Beta-adrenergic blocking agent use and mortality in patients with asymptomatic and symptomatic left ventricular systolic dysfunction: a post hoc analysis of the Studies of Left Ventricular Dysfunction

OBJECTIVES: This analysis was performed to assess whether beta-adrenergic blocking agent use is associated with reduced mortality in the Studies of Left Ventricular Dysfunction (SOLVD) and to determine if this relationship is altered by angiotensin-converting enzyme (ACE) inhibitor use. BACKGROUND: The ability of beta-blockers to alter mortality in patients with asymptomatic left ventricular dysfunction is not well defined. Furthermore, the effect of beta-blocker use, in addition to an ACE inhibitor, on these patients has not been fully addressed. METHODS: This retrospective analysis evaluated the association of baseline beta-blocker use with mortality in 4,223 mostly asymptomatic Prevention trial patients, and 2,567 symptomatic Treatment trial patients. RESULTS: The 1,015 (24%) Prevention trial patients and 197 (8%) Treatment trial patients receiving beta-blockers had fewer symptoms, higher ejection fractions and different use of medications than patients not receiving beta-blockers. On univariate analysis, beta-blocker use was associated with significantly lower mortality than nonuse in both trials. Moreover, a synergistic reduction in mortality with use of both a beta-blocker and enalapril was suggested in the Prevention trial. After adjusting for important prognostic variables with Cox multivariate analysis, the association of beta-adrenergic blocking agent use with reduced mortality remained significant for Prevention trial patients receiving enalapril. Lower rates of arrhythmic and pump failure death and risk of death or hospitalization for heart failure were observed. CONCLUSIONS: The combination of a beta-blocker and enalapril was associated with a synergistic reduction in the risk of death in the SOLVD Prevention trial.     

Clinical characteristics of patients in studies of left ventricular dysfunction (SOLVD).

The Studies of Left Ventricular Dysfunction (SOLVD) trials were designed to evaluate the effects of enalapril on long-term mortality in patients with severe left ventricular (LV) dysfunction. Patients with LV ejection fractions less than or equal to 0.35 and symptoms of congestive heart failure (CHF) were enrolled in the treatment trial, whereas those with no history of overt CHF and taking no treatment directed for LV dysfunction were enrolled in the prevention trial. The baseline clinical characteristics of SOLVD patients were compared to characterize differences between patients in these 2 separate but concurrent trials. From over 70,000 patients screened with LV dysfunction, 4,228 patients were enrolled in the prevention trial and 2,569 patients in the treatment trial. Ischemic heart disease was the primary cause of LV dysfunction in both prevention (83%) and treatment (71%) trial patients. Prior myocardial infarction was present in 80% of the prevention and 66% of the treatment trial patients (p less than 0.001). In the prevention trial, infarction was recent (less than or equal to 6 months) in 27% patients and remote (greater than 6 months) in 57% patients. Treatment trial patients had proportionately more women (20 vs 13%; p less than 0.001) and non-Caucasians (20 vs 14%; p less than 0.001), as well as the coexisting risk factors of hypertension (42 vs 37%; p less than 0.001) and diabetes (26 vs 15%; p less than 0.001) than did prevention trial patients. Clinical characteristics of patients in both trials were influenced by the gender and race of enrolled patients. Similarly, coronary artery bypass surgery was performed less often in women and non-Caucasians.(ABSTRACT TRUNCATED AT 250 WORDS)     

Relationship of current and past smoking to mortality and morbidity in patients with left ventricular dysfunction

