Physicians' knowledge, attitudes, and practice of pharmacologic treatment of hypertension.

OBJECTIVE: To explore how well physicians who treat hypertension know the indications and contraindications for particular antihypertensive therapies, and how closely their opinions and practice of hypertension treatment agree with national guidelines. METHODS: We surveyed by mail a stratified random sample of 10,000 US cardiologists, internists, and general/family practitioners. This survey explored their knowledge, attitudes, and practices with respect to the treatment of hypertension. Responses were compared with national guidelines and product labeling at the time of the survey. Results were stratified by physician specialty. RESULTS: A total of 1,023 physicians, or 10.2% of the sample, responded to the survey. Only 37.3% answered all four knowledge questions correctly, including 25.7% of general/family practitioners, 38.3% of internists, and 49.5% of cardiologists (p < 0.001). In their attitudes with respect to evaluating high blood pressure and establishing treatment goals, most respondents agreed with established guidelines. However, when asked how they would treat uncomplicated, mild hypertension, only 23% limited their selection to diuretics and beta-blockers in accordance with the guidelines. Cardiologists in particular were more likely than internists or general/family practitioners to choose other drug classes, such as angiotensin-converting enzyme Inhibitors or calcium-channel blockers. CONCLUSIONS: The results of our survey suggest that national efforts to educate physicians about the increasingly complex armamentarium for hypertension, and to persuade them to base their prescribing on the results of randomized, controlled trials of primary prevention, must be continued.

Cost effectiveness of HMG-CoA reductase inhibition in Canada.

OBJECTIVE: To assess the cost effectiveness of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor therapy, particularly atorvastatin, in primary and secondary prevention of coronary artery disease (CAD) in Canada. METHODS: A Markov model was developed in which costs and effectiveness of atorvastatin were compared with those of other statins and with no drug therapy in primary and secondary prevention of CAD. PATIENTS: Cost effectiveness was assessed for cohorts of patients with risk profiles defined by CAD status, age, sex, pretreatment low density lipoprotein cholesterol level and presence of sentinel coronary risk factors. Coronary risk was estimated by using initial and subsequent event coronary risk equations from the Framingham Heart Study, and risk factors were estimated by using Canadian population survey data. Recent estimates of the costs of CAD-related medical care in Canada were used to assign costs to health states and acute coronary events. INTERVENTIONS: Interventions included atorvastatin 10 mg, simvastatin 10 mg, pravastatin 20 mg, fluvastatin 20 mg, lovastatin 20 mg and no pharmacological therapy. RESULTS: Incremental cost effectiveness ratios (CDN$/year of life gained) relative to no therapy were lowest for atorvastatin and highest for pravastatin across all risk profiles. Atorvastatin was less costly and more effective than lovastatin, pravastatin and simvastatin in primary and secondary prevention, and conferred additional health benefits at a reduced cost per year of life gained compared with fluvastatin. CONCLUSIONS: Atorvastatin was found to be the most cost effective statin in primary and secondary prevention of CAD.

Primary and subsequent coronary risk appraisal: new results from the Framingham study.

BACKGROUND: Coronary heart disease continues to be one of the most common chronic illnesses in the United States and most of the developed world. Clinicians and health authorities have interest in identifying individuals at increased risk of CHD. The Framingham Heart Study has over the years produced mathematical "health risk appraisal models" that relate risk factors to the probability of developing CHD. METHODS AND RESULTS: New sex-specific models from The Framingham Heart Study for primary and secondary (subsequent) CHD have been produced. The primary CHD models are appropriate for assessing CHD risk in persons free of cardiovascular disease and contain risk factors such as triglyceride levels, alcohol use, and menopausal status, risk factors not included in previously published models. The subsequent CHD models are applicable for persons with a history of CHD or ischemic stroke who have survived the acute period after the event. Age, blood lipid levels (total cholesterol and HDL cholesterol), and diabetes status are significant for men and women. In addition, systolic blood pressure and cigarette smoking are significant predictors of subsequent CHD in women. CONCLUSIONS: These new models are useful tools for better understanding the relation between risk factors and the occurrences of CHD events in individuals who are free of cardiovascular disease as well as persons who have had a prior CHD event or stroke. With the development of these latter models, the importance of blood lipid levels, diabetes, and, in women, systolic blood pressure and cigarette smoking as independent predictors of risk is once again underscored.

