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Biomedical subjects

B G Koefoed

Publications and source records attributed to B G Koefoed.

10 recordsLinked to original sources
PubMed1999

Bleeding during warfarin and aspirin therapy in patients with atrial fibrillation: the AFASAK 2 study. Atrial Fibrillation Aspirin and Anticoagulation.

BACKGROUND: Treatment with warfarin sodium is effective for stroke prevention in atrial fibrillation but many physicians hesitate to prescribe it to elderly patients presumably because of the associated risk for bleeding and the inconvenience of frequent blood tests for the patients. METHODS: In the Second Copenhagen Atrial Fibrillation, Aspirin, and Anticoagulation (AFASAK 2) Study, we studied the rate of bleeding events associated with the incidence of thromboembolic events in patients receiving warfarin sodium, 1.25 mg/d; warfarin sodium, 1.25 mg/d, plus aspirin, 300 mg/d; aspirin, 300 mg/d; or adjusted-dose warfarin therapy aiming at an international normalized ratio of the prothrombin time ratio (INR) of 2.0 to 3.0. The study was scheduled for 6 years from May 1, 1993, but owing to evidence of inefficiency of low-intensity therapy plus aspirin from another study it was prematurely terminated on October 2, 1996. Minor and major bleeding events were recorded prospectively. The rate of bleeding was calculated using the Kaplan-Meier method and risk factors were identified by the Cox proportional hazards model. RESULTS: Of 677 included patients, 130 (median age, 77 years; range, 67-89 years) experienced bleeding. One woman and 12 men experienced major bleeding. Four had intracranial bleeding: 2 cases were fatal and 2 were nonfatal. During treatment with mini-dose warfarin, warfarin plus aspirin, aspirin, and adjusted-dose warfarin, the annual rate of major bleeding was 0.8%, 0.3%, 1.4%, and 1.1%, respectively (P = .20). After 3 years of treatment the cumulative rate of any bleeding was 24.7%, 24.4%, 30.0%, and 41.1% (P = .003), respectively. Increasing INRvalue (P<.001) and prior myocardial infarction (P = .001) were independent risk factors for bleeding, whereas increasing age was not. CONCLUSIONS: Fixed mini-dose warfarin and aspirin alone or in combination were associated with both minor and major bleeding. The small number of major bleeding events in patients receiving adjusted-dose warfarin therapy as compared with those receiving less intensive antithrombotic treatments and the finding of no significant influence of age on the risk for bleeding indicate that even elderly patients with atrial fibrillation tolerate adjusted-dose warfarin therapy (INR, 2.0-3.0).

Adult↗
PubMed1999

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.

Administration, Oral↗
PubMed1998

Fixed minidose warfarin and aspirin alone and in combination vs adjusted-dose warfarin for stroke prevention in atrial fibrillation: Second Copenhagen Atrial Fibrillation, Aspirin, and Anticoagulation Study.

BACKGROUND: Despite the efficacy of warfarin sodium therapy for stroke prevention in atrial fibrillation, many physicians hesitate to prescribe it to elderly patients because of the risk for bleeding complications and because of inconvenience for the patients. METHODS: The Second Copenhagen Atrial Fibrillation, Aspirin, and Anticoagulation Study was a randomized, controlled trial examining the following therapies: warfarin sodium, 1.25 mg/d; warfarin sodium, 1.25 mg/d, plus aspirin, 300 mg/d; and aspirin, 300 mg/d. These were compared with adjusted-dose warfarin therapy (international normalized ratio of prothrombin time [INR], 2.0-3.0). Stroke or a systemic thromboembolic event was the primary outcome event. Transient ischemic attack, acute myocardial infarction, and death were secondary events. Data were handled as survival data, and risk factors were identified using the Cox proportional hazards model. The trial was scheduled for 6 years from May 1, 1993, but due to scientific evidence of inefficiency of low-intensity warfarin plus aspirin therapy from another study, our trial was prematurely terminated on October 2, 1996. RESULTS: We included 677 patients (median age, 74 years). The cumulative primary event rate after 1 year was 5.8% in patients receiving minidose warfarin; 7.2%, warfarin plus aspirin; 3.6%, aspirin; and 2.8%, adjusted-dose warfarin (P = .67). After 3 years, no difference among the groups was seen. Major bleeding events were rare. CONCLUSIONS: Although the difference was insignificant, adjusted-dose warfarin seemed superior to minidose warfarin and to warfarin plus aspirin after 1 year of treatment. The results do not justify a change in the current recommendation of adjusted-dose warfarin (INR, 2.0-3.0) for stroke prevention in atrial fibrillation.

Adult↗
PubMed1997

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.

Aged↗
PubMed1997

Prevention of thromboembolic events in atrial fibrillation.

