). Enalapril treatment significantly reduced myocardial infarction, unstable angina, and cardiac mortality in patients with low ejection fractions.

Topics: Angina, Unstable; Blood Pressure; Death, Sudden, Cardiac; Enalapril; Female; Heart Failure; Humans; Incidence; Male; Myocardial Infarction; Prognosis; Prospective Studies; Risk Factors; Stroke Volume; Time Factors

The impact of sudden cardiac death (SCD) in heart failure (HF) patients is important and prevention of SCD is a reasonable and clinically justified endpoint if associated with a reduction in all-cause mortality. According to literature, in HF with reduced ejection fraction, only three classes of agents were found effective in reducing SCD and all-cause mortality: beta-blockers, mineralcorticoid receptor antagonists and, more recently, angiotensin-receptor neprilysin-inhibitors. In the PARADIGM trial that tested sacubitril/valsartan vs. enalapril, the 20% relative risk reduction in cardiovascular deaths obtained with sacubitril/valsartan was attributable to reductions in the incidence of both SCD and death due to HF worsening and this effect can be added to the known positive effect of implantable cardioverter-defibrillators in appropriately selected patients. In order to maximize the implementation of all the available treatments, patients with HF should be included in virtuous networks with a dialogue between all the physician involved, with commitment by all these physicians for appropriate decision-making on application of pharmacological and device treatments according to available evidence, as well as commitment for drug titration before and after device implant, taking advantage from remote monitoring, and with the safety of back up device therapy when indicated. There are potential synergistic effects of drug therapy, with all the therapies acting on neuro-hormonal and sympathetic activation, but specifically with sacubitril/valsartan, and device therapy, in particular cardiac resynchronization therapy, with added incremental benefits on positive cardiac remodelling, prevention of HF progression, and prevention of ventricular tachyarrhythmias.

Topics: Aminobutyrates; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Biphenyl Compounds; Death, Sudden, Cardiac; Drug Combinations; Enalapril; Heart Failure; Humans; Stroke Volume; Tetrazoles; Treatment Outcome

This retrospective study reports the survival time [onset of congestive heart failure (CHF) to death from any cause] of 21 dogs with mitral regurgitation (MR) and CHF treated with a combination of furosemide, angiotensin-converting enzyme inhibitor (ACEI, benazepril, or enalapril), pimobendan, spironolactone, and amlodipine. Baseline echocardiographic data: end-systolic and end-diastolic volume indices (ESVI and EDVI), left atrium to aorta ratio (LA/Ao), and regurgitant fraction (RF) are reported. Median survival time (MST) was 430 d. Initial dosage of furosemide (P = 0.0081) and LA/Ao (P = 0.042) were negatively associated with survival. Baseline echocardiographic indices (mean ± standard deviation) were 40.24 ± 16.76 for ESVI, 161.48 ± 44.49 mL/m(2) for EDVI, 2.11 ± 0.75 for LA/Ao, and 64.71 ± 16.85% for RF. Combining furosemide, ACEI, pimobendan, spironolactone, and amlodipine may result in long survival times in dogs with MR and CHF. Severity of MR at onset of CHF is at least moderate.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Benzazepines; Cardiotonic Agents; Death, Sudden, Cardiac; Dog Diseases; Dogs; Drug Therapy, Combination; Enalapril; Female; Furosemide; Heart Failure; Male; Mitral Valve Insufficiency; Pyridazines; Retrospective Studies; Ultrasonography

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Bisoprolol; Death, Sudden, Cardiac; Dose-Response Relationship, Drug; Drug Administration Schedule; Enalapril; Heart Failure; Humans; Randomized Controlled Trials as Topic; Survival Rate

