Chronic Nonvalvular Atrial Fibrillation Research Articles

Antiplatelet Therapy for Preventing Stroke in Patients With Nonvalvular Atrial Fibrillation and No Previous History of Stroke or Transient Ischemic Attacks

Antiplatelet agents such as aspirin are modestly efficacious for preventing serious vascular events in patients with atrial fibrillation (AF) who are not treated with more efficacious oral anticoagulants. Nonvalvular AF carries an increased risk of stroke. Antiplatelet therapy (APT) is proven effective for stroke prevention in most patients at high-risk for vascular events, but its value for primary stroke prevention in patients with nonvalvular AF merits separate consideration because of the suspected cardioembolic mechanism of most strokes in AF patients. The goal of this review is to assess the efficacy and safety of long-term APT for primary prevention of stroke in patients with chronic nonvalvular AF. We searched the Cochrane Stroke Group Trials Register (August 2004). In addition, …

Oral anticoagulation in nonvalvular atrial fibrillation.

Chronic nonvalvular atrial fibrillation is associated with an overall risk of thromboembolic complications of 4.5% per year. Advancing age, prior stroke or transient cerebral ischaemia, diabetes, hypertension, and impaired function of the left ventricle are known risk factors. Placebo-controlled trials have demonstrated that oral anticoagulant therapy with warfarin is effective for primary and secondary prevention of ischaemic stroke, reducing the risk by 68%. The effect of aspirin is still controversial, reducing the risk by 18-44%. Recent clinical trials have investigated the effect of warfarin given at a very low intensity alone or combined with aspirin. The results from the SPAF III study demonstrated that a combination of mini-intensity warfarin plus aspirin was insufficient for stroke prevention in atrial fibrillation. More trials have now confirmed that oral anticoagulation at INR-values below 2.0 is not effective for prevention of thromboembolic events in these patients. It is currently recommended that patients at a high risk of stroke are treated with warfarin at an intensity of INR 2.0-3.0. Patients younger than 65 years without other risk factors can be given aspirin 325 mg day-1.

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

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. A retrospective analysis of charts from all older persons seen during 1997 at an academic hospital-based geriatrics practice. An academic hospital-based geriatrics practice staffed by fellows in a geriatrics training program and full-time faculty geriatricians. Three hundred eighty men and 1183 women, mean age 80+/-8 years (range 59 to 103 years), were included in the study. 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. 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.

Transesophageal Echocardiography during and Three Months after Electrical Cardioversion of Chronic Nonvalvular Atrial Fibrillation

Transesophageal Echocardiography during and Three Months after Electrical Cardioversion of Chronic Nonvalvular Atrial Fibrillation

Atrial Fibrillation and Stroke: Elucidating a Newly Discovered Risk Factor

Atrial fibrillation is the most common sustained arrhythmia reported in the United States; an estimated 1–2 million Americans have chronic nonvalvular atrial fibrillation. This disorder is associated with a substantial risk of stroke. Several recent studies provide evidence that anticoagulation therapy is indicated for stroke prevention in patients with nonvalvular atrial fibrillation after recovery from a minor stroke. Clinical and echocardiographic criteria help to identify those patients who are at especially high risk for thromboembolic stroke and are candidates for carefully controlled anticoagulation. In an effort to reduce the possibility of thromboembolic events following either chemical or electrical cardioversion, the American College of Chest Physicians has recently prepared guidelines for the use of anticoagulation in the conversion of atrial fibrillation. The efficacy of antiarrhythmic drug therapy for cardioversion is often difficult to assess. Furthermore, it is associated with major risks, including heart failure and exacerbation of arrhythmia, and minor risks, including systemic intolerance. A new National Institutes of Health trial, Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM), will clarify the true risks and benefits of antiarrhythmic therapy for conversion of atrial fibrillation to sinus rhythm. Patients who cannot tolerate drug therapy may benefit from interruption of conduction in the bundle of His, followed by implantation of a permanent pacemaker, the use of radiofrequency energy ablation, or the implantation of an atrial defibrillator. Some patients may benefit from surgical procedures, such as left atrial isolation, the corridor operation, and the maze operation.