OBJECTIVES: The aim of this study was to evaluate the impact of smoking in patients with left ventricular dysfunction. BACKGROUND: The impact of smoking in patients with left ventricular dysfunction has not been well-studied. METHODS: We compared the incidence of death, hospitalization due to heart failure and myocardial infarction (MI) in current smokers to ex-smokers of < or =2 years and ex-smokers of >2 years duration to never-smokers among participants of the Study Of Left Ventricular Dysfunction (SOLVD) Prevention and Intervention trials. Participants all had left ventricular ejection fraction (LVEF) <35% and follow-up was over a mean of 41 months. RESULTS: Complete smoking status and outcome data were available in 6,704 subjects. There were 1,562 current smokers, 1,317 ex-smokers of < or =2 years, 2,354 ex-smokers of >2 years and 1,471 never-smokers. After adjusting for baseline differences of age, LVEF, race and etiology of heart failure, current smoking was associated with a significantly increased all-cause mortality (relative risk [RR]: 1.41, 95% confidence interval [CI]: 1.25 to 1.58, p < 0.001) compared with ex-smokers and never-smokers. The incidence of death or recurrent congestive heart failure requiring hospitalization or MI was significantly greater (RR: 1.39, 95% CI: 1.26 to 1.52, p < 0.001) in current smokers compared with ex-smokers and never-smokers. There were no significant differences in the number of deaths or hospitalizations due to heart failure between ex-smokers and never-smokers. This effect was consistent across both the SOLVD Prevention and Treatment trials. CONCLUSIONS: Current smoking is a powerful independent predictor of morbidity (recurrent heart failure and MI) and mortality in patients with left ventricular dysfunction. Quitting smoking appears to have a substantial and early effect (within two years) on decreasing morbidity and mortality in patients with left ventricular dysfunction, which is at least as large as proven drug treatments recommended in patients with left ventricular dysfunction.     

Third heart sound and elevated jugular venous pressure as markers of the subsequent development of heart failure in patients with asymptomatic left ventricular dysfunction

PURPOSE: To determine the independent prognostic value of a third heart sound (S(3)) and elevated jugular venous pressure in patients with asymptomatic left ventricular dysfunction. METHODS: We performed a post hoc analysis of 4102 participants from the Studies of Left Ventricular Dysfunction (SOLVD) prevention trial. In that trial, participants with asymptomatic or minimally symptomatic left ventricular dysfunction (New York Association class I or II, left ventricular ejection fraction < or =0.35, no treatment for heart failure) were allocated randomly to enalapril or placebo and followed for a mean (+/- SD) of 34 +/- 14 months. The presence of an S(3) and elevated jugular venous pressure was ascertained by physical examination at study enrollment. We used multivariate proportional hazards models to determine whether these physical examination findings were associated with the development of heart failure, a prespecified endpoint of the SOLVD prevention trial. RESULTS: At baseline, 209 subjects (5.1%) had an S(3) and 70 (1.7%) had elevated jugular venous pressure. Heart failure developed in 1044 subjects (25.5%). After adjusting for other markers of disease severity, an S(3) was associated with an increased risk of heart failure (relative risk [RR] = 1.38; 95% confidence interval [CI]: 1.09 to 1.73; P = 0.007) and the composite endpoint of death or development of heart failure (RR = 1.34; 95% CI: 1.09 to 1.64; P = 0.005). Elevated jugular venous pressure was also associated with these outcomes in multivariate models. CONCLUSION: The physical examination provides prognostic information among patients with asymptomatic or minimally symptomatic left ventricular dysfunction.     

Quality of life among 5,025 patients with left ventricular dysfunction randomized between placebo and enalapril: The studies of left ventricular dysfunction

Objectives. This study was performed to assess the quality of life of patients with left ventricular dysfunction for up to 2 years after randomization to enalapril or placebo.Background. Previous reports have documented that survival of patients with congestive heart failure can be extended by the angiotensin-converting enzyme inhibitor enalapril. However, it is unknown whether enalapril has a long-term favorable impact on the quality of life in patients with heart failure.Methods. A brief quality of life questionnaire assessing the quality of life was administered at baseline and at 6 weeks, 1 year and 2 years of follow-up to patients randomized to placebo or enalapril in the Studies of Left Ventricular Dysfunction (SOLVD). Participants had an ejection fraction ≤ 0.35, no other serious illnesses and either symptomatic heart failure (treatment trial, n = 2,465) or asymptomatic left ventricular dysfunction (prevention trial, n = 2,560).Results. Among the 14 scales of quality of life, better scores at one or more follow-up intervals were noted in 6 scales in the treatment trial and in 1 scale in the prevention trial among patients assigned to enalapril. Consistent superiority with enalapril at two consecutive follow-up intervals was noted in the treatment trial for social functioning and dyspnea but for no scale in the prevention trial. However, an average of 40% of quality of life responses were missing at 2 years of follow-up because of death or failure to complete the questionnaire. In the treatment trial, survivors with more severe heart failure were less likely to complete the questionnaire.Conclusions. Modest benefits in quality of life for ≥ 1 year occurred when patients with left ventricular dysfunction and symptomatic heart failure were treated with enalapril. No apparent beneficial or adverse effect on quality of life was observed with enalapril in asymptomatic patients with left ventricular dysfunction.     

