Patient preferences for healthcare delivery through community pharmacy settings in the USA: A discrete choice study.

WHAT IS KNOWN AND OBJECTIVE: In order to improve public health, it is necessary to facilitate patients' easy access to affordable high-quality primary health care, and one enhanced approach to do so may be to provide primary healthcare services in the community pharmacy setting. Discrete choice experiments to evaluate patient demand for services in pharmacy are relatively limited and have been hampered by a focus on only a few service alternatives, most focusing on changes in more traditional pharmacy services. The study aim was to gauge patient preferences explicitly for primary healthcare services that could be delivered through community pharmacy settings in the USA, using a very large sample to accommodate multiple service delivery options. METHODS: An online survey was administered to a total of 9202 adult patients from the general population. A subsequent online survey was administered to 50 payer reimbursement decision-makers. The patient survey included a discrete choice experiment (DCE) which showed competing scenarios describing primary care service offerings. The respondents chose which scenario would be most likely to induce them to switch from their current pharmacy, and an optimal patient primary care service model was derived. The likelihood this model would be reimbursed was then determined in the payer survey. RESULTS AND DISCUSSION: The final optimal service configuration that would maximize patient preference included the pharmacy: offering appointments to see a healthcare provider in the pharmacy, having access to their full medical record, provide point-of-care diagnostic testing, offer health preventive screening, provide limited physical examinations such as measuring vital signs, and drug prescribing in the pharmacy. The optimal model had the pharmacist as the provider; however, little change in demand was evident if the provider was a nurse-practitioner or physician's assistant. The demand for this optimal model was 2-fold higher (25.5%; 95% Bayesian precision interval (BPI) 23.5%-27.0%) than for a base pharmacy offering minimal primary care services (12.6%; 95% BPI 12.2%-13.2%), and was highest among Hispanic (30.6%; 95% BPI: 25.7%-34.3%) and African American patients (30.7%; 95% BPI: 27.1%-35.2%). In the second reimbursement decision-maker survey, the majority (66%) indicated their organization would be likely to reimburse the services described in the optimal patient model if provided in the pharmacy setting. WHAT IS NEW AND CONCLUSION: This United States national study provides empirical support for a model of providing primary care services through community pharmacy settings that would increase access, with the potential to improve the public health.

Adherence to controller asthma medications: 6-month prevalence across a US community pharmacy chain.

WHAT IS KNOWN AND OBJECTIVE: Non-adherence to controller asthma medications is an important public health problem. It is estimated to occur in 30-70% of individuals and is a significant risk factor for asthma morbidity and mortality. The aim of this study was to determine the level of adherence, as indicated by refill rates, to controller asthma medications in a community pharmacy setting. METHODS: Secondary analyses of a community pharmacy dispensing database in 15 locations throughout Utah. RESULTS AND DISCUSSION: The dispensing records of 2193 patients who received controller medications for asthma in a 12-month period, and had a minimum of 6-month potential coverage (180 days) from the date of their first receipt of a controller medication in that period, were examined. Using standard metrics to gauge adherence, the proportion of days covered (PDC) and the medication possession ratio (MPR), the average coverage for controller asthma medications across a 6-month period (180 days) was poor, averaging less than 50% of days' availability. Standard cut-offs (≥80% medication availability) indicated that only 14-16% of patients had 'satisfactory' adherence over their 6-month follow-on period. Females and older patients had significantly greater satisfactory adherence. Medication adherence was significantly greater with inhaled corticosteroid (ICS)-long-acting ß2 -agonist (LABA) combinations than with ICS alone. WHAT IS NEW AND CONCLUSION: This study confirms the considerable scope of the asthma therapy non-adherence problem. Therefore, it is imperative to conduct survey-based research linked directly to pharmacy-based dispensing data to derive patient behavioural, attitudinal and environmental factors that may contribute to the issue, and then pilot and evaluate interventions for change.

Aliskiren for geriatric lowering of systolic hypertension: a randomized controlled trial.

