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Biomedical subjects

B Pitt

Publications and source records attributed to B Pitt.

At least 91 records · Page 5Linked to original sources
PubMed1996

[Reduction of cardiovascular events with pravastatin. A pooled analysis of clinical events within the scope of the Pravastatin Atherosclerosis Intervention Program].

BACKGROUND: It has been documented that the HMG coenzyme A reductase inhibitors, or statins, can decrease cardiovascular events and mortality in patients with clinical coronary disease and moderately to severely elevated lipid levels. Additional data are required to demonstrate a reduction of vascular events in coronary patients with less than severely elevated lipid levels and in subgroups of this population. METHODS AND RESULTS: Clinical data from four atherosclerosis regression trials that evaluated pravastatin were pooled for a predetermined analysis of the effect of that agent on the risk of coronary events. All trials were double-masked, placebo-controlled designs that used pravastatin as monotherapy for 2 to 3 years. The 1891 participants in the trials had evidence of atherosclerosis and mildly to moderately elevated lipid levels. For fatal or nonfatal myocardial infarction, there was a 62% reduction in events attributable to pravastatin (p = .001). This effect was evident in younger and older patients, men and women, and patients with and without histories of hypertension and prior infarction. There was a 46% reduction in all-cause mortality (p = 17), which, although not statistically significant, is consistent with the results of other statin trials. There also was a 62% reduction in the risk of fatal or nonfatal stroke (p = .054). CONCLUSIONS: These pooled results provide strong evidence that pravastatin reduces the risk of cardiovascular events in patients with atherosclerotic disease and mildly to moderately elevated lipid levels. The benefit for reducing myocardial infarction is evident in older and younger patients, men and women, and patients with and without histories of hypertension and prior infarction.

Adult↗
PubMed1996

Effect of ACE inhibitors on endothelial dysfunction: unanswered questions and implications for further investigation and therapy.

Experimental studies have suggested that angiotensin-converting enzyme (ACE) inhibitors may have an important role in blocking the progression of and/or reversing endothelial dysfunction. The extrapolation of these experimental studies to the clinical situation has, however, been disappointing. Studies of forearm-mediated endothelial vasodilatation in patients with hypertension with captopril, enalapril, and cilazapril have been negative. The finding of the Trial in Reversing Endothelial Dysfunction (TREND) that the administration of quinapril to normotensive patients with coronary artery disease in part restores endothelial-mediated coronary vasodilation, as assessed by intracoronary administration of acetylcholine, has important implications for future therapy and raises several important questions. The differences in the TREND and previous studies of ACE inhibitors on endothelial dysfunction in patients with coronary artery disease and hypertension. Although in general there has been a good correlation between endothelial dysfunction as assessed by forearm flow and coronary endothelial dysfunction as assessed by acetylcholine, these vascular beds may be affected differently by therapeutic interventions, especially with an ACE inhibitor, which may affect shear stress and angiotensin II formation in different vascular beds differently. Third, one needs to question whether the effect of quinapril on coronary endothelial dysfunction is a class effect or unique to quinapril. It will be necessary to test the effectiveness of other ACE inhibitors on coronary endothelial dysfunction in humans before concluding that the beneficial effects of quinapril are due to a class effect.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

Importance of assessing changes in ventricular response to atrial fibrillation during evaluation of new heart failure therapies: experience from trials of flosequinan.

This study evaluated the effects of flosequinan on ventricular rate in patients with congestive heart failure and atrial fibrillation to determine whether this agent has a facilitatory effect on atrioventricular conduction and whether such an effect may be deleterious. Flosequinan is known to have a dose-dependent positive chronotropic effect on the sinus node, but its effect on atrioventricular conduction has not been evaluated. An excessive increase in ventricular rate during the treatment of heart failure could raise a safety concern and counterbalance beneficial responses. Data were analyzed from 338 patients participating in three similarly designed placebo-controlled exercise trials with flosequinan who also underwent ambulatory electrocardiographic monitoring. The effects of two doses of flosequinan on supine, standing, ambulatory, and exercise heart rates and on exercise capacity in patients in sinus rhythm and atrial fibrillation were compared. Flosequinan increased heart rate in a dose-dependent manner, in patients both with sinus rhythm and atrial fibrillation. A 100 mg once daily dose produced significant increases, in both rhythms, ranging from 6 to 11 beats/min, in supine and standing heart rate, ambulatory heart rate, and exercise heart rate. With a dose of 75 mg twice daily, heart rates under these conditions increased by >20 beats/min in flosequinan-treated patients in atrial fibrillation, a change significantly greater than that observed with placebo or flosequinan, 100 mg once daily and also more than in patients in sinus rhythm treated with the same dose. These results indicate that flosequinan facilitates atrioventricular nodal conduction, increasing the ventricular response in atrial fibrillation, especially at higher dosages. This finding could result from a direct drug action, such as phosphodiesterese inhibition, or reflex sympathetic activation. This response is of sufficient magnitude potentially to impair left ventricular function and interfere with clinical benefit. The effect of heart-failure drugs on ventricular responses in atrial fibrillation should be examined to provide insight into potential mechanisms of both action and safety in this common patient group.