Anti-inflammatory therapy reduces total costs of asthma care compared with bronchodilation: the Asthma Outcomes Registry.

BACKGROUND: Current consensus guidelines recommend reliance on anti-inflammatory drugs to treat asthma, reserving theophylline and other long-acting bronchodilators as adjuncts for patients whose symptoms are not well controlled with anti-inflammatory therapy. The effect of such recommendations on total costs of asthma care has not yet been examined, however. OBJECTIVE: To explore the relation between choice of maintenance therapy with anti-inflammatory agents vs long-acting bronchodilators and annual costs of asthma care using data from the Asthma Outcomes Registry. METHODS: Patients 16 years and older were selected from the Asthma Outcomes Registry cohort if they had received either anti-inflammatories (inhaled corticosteroids or cromones) or long-acting bronchodilators (theophylline, salmeterol, oral beta-agonists, or ipratropium bromide), but not both, for at least 1 year before study entry. Oral corticosteroid-dependent patients, those with other chronic lung disease, and those with incomplete cost data during the 365 days before and after their enrollment in the Asthma Outcomes Registry (baseline and follow-up years) were excluded. The effect of anti-inflammatory vs bronchodilator therapy was assessed by comparing the change (follow-up minus baseline) in total costs of asthma care. RESULTS: A total of 314 patients met criteria for study inclusion (237 treated with anti-inflammatories and 77 treated with bronchodilators). Median costs during the baseline year were similar in the anti-inflammatory and bronchodilator groups ($341 and $335, respectively). In the follow-up year, the median change in cost in the anti-inflammatory group was a decline of $93 compared with an increase of $76 in the bronchodilator group (P < .0001). This treatment effect was consistent across subgroups defined by age and amount of medication consumed. CONCLUSIONS: These findings add support to current guidelines recommending reliance on anti-inflammatory therapy to control asthma. The emergence of new therapeutic agents to control inflammation may continue to reduce the costs of treating this important disease.

Selective use of calcium channel blockers to treat high-risk hypertensive patients.

PURPOSE: While hypertension treatment is aimed at reducing cardiovascular disease (CVD) risk, there are reports of association between calcium channel blockers (CCB) use and increased risk. However, these studies may be misleading if CCBs are used selectively in high-risk patients. METHODS: We conducted a knowledge, attitudes, and practice (KAP) survey by mail of a stratified random sample of 10,000 US cardiologists, internists, and family/general practitioners. Completed surveys were received from 1023 physicians, and population means and frequencies (+/-standard errors) were estimated RESULTS: While only 36.3 (+/-0.6)% of physicians use long-acting CCBs for mild hypertension without additional risk factors, use increases with moderate or severe hypertension and other risk factors, including history of myocardial infarction (48.4 (+/-0.6)%), family history of CVD (54.6 (+/-0.6)%), diabetes (57.3 (+/-0.6)%), and angina (63.8 (+/-0.5)%). Physicians use CCBs as initial therapy for 24.8 (+/-0.3)% of mildly and 33.1 (+/-0.3)% of moderately hypertensive patients, and add CCBs to the regimens of 39.0 (+/-0.3)% of moderately hypertensive patients not controlled on other antihypertensive therapy. In multiple regression analysis, the proportion of hypertensive patients treated with CCBs was significantly elevated among geriatricians and physicians who believe severity of hypertension is an indication for their use. CONCLUSION: These findings suggest that CCBs are used selectively for high-risk hypertensive patients. Copyright (c) 2000 John Wiley & Sons, Ltd.

Cost-effectiveness of statins.