Efficacy and safety of the direct renin inhibitor aliskiren was compared with ramipril for treatment of essential systolic hypertension in elderly patients. A 36-week, randomized, double-blind, parallel-group, active-controlled, optional-titration study was performed in 901 patients (aliskiren, n=457; ramipril, n=444) > or =65 years of age with systolic blood pressure (SBP) > or =140 mm Hg. Aliskiren 150-300 mg per day or ramipril 5-10 mg per day for was administered for 12 weeks with optional add-on therapy of hydrochlorothiazide (12.5-25 mg per day) at week 12 and amlodipine (5-10 mg per day) at week 22. The primary end point was non-inferiority of aliskiren vs ramipril monotherapy for change from baseline in mean sitting SBP (msSBP) at week 12. Decreases from baseline msSBP and mean sitting diastolic BP with aliskiren monotherapy (-14.0 and -5.1 mm Hg, respectively) were non-inferior (P<0.001 for both values) and superior to ramipril monotherapy (-11.6, -3.6 mm Hg; P=0.02, P<0.01, respectively). More patients achieved BP control with aliskiren (42%) than ramipril (33%; P<0.01). At week 36, fewer patients receiving aliskiren-based therapy required add-on treatment with hydrochlorothiazide or amlodipine (P=0.01 and 0.048, respectively). Tolerability was similar, but more patients receiving ramipril reported cough (P<0.001). In elderly patients with systolic hypertension, aliskiren proved to be more effective and better overall anti-hypertensive therapy compared to ramipril.

New recommendations from the 1999 American College of Cardiology/American Heart Association acute myocardial infarction guidelines.

OBJECTIVE: To review literature relating to significant changes in drug therapy recommendations in the 1999 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines for treating patients with acute myocardial infarction (AMI). DATA SOURCES: 1999 ACC/AHA AMI guidelines, English-language clinical trials, reviews, and editorials researching the role of drug therapy and primary angioplasty for AMI that were referenced in the guidelines were included. Additional data published in 2000 or unpublished were also included if relevant to interpretation of the guidelines. STUDY SELECTION: The articles selected influence AMI treatment recommendations. DATA SYNTHESIS: Many clinicians and health systems use the ACC/AHA AMI guidelines to develop treatment plans for AMI patients. This review highlights important changes in AMI drug therapy recommendations by reviewing the results of recent clinical trials. Insights into evolving drug therapy strategies that may impact future guideline development are also described. CONCLUSIONS: Several changes in drug therapy recommendations were included in the 1999 AMI ACC/AHA guidelines. There is emphasis on administering fibrin-specific thrombolytics secondary to enhanced efficacy. Selection between fibrin-specific agents is unclear at this time. Low response rates to thrombolytics have been noted in the elderly, women, patients with heart failure, and those showing left bundle-branch block on the electrocardiogram. These patient groups should be targeted for improved utilization programs. The use of glycoprotein (GP) IIb/IIIa receptor inhibitors in non-ST-segment elevation MI was emphasized. Small trials combining reduced doses of thrombolytics with GP IIb/IIIa receptor inhibitors have shown promise by increasing reperfusion rates without increasing bleeding risk, but firm conclusions cannot be made until the results of larger trials are known. Primary percutaneous coronary intervention (PCI) trials suggest lower mortality rates for primary PCI when compared with thrombolysis alone. However, primary PCI, including coronary angioplasty, is only available at approximately 13% of US hospitals, making thrombolysis the preferred strategy for most patients. Clopidogrel has supplanted ticlopidine as the recommended antiplatelet agent for patients with aspirin allergy or intolerance following reports of a better safety profile. The recommended dose of unfractionated heparin is lower than previously recommended, necessitating a separate nomogram for patients with acute coronary syndromes. Routine use of warfarin, either alone or in combination with aspirin, is not supported by clinical trials; however, warfarin remains a choice for antithrombotic therapy in patients intolerant to aspirin. Beta-adrenergic receptor blockers continue to be recommended, and emphasis is placed on improving rates of early administration (during hospitalization), even in patients with moderate left ventricular dysfunction. New recommendations for drug treatment of post-AMI patients with low high-density lipoprotein cholesterol and/or elevated triglycerides are included, with either niacin or gemfibrozil recommended as an option. Supplementary antioxidants are not recommended for either primary or secondary prevention of AMI, with new data demonstrating lack of efficacy vitamin E in primary prevention. Estrogen replacement therapy or hormonal replacement therapy should not be initiated solely for prevention of cardiovascular disease, but can be continued in cardiovascular patients already taking long-term therapy for other reasons. Bupropion has been added as a new treatment option for smoking cessation. As drug therapy continues to evolve in treating AMI, more frequent updates of therapy guidelines will be necessary.