Atrial Fibrillation↗
PubMed1996

IL-1 beta stimulates superoxide and delayed peroxynitrite production by pulmonary vascular smooth muscle cells.

Our previous studies have shown that rat pulmonary microvascular smooth muscle cells (RPMSMC) upregulate inducible nitric oxide synthase (iNOS) and produce nitric oxide (NO) when treated with interleukin-1 beta (IL-1 beta). We now report that an additional effect of IL-1 beta stimulation in RPMSMC is an increase in production of superoxide (O2-) that results in the formation of peroxynitrite (ONOO-). IL-1 beta produced a rapid (within 1 h) concentration-dependent increase in O2-, as detected by ferricytochrome c reduction and lucigenin-enhanced chemiluminescence. O2- production was sensitive to quinacrine and diphenyliodinium, suggesting that NADH and NADPH oxidoreductases were responsible. After induction of iNOS and production of iNOS-derived NO, ONOO- was detected by luminol-enhanced chemiluminescence and was found to cause lipid peroxidation and to form nitrotyrosine in the cytoskeleton, detected by immunostaining. Cell viability, however, appeared to be unaffected. IL-1 beta-mediated induction of RPMSMC-derived ONOO- may have significant effects on pulmonary vascular function in sepsis and inflammatory states.

Animals↗
PubMed1996

ACE inhibitor use in elderly patients with systolic left ventricular dysfunction: problems and opportunities.

The ACE inhibitors have been found effective in reducing the morbidity and mortality of both post-infarction patients and those with chronic systolic left ventricular dysfunction. However, their use is limited--particularly in elderly patients because of poor tolerance partly due to bradykinin-induced side-effects such as renal dysfunction, first-dose hypotension, and cough. Thus, the introduction of the angiotensin II type I receptor antagonists--that block the effects of angiotensin II without increasing bradykinin concentration--may be particularly important in the treatment of elderly patients. The role of the angiotensin II type I receptor antagonists in patients with systolic left ventricular dysfunction is currently being explored in direct comparison with and in conjunction with the ACE inhibitors. Furthermore, important questions about the most effective dose of ACE inhibitor and ACE inhibitor use in conjunction with aspirin and the NSAIDs still have to be answered. Thus, although we have learnt much about the role of ACE inhibitors in heart failure treatment, we are still at an early stage in the application of this knowledge, particularly in elderly patients.

Aged↗
PubMed1995

Pravastatin limitation of atherosclerosis in the coronary arteries (PLAC I): reduction in atherosclerosis progression and clinical events. PLAC I investigation.