Lessons from recent randomized controlled trials for the management of congestive heart failure

In 1987 the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS) was published, which was a milestone for the treatment of patients with heart failure. The study showed a highly significant reduction in mortality in patients with severe heart failure treated with enalapril in comparison to placebo in combination with conventional treatment for heart failure, including the use of other vasodilators. The improvement in survival was exclusively due to a reduction of progression of pump failure. The incidence of sudden cardiac death was not affected. In 1991 2 studies were published in which patients with mild and moderate heart failure were included. The Second Vasodilator-Heart Failure Trial (V-HeFT II) compared the efficacy of enalapril with the effects of a vasodilator therapy consisting of the combination of hydralazine and isosorbide dinitrate. The study showed a highly significant reduction in mortality in the group of patients on the angiotensin-converting enzyme (ACE) inhibitor. In contrast to CONSENSUS, the benefit on survival was due to a reduction of sudden cardiac death. The second study was the Studies of Left Ventricular Dysfunction (SOLVD) treatment arm trial, which compared enalapril and placebo in combination with standard therapy in symptomatic patients with mild-to-moderate heart failure. The SOLVD treatment trial showed a highly significant improvement in survival on enalapril in comparison with placebo. ACE inhibition resulted in a borderline significant reduction of fatal myocardial infarctions, suggesting an impact of ACE inhibition on the pathogenesis of coronary artery disease. The data available show a clear indication for the treatment of symptomatic patients with mild and moderate-to-severe heart failure with ACE inhibitors as a first-line therapy.     

Warfarin Anticoagulation and Survival: A Cohort Analysis From the Studies of Left Ventricular Dysfunction

Objectives. We sought to evaluate the relation between warfarin anticoagulation and survival and morbidity from cardiac disease in patients with left ventricular (LV) dysfunction.Background. Warfarin anticoagulation plays a major role in the management of patients who have had a large myocardial infarction and in those with atrial fibrillation. However, its use in patients with LV systolic dysfunction has been controversial.Methods. We reviewed data on warfarin use in 6,797 patients enrolled in the Studies of Left Ventricular Dysfunction (SOLVD) trial and analyzed the relation between warfarin use and all-cause mortality, as well as the combined end point of death or hospital admission for heart failure. We used Cox regression to adjust for differences in baseline characteristics and to test for the interaction between warfarin use and selected patient variables in relation to outcome.Results. On multivariate analysis, use of warfarin was associated with a significant reduction in all-cause mortality (adjusted hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.65 to 0.89, p = 0.0006) and in the risk of death or hospital admission for heart failure (HR 0.82, 95% CI 0.72 to 0.93, p = 0.0002). Risk reduction was observed when each trial or randomization arm was analyzed separately, as well as in both genders. It was not significantly influenced by the presence of atrial fibrillation, age, ejection fraction, New York Heart Association functional class or etiology.Conclusions. In patients with LV systolic dysfunction, warfarin use is associated with improved survival and reduced morbidity. This association is primarily due to a reduction in cardiac events and does not appear to be limited to any particular subgroup.     

Hypertension: an important precursor of heart failure

Hypertension is an important risk factor for cardiovascular morbidity and mortality. Hypertension is associated with the development of congestive heart failure by way of left ventricular hypertrophy, with left ventricular dilatation and through myocardial ischemia and left ventricular damage. Reports on the natural history of untreated hypertension indicate that at least 50% of affected subjects develop congestive heart failure. Hypertension is an important precursor of heart failure, and still the most common risk factor for congestive heart failure in the population. In clinical trials, particularly in elderly patients, a reduction in the incidence of congestive heart failure has been observed. Despite increments in the use of antihypertensive drugs, mortality from congestive heart failure among the elderly is increasing. Moreover, several patients with hypertension are unaware, untreated and uncontrolled for the most important risk factor for congestive heart failure. For the primary prevention of heart failure, improvements in blood pressure control are of vast importance.     