A chronobiologic approach to the pharmacotherapy of hypertension and angina.

OBJECTIVE: To review the chronobiology of hypertension and coronary artery disease and the application of chronotherapeutics to their treatment and prevention. DATA SOURCES: Clinical trials and review articles (English-language) on the topic of chronotherapy and cardiovascular disease were identified via a MEDLINE search from 1990 to March 2000, using the search terms chronotherapy, circadian rhythm, cardiovascular disease, hypertension, and angina. DATA EXTRACTION: Search and evaluation focused on published clinical trials and review articles of circadian variation associated with pharmacotherapy for cardiovascular disease. DATA SYNTHESIS: The existence of circadian rhythm in cardiovascular disease is well established. Heart rate and blood pressure peak during the morning hours and reach a nadir at bedtime. The incidence of myocardial infarction, stroke, sudden cardiac death, and myocardial ischemia also increases during the early-morning hours. Based on these relationships, researchers have begun to apply the science of chronotherapeutics, or timing of drug effect with biologic need, to improve cardiovascular outcomes. This includes administering traditional agents at specific times throughout the day and developing new agents--chronotherapeutic formulations with special release mechanisms--targeted at inducing the greatest effect during the morning surges. Chronotherapeutic agents are specifically designed to provide peak plasma concentrations during the early-morning hours, when effect appears most needed; lowest concentrations occur at night, when heart rate and blood pressure are lowest and, consequently, cardiovascular events are least likely to occur. CONCLUSIONS: Whether chronotherapy of cardiovascular disease offers an advantage in long-term outcomes over traditional therapy must be studied in clinical trials.

beta-blocker therapy: a standard of care for heart failure.

beta-Adrenergic-blocking agents underwent extensive research over the past 2 decades and emerged as a proven state-of-art therapy for the failing human heart. Through blockade of chronically elevated cardiac adrenergic stimulation, selective and nonselective agents with vasodilating properties prevent progression of myocardial dysfunction and cardiac remodeling. Most important, beta-adrenergic blockers added to conventional therapy of vasodilators and diuretics significantly increase survival to a 5-year rate similar to that of cardiac transplantation. The agents also significantly reduce hospitalizations, improve quality of life, and are well tolerated in clinical trials. The challenge in treating heart failure is to ensure that every eligible patient receives these life-saving drugs.

Growth hormone: a promising treatment for the failing heart?

Many pathologic processes that accelerate the progression of heart failure, such as cardiac remodeling and impaired contractility, may be modulated by administration of recombinant growth hormone. The agent improves structural and functional aspects of the failing heart both in the short term and after several months of therapy. However, conflicting clinical results cast doubt on whether it has a clear benefit in all of these patients. In addition, growth hormone therapy may be associated with cardiac and noncardiac adverse effects. Many questions must be addressed before its place in heart failure therapy is established. Optimal patient population, dosing regimen, duration of therapy, and effect on patient survival are unknown. Until larger, blinded studies are completed, growth hormone therapy remains an investigational approach to managing refractory heart failure.

Cardiopulmonary events during hemodialysis: effects of dialysis membranes and dialysate buffers.

Adverse cardiac and pulmonary events are frequently observed during hemodialysis and contribute to significant morbidity and mortality. The temporal relationship between these events during the intradialytic period has not been well defined. To examine the event rate and timing of silent ischemia, cardiac ectopy, and hypoxemia, we conducted a prospective, single-blind, randomized study of 10 subjects undergoing maintenance hemodialysis with four contiguous combinations of dialysis membranes (cuprammonium or polysulfone) and dialysates (acetate or bicarbonate). The frequency of oxygen desaturation events peaked during the first 2 hours, whereas silent myocardial ischemia and supraventricular ectopies occurred more often in the later hours. Ventricular ectopy occurred steadily throughout the intradialytic period. The combination of acetate dialysis and cuprammonium membrane is associated with the most frequent events. We conclude that cardiopulmonary events can occur frequently during hemodialysis, and the frequency is dependent on the type of dialysis membrane and dialysate buffer used.

Pharmacy practice acts: a decade of progress.