OBJECTIVES: This study was designed to evaluate the effect of pravastatin on progression of coronary atherosclerosis and ischemic events in patients with coronary artery disease and mild to moderate hyperlipidemia. BACKGROUND: Few clinical trial data support the use of lipid-lowering therapy in patients with coronary artery disease and mild to moderate elevations in cholesterol levels. METHODS: Four hundred eight patients (mean age 57 years) with coronary artery disease and low density lipoprotein (LDL) cholesterol > or = 130 mg/dl (3.36 mmol/liter) but < 190 mg/dl ([4.91 mmol/liter]) despite diet were randomized in a 3-year study to receive pravastatin or placebo. Atherosclerosis progression was evaluated by quantitative coronary arteriography. RESULTS: Baseline mean LDL cholesterol was 164 mg/dl (4.24 mmol/liter). Pravastatin decreased total and LDL cholesterol and triglyceride levels by 19%, 28% and 8%, respectively, and increased high density lipoprotein cholesterol by 7% (p < or = 0.001 vs. placebo for all lipid variables). Progression of atherosclerosis was reduced by 40% for minimal vessel diameter (p = 0.04), particularly in lesions < 50% stenosis at baseline. There was a consistent although not statistically significant effect on mean diameter and percent diameter stenosis. There were also fewer new lesions in those assigned pravastatin (p < or = 0.03). Myocardial infarction was reduced during active treatment (8 in the pravastatin group, 17 in the placebo group; log-rank test, p < or = 0.05; 60% risk reduction), with the benefit beginning to emerge after 1 year. CONCLUSIONS: In patients with coronary artery disease and mild to moderate cholesterol elevations, pravastatin reduces progression of coronary atherosclerosis and myocardial infarction. The time course of event reduction increases the potential for a relatively rapid decrease in the clinical manifestations of coronary artery disease with lipid lowering.

Aged↗
PubMed1995

Better functional status in American than Canadian patients with heart disease: an effect of medical care?

OBJECTIVES: This study compared functional status in Americans and Canadians with and without prior symptoms of heart disease to separate the effects of medical care from nonmedical factors. BACKGROUND: Coronary angiography and revascularization are used more often in the United States than in Canada, yet rates of mortality and myocardial infarction are similar in the two countries. Recent data suggest that functional status after myocardial infarction is better among Americans than Canadians, but it is uncertain whether this difference is due to medical care or nonmedical factors. METHODS: Quality of life was measured in patients enrolled in seven American and one Canadian site in the Bypass Angioplasty Revascularization Investigation. Prior symptoms of heart disease were defined as angina, myocardial infarction or congestive heart failure before the episode of illness leading to randomization. Functional status was measured with the Duke Activity Status Index and overall emotional and social health using Medical Outcome Study measures on the basis of patient status before the index episode of acute ischemic heart disease. RESULTS: Quality of life was generally better in the 934 Americans than in the 278 Canadians, with overall health rated as excellent or very good in 30% of Americans versus 20% of Canadians (p = 0.0001), higher median Duke Activity Status Index scores (16 vs. 13.5, p = 0.03) but equivalent emotional health (76 vs. 76, p = 0.74) and social health scores (100 vs. 80, p = 0.07). Among the 350 patients without prior symptoms of heart disease, Americans and Canadians had similar overall health, Duke Activity Status Index and emotional and social health scores. However, of the 860 patients with previous symptoms of heart disease, Americans had higher overall health (p = 0.0001) and Duke Activity Status Index scores (p = 0.0008) but similar emotional and social health scores. The results were essentially unchanged after statistical adjustment for potential confounding factors. CONCLUSIONS: The functional status of patients without prior symptoms of heart disease is similar in Americans and Canadians. However, among patients with previous symptomatic heart disease, functional status is higher in Americans than in Canadians. This difference may be due to different patterns of medical management of heart disease in the two countries.

Aged↗
PubMed1995

Reduction in cardiovascular events during pravastatin therapy. Pooled analysis of clinical events of the Pravastatin Atherosclerosis Intervention Program.

BACKGROUND: It has been documented that the HMG coenzyme A reductase inhibitors, or statins, can decrease cardiovascular events and mortality in patients with clinical coronary disease and moderately to severely elevated lipid levels. Additional data are required to demonstrate a reduction of vascular events in coronary patients with less than severely elevated lipid levels and in subgroups of this population. METHODS AND RESULTS: Clinical data from four atherosclerosis regression trials that evaluated pravastatin were pooled for a predetermined analysis of the effect of that agent on the risk of coronary events. All trials were double-masked, placebo-controlled designs that used pravastatin as monotherapy for 2 to 3 years. The 1981 participants in the trials had evidence of atherosclerosis and mildly to moderately elevated lipid levels. For fatal or nonfatal myocardial infarction, there was a 62% reduction in events attributable to pravastatin (P = .001). This effect was evident in younger and older patients, men and women, and patients with and without histories of hypertension and prior infarction. There was a 46% reduction in all-cause mortality (P = .17), which, although not statistically significant, is consistent with the results of other statin trials. There also was a 62% reduction in the risk of fatal or nonfatal stroke (P = .054). CONCLUSIONS: These pooled results provide strong evidence that pravastatin reduces the risk of cardiovascular events in patients with atherosclerotic disease and mildly to moderately elevated lipid levels. The benefit for reducing myocardial infarction is evident in older and younger patients, men and women, and patients with and without histories of hypertension and prior infarction.

