Cardiovascular specialists have been leaders in medicine because of our willingness to study major clinical issues by means of randomized clinical trials. Consequently, the evidence supporting many cardiovascular treatments is substantial, especially when the results of multiple large clinical trials are consistent in showing strong benefits. Cardiovascular professional societies also have been at the forefront in forging consensus among clinical experts and codifying best practice into practice guidelines. It is reasonable to expect that a treatment demonstrated to be effective in clinical trials and strongly endorsed by professional guidelines will be adopted by practicing physicians and consistently used in day-to-day patient care.

Angiotensin-converting enzyme (ACE) inhibitors have followed this pathway of building evidence and professional consensus. Many randomized clinical trials have clearly shown that ACE inhibitors reduce mortality and morbidity rates among patients with heart failure and left ventricular systolic dysfunction. Pooled data from 5 large trials showed the odds of death of patients randomized to ACE inhibitors were reduced by 26% compared with placebo, translating into roughly 6 fewer deaths per 100 patients treated. The economic outcomes also are favorable because much of the cost of prescribing ACE inhibitors for heart failure is recouped by the reduced need for hospital admissions. Consequently, the use of ACE inhibitors for heart failure is quite cost-effective. The American College of Cardiology/American Heart Association Guidelines Committee has weighed the evidence and given ACE inhibitors for treatment of heart failure a Class I recommendation. Indeed, use of ACE inhibitors is so well accepted that it is part of the quality-of-care clinical performance measure for heart failure. There is little, if any, controversy that ACE inhibitors should be generally prescribed for patients with heart failure due to systolic dysfunction.

Use of ACE inhibitors increased progressively for heart failure through the early 1990s, but growth in use has stalled more recently, and a substantial number of patients with heart failure still do not receive ACE inhibitors. The data reported by Masoudi and associates in this issue of Circulation show a stubborn, persistent gap between ideal practice and actual use of ACE inhibitors for heart failure. These investigators found that between 1998 and 2001, only 68% of patients 65 years of age and older with heart failure, systolic dysfunction, and no contraindications to treatment received an ACE inhibitor. This percentage rose only to 76% of patients when either ACE inhibitor or angiotensin receptor blocker (ARB) use was counted. The percentage of patients receiving ACE inhibitors or ARBs was below 80% in all but 3 of the 55 subgroups examined by Masoudi and associates. The investigators found little explanation for this persistent and vexing gap between actual and ideal performance, inasmuch as the only strong predictor of ACE inhibitor use versus nonuse was the presence of preexisting renal dysfunction. The latest national report card on this important aspect of heart failure treatment shows a "D+" for ACE inhibitor use (68%), rising only to a "C" (76%) if extra credit is given for ARB use. Should we accept these grades?

Closing the Gap

Perhaps the most optimistic interpretation of the data reported by Masoudi and associates is that evidence from clinical trials, by itself, will only go so far in changing clinical practice. Evidence may be necessary to alter the knowledge and attitudes of physicians about treatment, but this may not be sufficient to change their management consistently. To close the gap between actual and ideal performance, additional, specific measures are probably needed. A variety of active interventions have been shown to improve use of evidence-based therapies. Masoudi and associates did not report any data on use of measures within the hospitals or physician practices that might improve quality of care, so there may be an opportunity to adopt such measures more widely. Reminder systems for physicians, either simple chart-based measures or more sophisticated computerized approaches, can be quite effective in improving use of medications when physicians agree that the medication is effective. Critical pathways, care maps, and other structured approaches to quality improvement also may work well within hospitals to increase adherence to evidence-based practice guidelines. Reorganization of care by use of heart failure care teams or nurse facilitators may be even more effective, but these approaches require a much greater commitment of resources. Nevertheless, multidisciplinary approaches are particularly attractive in the care of patients with chronic diseases such as heart failure, because management of multiple factors, including adherence to diet and medication recommendations, is needed for successful outcomes. The structure of our medical care system also may contribute to the gap between actual and ideal clinical management; paying for innovative practice improvement programs has been difficult because they are not readily reimbursed in the fee-for-service model (although they may be well suited to prepaid integrated healthcare systems).

We have paid a lot of attention to translation of novel therapies from the basic laboratory to proof of efficacy in clinical trials, yet we've not paid enough attention to the final steps of learning how to best deliver consistent, high-quality care. With more attention to the nitty-gritty details of practice improvement, the grade for ACE inhibitor use in patients with heart failure could (and should) be raised to an "A" on the next report card.