OBJECTIVE: This 10-year follow-up study of previously published surveys of pharmacy practice acts examines 50 state and the District of Columbia pharmacy practice acts to assess the range of statutory definitions and determine the direction and magnitude of statutory changes since 1988. DATA SOURCES: State codes for 50 states and the District of Columbia, with attention focused on the pharmacy practice acts; Puerto Rico and the Virgin Islands were excluded. DATA EXTRACTION: The focus on each statute was the statutory definition of the "practice of pharmacy." DATA SYNTHESIS: Comparing 1998 with 1988, codification of interpreting and evaluating prescriptions increased 22% (1998; 39/47, four states contain no definition of the practice of pharmacy), compounding 8% (47/47), consultation 19% (41/47), dispensing 2.5% (47/47), drug administration threefold (24/47), drug product selection twofold (45/47), drug utilization review 70% (35/47), patient assessment 6.5-fold (6/47), pharmacokinetic services threefold (3/47), pharmacist prescribing 4.6-fold (15/47), and participation in drug research 10.5-fold (10/47). CONCLUSIONS: Since 1988, state pharmacy practice acts have increased the codification of pharmaceutical care services as integral pharmacy functions. Although substantial progress has been made over the past decade, a number of states have not incorporated definitions of pharmaceutical care functions into their state statutes. Enactment of the National Association Boards of Pharmacy Model State Pharmacy Act is one way for pharmacists' practice to expand with the evolution of the practice of pharmacy.

Candesartan cilexetil: comparison of once-daily versus twice-daily administration for systemic hypertension. Candesartan Cilexetil Study Investigators.

This randomized, double-masked, placebo-controlled, forced-titration, parallel-arm study was designed to compare the blood pressure (BP)-lowering effect of candesartan cilexetil, a potent antagonist of the angiotensin II receptor subtype AT1, administered once daily with that of the same agent administered twice daily at the same total daily dose of 16 mg. After a 4- to 5-week placebo run-in period, 277 patients with a sitting diastolic BP of 95 to 109 mm Hg were randomly allocated to receive placebo (n = 92) or candesartan cilexetil 8 mg once daily for 4 weeks, followed by forced titration to either 16 mg once daily (n = 91) or 8 mg twice daily (n = 94) for 4 weeks. At 8 weeks, mean reductions in trough sitting diastolic BP were similar for the once- and twice-daily treatment groups (9.4 and 10.3 mm Hg, respectively). After 8 weeks of treatment, no statistically significant differences were observed in diastolic or systolic BP, peak or trough BP, or sitting or standing BP between the 2 active-treatment groups. The rates of positive responses (defined as a trough sitting diastolic BP of <90 mm Hg or a decrease in BP of > or =10 mm Hg) were also similar (approximately 60%) in the once- and twice-daily candesartan cilexetil groups. Furthermore, placebo-corrected trough-to-peak ratios for sitting diastolic BP exceeded 75% for both candesartan cilexetil regimens, indicating a persistent 24-hour duration of drug effect. Ambulatory BP monitoring performed in a subset of patients (n = 44) confirmed the consistent 24-hour BP-lowering effect and preservation of diurnal variation with once-daily dosing. No significant between-group differences were observed in the incidence or severity of clinical or laboratory adverse events. The results of this study suggest that identical daily doses of candesartan cilexetil administered once or twice daily have comparable efficacy and tolerability and that no additional clinical benefit is derived from twice-daily administration.

Dose-related beneficial long-term hemodynamic and clinical efficacy of irbesartan in heart failure.

OBJECTIVES: The primary purpose of this study was to determine the acute and long-term hemodynamic and clinical effects of irbesartan in patients with heart failure. BACKGROUND: Inhibition of angiotensin II production by angiotensin-converting enzyme (ACE) inhibitors reduces morbidity and mortality in patients with heart failure. Irbesartan is an orally active antagonist of the angiotensin II AT1 receptor subtype with potential efficacy in heart failure. METHODS: Two hundred eighteen patients with symptomatic heart failure (New York Heart Association [NYHA] class II-IV) and left ventricular ejection fraction < or = 40% participated in the study. Serial hemodynamic measurements were made over 24 h following randomization to irbesartan 12.5 mg, 37.5 mg, 75 mg, 150 mg or placebo. After the first dose of study medication, patients receiving placebo were reallocated to one of the four irbesartan doses, treatment was continued for 12 weeks and hemodynamic measurements were repeated. RESULTS: Irbesartan induced significant dose-related decreases in pulmonary capillary wedge pressure (average change -5.9+/-0.9 mm Hg and -5.3+/-0.9 mm Hg for irbesartan 75 mg and 150 mg, respectively) after 12 weeks of therapy without causing reflex tachycardia and without increasing plasma norepinephrine. The neurohormonal effects of irbesartan were highly variable and none of the changes was statistically significant. There was a significant dose-related decrease in the percentage of patients discontinuing study medication because of worsening heart failure. Irbesartan was well tolerated without evidence of dose-related cough or azotemia. CONCLUSIONS: Irbesartan, at once-daily doses of 75 mg and 150 mg, induced sustained hemodynamic improvement and prevented worsening heart failure.