Currently, 6 hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are marketed in the United States (US). Given the wide variation in the prices and efficacy of statins, formal cost-effectiveness analysis may improve drug selection decisions. To assess the cost-effectiveness of statin therapy in primary and secondary prevention of coronary heart disease, we developed a model of the costs and consequences of lipid-regulating therapy and estimated the incremental cost-effectiveness of 5 statins (atorvastatin, fluvastatin, lovastatin, pravastatin, simvastatin) at usual starting doses versus no therapy. Drug effects on serum lipids were assessed using data approved by the US Food and Drug Administration for product labeling. Annual risks of coronary event occurrence were estimated using Framingham Heart Study coronary risk equations developed for use in this model. Current estimates of direct medical costs of coronary heart disease were used to assign costs to health states and acute coronary events. Main outcome measurements were net cost (statin therapy minus savings in coronary heart disease treatment), gain in life expectancy, and cost per life-year saved. The maximum gain in life expectancy was achieved with atorvastatin, which also had a lower net cost than lovastatin, pravastatin, and simvastatin. Compared with fluvastatin, atorvastatin's greater effectiveness is attained at a lower cost per life-year saved. The cost-effectiveness of HMG-CoA reductase inhibition in primary and secondary prevention of coronary heart disease has been improved with the introduction of atorvastatin.

Direct medical costs of coronary artery disease in the United States.

To generate current incidence-based estimates of the direct medical costs of coronary artery disease (CAD) in the United States, a Markov model of the economic costs of CAD-related medical care was developed. Risks of initial and subsequent CAD events (sudden CAD death, fatal/nonfatal acute myocardial infarction [AMI], unstable angina, and stable angina) were estimated using new Framingham Heart Study risk equations and population risk profiles derived from national survey data. Costs were assumed to be those related to treatment of initial and subsequent CAD events ("event-related") and follow-up care ("nonevent-related"), respectively. Cost estimates were derived primarily from national public-use databases. First-year direct medical costs of treating CAD events are estimated to be $17,532 for fatal AMI, $15,540 for nonfatal AMI, $2,569 for stable angina, $12,058 for unstable angina, and $713 for sudden CAD death. Nonevent-related direct costs of CAD treatment are estimated to be $1,051 annually. The annual incidence of CAD in the United States is estimated at 616,900 cases, with first-year costs of treatment totaling $5.54 billion. Five- and 10-year cumulative costs in 1995 dollars for patients who are initially free of CAD are estimated at $9.2 billion and $16.5 billion, respectively; for all patients with CAD, these costs are estimated to be $71.5 billion and $126.6 billion, respectively. The direct medical costs of CAD create a large economic burden for the United States health-care system.

Economic evaluation of famciclovir in reducing the duration of postherpetic neuralgia.

The economic impact of famciclovir therapy for postherpetic neuralgia (PHN) in patients with acute herpes zoster was studied. A decision-analytic model of the treatment of herpes zoster and PHN was used to compare the cost of PHN between patients treated with oral famciclovir 500 mg three times daily for seven days and patients not receiving any antiviral therapy. The effects of famciclovir on PHN in the model were based on the results of a randomized, double-blind trial in 419 adult outpatients. The cost of the course of famciclovir therapy (21 tablets) was estimated as the sum of the drug's wholesale acquisition cost and the pharmacy dispensing cost. The cost of treating PHN (physician visits, medications, and miscellaneous nondrug therapy) was estimated by consulting a panel of physicians. According to the model, the cost of treating PHN was $85 lower per famciclovir recipient ($294 for famciclovir versus $379 for no antiviral therapy). The net cost of famciclovir therapy was $23 per patient ($108 for acquisition and dispensing minus the $85 savings). Among patients 50 years of age or older, famciclovir reduced the average cost of PHN by $155 ($414 for famciclovir versus $569 for no antiviral therapy) and yielded a net savings of $7 per patient. A model for the use of famciclovir to treat acute herpes zoster showed that the cost of such therapy was largely offset by savings in the cost of treating this complication.

The benefits and risks of over-the-counter availability of nicotine polacrilex ("nicotine gum").