Nonvalvular atrial fibrillation is associated with an overall risk of stroke of 4.5% per year. Advancing age, prior stroke or transcient cerebral ischemia, diabetes and hypertension are known risk factors. Ischemic stroke in patients with atrial fibrillation are generally more severe than ischemic stroke in patients with sinus rhythm. Warfarin is effective for primary and secondary prevention of ischemic 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 either 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. Other trials now indicate, that oral anticoagulation at INR-values below 2.0 is not effective for stroke prevention in these patients. It is recommended that patients at high risk of stroke are treated with warfarin at an intensity of INR 2.0-3.0. Patients younger than 65 without other risk factors can be given aspirin 325 mg/day. The present clinical challenge is to ensure effective and safe oral anticoagulation to patients with atrial fibrillation at high risk of stroke.

Anticoagulants↗
PubMed1996

[Interaction between warfarin and nalidic acid].

A case of presumed interaction between warfarin and nalidixic acid is reported in an 84 year-old female in whom INR rose from 1.9 to 9.6 after start of treatment with nalidixic acid. The interaction may be caused by several factors: 1) Nalidixic acid may displace warfarin from plasma proteins and thereby increase the anticoagulant effect. 2) The fluoroquinolone drug enoxacin reduces the hepatic clearance of the R-stereomere of warfarin but without prolongation of the prothrombin time ratio. 3) Fluoroquinolones may affect the vitamin-K producing bacteria in the gut and thereby influence the vitamin-K: warfarin ratio in plasma. Only some patients develop hypoprothrombinaemia during concomitant therapy with warfarin and quinolone antimicrobials. It is hypothesized that the interaction may partly be related to age, sex or concomitant disease. Frequent control of INR in patients treated with both warfarin and quinolone antimicrobials is recommended.

Aged↗
PubMed1996

[Atrial fibrillation and apoplexy--risks and prevention].

The annual incidence of ischemic stroke among patients with chronic non-valvular atrial fibrillation is about 4.5 percent. In five controlled trials, oral anticoagulant therapy with warfarin reduced the annual incidence of stroke by 68 percent to 1.4 percent. The effect of aspirin has not been unequivocally determined. Aspirin reduced the annual risk of stroke by 18 percent (n.s.) in one trial, and by 44 percent in another, though the two trials differed both in mean age of the patients and in aspirin doses. Direct comparison of warfarin and aspirin revealed no difference in efficacy. Advanced age, previous stroke or transient ischemic attack (TIA), hypertension and diabetes were all found to be risk factors for stroke in patients with atrial fibrillation. In patients under 65 years of age without risk factors, the annual risk of stroke was 1 percent. After TIA or minor stroke, warfarin reduced the annual risk of a second stroke from 12 percent to 4 percent. Aspirin had no such effect. The annual incidence of major bleeding episodes was 0.2-2.0 percent in the warfarin-treated subgroup, 0.2-1.5 percent in the aspirin subgroup and 0-1.6 percent in the placebo subgroup. Based on findings in the above mentioned trials, warfarin (INR 2.0-3.0) is recommended for stroke prevention in patients over 60 years of age with non-valvular atrial fibrillation. Trials are under way to ascertain whether conventional warfarin treatment can be replaced by less complicated and safer treatments in patients with chronic atrial fibrillation.

Aged↗
PubMed1995

[Cerebral comlications of surgery using cardiopulmonary bypass].

The number of open heart surgery procedures using cardiopulmonary bypass increases each year. The objective of this review is to describe the frequency of cerebral complications to such open heart surgery in 18 retrospective and prospective studies published after 1980. In prospective studies the overall frequency of central nervous system complications was 5-61% and the frequency of stroke and transitory ischaemic attack (TIA) was 2-24%. A total of 1-12% suffered from prolonged encephalopathy. In retrospective studies the frequency of central nervous complications was 1-2%. At neuropsychological tests 30-79% showed significant deterioration at the seventh to ninth postoperative day. After six months 80% achieved the same test results as prior to surgery. It is difficult to compare the studies because of major differences in study design. Stroke and TIA seemed to occur more frequent in older studies, in prospective studies and in studies based on valve surgery. Most studies were uncontrolled. We conclude that the risk of central nervous system complications to open heart surgery needs to be re-evaluated in prospective studies of well-defined patients, including matched control groups and a long follow-up period.

Cardiopulmonary Bypass↗
PubMed1995

[Bleeding complications in oral anticoagulant treatment].

Vitamin K-antagonists are recommended for the prevention of stroke in patients with chronic atrial fibrillation, recent myocardial infarction or prostatic heart valves. Anticoagulant therapy is seldom prescribed, however, presumably for fear of haemorrhagic sequelae. The risk of bleeding during anticoagulant therapy has been evaluated in 10 recent studies of warfarin treatment for the prevention of arterial thromboembolism. The mean annual incidences of fatal and major bleeding was 0.5 percent and 1.6 percent, respectively, as compared with the placebo figures of 0.1 percent and 0.6 percent, respectively. In 3 studies where the effect of aspirin has been evaluated the mean annual incidence of fatal and major bleeding was 0.2 percent and 0.8 percent, respectively. The figures for warfarin therapy where lower than those reported from older studies. The reasons for the reduction in incidence may be less intensive anticoagulant treatment than formerly, improved laboratory control by the introduction of the International Normalized Ratio, and careful pretreatment evaluation of patients selected for clinical trials.

Anticoagulants↗