In 1999, the American College of Physicians (ACP), then the American College of Physicians-American Society of Internal Medicine, and the American College of Cardiology/American Heart Association (ACC/AHA) developed joint guidelines on the management of patients with chronic stable angina. The ACC/AHA then published an updated guideline in 2002, which the ACP recognized as a scientifically valid review of the evidence and background paper. This ACP guideline summarizes the recommendations of the 2002 ACC/AHA updated guideline and underscores the recommendations most likely to be important to physicians seeing patients in the primary care setting. This guideline is the first of 2 that will provide guidance on the management of patients with chronic stable angina. This document will cover diagnosis and risk stratification for symptomatic patients who have not had an acute myocardial infarction or revascularization procedure in the previous 6 months. Sections addressing asymptomatic patients are also included. Asymptomatic refers to patients with known or suspected coronary disease based on history or on electrocardiographic evidence of previous myocardial infarction, coronary angiography, or abnormal results on noninvasive tests. A future guideline will cover pharmacologic therapy and follow-up.

PURPOSE

Smoking is the leading controllable risk factor for heart disease. Only about 69% of U.S. indoor workers are currently covered by a smoke-free workplace policy. This analysis projects the cardiovascular health and economic effects of making all U.S. workplaces smoke free after 1 year and at steady state.

METHODS

We estimated the number of U.S. indoor workers not covered by smoke-free workplace policies, and the effects of making all workplaces smoke free on smoking behavior and on the relative risks of acute myocardial infarctions and strokes. One-year and steady-state results were calculated using an exponential decline model. A Monte Carlo simulation was performed for a sensitivity analysis.

RESULTS

The first-year effect of making all workplaces smoke free would produce about 1.3 million new quitters and prevent over 950 million cigarette packs from being smoked annually, worth about $2.3 billion in pretax sales to the tobacco industry. In 1 year, making all workplaces smoke free would prevent about 1500 myocardial infarctions and 350 strokes, and result in nearly $49 million in savings in direct medical costs. At steady state, 6250 myocardial infarctions and 1270 strokes would be prevented, and $224 million would be saved in direct medical costs annually. Reductions in passive smoking would account for 60% of effects among acute myocardial infarctions.

CONCLUSION

Making all U.S. workplaces smoke free would result in considerable health and economic benefits within 1 year. Reductions in passive smoking would account for a majority of these savings. Similar effects would occur with enactment of state or local smoke-free policies.

Alleviating health disparities in the United States is a goal with broad support. Medical research undertaken to achieve this goal typically adopts the well-established perspective that racial discrimination and poverty are the major contributors to unequal health status. However, the suggestion is increasingly made that genetic research also has a significant role to play in alleviating this problem, which likely overstates the importance of genetics as a factor in health disparities. Overemphasis on genetics as a major explanatory factor in health disparities could lead researchers to miss factors that contribute to disparities more substantially and may also reinforce racial stereotyping, which may contribute to disparities in the first place. Arguments that promote genetics research as a way to help alleviate health disparities are augmented by several factors, including research funding initiatives and the distinct demographic patterns of health disparities in the United States.

PURPOSE:

Clopidogrel is more effective than aspirin in preventing recurrent vascular events, but concerns about its cost-effectiveness have limited its use. We evaluated the cost-effectiveness of clopidogrel and aspirin as secondary prevention in patients with a prior myocardial infarction, a prior stroke, or peripheral arterial disease.

METHODS:

We constructed Markov models assuming a societal perspective, and based analyses on the lifetime treatment of a 63-year-old patient facing event probabilities derived from the Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE) trial as the base case. Outcome measures included costs, life expectancy in quality-adjusted life-years (QALYs), incremental cost-effectiveness ratios, and events averted.

RESULTS:

In patients with peripheral arterial disease, clopidogrel increased life expectancy by 0.55 QALYs at an incremental cost-effectiveness ratio of $25,100 per QALY, as compared with aspirin. In poststroke patients, clopidogrel increased life expectancy by 0.17 QALYs at a cost of $31,200 per QALY. Aspirin was both less expensive and more effective than clopidogrel in post-myocardial infarction patients. In probabilistic sensitivity analyses, our evaluation for patients with peripheral vascular disease was robust. Evaluations of stroke and myocardial infarction patients were sensitive predominantly to the cost and efficacy of clopidogrel, with aspirin therapy more effective and less expensive in 153 of 1000 simulations (15.3%) in poststroke patients and clopidogrel more effective in 119 of 1000 simulations (11.9%) in the myocardial infarction sample.

CONCLUSION:

Clopidogrel provides a substantial increase in quality-adjusted life expectancy at a cost that is within traditional societal limits for patients with either peripheral arterial disease or a recent stroke. Current evidence does not support increased efficacy with clopidogrel relative to aspirin in patients following myocardial infarction.