Carvedilol: therapeutic application and practice guidelines.

Current knowledge of the mechanisms contributing to progression of heart failure suggests that therapies that limit or interfere with the consequences of neurohormonal activation and improve myocardial energetics appear to be most beneficial. Carvedilol, a nonselective beta-adrenergic blocker with peripheral vasodilating properties, reduces mortality, slows progression of disease, and improves quality of life in patients with heart failure when added to standard therapy. When administered according to recommended guidelines, carvedilol is well tolerated. Clinical guidelines on the use of carvedilol in heart failure are provided.

ACE inhibitor effects on platelet function in stages I-II hypertension.

Angiotensin II enhances platelet aggregation through activation of the G protein-linked pathway present in platelets. Studies of several angiotensin-converting enzyme (ACE) inhibitors have demonstrated marked differences on platelets. Therefore this prospective, randomized, double-blind, crossover study compared the ex vivo effects of equivalent antihypertensive doses of captopril, enalapril, and fosinopril on platelet aggregation and thromboxane B2 (TxB2) formation in subjects with stage I-II essential hypertension. Nineteen male subjects with a baseline mean seated blood pressure of 141 +/- 3/100 +/- 1 mm Hg were enrolled. The decline in mean arterial pressure after 4 weeks of stable dosing was 10 +/- 1, 12 +/- 1, and 11 +/- 1 mm Hg for captopril, enalapril, and fosinopril, respectively (p = NS). There was no significant change in adenosine diphosphate (ADP)-, epinephrine-, or thrombin-stimulated platelet aggregation from baseline or between ACE inhibitors. Compared with baseline, fosinopril decreased TxB2 concentrations 27.5-67.6% with all stimuli after 1 and 5 min. Captopril also decreased TxB2 formation, but this effect was stimulus and time dependent. Enalapril consistently increased TxB2 concentrations, independent of stimuli or time. We conclude that different ACE inhibitors have distinct effects on platelet TxB2 formation without significant effects on platelet aggregation. Fosinopril may be a direct antagonist ofTxA2 synthase, suggesting benefit in syndromes of platelet activation or vascular occlusion.

High-dose versus standard-dose epinephrine treatment of cardiac arrest after failure of standard therapy.

STUDY OBJECTIVE: To assess the efficacy of high-dose epinephrine (HDE) compared with standard-dose epinephrine (SDE) in emergency department patients in cardiac arrest after SDE failed to improve asystole or ventricular fibrillation. DESIGN: Prospective, multicenter, blinded, controlled trial. SETTING: Eight academic center emergency departments. PATIENTS: One hundred forty patients treated for cardiac arrest. MEASUREMENTS AND MAIN RESULTS: Primary outcomes were either improvement in cardiac rhythm or return of spontaneous circulation (ROSC). Of the 140 patients enrolled, 78 received HDE and 62 received SDE. Of the 34 patients with ventricular fibrillation, 3 were resuscitated with HDE and 2 with SDE (p = 0.60). Of those with asystole, ROSC occurred in 12 of HDE and 5 of SDE recipients (p = 0.11). No patient had return of significant neurologic function and none survived to hospital discharge. Overall, there was no advantage to HDE after failure of SDE. CONCLUSION: Our results are similar to those of controlled clinical trials comparing HDE with SDE in cardiac arrest.

Evaluation of the indomethacin-nitroglycerin interaction with positron-emission tomography.