Stroke prevention in patients with non-valvular atrial fibrillation: a current community perspective

Non-valvular atrial fibrillation (NVAF) is responsible for up to 10% of all ischaemic strokes. The risk of stroke in these patients is substantial, particularly when associated with past cerebral ischaemia, hypertension, diabetes and age over 65. Warfarin has recently been shown to reduce this risk by two-thirds with relative safety. The files of 103 patients with chronic NVAF on recent presentation to hospital were studied to see if they had been given warfarin beforehand. Two-thirds would have been ideal candidates, having at least one added risk factor for stroke, and no contraindication for the use of warfarin. Yet fewer than 10% were taking it. Sixteen of these 103 patients had an ischaemic event at presentation, mostly stroke. Twelve were ideal candidates for warfarin prophylaxis, but none had received it for this purpose. Much more must be done to prevent stroke in these patients.

Effect of Fixed Minidose Warfarin, Conventional Dose Warfarin and Aspirin on INR and Prothrombin Fragment 1 + 2 in Patients with Atrial Fibrillation

The efficacy of conventional dose adjusted oral anticoagulation for stroke prevention in patients with non-valvular atrial fibrillation is well-documented but not considered ideal as primary antithrombotic treatment in elderly patients. The antithrombotic effect of fixed minidose warfarin 1.25 mg/day alone or in combination with aspirin 300 mg/day, of conventional dose adjusted warfarin (INR 2.0-3.0), and of aspirin 300 mg/day have been investigated in outpatients with chronic nonvalvular atrial fibrillation in the second Copenhagen Atrial Fibrillation, Aspirin and Anticoagulant Therapy Study (AFASAK 2). In order to investigate the effect on the coagulation system of the treatments, the International Normalized Ratio of the prothrombin time (INR) and prothrombin fragment 1 + 2 (F1 + 2) were monitored at baseline and after three months of treatment in 100 patients consecutively included in the trial. At baseline no differences in INR and F1 + 2 between the four treatment groups were present. After three months of therapy the level of INR increased significantly from baseline in patients receiving warfarin in any dose and the level of F1 + 2 decreased significantly by combined minidose warfarin-aspirin and by dose adjusted warfarin. When comparing the changes over time in F1 + 2 (three-month value minus baseline value) during therapy with fixed minidose warfarin, combined minidose warfarin-aspirin and aspirin alone no significant difference between the groups was found. In conclusion, INR was changed by all three warfarin regimens but only dose adjusted warfarin (INR 2.0-3.0) had a marked effect on F1 + 2.

Atrial reservoir and active transport function after cardioversion of chronic atrial fibrillation.

Atrial reservoir function has not been studied after successful cardioversion of chronic atrial fibrillation. Using transthoracic and transesophageal Doppler echocardiography, we measured flow velocity-time integrals of the systolic forward (Sa), diastolic forward (Da), and diastolic reversed (rAa) waves of flow velocity waveforms in the pulmonary vein and the superior vena cava, and those of the early diastolic (Ea) and late diastolic (Aa) waves of the transmitral and transtricuspid flow velocity waveforms. The left and right atrial storage fractions (LASF, RASF), indexes of atrial reservoir function, were determined as the ratios of the atrial storage volume to the ventricular stroke volume; (Sa - rAa)/(Sa - rAa + Da). The left and right atrial active contraction fractions (LAACF, RAACF), indexes of atrial active transport function, were also determined as the ratios of the atrial active contraction volume to the left ventricular stroke volume; Aa/(Ea + Aa). These indices were evaluated periodically in 12 patients with non-valvular chronic atrial fibrillation before and 1-4 days after direct current cardioversion of atrial fibrillation; in 8 of the patients, the indices were also evaluated 1-3 months after the cardioversion. An additional 10 patients in sinus rhythm served as controls. Both the LASF and RASF were low during atrial fibrillation; the values increased significantly 14 days after successful cardioversion (P < 0.01 P < 0.01), and continued to increase at 1-3 months. The LASF and RASF values 1-3 months after cardioversion were comparable to those in control subjects. Both the LAACF and RAACF also increased significantly from 1-4 days to 1-3 months after cardioversion (P < 0.05, P < 0.01), becoming comparable to those in control subjects. During the 3 months after successful cardioversion of non-valvular chronic atrial fibrillation, left and right atrial reservoir function and left and right atrial active transport function increased progressively, becoming comparable to values in the control subjects.