Nicotine polacrilex ("nicotine gum") is effective in helping persons to quit smoking cigarettes. Because many persons try to quit without formal assistance, it may be an appropriate product for over-the-counter (OTC) purchase. Some smokers, however, might use such a product in lieu of more effective methods of cessation, and still others might use it to cope with enforced periods of nicotine abstinence (eg, at the work place) and thereby delay their decision to quit. The study's objective was to assess the public health benefits and risks of OTC availability of nicotine gum. A Markov model was developed and used to contrast two alternative policy scenarios: one in which nicotine gum was assumed to remain available only by prescription, and another in which it was assumed to be made available for OTC purchase. Various data sources were used to estimate the model, including the Health Promotion and Disease Prevention Supplement to the 1991 National Health Interview Survey and the 1986 Adult Use of Tobacco Survey. Primary outcome measures included the numbers of persons who would try to quit smoking, the numbers who would use various methods of smoking cessation, including OTC nicotine gum, and the numbers of current adult smokers who would be abstinent at the end of 10 years. Findings suggest that an average of 3 million persons each year would use OTC nicotine gum. As a consequence of OTC availability, an additional 450,000 smokers would be abstinent at the end of 10 years. These results are sensitive to assumptions regarding the effectiveness of OTC nicotine gum, as well as to the effect of OTC availability on the use of other methods of smoking cessation. The number of persons who would quit smoking, however, increases under a fairly wide range of assumptions. Over-the-counter availability of nicotine gum may confer significant public health benefits.

Effects of recombinant human DNase therapy on healthcare use and costs in patients with cystic fibrosis.

OBJECTIVE: To assess the effects of recombinant human DNase (rhDNase) therapy on the cost of treating respiratory tract infections (RTIs) in patients with cystic fibrosis. DESIGN: We prospectively documented the use of healthcare services among 968 patients with cystic fibrosis who participated in a recent Phase III double-blind, multicenter, clinical trial in which patients were assigned randomly to receive either rhDNase 2.5 mg once daily, rhDNase 2.5 mg twice daily, or placebo. All patients were followed for 24 weeks. Data from secondary sources were used to estimate a total cost of RTI-related care (excluding the cost of study therapy) for each trial participant, based on observed levels of resource use. MAIN OUTCOME MEASURES: Number of RTI-related hospital admissions, days of RTI-related outpatient antibiotic therapy (intravenous and oral), and total costs of RTI-related care (excluding the cost of study therapy). RESULTS: Patients randomized to receive rhDNase once daily averaged 0.15 fewer RTI-related hospital admissions (0.41 vs 0.56 for placebo; p < 0.05) and 1.5 fewer days of RTI-related outpatient intravenous antibiotic therapy (2.9 vs 4.4; p < 0.05). Patients randomized to receive rhDNase twice daily had 0.14 fewer hospital admissions (p < 0.01), but no reduction in outpatient intravenous antibiotic therapy. Compared with placebo, the cost of treating RTIs over 24 weeks was $814-1682 less among patients receiving rhDNase. CONCLUSIONS: rhDNase therapy reduced the costs of treating RTIs in patients with cystic fibrosis; assuming once-daily dosing, these savings would offset about one-third of the cost of such therapy.

Growth patterns of hyperlipidemic children enrolled in a preventive cardiovascular health clinic.

The objective of this study was to assess growth patterns of hyperlipidemic children enrolled in a preventive cardiovascular health clinic. A retrospective chart review of hyperlipidemic children enrolled in the Mayo Clinic Cardiovascular Health Clinic for the Young was performed. All participants were counseled to eat an American Heart Association Step-One Diet and exercise regularly. Weight and height were measured every 3 months. Growth was assessed using attained heights and weights and body-mass index Z scores compared to standard distributions for North American children. Sixty-three patients (33 males and 30 females) were enrolled in the study. Mean age at clinic entrance was 7.8 +/- 3.5 years (range: 2 to 16 years). We conclude that participation in a preventive health clinic is generally safe for hyperlipidemic children. However, medical management of hyperlipidemic children must include meticulous surveillance to detect the infrequent occurrence of excessive weight loss or weight stabilization resulting from inappropriate response to dietary counseling.

Childhood vaccination against chickenpox: an analysis of benefits and costs.