Age Factors↗
PubMed1995

Reduction in coronary events during treatment with pravastatin. PLAC I and PLAC II Investigators. Pravastatin Limitation of Atherosclerosis in the Coronary Arteries.

The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or statins, are more efficacious than older lipid-lowering agents and therefore may be more effective in reducing the incidence of coronary events. The objective of this prespecified analysis was to examine in coronary patients the effect of the lipid-lowering agent pravastatin on 3-year rates of coronary event incidence, all-cause mortality, and nonfatal myocardial infarction (MI), and to determine whether any observed benefit was also evident in patients > or = 65 years of age. The design of this analysis was to pool the data from 2 concurrent 3-year placebo-controlled clinical trials of pravastatin monotherapy in coronary patients (Pravastatin Limitation of Atherosclerosis in the Coronary Arteries [PLAC I] and the Pravastatin, Lipids, and Atherosclerosis in the Carotid Arteries [PLAC II]). This pooled database included 559 coronary patients with moderately elevated levels of low density lipoprotein cholesterol (between the 60th and 90th percentiles for age and gender in the United States). Over the 3 years of follow-up, use of pravastatin was associated with a 55% reduction in coronary incidence (p = 0.014). Pravastatin was also associated with a 67% reduction in nonfatal MI (p = 0.006). Eleven placebo patients died over the 3 years of follow-up compared with 7 in the pravastatin groups (a 40% reduction). Among older patients (age > or = 65 years), pravastatin therapy was associated with a 79% reduction in coronary event incidence (95% confidence interval [CI] 33-100%) and with a 86% reduction in nonfatal myocardial infarction (CI, 35-100%).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1995

Survival with oral d-sotalol in patients with left ventricular dysfunction after myocardial infarction: rationale, design, and methods (the SWORD trial).

Impaired left ventricular function after acute myocardial infarction (AMI) is associated with an increased risk of death. Despite recent advances in the management of these patients, sudden death accounts for up to 50% of this mortality, and effective treatment strategies have yet to be identified. Preliminary trials with amiodarone have offered promise that drugs that prolong action potential duration by blocking the potassium channel may be useful in reducing this mortality. The Survival With Oral d-Sotalol (SWORD) trial is a multicenter, multinational study which tests the hypothesis that the class III agent d-sotalol will reduce all-cause mortality in high-risk survivors of AMI. The trial will enroll 6,400 patients with left ventricular dysfunction (ejection fraction < or = 40%) and a recent (6 to 42 days) or a remote (> 42 days) AMI with overt heart failure (New York Heart Association class II or III). In approximately 500 centers throughout the world, men and women aged > or = 18 years will be enrolled and randomized to placebo or d-sotalol (200 mg/day). The minimal follow-up will be 18 months. The trial has a 90% power to detect a 20% reduction in all-cause mortality. The rationale, design, and trial methods are described.

Administration, Oral↗
PubMed1995

Initial functional and economic status of patients with multivessel coronary artery disease randomized in the Bypass Angioplasty Revascularization Investigation (BARI).

Randomized trials of coronary angioplasty and bypass surgery have hypothesized that these procedures will have equivalent long-term rates of death and myocardial infarction. Functional status, quality of life, employment, and healthcare cost will therefore be critical measures of the efficacy of these alternative revascularization procedures. Patients at 7 sites in the Bypass Angioplasty Revascularization Investigation (BARI) were enrolled in an ancillary Study of Economics and Quality of Life (SEQOL). Physical function was assessed by the Duke Activity Status Index and emotional status by the Mental Health Inventory. Employment patterns and health care utilization were also measured at study entry and at 3-month intervals in follow-up. The 934 patients enrolled in SEQOL were similar to the 895 remaining BARI randomized patients. Most patients (63%) aged < or = 64 years were working, and almost all working patients (96%) intended to return to work. Patients aged > or = 65 years had lower household incomes but better health insurance coverage. Overall health ratings were significantly correlated with both physical and emotional status (p < 0.001). Patients enrolled in SEQOL are representative of the overall BARI population. Data collected in SEQOL will provide a detailed picture of the physical, emotional, and economic well-being after coronary angioplasty and bypass surgery.