Left ventricular beat-to-beat performance in atrial fibrillation: Contribution of frank-starling mechanism after short rather than long RR intervals

This study sought to evaluate control mechanism of the varying left ventricular performance in atrial fibrillation. Atrial fibrillation is characterized by a randomly irregular ventricular response, resulting in continuous variation in left ventricular beat-to-beat mechanical behavior and hemodynamic variables. Fourteen patients with chronic nonvalvular atrial fibrillation were studied, using a nonimaging computerized nuclear probe linked to a personal computer. Left ventricular ejection fraction, end-diastolic and end-systolic volume counts, stroke volume counts and filling time were calculated on a beat-to-beat basis during 500 consecutive RR intervals. Multiple regression analysis was used to assess how ejection fraction was predicted by these variables. The preceding RR interval and end-diastolic volume showed a positive relation, and prepreceding interval and end-systolic volume an inverse relation, with ejection fraction (all p < 0.001). Sensitivity analysis suggested that the preceding interval and the end-diastolic volume were equally important in predicting ejection fraction. There was a relatively strong interaction between the preceding interval and end-diastolic volume, indicating that the influence of the end-diastolic volume on ejection fraction was diminished after long intervals. A second interaction showed that the effect of end-diastolic volume on ejection fraction was attenuated after short prepreceding cycles. Cycle length-dependent contractile mechanisms, including postextrasystolic potentiation and mechanical restitution, determine the varying left ventricular systolic performance during atrial fibrillation over the entire range of intervals. Beat-to-beat changes in preload, consistent with the Frank-Starling mechanism, also play a role, but their influence is diminished after long preceding and short prepreceding intervals.

Alternations in atrial natriuretic peptide release after DC cardioversion of non-valvular chronic atrial fibrillation.

The response of atrial natriuretic peptide (ANP) release to haemodynamic influences after cardioversion of atrial fibrillation has not been fully examined. We measured plasma concentrations of ANP and assessed haemodynamic changes 60-120 min after DC cardioversion in 22 patients with non-valvular chronic atrial fibrillation. Passive leg elevation to enhance volume expansion was performed 60 min after DC cardioversion. Sinus rhythm was restored in 18 of the 22 patients (successful DC cardioversion group). The control group consisted of seven patients with non-valvular chronic atrial fibrillation who did not undergo DC cardioversion (atrial fibrillation control group). In the successful DC cardioversion group, the mean pulmonary artery wedge pressure decreased significantly 15 min after cardioversion (P < 0.05) and then remained unchanged. Plasma concentrations of ANP also decreased significantly 15 min after cardioversion (P < 0.05). Furthermore, there was an additional significant decrease in ANP levels for up to 60 min after cardioversion (P < 0.05 from 15 min). Passive leg elevation for 15 min led to an increase in the mean pulmonary artery wedge pressure (P < 0.01) and right atrial pressure (P < 0.05), but did not result in increased plasma concentrations of ANP (47.1 +/- 27.6 vs 43.9 +/- 34.4 pg.ml-1, mean +/- SD, P = ns). In the atrial fibrillation control group, passive leg elevation increased the mean pulmonary artery wedge pressure (P < 0.01), the mean right atrial pressure (P < 0.05) and plasma concentrations of ANP (139.9 +/- 85.8 vs 168.1 +/- 108.2, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Chronic Rapid Atrial Pacing

