Cost-effectiveness of preference-based antithrombotic therapy for patients with nonvalvular atrial fibrillation

BACKGROUND AND PURPOSE: Recent atrial fibrillation guidelines recommend the incorporation of patient preferences into the selection of antithrombotic therapy. However, no trial has examined how incorporating such preferences would affect quality-adjusted survival or medical expenditure. We compared 10-year projections of quality-adjusted survival and medical expenditure associated with two atrial fibrillation treatment strategies: warfarin-for-all therapy versus preference-based therapy. The preference-based strategy prescribed whichever antithrombotic therapy, warfarin or aspirin, had the greater projected quality-adjusted survival. METHODS: We used decision analysis stratified by the number of stroke risk factors (history of stroke, transient ischemic attack, hypertension, diabetes, or heart disease). The base case focused on compliant 65-year-old patients who had nonvalvular atrial fibrillation and no contraindications to antithrombotic therapy. RESULTS: In patients whose only risk factor for stroke was atrial fibrillation, preference-based therapy improved projected quality-adjusted survival by 0.05 quality-adjusted life year (QALY) and saved $670. For patients who had atrial fibrillation and one additional risk factor for stroke, preference-based therapy improved quality-adjusted survival by 0.02 QALY and saved $90. In patients who had atrial fibrillation and multiple additional risk factors for stroke, preference-based therapy increased medical expenditures and did not improve quality-adjusted survival substantially. The benefits of preference-flexible therapy arose from the minority of patients who would have had a longer quality-adjusted survival if they had been prescribed aspirin rather than warfarin. CONCLUSIONS: As do risks of stroke and of hemorrhage, patients' preferences help to determine which antithrombotic therapy is optimal. Preference-based treatment should improve quality-adjusted survival and reduce medical expenditure in patients who have nonvalvular atrial fibrillation and not more than one additional risk factor for stroke.     

Cerebral embolism in elderly patients with atrial fibrillation

Novalvular (nonrheumatic) atrial fibrillation (NVAF) is the most common cardiac condition associated with presumed embolic stroke, accounting for approximately half of the cardiogenic embolic infarctions. Of autopsied stroke patients in the Tokyo Metropolitan Geriatric Hospital, cerebral infarction was found in 75%, intracranial hemorrhage in 19%, and coexisting cerebral hemorrhage and cerebral infarction in 6%. Twenty-eight percent of the cerebral infarctions were embolic infarctions of cardiac origin, 56% of which were caused by NVAF. The incidence of cardiogenic brain embolism ranged from 6 to 23% of the ischemic strokes, and NVAF is the most frequent substrate for brain embolism. Atrial fibrillation increases in its incidence with increasing age. Chronic AF was observed in 10%, and paroxysmal AF in 7% of the autopsied elderly patients. Most of them were nonrheumatic AF. Twenty-two percent of the AF patients had large cerebral infarction, and 15% had medium-sized cortical infarction at the autopsy. NVAF is a very important cause of fatal massive cerebral infarction in the elderly. Of 56 patients with fatal massive cerebral infarction who died within 2 weeks after the strokes, 25 (45%) had embolic stroke associated with NVAF. Anticoagulant therapy prevents recurrent cerebral embolism of cardiac origin. The proper time to initiate anticoagulant therapy following cardiac brain embolism is controversial. Immediate initiation of anticoagulant therapy can reduce the early recurrence, but can result in secondary brain hemorrhage or hemorrhatic transformation. Patients with NVAF may have a lower risk of recurrence during the first 2 to 4 weeks following the initial embolic stroke compared with other cardioembolic sources. Cerebral embolism with NVAF can recur during a long period.(ABSTRACT TRUNCATED AT 250 WORDS)     

Warfarin reduces silent cerebral infarction in elderly patients with atrial fibrillation