OBJECTIVE: To estimate the economic costs and benefits of routine childhood vaccination against varicella infection. DESIGN: Decision-analytic model of the incidence and costs of chickenpox in children assumed to receive varicella vaccine at age 15 months in conjunction with the measles-mumps-rubella vaccine, or not to be vaccinated against varicella. PATIENTS: Hypothetical cohort of 100,000 children. MAIN OUTCOME MEASURES: Costs of vaccination, cumulative incidence of chickenpox to age 25 years, and related disease costs, including medical treatment and work loss. RESULTS: Vaccination of 100,000 children against varicella at age 15 months would cost $4,812,000. The expected number of cases of chickenpox to age 25 years would be reduced from 95,400 to 4800; costs of medical treatment and work loss would correspondingly decline by $1,678,000 and $9,781,000, respectively. On balance, vaccination is estimated to yield net economic benefits of $6,647,000, or $66.47 per vaccinee. CONCLUSION: Vaccination against varicella infection is cost-effective and should be part of the routine immunization schedule for U.S. children.

Cost-effectiveness of ticlopidine in preventing stroke in high-risk patients.

BACKGROUND: Ticlopidine, an antiplatelet agent, when compared with aspirin has been found to reduce the risk of stroke in high-risk patients, ie, those with recent transient ischemic attack, reversible ischemic neurological deficit, amaurosis fugax, or minor stroke. Its cost-effectiveness in such use, however, is unknown. METHODS: We developed a model of primary stroke prevention in which a hypothetical cohort of 100 high-risk men and women 65 years of age was assumed to receive either ticlopidine (500 mg daily) or aspirin (1300 mg daily). Using published data, we estimated lifetime incidence of stroke, life expectancy (unadjusted and adjusted for changes in quality of life), and lifetime medical care costs associated with each therapy. RESULTS: Patients who receive ticlopidine would experience two fewer initial strokes per hundred than those treated with aspirin. Life expectancy would be extended by approximately one-half month, and lifetime medical care costs (discounted at 5%) would increase by about $2300. The cost-effectiveness of ticlopidine, compared with aspirin, is estimated to range from $31,200 to $55,500 per quality-adjusted life-year gained as the utility of life after nonfatal stroke is assumed to vary from 0.75 to 0.95. CONCLUSIONS: Ticlopidine therapy to prevent stroke in high-risk patients is cost-effective by current standards of medical practice.

The costs of prostatectomy for benign prostatic hyperplasia.

Using claims data for a 5% random sample of Medicare beneficiaries, we estimated the costs of surgical treatment for benign prostatic hyperplasia (BPH), including those related to the initial prostatectomy, the treatment of postsurgical complications, and reoperation within one year. We identified 14,480 men who underwent prostatectomy for BPH during 1986-1987, including 13,730 transurethral and 750 open procedures. Mean total inpatient costs (including all hospital charges and professional service fees) for these procedures were estimated to be $6,501 and $10,223, respectively. Among patients who underwent transurethral and open prostatectomy, we identified 938 (6.8%) and 39 (5.2%) individuals who had at least one readmission for postsurgical complications or reoperation. Total expected costs of transurethral and open prostatectomy, inclusive of readmissions for complications and reoperations within one year, were estimated to be $6,823 and $10,477, respectively. Our study indicates the economic burden represented by surgical treatment of BPH.

Outcomes of cefazolin versus ceftriaxone therapy in treating lower respiratory tract infections in adults.

OBJECTIVE: To determine whether choice of a first- versus third-generation cephalosporin as initial therapy for lower respiratory tract infections in hospitalized adults affects the course and duration of care, both of which may influence antimicrobial treatment cost. DESIGN: Retrospective analysis of discharge abstracts and hospital pharmacy records. SETTING: Forty-eight US acute-care hospitals. PATIENTS: One thousand ninety-two hospitalized adults (aged > 17 y) with principal diagnoses of lower respiratory tract infections (DRGs 79-80, 89-90). INTERVENTIONS: Cefazolin or ceftriaxone, given as sole antimicrobial therapy for at least one day. MAIN OUTCOME MEASURES: (1) The number of patients who received another parenteral antibiotic anytime prior to hospital discharge; (2) the number of days during which patients received any parenteral antibiotic while in the hospital; and (3) the number of days patients remained hospitalized following the start of antibiotic therapy. RESULTS: Patients treated with cefazolin (n = 763) were more likely to receive another parenteral antibiotic while in the hospital (30.3 vs. 20.7 percent; p < 0.001) and received more total days of therapy (7.2 vs. 6.7 d; p < 0.05) than those treated with ceftriaxone (n = 329). Although the time to hospital discharge did not differ in the full sample (9.2 d for both groups), it was greater among those receiving cefazolin (8.6 vs. 8.0 d; p < 0.05) when patients with lengths of stay exceeding 24 days were excluded from both groups. CONCLUSIONS: In addition to acquisition cost, differences in course and duration of care should be considered when determining the most cost-effective choice for antimicrobial therapy.