The hypothesis that local release of prostanoids may contribute to the pharmacologic effect of nitroglycerin (NTG) has long been debated. Results of prostanoid blockade by indomethacin on NTG-induced effects, to date, have been inconclusive. To quantitate the effects of intravenous indomethacin on NTG-induced myocardial blood flow by using positron-emission tomography, we conducted a prospective, controlled, parallel-design study comparing patients with coronary artery disease with healthy volunteers. Eight subjects, four Canadian Class II-III coronary artery disease (CAD) with luminal narrowing of > 80% in a minimum of two vessels, and four healthy volunteers were evaluated. Baseline global myocardial blood flow was equivalent between the groups. NTG produced a 49.3 +/- 4.7% increase in myocardial blood flow in healthy volunteers (p = 0.006) and an -0.5 +/- 19.8% decrease in the group with CAD (p = 0.62 between groups). After indomethacin, both groups had a 24% decline in myocardial blood flow (CAD, p = 0.25; healthy, p = 0.03). One patient with CAD had acute ischemia after indomethacin. The study demonstrated that short-term intravenous indomethacin decreases NTG-induced myocardial blood flow to the same degree in both subjects with CAD and healthy individuals. Impairment of myocardial blood flow from this pharmacologic combination may be most important in patients with severe fixed lesions.

Comparison of publication rates for basic sciences versus practice from pharmacy-based grant programs.

The future of a profession in an era of scarce resources depends on maintaining a focus on science. The times demand that pharmacy practice examine its commitment to science. To address this concern, pharmacy practice-based research awards from the American College of Clinical Pharmacy Research Institute Award Program, American Society of Health-System Pharmacists Research and Education Foundation Grant Program, and American Association of Colleges of Pharmacy New Investigator Program were compared with basic sciences awards from the American Association Colleges of Pharmacy New Investigator Program from their inception to 1991 to determine the percentage of awarded grants successfully published (publication rate). Pharmacy practice published awarded grants at 46% (70/154) versus 62% (26/42) for basic sciences (p = 0.09). A significant decline of 37% in pharmacy practice publication rate was observed over the study period. Economically, an average of $11,393 was spent to publish one manuscript in pharmacy practice versus $8077 in basic sciences. The results suggest that pharmacy practice should redefine a paradigm of commitment to scholarship to provide firm evidence for supporting science and sustaining professional growth.

Circulating concentrations of proinflammatory cytokines in mild or moderate heart failure secondary to ischemic or idiopathic dilated cardiomyopathy.

Proinflammatory cytokines are capable of modulating cardiovascular function by a variety of mechanisms. These cytokines are elevated in patients with severe heart failure, but changes in mild or moderate heart failure have not been reported. Therefore, simultaneous arterial and coronary sinus concentrations of interleukin-1alpha, soluble interleukin-2 receptor, interleukin-6, and tumor necrosis factor-alpha were measured in 78 patients with New York Heart Association functional class II to IV heart failure and compared with 17 healthy volunteers. Concentrations of interleukin-1alpha, soluble interleukin-2 receptor, and interleukin-6 were determined by a "sandwich" enzyme-linked immunosorbent assay and tumor necrosis factor-alpha by tissue culture technique. There were no statistical differences in interleukin-1alpha, soluble interleukin-2 receptor, or tumor necrosis factor-alpha concentrations in mild to moderate heart failure versus control subjects. Interleukin-6 was significantly elevated, 75 +/- 16 versus 0.4 +/- 0.4pg/ml (p = 0.002). Cytokine concentrations did not differ by heart failure etiology. Paired arterial and coronary sinus concentrations were not significantly different. Soluble interleukin-2 receptor concentrations were significantly correlated with New York Heart Association functional class (r = 0.59, p = 0.04) and negatively associated with exercise tolerance time (r = -0.59, p = 0.007). Thus, interleukin-6 is significantly elevated in mild or moderate heart failure.

Angiotensin II receptor blockers: novel therapy for heart failure?

Heart failure is a severe, disabling disease that portends a short life expectancy. This grave prognosis may be explained by growth-promoting effects of angiotensin II implicated in heart failure that mediate a genetic response called programmed cell death. The effects of angiotensin II are inhibited by angiotensin-converting enzyme (ACE) inhibitors, which improve exercise performance and quality of life, attenuate disease progression, and modestly lengthen survival. Unfortunately, mortality remains exceedingly high and may be partly attributable to augmented production of angiotensin II from a non-ACE chymase pathway. Angiotensin II production may therefore increase despite treatment with ACE inhibitors. The angiotensin II receptor antagonists are a new class of nonpeptide-reversible inhibitors that may offer clinical promise in heart failure through blockade of angiotensin II actions, whether produced from ACE or non-ACE chymase pathways.