A simple, fast, reliable, and specific immunoassay has been developed to detect and measure AD7C-NTP, a biochemical marker for Alzheimer's disease, in cerebrospinal fluid (CSF). This assay, called the AD7C Test, is an enzyme-linked sandwich immunoassay (ELSIA) using 96 well microtiter plates. The plate surface is coated with a monoclonal antibody (N3I4) which has a high affinity and specificity for AD7C-NTP, capturing it effectively from CSF samples. The detection was achieved using a polyclonal antibody (ADRI). Both N3I4 and ADRI were generated using recombinantly produced AD7C-NTP. The assay is highly sensitive (30-50 pg), linear to 2.0 ng (r2 > 0.99), and reproducible (C.V. < 10%). The utility of the assay has been demonstrated using CSF specimens from early Alzheimer's disease patients and age matched controls (sensitivity of 89% and specificity of 89%).     

Antithrombotic therapy prescribed for patients with non-rheumatic atrial fibrillation

Patients with non-rheumatic atrial fibrillation have a fivefold increased risk of stroke. Warfarin reduces this risk by approximately two thirds, but evidence for benefit from aspirin is less compelling. We assessed whether our current practice reflects the message of the trials. In a retrospective case record study we reviewed notes of 131 patients with atrial fibrillation (AF), mean age 79 (range 53-95) years, admitted to a medical unit (72) or geriatric assessment unit (59). Thirty-two patients had paroxysmal AF. Of 115 patients with nonrheumatic AF, 36 (31%) had one or more recorded contraindication to anti-coagulation. Although 79 patients (69%) had no recorded contraindication to warfarin, only 2 took warfarin and 15 aspirin prior to admission. Ten patients commenced warfarin and 8 aspirin before discharge. Thirty-nine patients (53%) without contraindication, were discharged without antithrombotic therapy. Despite evidence to support anticoagulating patients with non-rheumatic AF, this rarely occurs.     

Underutilization of warfarin in older persons with chronic nonvalvular atrial fibrillation at high risk for developing stroke

OBJECTIVE: To investigate the prevalence of the use of warfarin to maintain an international normalized ratio (INR) between 2.0 and 3.0 in older persons with chronic nonvalvular atrial fibrillation (AF), and without contraindications to warfarin, who are at high risk for developing new thromboembolic (TE) stroke. DESIGN: A retrospective analysis of charts from all older persons seen during 1997 at an academic hospital-based geriatrics practice. SETTING: An academic hospital-based geriatrics practice staffed by fellows in a geriatrics training program and full-time faculty geriatricians. PATIENTS: Three hundred eighty men and 1183 women, mean age 80+/-8 years (range 59 to 103 years), were included in the study. MEASUREMENTS AND MAIN RESULTS: Of 1563 persons studied, 141 (9%) had chronic nonvalvular AF. Of 141 persons with AF, 127 (90%) were at high risk for developing TE stroke because they had either a previous thromboembolism, congestive heart failure, or echocardiographic evidence of abnormal left ventricular systolic function; a systolic blood pressure >160 mm Hg; or they were women older than 75 years of age. Of the 127 persons with AF at high risk for developing TE stroke, three (2%) had contraindications to warfarin. Of the 124 persons with AF at high risk for developing TE stroke and no contraindications to warfarin, 61 (49%) were treated with warfarin to maintain an INR between 2.0 and 3.0, and 45 (36%) were treated with 325 mg aspirin daily. Of 14 persons with AF at low risk for developing TE stroke, one (7%) was treated with warfarin to maintain an INR between 2.0 and 3.0, and six (43%) were treated with 325 mg aspirin daily. CONCLUSIONS: Warfarin is underutilized as a treatment to maintain an INR between 2.0 and 3.0 in older persons with chronic nonvalvular AF at high risk for developing TE stroke.     