Hypertension: an important precursor of heart failure

Hypertension is an important risk factor for cardiovascular morbidity and mortality. Hypertension is associated with the development of congestive heart failure by way of left ventricular hypertrophy, with left ventricular dilatation and through myocardial ischemia and left ventricular damage. Reports on the natural history of untreated hypertension indicate that at least 50% of affected subjects develop congestive heart failure. Hypertension is an important precursor of heart failure, and still the most common risk factor for congestive heart failure in the population. In clinical trials, particularly in elderly patients, a reduction in the incidence of congestive heart failure has been observed. Despite increments in the use of antihypertensive drugs, mortality from congestive heart failure among the elderly is increasing. Moreover, several patients with hypertension are unaware, untreated and uncontrolled for the most important risk factor for congestive heart failure. For the primary prevention of heart failure, improvements in blood pressure control are of vast importance.     

Rationale for the Atrial Fibrillation and Congestive Heart Failure (AF-CHF) Trial

Congestive heart failure and atrial fibrillation (AF) are two important and growing problems in medicine and cardiology. Both conditions often coexist and complicate each other's management. Two therapeutic strategies are available for patients with AF and congestive heart failure: the first aims at restoring and maintaining sinus rhythm, whereas the second focuses exclusively on optimizing ventricular rate. Prior studies of AF and congestive heart failure were not randomized and most were retrospective. Although some studies suggested that AF had no effect on survival, in most recent large congestive heart failure trials, AF was reported to be an independent risk factor for mortality or major morbidity. The primary objective of the Atrial Fibrillation in Congestive Heart Failure (AF-CHF) trial is to compare the two widely used treatment strategies with respect to cardiovascular mortality. AF-CHF is a prospective, multicenter trial that will randomize 1450 CHF patients with left ventricular ejection fraction (LVEF) < or =35% and a documented recent episode of atrial fibrillation to either a rhythm control or a rate control strategy. From recent trial data, we anticipate an 18.75% 2-year cardiovascular mortality in the rate control arm and a 25% event reduction in the rhythm control group. As of December 2003, 960 patients have been randomized. Enrollment is expected to be completed in September 2004 with a minimum follow-up of 2 years.     

Reduction of ischemic events with angiotensin-converting enzyme inhibitors: Lessons and controversy emerging from recent clinical trials

Summary Angiotensin-converting enzyme (ACE) inhibitor therapy has been associated with a substantial (20%) reduction in the risk of major ischemic events in two recent clinical trials with long-term follow-up: Studies of Left Ventricular Dysfunction (SOLVD) and the Survival and Ventricular Enlargement (SAVE) study. Participants in these studies included patients with a low ejection fraction (0.35 in SOLVD and 0.40 in SAVE), generally without symptoms of congestive heart failure. Approximately 80% of patients enrolled in SOLVD and all participants in SAVE had histories of ischemic heart disease or acute myocardial infarction (SAVE). In both SOLVD and SAVE the risk of experiencing a major ischemic event such as myocardial infarction was reduced significantly following prolonged ACE inhibitor therapy. In the SOLVD trial, this effect was evident across a range of patient subgroups, including varying concomitant drug therapies. In both studies, several months elapsed before this benefit became apparent, suggesting an effect on underlying ischemic pathophysiology. A third trial of ACE inhibitor therapy postinfarction, the Acute Infarction Ramipril Efficacy (AIRE) Study, demonstrated a 27% reduction in all cause mortality but no effect on myocardial infarction after a 15-month mean follow-up. No effect of ACE inhibition on risk of survival or reinfarction was reported in the Cooperative New Scandinavian Enalapril Survival Study (CONSENSUS-II), which began the drug within 24 hours of infarction and terminated follow-up at 6 months, a time not likely to demonstrate infarction reduction benefit based on the SOLVD and SAVE observations. Neither AIRE nor CONSENSUS-II had objectively determined left ventricular dysfunction as an entry criterion, as did SOLVD and SAVE, but AIRE mandated clinical congestive heart failure prior to randomization. More recently, preliminary results from the third Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI-3), the Fourth International Study of Infarct Survival (ISIS-4), and the Chinese Captopril Trial suggested that angiotensin-converting enzyme (ACE) inhibitor mortality benefits post-myocardial infarction would be detected in these megatrials as early as 35 days after the event. The mechanism of ACE inhibitor benefit is likely multifactorial and linked to a variety of cardiac and vascular protective mechanisms currently being elucidated. Additional trials are required to ascertain if ACE inhibitors might effect similar benefits in other high-risk populations, such as patients with hypertension or diabetes alone, and to determine if this is a drug class effect or is specific to individual medications studied.     