Angioplasty, Balloon, Coronary↗
PubMed1995

"Escape" of aldosterone production in patients with left ventricular dysfunction treated with an angiotensin converting enzyme inhibitor: implications for therapy.

Despite the findings in randomized trials of a significant effect of angiotensin-converting enzyme (ACE) inhibitors in reducing morbidity and mortality of patients with symptomatic left ventricular dysfunction, the morbidity and mortality of these patients remains relatively high. One potential strategy to further improve morbidity and mortality in these patients is blockade of a aldosterone. Many clinicians have assumed that ACE inhibitors would block both angiotensin II and aldosterone. However, there are data to suggest that aldosterone production may "escape" despite the use of an ACE inhibitor. An escape of aldosterone production has several important consequences, including: sodium retention, potassium and magnesium loss, myocardial collagen production, ventricular hypertrophy, myocardial norepinephrine release, endothelial dysfunction, and a decrease in serum high density lipoprotein cholesterol. Due to the potential importance of these mechanisms, the finding that there is a significant correlation between aldosterone production and mortality in patients with heart failure, as well as evidence that an aldosterone antagonist, spironolactone, when administered to patients with heart failure treated with conventional therapy including an ACE inhibitor results in increased diuresis and symptomatic improvement, an international prospective multicenter study has been organized, the Randomized Aldactone Evaluation Study (RALES Pilot Study), to evaluate the safety of blocking the effects of aldosterone in patients with heart failure treated with an ACE inhibitor.

Aldosterone↗
PubMed1995

Angiotensin II receptor antagonists in heart failure: rationale and design of the evaluation of losartan in the elderly (ELITE) trial.

Angiotensin-converting enzyme inhibitors (ACE-I) have been proven to be effective in reducing morbidity and mortality in patients with heart failure or post-myocardial infarction left ventricular dysfunction. Despite evidence from several large-scale randomized trials, the use of ACE-I in patients with heart failure remains relatively low. In part, the failure to achieve more widespread use of ACE-I in patients with heart failure may be due to physician's perceptions of the side effects associated with ACE-I, such as angioedema, renal dysfunction, cough, and hypotension. Many of these side effects are thought to be due to ACE-I-induced bradykinin accumulation. It is possible to inhibit the effect of angiotensin II without increasing bradykinin levels using an angiotensin II type I blocking agent such as losartan. How effective losartan is compared with an ACE-I is uncertain, however. Some of the beneficial effects of ACE-I have been attributed to bradykinin accumulation, and therefore ACE-I might have an advantage compared with an angiotensin II type I receptor antagonist such as losartan. On the other hand, angiotensin II may be produced by non-ACE-I-dependent mechanisms, which would suggest that an angiotensin II type I receptor blocking agent would be advantageous. To determine the relative safety and efficacy of an ACE-I, which results in bradykinin accumulation and inhibitors of angiotensin II, versus an angiotensin II type I receptor blocking agent, which does not result in bradykinin accumulation, we have begun the Evaluation of Losartan In The Elderly (ELITE) trial, which will compare the safety and efficacy of captopril and losartan in elderly patients with heart failure.

Aged↗
PubMed1995

Costs and effects of enalapril therapy in patients with symptomatic heart failure: an economic analysis of the Studies of Left Ventricular Dysfunction (SOLVD) Treatment Trial.

The clinical results of the Studies of Left Ventricular Dysfunction (SOLVD) Treatment Trial have been published previously, but no evaluation of cost-effectiveness based on the primary data has been reported. The authors used a decision analytic model based on primary data from SOLVD to estimate years of survival (overall, by New York Heart Association Class, and quality-adjusted) and to estimate costs of nonfatal hospitalizations, ambulatory care, therapy with enalapril, and deaths. Clinical and resource utilization data were derived from participants in SOLVD, and cost data were derived from the United States. Therapy with enalapril during the approximate 48-month follow-up period in SOLVD resulted in a gain of 0.16 year of life and savings of dollars 718. During the patient's lifetime, a survival benefit of 0.40 year, a cost per year of life saved of dollars 80, and a cost per quality-adjusted life year of dollars 115 with the use of enalapril were projected. The results indicated a net savings and gain in life expectancy during the SOLVD treatment trial. The lifetime projection suggests that therapy with angiotensin-converting enzyme inhibitors, such as enalapril, is extremely attractive when compared with many commonly used interventions in patients with cardiovascular disease or heart failure.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1995

Potential role of angiotensin converting enzyme inhibitors in treatment of atherosclerosis.