Beta-adrenergic blockade as adjunctive oral therapy in patients with chronic atrial fibrillation

In many patients with chronic atrial fibrillation, it is difficult to prevent an excessive ventricular rate under stress, even with high levels of digoxin in the blood. The effect of adding beta-adrenergic blockade with practolol to digoxin on the heart rate at rest and during low-grade controlled exercise was investigated in 28 patients with chronic atrial fibrillation and in ten normal control subjects who were receiving maintenance dosages (0.25 to 0.75 mg) of digoxin. In atrial fibrillation, therapy with practolol decreased the mean heart rate at rest from 99.8 beats per minute to 77.5 beats per minute (23 percent reduction; P less than 0.01) and during mild exercise from 148.9 beats per minute to 105.4 beats per minute (29 percent) reduction (P less than 0.001). Fifteen patients had clinically significant heart failure; therapy with practolol did not worsen it. Reversible side effects were detected in two patients. When therapy with digoxin is not sufficient to control atrial fibrillation, the addition of a beta-adrenergic blocking agent is recommended as adjunctive treatment in selected patients.     

The effect of sotalol hydrochloride therapy on atrial signal-averaged ECG in patients with paroxysmal atrial fibrillation

BACKGROUND: There has been a continuing public debate about assisted suicide and the proper role, if any, of physicians in this practice. Legislative bans and various forms of legalization have been proposed. METHODS: We mailed questionnaires to three stratified random samples of Michigan physicians in specialties likely to involve the care of terminally ill patients: 500 in the spring of 1994, 500 in the summer of 1994, and 600 in the spring of 1995. Similar questionnaires were mailed to stratified random samples of Michigan adults: 449 in the spring of 1994 and 899 in the summer of 1994. Several different questionnaire forms were used, all of which included questions about whether physician-assisted suicide should be banned in Michigan or legalized under certain conditions. RESULTS: Usable questionnaires were returned by 1119 of 1518 physicians eligible for the study (74 percent), and 998 of 1307 eligible adults in the sample of the general public (76 percent). Asked to choose between legalization of physician-assisted suicide and an explicit ban, 56 percent of physicians and 66 percent of the public support legalization, 37 percent of physicians and 26 percent of the public preferred a ban, and 8 percent of each group were uncertain. When the physicians were given a wider range of choices, 40 percent preferred legalization, 37 percent preferred "no law" (i.e., no government regulation), 17 percent favored prohibition, and 5 percent were uncertain. If physician-assisted suicide were legal, 35 percent of physicians said they might participate if requested--22 percent would participate in either assisted suicide or voluntary euthanasia, and 13 percent would participate only in assisted suicide. Support for physician-assisted suicide was lowest among the strongly religious. CONCLUSIONS: Most Michigan physicians prefer either the legalization of physician-assisted suicide or no law at all; fewer than one fifth prefer a complete ban on the practice. Given a choice between legalization and a ban, two thirds of the Michigan public prefer legalization and one quarter prefer a ban.     

Surgical therapy for atrial fibrillation

Women who presented to a University psychiatric hospital were categorized into those with childbearing-related onset illness (CBROI, n = 168) and compared to those with non-childbearing-related onset illness (NCBROI, n = 1004). Women with CBROI were an average of five years younger. The two groups did not differ in membership across five major psychiatric diagnostic categories. However, women with CBROI were given the specific diagnosis adjustment disorder with depressed mood more frequently. Anxiety disorders were also common in women with CBROI. Most women with CBROI had the onset of illness during the postpartum period compared to during pregnancy or after pregnancy loss.     

Efficacy of serial electrical cardioversion therapy in patients with chronic atrial fibrillation after valve replacement and implications for surgery to cure atrial fibrillation