BACKGROUND:

Screening for hepatocellular carcinoma in cirrhotic patients using abdominal ultrasonography and alpha-foetoprotein levels is widely practiced. AIM: To evaluate its cost-effectiveness using a Markov decision model.

METHODS:

Several screening strategies with abdominal ultrasonography or computerized tomography and serum alpha-foetoprotein at 6-12-month intervals in 40-year-old patients with chronic hepatitis C and compensated cirrhosis were simulated from a societal perspective, resulting in discounted costs per quality-adjusted life-year saved. Extensive sensitivity analysis was performed.

RESULTS:

For the least efficacious strategy, annual alpha-foetoprotein/ultrasonography, the incremental cost-effectiveness ratio (vs. no screening) was $23 043/quality-adjusted life-year. Biannual alpha-foetoprotein/annual ultrasonography, the most commonly used strategy in the United States, was more efficacious, with a cost-effectiveness ratio of $33 083/quality-adjusted life-year vs. annual alpha-foetoprotein/ultrasonography. The most efficacious strategy, biannual alpha-foetoprotein/ultrasonography, resulted in a cost-effectiveness ratio of $73 789/quality-adjusted life-year vs. biannual alpha-foetoprotein/annual ultrasonography. Biannual alpha-foetoprotein/annual computerized tomography screening resulted in a cost-effectiveness ratio of $51 750/quality-adjusted life-year vs. biannual alpha-foetoprotein/annual ultrasonography screening.

CONCLUSIONS:

Screening for hepatocellular carcinoma is as cost-effective as other accepted screening protocols. Of the strategies evaluated, biannual alpha-foetoprotein/annual ultrasonography gives the most quality-adjusted life-year gain while still maintaining a cost-effectiveness ratio $50 000/quality-adjusted life-year. Biannual alpha-foetoprotein/annual computerized tomography screening may be cost-effective.

OBJECTIVE: Although an increasing fraction of Medicare beneficiaries die outside the hospital, the proportion of total Medicare expenditures attributable to care in the last year of life has not dropped. We sought to determine whether disproportionate increases in hospital treatment intensity over time among decedents are responsible for the persistent growth in end-of-life expenditures.

DATA SOURCE: The 1985-1999 Medicare Medical Provider Analysis and Review (MedPAR) and Denominator files.

STUDY DESIGN: We sampled inpatient claims for 20 percent of all elderly fee-for-service Medicare decedents and 5 percent of all survivors between 1985 and 1999 and calculated age-, race-, and gender-adjusted per-capita inpatient expenditures and rates of intensive care unit (ICU) and intensive procedure use. We used the decedent-to-survivor expenditure ratio to determine whether growth rates among decedents outpaced growth relative to survivors, using the growth rate among survivors to control for secular trends in treatment intensity. Data Collection. The data were collected by the Centers for Medicare and Medicaid Services.

PRINCIPAL FINDINGS: Real inpatient expenditures for the Medicare fee-for-service population increased by 60 percent, from $58 billion in 1985 to $90 billion in 1999, one-quarter of which were accrued by decedents. Between 1985 and 1999 the proportion of beneficiaries with one or more intensive care unit (ICU) admission increased from 30.5 percent to 35.0 percent among decedents and from 5.0 percent to 7.1 percent among survivors; those undergoing one or more intensive procedure increased from 20.9 percent to 31.0 percent among decedents and from 5.8 percent to 8.5 percent among survivors. The majority of intensive procedures in the United States were performed in the more numerous survivors, although in 1999 50 percent of feeding tube placements, 60 percent of intubations/tracheostomies, and 75 percent of cardiopulmonary resuscitations were in decedents. The proportion of beneficiaries dying in a hospital decreased from 44.4 percent to 39.3 percent, but the likelihood of being admitted to an ICU or undergoing an intensive procedure during the terminal hospitalization increased from 38.0 percent to 39.8 percent and from 17.8 percent to 30.3 percent, respectively. One in five Medicare beneficiaries who died in the hospital in 1999 received mechanical ventilation during their terminal admission.

CONCLUSIONS: Inpatient treatment intensity for all fee-for-service beneficiaries increased between 1985 and 1999 regardless of survivorship status. Absolute changes in per-capita hospital expenditures, ICU admissions, and intensive inpatient procedure use were much higher among decedents. Relative changes were similar except for ICU admissions, which grew faster among survivors. The secular decline in in-hospital deaths has not resulted in decreased per capita utilization of expensive inpatient services in the last year of life. This could imply that net hospital expenditures for the dying might have been even higher over this time period if the shift toward hospice had not occurred.