Despite the clinical importance of atrial fibrillation (AF), the development of chronic nonvalvular AF models has been difficult. Animal models of sustained AF have been developed primarily in the short-term setting. Recently, models of chronic ventricular myopathy and fibrillation have been developed after several weeks of continuous rapid ventricular pacing. We hypothesized that chronic rapid atrial pacing would lead to atrial myopathy, yielding a reproducible model of sustained AF. Twenty-two halothane-anesthetized mongrel dogs underwent insertion of a transvenous lead at the right atrial appendage that was continuously paced at 400 beats per minute for 6 weeks. Two-dimensional echocardiography was performed in 11 dogs to assess the effects of rapid atrial pacing on atrial size. Atrial vulnerability was defined as the ability to induce sustained repetitive atrial responses during programmed electrical stimulation and was assessed by extrastimulus and burst-pacing techniques. Effective refractory period (ERP) was measured at two endocardial sites in the right atrium. Sustained AF was defined as AF > or = 15 minutes. In animals with sustained AF, 10 quadripolar epicardial electrodes were surgically attached to the right and left atria. The local atrial fibrillatory cycle length (AFCL) was measured in a 20-second window, and the mean AFCL was measured at each site. Marked biatrial enlargement was documented; after 6 weeks of continuous rapid atrial pacing, the left atrium was 7.8 +/- 1 cm2 at baseline versus 11.3 +/- 1 cm2 after pacing, and the right atrium was 4.3 +/- 0.7 cm2 at baseline versus 7.2 +/- 1.3 cm2 after pacing. An increase in atrial area of at least 40% was necessary to induce sustained AF and was strongly correlated with the inducibility of AF (r = .87). Electron microscopy of atrial tissue demonstrated structural changes that were characterized by an increase in mitochondrial size and number and by disruption of the sarcoplasmic reticulum. After 6 weeks of continuous rapid atrial pacing, sustained AF was induced in 18 dogs (82%) and nonsustained AF was induced in 2 dogs (9%). AF occurred spontaneously in 4 dogs (18%). Right atrial ERP, measured at cycle lengths of 400 and 300 milliseconds at baseline, was significantly shortened after pacing, from 150 +/- 8 to 127 +/- 10 milliseconds and from 147 +/- 11 to 123 +/- 12 milliseconds, respectively (P < .001). This finding was highly predictive of inducibility of AF (90%). Increased atrial area (40%) and ERP shortening were highly predictive for the induction of sustained AF (88%). Local epicardial ERP correlated well with local AFCL (R2 = .93). Mean AFCL was significantly shorter in the left atrium (81 +/- 8 milliseconds) compared with the right atrium 94 +/- 9 milliseconds (P < .05). An area in the posterior left atrium was consistently found to have a shorter AFCL (74 +/- 5 milliseconds). Cryoablation of this area was attempted in 11 dogs. In 9 dogs (82%; mean, 9.0 +/- 4.0; range, 5 to 14), AF was terminated and no longer induced after serial cryoablation. Sustained AF was readily inducible in most dogs (82%) after rapid atrial pacing. This model was consistently associated with biatrial myopathy and marked changes in atrial vulnerability. An area in the posterior left atrium was uniformly shown to have the shortest AFCL. The results of restoration of sinus rhythm and prevention of inducibility of AF after cryoablation of this area of the left atrium suggest that this area may be critical in the maintenance of AF in this model.

Physician Attitudes About Anticoagulation for Nonvalvular Atrial Fibrillation in the Elderly

Our goal was to determine whether patient age affects a physician's reported likelihood of using anticoagulant therapy or the intensity of anticoagulant therapy for patients with nonvalvular atrial fibrillation. We surveyed a nationwide sample of 1189 randomly selected office-based practitioners in three strata: primary care (geriatrics, internal medicine, family practice, and general practice), cardiology, and neurology. A vignette-based questionnaire was used to measure attitudes and beliefs regarding anticoagulation risks and effectiveness, barriers to anticoagulation in clinical practice, and likelihood of using anticoagulation and target intensity of anticoagulation at three patient ages (55, 65, and 75 years) for four clinical scenarios (chronic non-valvular atrial fibrillation with mild left atrial enlargement, intermittent or paroxysmal atrial fibrillation, recent-onset atrial fibrillation, and atrial fibrillation with recent [3 months] embolic stroke). The overall response rate was 38%. The mean likelihoods of using anticoagulation for the three ages were unequal (P < .0001) for each scenario. Most physicians were "very" or "somewhat" likely to use anticoagulant therapy for a 65-year-old with left atrial enlargement (71%), intermittent or paryoxysmal atrial fibrillation (68%), recent-onset atrial fibrillation (86%), or embolic stroke (96%). Fewer physicians were likely to use anticoagulant therapy for a 75-year-old with left atrial enlargement (63%), intermittent or paroxysmal atrial fibrillation (56%), recent-onset atrial fibrillation (80%), or embolic stroke (93%). Among physicians equally likely to use anticoagulation for 65- and 75-year-old patients, intensity of anticoagulant therapy (target international normalized ratio or prothrombin time ratio) was lower (P < .04) for the 75-year-old. Anticoagulant therapy may be less often and less intensively used for elderly patients with nonvalvular atrial fibrillation.

Second Copenhagen Atrial Fibrillation, Aspirin, and Anticoagulant Therapy Study (AFASAK 2): Methods and Design.