Lack of long-term ventricular arrhythmia reduction by enalapril in heart failure

Previous studies have indicated that angiotensin-converting enzyme inhibitors may reduce the frequency of ventricular arrhythmias in patients with heart failure. These reports were mostly small and of short duration. We prospectively studied 734 patients recruited in 11 universities for 1 year who were enrolled in the Studies of Left Ventricular Dysfunction (SOLVD) to determine the long-term effects of enalapril and placebo on the frequency and complexity of ventricular arrhythmias in patients with symptomatic (treatment trial) or asymptomatic (prevention trial) heart failure and depressed left ventricular function (ejection fraction ≤35%). Five hundred fifty-three patients from the prevention trial and 181 from the treatment trial of SOLVD underwent ambulatory electrocardiographic monitoring at baseline, and then at 4 and 12 months of double-blind therapy with either placebo or enalapril (2.5 to 10 mg twice daily). The prospectively defined primary analysis was by intent-to-treat and revealed no significant differences in ventricular premature complexes between the placebo and enalapril groups at baseline (87 ± 13 vs 84 ± 13/hour), 4 months (100 ± 15 vs 85 ± 12/hour), or 12 months (80 ± 12 vs 90 ± 14/hour). Likewise, there was no difference between the placebo and enalapril groups in runs of nonsustained ventricular tachycardia: baseline (8.3 ± 4.1 vs 1.9 ± 0.4 runs/day), 4 months (16 ± 12 vs 7.2 ± 4.1 runs/day), or after 12 months of blinded therapy (11 ± 7.0 vs 6.1 ± 4.4 runs/day). Over the 1 -year trial, an equal number of patients in the placebo and enalapril groups developed new ventricular arrhythmias or had comparable reductions in ventricular arrhythmias which had been present at baseline. Our conclusion is that enalapril has no antiarrhythmic effect in a spectrum of patients with heart failure representing New York Heart Association classes I to III. These observations are consistent with the absence of any observed effect of enalapril on sudden death or hospitalization for arrhythmias in the 6,797 patients enrolled in SOLVD.     

Mitral insufficiency and morbidity and mortality in left ventricular dysfunction

BACKGROUND: Mitral insufficiency is known to occur in a substantial proportion of patients with heart failure. Its relationship with morbidity and mortality is poorly described. METHODS: The mortality and hospitalization for heart failure were retrospectively examined in patients who underwent baseline echocardiography in the Studies Of Left Ventricular Dysfunction (SOLVD) treatment and prevention trials. The presence and grade of mitral insufficiency was assessed, and patients with and without mitral insufficiency were compared. RESULTS: Patients with left ventricular dysfunction and mitral insufficiency had greater than twofold increased risk of death or admission for heart failure over two years (RR 2.38, 95% CI 1.43 to 3.97). This excess risk persisted after adjustment for the severity of heart failure, etiology and differences in treatment (RR 1.82, 95% CI 1.04 to 3.17; P=0.04). The presence of moderate mitral insufficiency versus no insufficiency was associated with even greater independent risk (RR 2.20, 95% CI 1.01 to 4.80; P=0.05). Results were consistent with binary and ordinal analysis of mitral insufficiency. CONCLUSION: The presence of mitral insufficiency in patients with left ventricular dysfunction is independently associated with adverse outcomes, including death and hospitalization for heart failure. This has potentially important clinical implications for the assessment and management of patients with heart failure.     