Economic evaluation of oral ofloxacin versus standard parenteral therapy in the treatment of pneumonia.

The purpose of this study was to examine how inpatient use of oral ofloxacin, a fluoroquinolone antibiotic, affects utilisation of healthcare resources in the treatment of pneumonia. We collected data via chart review from a recent multicentre trial that randomised hospitalised adult patients with pneumonia to oral ofloxacin or standard parenteral therapy of the investigators' choice. We followed a total of 126 patients from randomisation until rule-out of pneumonia, death, loss to follow-up, or 30 days following cure, whichever occurred first. For each patient, we collected data on all inpatient antibiotic usage, duration of stay in hospital, and the utilisation of selected healthcare services following discharge from hospital. While length of stay did not differ between ofloxacin and standard-therapy patients (9.2 vs 11.1 days, respectively; p = 0.28), the cost of inhospital antibiotic therapy for those who received ofloxacin was one-fifth that of patients who were randomised to parenteral therapy ($US47 vs $US268). Costs of outpatient antibiotic therapy were slightly higher for the group receiving ofloxacin ($US26 vs $US3). No difference was noted in the rate of hospital readmission during follow-up. Our study therefore suggests that the use of oral ofloxacin among inpatients with pneumonia reduces the costs of antibiotic treatment compared to standard parenteral therapy.

Variability in response to a low-fat, low-cholesterol diet in children with elevated low-density lipoprotein cholesterol levels.

The reduction of dietary cholesterol and fat lowers low-density lipoprotein cholesterol (LDL-C) and reduces risk of coronary heart disease in adults. The purpose of this study was to determine the individual variability of response of serum lipid and lipoprotein levels to a low-fat, low-cholesterol diet in children with elevated LDL-C levels. Thirty-two children (2 to 16 years of age) enrolled in a diet modification program, who had LDL-C levels of at least 110 mg/dL but normal triglyceride levels for their ages, were studied. Lipid levels and dietary nutrients were analyzed at the time of admission, and final assessments were made at least 3 months after entry. There was a significant correlation, for the group as a whole, between change in LDL-C concentration and change in grams of dietary saturated fat; however, there was marked individual variability in LDL-C response. There were no significant correlations between changes in LDL-C levels and changes in either total fat, polyunsaturated fat, or cholesterol intake. It is concluded that modest decreases in dietary saturated fat coincide with a lowering of LDL-C concentration, over a short term, in many children, but the degree of lowering varies considerably from one child to another. This variability is consistent with the concept that response of serum lipid levels to dietary changes is modified by genetic, metabolic, and other, as of yet, undefined variables.

Benzodiazepine tranquilizers and the risk of accidental injury.

To determine whether benzodiazepine tranquilizers increase the risk of accidental injury requiring medical attention, we used pharmacy claims submitted to a large third-party payer to identify 4,554 persons who had been prescribed these agents and a matched control group of 13,662 persons who had been prescribed drugs other than benzodiazepines. We then used diagnoses recorded on claims submitted by medical care providers to identify all accident-related care received by these persons during three months before their first-observed prescription for a benzodiazepine or nonbenzodiazepine agent, respectively, and six months subsequently. We found accident-related care was more likely among persons who had been prescribed benzodiazepines; among these persons, the probability of an accident-related medical encounter was higher during months in which a prescription for a benzodiazepine had recently been filled compared to other months; and persons who had filled three or more prescriptions for these agents in the six months following initiation of therapy had a significantly higher risk of an accident-related medical event than those who had filled only one such prescription. Approximately two-fold risks of accident-related care were found, after controlling for age, sex, and prior utilization.