Background: Seven randomized trials have demonstrated that anticoagulant therapy is effective for primary and secondary prevention of stroke and other thromboembolic events in patients with chronic nonvalvular atrial fibrillation. The effect of aspirin is still not clarified. Conventional anticoagulant therapy is inconvenient as a primary preventive therapy as it requires frequent blood tests and implies a risk of bleeding complications. Purpose and methods: The Second Copenhagen Atrial Fibrillation, Aspirin and Anticoagulant Therapy Study (The AFASAK 2 study) is a randomized, one center, primary prevention trial. Its purpose is to investigate the effect of four antithrombotic regimens in patients with atrial fibrillation (1) fixed dose warfarin 1.25 mg per day, (2) a combination of warfarin 1.25 mg per day and aspirin 300 mg per day, (3) aspirin 300 mg per day, and (4) conventional warfarin therapy (INR 2.0-3.0). The primary endpoint is a stroke or a thromboembolic event in viscera or extremities. Secondary endpoints are transient ischemic attack, myocardial infarction, or death. The study will evaluate outcome events on intention-to-treat principles. The rate of bleeding complications is evaluated. The aim is to obtain an antithrombotic therapy for patients with nonvalvular atrial fibrillation that is effective, safe, easy to administer, and inexpensive. The methods and design of the study are presented in this paper.

Transthoracic echo/Doppler in the identification of patients with chronic non-valvular atrial fibrillation at risk for thromboembolic events

Left atrial spontaneous echo contrast, detected by transoesophageal echocardiography in patients with non-valvular atrial fibrillation reflects slow blood flow and is associated with an increased risk of cardio-embolism. The purpose of this study was to find echo/Doppler predictors of left atrial spontaneous echo contrast by transthoracic examination. In a retrospective case control study, 17 patients with chronic non-valvular atrial fibrillation who had suffered a recent cerebral ischaemic event (group A) and 17 patients with chronic non-valvular atrial fibrillation who had not suffered such an event (group B) were studied. Both groups were matched for age and sex. All patients underwent standard transthoracic echocardiography with transmitral Doppler as well as transoesophageal echocardiography. Left atrial spontaneous echo contrast was demonstrated by transoesophageal echocardiography in nine group A patients and in two group B patients (P = 0.028); left atrial spontaneous echo contrast was not detected by transthoracic echocardiography in these patients. All patients with left atrial spontaneous echo contrast (11 patients) had a left atrial size, corrected for base index, exceeding 24 mm and a transmitral time velocity integral < 10 cm (sensitivity 100%). Left atrial spontaneous echo contrast was absent in six patients with both characteristics (specificity 74%). transthoracic echo/Doppler aids in the prediction of the presence of left atrial spontaneous echo contrast and the identification of patients with non-valvular atrial fibrillation with increased cardioembolic risk, thus avoiding transoesophageal echocardiography.

Left and right atrial function before and after DC cardioversion of nonvalvular chronic atrial fibrillation

Left and right atrial function before and after DC cardioversion of nonvalvular chronic atrial fibrillation

Clinical Implications and Factors Related to Left Atrial Spontaneous Echo Contrast in Chronic Nonvalvular Atrial Fibrillation

The mechanisms leading to formation of spontaneous echo contrast (SEC), a smoke-like echo on echocardiography, are still controversial. To further explore the clinical implications and factors related to SEC formation, the correlation among echocardiographic variables, hematologic parameters or platelet aggregability, and the occurrence of SEC was studied in 119 patients with chronic nonvalvular atrial fibrillation. There were 75 men and 44 women with a mean age of 65 +/- 10 years (range 38-88). Left atrial SEC was detected in 39 patients (33%) by transesophageal echocardiography. Patients with history of systemic embolism were more frequently found to have left atrial SEC and left atrial thrombus by univariate analysis. Multivariate analysis showed that left atrial SEC (p < 0.001) was the only independent predictor of history of systemic embolism. Age, sex, left atrial or left ventricular dimension, left ventricular ejection fraction, antiplatelet or anticoagulant therapy and the percentage of lone atrial fibrillation were not significantly different between patients with and without left atrial SEC. Among the hematologic parameters, higher hematocrit was found in patients with left atrial SEC, while white blood cell and platelet counts were comparable in both groups. Platelet aggregability with different concentrations of inducers, adenosine diphosphate and collagen, was evaluated by the turbidimetric method in 15 patients with left atrial SEC and in 42 patients without left atrial SEC who were not receiving antiplatelet or anticoagulant therapy. No significant difference was found in platelet aggregability using four inducer concentrations between two groups of patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Silent cerebral infarcts in patients with ischemic infarction

Silent cerebral infarcts occur in patients with chronic nonvalvular atrial fibrillation and asymptomatic or symptomatic carotid stenosis. There is not a well-defined prevalence of asymptomatic lesions in patients with transient ischemic attack or completed strokes. We attempted to determine the occurrence rate of silent brain infarction in a hospital population, including a comparison of the risk factors with those of symptomatic infarction and an evaluation of the relevance of infarction size and location.