In April 1993, a 51-year-old woman had a fever, and an infiltrative shadow was seen in the left upper lobe on a chest X-ray film. Repeated sputum cultures were positive for Mycobacterium avium complex. She underwent antituberculosis therapy consisting of pyrazinamide, ofloxacin, and streptomycin. Her symptom disappeared and the abnormal shadow resolved. In January 1994, she was admitted to the hospital because of bloody sputum and abnormal chest X-ray findings consisting of a left hilar mass and atelectasis of the left upper lobe. Bronchoscopy revealed multiple polypoid lesions without necrosis in the left upper-lobe bronchus. Histological examination showed that the tumor consisted of an aggregation of lymphocytes and plasma cells, and was positive for Ziehl-Neelsen stain. The acid-fast bacillus was identified as Mycobacterium avium by the DNA probe method. Anti-tuberculosis treatment was given: rifampicin, isoniazid, sparfloxacin, and clarithromycin. Three months later, the atelectasis and the polypoid mass in the left upper-lobe bronchus had disappeared. We believe that the polypoid lesions in the left upper-lobe bronchus were due to infection by Mycobacterium avium. The patient was HIV-negative and immunocompetent. Such endobronchial lesions caused by Mycobacterium avium are rare in HIV-negative hosts.     

Ischemic cerebrovascular disease in patients with atrial fibrillation

The purpose of this retrospective study was to elucidate 1) which subgroups are prone to have ischemic cerebrovascular disease (CVD) among patients with atrial fibrillation (Af), 2) vulnerable period of CVD after the diagnosis of chronic Af and 3) the clinical efficacy of antiplatelet therapy in chronic nonvalvular Af patients. During 9 years, a total of 479 patients included 124 cases with paroxysmal Af, 30 cases with paroxysmal Af initially which later changed to chronic Af and 325 cases with chronic Af were enrolled. Among these 355 cases with chronic Af, 57 cases had valvular heart disease (VHD). The results were as follows: 1) The high risk subgroups (incidence rate/100 person-years is more than 6) were chronic Af with VHD or hypertension. The low risk subgroups (less than 2) were paroxysmal Af under 60 years of age, chronic Af with mitral valve prolapse syndrome or with hyperthyroidism. 2) There was no vulnerable period for occurrence of CVD during 9 years' follow-up from the onset of Af. 3) No significant difference in the incidence of CVD was seen in the groups with antiplatelet therapy and without.     

Left atrial spontaneous contrast echoes--markers of thromboembolic risk in patients with atrial fibrillation

A consecutive series of 80 patients with atrial fibrillation were studied with both precordial and transoesophageal echocardiography. Left atrial spontaneous contrast echoes were observed in one patient with precordial echocardiography and in 26 patients (33%) with transoesophageal echocardiography. They were found most commonly in patients with rheumatic mitral valve disease (67%) but were observed in 28% of patients with lone atrial fibrillation. Their presence was unrelated to the age, gender and therapy of the patient. Although they were more common in patients with a large left atrium, they were sometimes observed in a normal sized atrial chamber. They were more common in chronic (40%) than in paroxysmal atrial fibrillation (5.6%). No patient had severe mitral regurgitation, but contrast echoes were observed in some patients with mild or moderate mitral regurgitation. Of the 26 patients with spontaneous contrast echoes, six (23%) had echoes consistent with left atrial thrombus compared to one of the 54 patients without these echoes (1.9%) (P = 0.006); 17 (65%) had suffered a previous thromboembolic event compared to 17 of the 54 without these echoes (32%) (P = 0.009). These data support the concept that spontaneous contrast echoes in the left atrium are associated with sluggish blood flow and a thrombogenic environment. Transoesophageal echocardiography may thus be useful in assessing which patients with atrial fibrillation might most benefit from anticoagulation. This hypothesis needs to be evaluated further in a prospective study.     

Cost-effectiveness of therapies for patients with nonvalvular atrial fibrillation