OBJECTIVES: This study was designed to evaluate the cost-effectiveness of screening patients with a B-type natriuretic peptide (BNP) blood test to identify those with depressed left ventricular systolic function. BACKGROUND: Asymptomatic patients with depressed ejection fraction (EF) may have less progression to heart failure if they can be identified and treated. METHODS: We used a decision model to estimate economic and health outcomes for different screening strategies using BNP and echocardiography to detect left ventricular EF 40% for men and women age 60 years. We used published data from community cohorts (gender-specific BNP test characteristics, prevalence of depressed EF) and randomized trials (benefit from treatment). RESULTS: Screening 1,000 asymptomatic patients with BNP followed by echocardiography in those with an abnormal test increased the lifetime cost of care (176,000 US dollars for men, 101,000 US dollars for women) and improved outcome (7.9 quality-adjusted life years [QALYs] for men, 1.3 QALYs for women), resulting in a cost per QALY of 22,300 US dollars for men and 77,700 US dollars for women. For populations with a prevalence of depressed EF of at least 1%, screening with BNP followed by echocardiography increased outcome at a cost 50,000 US dollars per QALY gained. Screening would not be attractive if a diagnosis of left ventricular dysfunction led to significant decreases in quality of life or income. CONCLUSIONS: Screening populations with a 1% prevalence of reduced EF (men at age 60 years) with BNP followed by echocardiography should provide a health benefit at a cost that is comparable to or less than other accepted health interventions.

OBJECTIVES: This study seeks to further characterize the role of exercise testing in the elderly for prognosis and diagnosis of coronary artery disease. BACKGROUND: Recent exercise testing guidelines have recognized that statements regarding the elderly do not have an adequate evidence-based quality because the studies they are based on have limitations in sample size and design. The Duke Treadmill Score has been recommended for risk stratification, but recent evidence has suggested that it does not function in the elderly.

METHODS: The study population consisted of male veterans (1872 patients >or=65 years; 3798 patients <65 years) who underwent routine clinical exercise testing with a mean follow-up of six years. A subset who underwent coronary angiography as clinically indicated (elderly, n = 405; younger, n= 809) were included. The primary outcome for all subjects was cardiovascular mortality with coronary angiographic findings as the outcome in those selected for angiography.

RESULTS: In survival analysis, exercise-induced ST depression was prognostic in both age groups only when cardiovascular death was considered as the end point. Peak metabolic equivalents were the most significant predictor for both age groups only when all-cause death was considered as the end point. New age-specific prognostic scores were developed and found to be predictive for cardiovascular mortality in the elderly. Moreover, in the angiographic subset of the elderly, a specific diagnostic score provided significantly better discrimination than exercise ST measurements alone. For any new score, there is a need for validation in another elderly population.

CONCLUSIONS: The mortality end point affected the choice of prognostic variables. This study demonstrates that exercise test scores can be helpful for the diagnosis and prognosis of coronary disease in the elderly.

OBJECTIVES: The goal of this study was to examine mortality associated with tricuspid regurgitation (TR) after controlling for left ventricular ejection fraction (LVEF), right ventricular (RV) dilation and dysfunction, and pulmonary artery systolic pressure (PASP). BACKGROUND: Tricuspid regurgitation is a frequent echocardiographic finding; however, the association with prognosis is unclear. METHODS: We retrospectively identified 5,223 patients (age 66.5 +/- 12.8 years; predominantly male) undergoing echocardiography at one of three Veterans Affairs Medical Center laboratories over a period of four years. Follow-up data were available for four years (mean 498 +/- 402 days). Kaplan-Meier and proportional hazards methods were used to compare differences in survival among TR grades. RESULTS: Mortality increased with increasing severity of TR. The one-year survival was 91.7% with no TR, 90.3% with mild TR, 78.9% with moderate TR, and 63.9% with severe TR. Moderate or greater TR was associated with increased mortality regardless of PASP (hazard ratio [HR] 1.31, 95% confidence interval [CI] 1.16 to 1.49 for PASP >40 mm Hg; HR 1.32, 95% CI 1.05 to 1.62 for PASP or =40 mm Hg) and LVEF (HR 1.49, 95% CI 1.34 to 1.66 for EF 50%; HR 1.54, 95% CI 1.37 to 1.71 for EF > or =50%). When adjusted for age, LVEF, inferior vena cava size, and RV size and function, survival was worse for patients with moderate (HR 1.17, 95% CI 0.96 to 1.42) and severe TR (HR 1.31, 95% CI 1.05 to 1.66) than for those with no TR. CONCLUSIONS: We conclude that increasing TR severity is associated with worse survival in men regardless of LVEF or pulmonary artery pressure. Severe TR is associated with a poor prognosis, independent of age, biventricular systolic function, RV size, and dilation of the inferior vena cava.