Recent clinical data from the SOLVD (Studies on Left Ventricular Dysfunction) and SAVE (Survival and Ventricular Enlargement) studies have shown a significant reduction in ischaemic events with ACE inhibition. When the results of the two SOLVD and the SAVE trials were combined, the overall risk reduction in myocardial infarction with long-term ACE inhibitor treatment was 23% (P < 0.001) and the overall risk reduction for hospitalizations for unstable angina 15%. The time frame of the clinical effects suggests that ACE inhibitors may be working through an antiatherosclerotic mechanism, and genetic, epidemiological and mechanistic data suggest that the renin-angiotensin-aldosterone system may play a role in the atherosclerotic process. Genetic and epidemiological evidence has shown that an activated renin-angiotensin aldosterone system is associated with a higher incidence of myocardial infarction, and mechanistic studies have demonstrated that ACE inhibition can produce antiatherosclerotic effects in animal models. The antiatherosclerotic effects of ACE inhibitors may be mediated at one of several steps in the atherosclerotic pathway: blocking plaque formation, plaque rupture, or thrombus formation.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1995

Importance of angiotensin-converting enzyme inhibitors in myocardial infarction and congestive heart failure: implications for clinical practice.

Angiotensin-converting enzyme inhibitors (ACE inhibitors) have been shown to be effective in improving symptoms and survival in patients with systolic left ventricular dysfunction. Despite their proven benefits the use of ACE inhibitors is still limited in many parts of the western world. In part, the underutilization of ACE inhibitors is due to the occurrence of side effects such as cough, renal dysfunction and first dose hypotension. These side effects are in part due to ACE inhibitor-induced bradykinin formation. Blockade of the effects of angiotensin II can however also be achieved with an angiotensin II type I receptor blocking agent such as losartan. To determine the relative safety and effectiveness of ACE inhibitors compared to an angiotensin II type I receptor blocking agent the evaluation of losartan and the elderly trial (Elite) is comparing the ACE inhibitor captopril to the angiotensin II type I receptor blocking agent losartan in elderly patients. When used ACE inhibitors are often given in doses lower than those shown to be effective in reducing mortality in the major randomized trials. Several trials are currently under way comparing low to high doses of ACE inhibitors which should provide information on the need to achieve the doses used in the major mortality studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1994

Management of heart failure. I. Pharmacologic treatment.

OBJECTIVE: This review of the pharmacologic treatment of heart failure due to left ventricular systolic dysfunction summarizes the recommendations of the expert panel for the Agency for Health Care Policy and Research Heart Failure Guideline. It provides specific advice to help guide practitioners through clinical decision making. DATA SOURCES: Data were obtained from English-language studies and referenced in MEDLINE or EMBASE between 1966 and 1993. We used the search terms heart failure, congestive; congestive heart failure; heart failure; cardiac failure; and dilated cardiomyopathy in conjunction with terms for the specific treatments. Where data were lacking, we relied on opinions of panel members and peer reviewers. STUDY SELECTION: Only large prospective trials were used to estimate treatment efficacy. Smaller trials, case series, and case reports were reviewed for the incidence of adverse effects. DATA EXTRACTION AND SYNTHESIS: Randomized clinical trials were reviewed for inclusion and exclusion criteria, patient outcomes, adverse effects, and eight categories of study quality using a defined list of study flaws. CONCLUSION: Angiotensin-converting enzyme (ACE) inhibitors should be given to all patients unless specific contraindications exist. Diuretics should be used judiciously early in treatment to prevent excessive diuresis that could prevent titration of ACE inhibitors to target doses. Digoxin has not been shown to affect the natural history of heart failure and should be reserved for patients who remain symptomatic after treatment with ACE inhibitors and diuretics. Isosorbide dinitrate and hydralazine hydrochloride should be tried in patients who cannot tolerate ACE inhibitors or who have refractory symptoms.

Angiotensin-Converting Enzyme Inhibitors↗