Cardiac resynchronization: a novel therapy for heart failure

Despite advances in medical therapy for patients with congestive heart failure, morbidity and mortality remain high. Conduction abnormalities, such as left bundle branch block, right bundle branch block, and nonspecific conduction delay, are observed commonly in patients with dilated cardiomyopathy. In patients with heart failure, the presence of intraventricular conduction delay is associated with more severe mitral regurgitation and worsened left ventricular systolic and diastolic function, and is an independent risk factor for increased mortality. Conventional dual-chamber (right atrial and right ventricular) pacing with a short atrioventricular delay was initially introduced as therapy for patients with advanced congestive heart failure to improve diastolic dysfunction and reduce mitral regurgitation. The acute beneficial hemodynamic effects observed in early, uncontrolled studies were not confirmed in subsequent randomized, controlled studies with longer follow-up. Cardiac resynchronization with novel biventricular (left and right ventricular) pacing systems has resulted in hemodynamic and functional benefits in patients with congestive heart failure and an underlying intraventricular conduction delay. Improvements in cardiac index, systolic blood pressure, and functional class have been reported with biventricular pacing, both acutely and at more than 1 year of follow-up. These encouraging preliminary results with biventricular pacing in patients with congestive heart failure will be validated in two prospective, randomized, controlled trials, Multicenter InSync Randomized Clinical Evaluation (MIRACLE) and Comparison of Medical Therapy, Pacing, and Defibrillation in Chronic Heart Failure (COMPANION). These studies are designed to evaluate the long-term efficacy of biventricular pacing in improving exercise capacity and in reducing morbidity and mortality in patients with advanced, symptomatic congestive heart failure. (c)2001 by CHF, Inc.     

Comment--Val-HeFT and angiotensin-receptor blockers in perspective: A tale of the blind man and the elephant

BACKGROUND: The role of angiotensin-receptor blockers (ARBs) in the therapy of chronic heart failure (CHF) has not been clarified. There are no large placebo-controlled trials with these agents. The second Evaluation of Losartan in the Elderly trial (ELITE-II) compared the ARB losartan with captopril in 3,152 patients >/=60 years old with New York Heart Association (NYHA) class II-IV and left ventricular ejection fraction 相似文献   

Effect of the angiotensin-converting enzyme inhibitor trandolapril on mortality and morbidity in diabetic patients with left ventricular dysfunction after acute myocardial infarction. Trace Study Group.

OBJECTIVES: This study evaluated the efficacy of long-term treatment with the angiotensin-converting enzyme (ACE) inhibitor trandolapril in diabetic patients with left ventricular dysfunction after acute myocardial infarction (AMI). BACKGROUND: Patients with diabetes mellitus have a high mortality following AMI, probably due to a high risk of congestive heart failure and reinfarction. Because ACE inhibition effectively reduces progression of heart failure, it could be particularly beneficial in diabetic patients after AMI. METHODS: The study is a retrospective analysis using data from the Trandolapril Cardiac Evaluation (TRACE) study, which was a randomized, double-blind, placebo-controlled trial of trandolapril in 1,749 patients with AMI and ejection fraction < or =35%. The mean follow-up time was 26 months. RESULTS: A history of diabetes was found in 237 (14%) of the 1,749 patients. Treatment with trandolapril resulted in a relative risk (RR) of death from any cause for the diabetic group of 0.64 (95% confidence interval 0.45 to 0.91) versus 0.82 (0.69 to 0.97) for the nondiabetic group. In the diabetic group, trandolapril reduced the risk of progression to severe heart failure markedly (RR, 0.38 [0.21 to 0.67]), and no significant reduction of this end point was found in the nondiabetic group. CONCLUSIONS: The ACE inhibition after myocardial infarction complicated by left ventricular dysfunction appears to be of considerable importance in patients with diabetes mellitus by saving lives and substantially reducing the risk of progression to severe heart failure.     

Angiotensin-converting enzyme inhibition and cardiovascular prevention: more than twenty years of clinical success]

Angiotensin-converting enzyme (ACE) inhibitors are widely used for the treatment of cardiovascular disease since they improve blood pressure control in patients with hypertension and prolong survival in patients with acute myocardial infarction, asymptomatic left ventricular dysfunction and congestive heart failure. Most of the information about the therapeutic role of ACE-inhibitors has been achieved during the last 20 years since the publication of some pivotal trials mostly involving the use of ACE-inhibitors like captopril and enalapril. In particular the treatment with enalapril has considerably improved the clinical outcome of patients with either mild-to-moderate (SOLVD studies) or severe (CONSENSUS trial) congestive heart failure. The benefit of ACE-inhibitors in patients with congestive heart failure has also involved a remarkable reduction in the rate of hospitalization, thus contributing to improve the pharmaco-economic approach to the disease. Most of the beneficial effect of ACE-inhibitors in clinical practice is dependent on their capacity of inhibiting the renin-angiotensin system, although some recent trials have supported a primary role for such drugs (in particular enalapril) in the prevention of atrial fibrillation. After more than 25 years from their discovery, ACE-inhibitors must be again considered among the first-line treatment in many patients with cardiovascular disease.     