Hemostatic Activity in Patients with a Transient Ischemic Attack or Minor Ischemic Stroke with or without Chronic Non-Valvular Atrial Fibrillation

In this study we determined the prevalence of hemostatic hyperactivity in patients with recent cerebral ischemia and its relation to the presence of chronic nonvalvular atrial fibrillation. Plasma levels of thrombin-antithrombin III complexes (TAT) and prothrombin fragments 1+2 (F1+2) were used as hemostatic parameters and were studied in four groups of 14 patients each: patients with or without recent cerebral ischemia, and with or without chronic nonvalvular atrial fibrillation. Irrespective of their cardiac rhythm, patients with recent cerebral ischemia showed significantly higher F1+2 levels than patients without signs of previous cerebral ischemic events (median 1.16 vs. 0.96 nmol/1; p < 0.001). No significant differences were found between the TAT levels in the different groups. A higher level of hemostatic activity was found in the patients over 70 years of age compared to those younger than 70 years.

Anticoagulant and Antiplatelet Therapy in Acute Coronary Syndromes and Atrial Fibrillation

Acute coronary syndromes are mainly due to disruption of an atherosclerotic plaque with less than a 50-75% stenosis with secondary formation of thrombus. Mechanisms of arterial thrombosis including local substrates and flow and the pivotal role of thrombin in the formation of thrombus are discussed. A direct antithrombin with high affinity binding totally prevented arterial thrombus; lower doses inhibit fibrin and the higher doses inhibit platelets. Potent antithrombotic therapy accelerates exogenous lysis, nearly assures endogenous lysis, and should reduce previously neglected residual thrombus which causes recurrent infarction, death, or need for revascularization. Maximal available therapy for the acute coronary syndromes includes an intravenous heparin bolus at 100 units/kg followed by an intravenous infusion at 1200 units/h (if <80 kg) or 1300 units/h (if ≥80 kg) to maintain the activated partial thromboplastin time at two to three times control for 5-7 days. To convert to subcutaneous administration use 14,000-17,000 units every 12 h and overlap the intravenous infusion for the first 2 h. Start aspirin at a loading dose of 160 mg on admission to hospital and continue at 80 mg/day. In high risk patients consider conversion of heparin to warfarin for 3 mo (international normalized ratio 2.5-4.0) to maximize endogenous lysis of residual thrombus and reduce reactivation of thrombosis after heparin is stopped. Patients with paroxysmal or chronic nonvalvular atrial fibrillation (stroke risk 5-8%/yr) significantly reduce the risk of stroke using warfarin (international normalized ratio of 2.0-3.0). Patients under age 75 with no diabetes mellitus or clinical risk factors for stroke [hypertension (even under treatment) previous thromboembolism, or heart failure or left ventricular dysfunction] are at low risk for stroke (1.4%/yr) and may use aspirin 325 mg/day) to reduce stroke and bleeding risks. (Cardiol Rev 1993;1:3, 167-176)

Treatment of Chronic Nonvalvular Atrial Fibrillation in the Elderly

The objective of the study was to determine the preferred treatment strategy for elderly patients with chronic nonvalvular atrial fibrillation (CNVAF). A Markov decision-analytic model was used to compare three treatment strategies for CNVAF: 1) warfarin; 2) aspirin; and 3) no treatment. Five-year quality-adjusted life years (QALYs) were calculated for male and female cohorts aged 70 and 75 years. In the baseline analysis (effectiveness of warfarin = 0.70, effectiveness of aspirin = 0.45, utility of warfarin = 0.99, and utility of aspirin = 0.999) the quality-adjusted survival rates for 70-year-old males were 4.03 QALYs on warfarin, 4.02 QALYs on aspirin, and 3.95 QALYs on no treatment. Results were similar for all age and sex cohorts. Sensitivity analyses revealed that the results were very sensitive to the effectiveness of aspirin and the disutility of warfarin. The authors conclude that the optimal strategy for the treatment of CNVAF in elderly patients varies with the disutility assigned to warfarin therapy and the effectiveness value for aspirin therapy.