BACKGROUND: The most appropriate treatment(s) for patients with atrial fibrillation remains uncertain. OBJECTIVE: To examine the cost-effectiveness of anti-thrombotic and antiarrhythmic treatment strategies for atrial fibrillation. METHODS: We performed decision and cost-effectiveness analyses using a Markov state transition model. We gathered data from the English-language literature using MEDLINE searches and bibliographies from selected articles. We obtained financial data from nationwide physician-fee references, a medical center's cost accounting system, and one of New England's larger managed care organizations. We examined strategies that included combinations of cardioversion, antiarrhythmic therapy with quinidine, sotalol hydrochloride, or amiodarone, and anticoagulant or antiplatelet therapy. RESULTS: For a 65-year-old man with nonvalvular atrial fibrillation, any intervention results in a significant gain in quality-adjusted life years (QALYs) compared with no specific therapy. Use of aspirin results in the largest incremental gain (1.2 QALYs). Cardioversion followed by the use of amiodarone and warfarin together is the most effective strategy, yielding a gain of 2.3 QALYs compared with no specific therapy. The marginal cost-effectiveness ratios of cardioversion followed by aspirin, with or without amiodarone, are $33800 per QALY and $10800 per QALY, respectively. Cardioversion followed by amiodarone and warfarin has a marginal cost-effectiveness ratio of $92400 per QALY compared with amiodarone and aspirin. Strategies that include cardioversion followed by either quinidine or sotalol are both more expensive and less effective than competing strategies. CONCLUSIONS: Cardioversion of patients with nonvalvular atrial fibrillation followed by the use of aspirin alone or with amiodarone has a reasonable marginal cost-effectiveness ratio. While cardioversion followed by the use of amiodarone and warfarin results in the greatest gain in quality-adjusted life expectancy, it is expensive (ie, has a high marginal cost-effectiveness ratio) compared with aspirin and amiodarone. Finally, for patients who are bothered little by symptoms of atrial fibrillation, cardioversion followed by either aspirin or warfarin without subsequent antiarrhythmic therapy is the treatment of choice.     

Antiarrhythmic drug therapy in the treatment of atrial fibrillation

Treatment of atrial fibrillation is often unsatisfactory because no available drug has been shown to be clearly superior for maintaining patients in sinus rhythm, and all agents have significant potential for toxicity. Selection of an antiarrhythmic drug is more likely to be based on the drug's potential for toxicity, rather than its demonstrated superior efficacy in the treatment of atrial fibrillation. Careful assessment of each patient for contraindications to individual agents and the likelihood of treatment success needs to be done before initiating antiarrhythmic therapy.     

-Differential antithrombotic therapy in patients with low and high PTCA risk-

Acute coronary occlusion as well as restenosis still represent the major limitations of coronary interventions. Either event seems to be related to thrombus formation. The purpose of this overview is to summarize the current status of the usefulness of conventional and newer antithrombotic drugs regarding the prevention of acute occlusion and restenosis (excluding stents). ANTICOAGULATION: For ethical reasons, no placebo-controlled studies were conducted to prove the usefulness of heparin in preventing acute occlusions. The dosage mostly used is 10,000 U, although a relationship between dosage and complication rate has not been documented. A prolonged heparin infusion in patients with low risk and uncomplicated PTCA has no advantages. Restenosis is not influenced by prolonged infusion of heparin or administration of coumadin as well. Low molecular weight heparin is currently under investigation. Hirudin and hirulog have shown promising results with less acute occlusions; however, their therapeutic range must be considered. ANTIAGGREGATION: In controlled studies, ASA significantly reduced acute occlusions during PTCA when given in addition to heparin. Ticlopidin is as effective as ASA, but due to its side effects should only be administered when contraindications to ASA exist. ASA significantly reduced restenosis in only 1 of 4 studies with limited number of patients. Thromboxane inhibitors such as ridogrel or clopidogrel showed promising initial results. Trapidil significantly reduced restenosis in 2 studies; quantitative stenosis analysis, however, was not performed. Inhibition of platelets by glycoprotein (GP) IIb/IIIa receptor antagonists represents an innovative therapeutic concept: numerous controlled trials have documented a significant reduction in cardiac ischemic events and therefore indirectly in restenosis rates. The recombinant monoclonal antibody c7E3 Fab seems to be more effective than the synthetic integrelin. Unfortunately, efficacy appears to be in direct relationship to the risk of bleeding complications. The clinical role of oral GP IIb/IIIa inhibitors has yet to be established. For patients with high risk PTCA, the use of hirudin instead of heparin as well as the addition of GP IIb/IIIa inhibitors should be considered.