Cardiomyopathy caused by antineoplastic therapies

Opinion statement The goals of care for patients at risk for cardiomyopathy induced by cancer treatment should include prevention, early diagnosis, treatment of subclinical cardiac dysfunction, prevention of disease progression, and prolongation of patient survival. Any strategy aimed to minimize the cardiotoxic effects of cancer treatment should maintain the treatment’s antineoplastic efficacy. Successful therapy achieves the highest health-related quality of life that is defined by the balance between maximizing the efficacy of oncologic therapy and minimizing the toxicity of this therapy. Doxorubicin-induced cardiotoxicity can be reduced by limiting the overall cumulative dose. There is no specific treatment for cancer therapy-related cardiomyopathy, and symptomatic patients should receive standard treatments for congestive heart failure such as afterload reduction, beta-blockers, diuresis, and digoxin. Afterload reduction with angiotensin-converting enzyme inhibitors such as enalapril and captopril may be indicated in patients with elevated afterload and asymptomatic left ventricular dysfunction diagnosed by echocardiography. Beta-blockers may improve myocardial systolic dysfunction and may be useful in the treatment of cancer treatment-induced cardiomyopathy. Cardiac transplantation remains a viable option in patients with cancer treatment-induced end-stage heart disease.     

Role of beta blockers in congestive heart failure

Prolonged activation of the adrenergic nervous system has adverse consequences on the cardiovascular system in patients with congestive heart failure. Beta adrenergic receptor-blocker therapy modifies these deleterious effects. Beta blockers have been shown to improve myocardial function and survival when used in conjunction with conventional treatment with diuretics, angiotensin-converting enzyme inhibitors, and digoxin. Beta blocker therapy in mild-to-moderate heart failure should not be delayed because it causes some reversal of both neurohormonal compensatory mechanisms and the deleterious myocardial remodeling process. This paper reviews the beneficial effects of beta adrenergic receptor-blocker therapy on the pathophysiology, symptoms, left ventricular function, morbidity, and mortality in patients with congestive heart failure. (c)2000 by CHF, Inc.     

The cost and cardioprotective effects of enalapril in hypertensive patients with left ventricular dysfunction

This study examined the effect of enalapril on survival, resource use, and cost of care in patients with left ventricular dysfunction and hypertension using a retrospective analysis of patients who participated in the Studies of Left Ventricular Dysfunction (SOLVD). Among the 6797 SOLVD participants, 1917 patients had either elevated systolic (≥140 mm Hg) or diastolic (≥90 mm Hg) blood pressure. Therapy with enalapril was associated with a significant relative risk reduction for mortality (RR = 0.819, 95% CI: 0.68 to 0.98; P = .03).This resulted in a gain of 0.11 years (95% CI: 0.00 to 0.20 years) of survival during the average 2.8 year follow-up for this subgroup and was projected to result in a gain of 2.14 years (95% CI: 0.05 to 4.21 years) during the patient’s lifetime. Enalapril significantly reduced the risk of first hospitalization for heart failure by 37%. For all types of hospitalizations, there was an average reduction of 32 hospitalizations per 100 patients treated with enalapril during the trial period (95% CI: 11.8 to 52.2 hospitalizations avoided per 100 patients), resulting in an estimated net savings of $1656 per patient during the trial period (95% CI: increased cost of $191 to savings of $3502). Although the projected lifetime net savings of $1456 was not significant (95% CI: increased cost of $9243 to saving of $12,527), evaluation of the cost per life year saved indicated that enalapril represented a cost-effective strategy. The estimated clinical benefit of enalapril among the hypertensive subgroup in SOLVD supports the recommendation that angiotensin converting enzyme (ACE) inhibitors should be considered as first line pharmacologic therapy for hypertensive patients with left ventricular dysfunction. From both the clinical and economic viewpoints, ACE inhibitors provide important clinical benefits and are cost-effective.