The aim of this study was to determine the effect of an angiotensin-converting enzyme inhibitor (ACEI), initiated within 24 hours of an acute myocardial infarction (AMI), on the QT dispersion (QTd). ACEIs have proven beneficial in improving left ventricular remodeling, following an AMI while contributing to a reduction in sudden cardiac death (SCD). A prolonged QTd is a marker of electrical instability predisposing to ventricular arrhythmias and SCD. No one has looked at the effects on the QTd of ACEI therapy initiated within 24 hours of an AMI. The study included 239 consecutive patients who presented with an AMI between January 1, 1998 and December 31, 1998. A total of 105 patients had never been treated with an ACEI, and 51 patients were started on enalapril within 24 hours of presentation. Patient demographics were similar in both groups. All patients were treated with aspirin and beta-blocker therapy. A baseline QTd was determined and recalculated on days 3-4 and 6-7 following the AMI. There was no significant difference in the baseline QTd, heart rate, QTc(min), and QTc(max) between the two groups. On days 3-4 the QTd in the treatment group (A) was 39.2 +/- 19.4 ms, as opposed to 84.4 +/- 31.2 ms in the control group (B) (P = 1.0E-06). This reduction in QTd was accounted for by a significant difference in the QTc(max). The QTd shortened in both groups on days 6-7 with a QTd of 30.0 +/- 17.5 in group A and a QTd of 54.1 +/- 26.3 in group B (P = 1.0E-05). There was a significant difference in ejection fraction (EF) between the two groups with the ACEI treated group exhibiting a lower EF, (0.403 (A), 0.494 (B), P < 0.043). The mean dose of enalapril was 6.45 mg daily in the treatment group. ACEIs have been previously shown to reduce the QTd after two months of therapy following an AMI. This study shows that the beneficial effects of ACEI occur early following administration of the drug. The authors speculate that the reduction in SCD conferred by ACEI therapy may be attributed to its effect on reducing the degree of ventricular dispersion of repolarization following a myocardial infarction.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Case-Control Studies; Death, Sudden, Cardiac; Electrocardiography; Enalapril; Female; Heart Rate; Humans; Male; Myocardial Infarction; Retrospective Studies; Time Factors; Treatment Outcome

A common late effect of doxorubicin therapy for childhood cancer is reduced left-ventricular (LV) wall thickness resulting in elevated LV afterload and depressed LV function. Many children are given angiotensin-converting enzyme inhibitors, which have been studied primarily in adults. We document the long-term effects of angiotensin-converting enzyme inhibitors in doxorubicin-treated survivors of childhood cancer.. In this retrospective study, we reviewed records of 18 children who had regular echocardiographic examinations during enalapril therapy (mean age at cancer diagnosis, 8 years; mean time between completion of doxorubicin therapy and start of enalapril, 7 years; median follow-up since the start of enalapril, 10 years).. Over the first 6 years of enalapril therapy, there was progressive improvement toward normal values in LV dimension, afterload, fractional shortening, and mass, but all these parameters deteriorated between 6 and 10 years. LV wall thickness deteriorated throughout the study period, as did LV contractility and systolic blood pressure. Diastolic blood pressure fell slightly. By 6 years on enalapril, all six patients who had had congestive heart failure at the start of enalapril therapy had either died or undergone cardiac transplantation, compared with three of the 12 asymptomatic patients.. In doxorubicin-treated long-term survivors of childhood cancer, enalapril-induced improvement in LV structure and function is transient. The primary defect, which is LV wall thinning, continues to deteriorate, and thus the short-term improvement was mostly related to lowered diastolic blood pressure.

Topics: Adolescent; Adult; Angiotensin-Converting Enzyme Inhibitors; Antibiotics, Antineoplastic; Antihypertensive Agents; Blood Pressure; Child; Death, Sudden, Cardiac; Diastole; Doxorubicin; Drug Administration Schedule; Echocardiography; Enalapril; Heart Failure; Heart Transplantation; Humans; Neoplasms; Retrospective Studies; Risk; Survivors; Ventricular Dysfunction, Left

Topics: Death, Sudden, Cardiac; Enalapril; Heart Failure; Humans