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Primary prevention of arterial thromboembolism in non-rheumatic atrial fibrillation in primary care: randomised controlled trial comparing two intensities of coumarin with aspirin - PATAF
Description:
The PATAF trial was a prospective, randomized trial to investigate the effectiveness of aspirin and coumarin in preventing thromboembolism in patients with non-rheumatic atrial fibrillation in general practice.
Hypothesis:
In a general practice population (without established indications for coumarin), low or standard intensity anticoagulation is better than aspirin in preventing primary outcome events.
Study Design
Study Design:
Patients Enrolled: 792
Mean Follow Up: Mean follow-up 2.7 years
Patient Populations:
Patients age >60 years with electrocardiographically confirmed chronic atrial fibrillation or intermittent atrial fibrillation (electrocardiography within past two years).
Exclusions:
Treatable causes of atrial fibrillation, previous stroke, rheumatic valvular disease, myocardial infarction or cardiovascular surgery in past year, cardiomyopathy (left ventricular ejection fraction <40%), chronic heart failure, cardiac aneurysm, history of systemic embolism, retinal infarction, coumarin use in the past three months, contraindications for aspirin or coumarin (haemoglobin concentration <7.0 mmol/l, ventricular or duodenal ulcer in the past three years, gastrointestinal or urogenital bleeding in the past year, aspirin intolerance, coagulation disorder, and severe hepatic or renal disease), pacemaker, and a life expectancy less than two years. Exclusion criteria for standard anticoagulation were age >78, retinopathy, ventricular or duodenal ulcer, history of gastrointestinal or genitourinary bleeding, and diastolic blood pressure >105 mm Hg or systolic pressure >185 mm Hg, or both.
Primary Endpoints:
Stroke, systemic embolism, major hemorrhage, and vascular death.
Secondary Endpoints:
Non-fatal myocardial infarction (electrocardiographically or laboratory confirmed), retinal infarction, transient ischaemic attack, minor bleeding complication, or non-vascular death.
Drug/Procedures Used:
Patients eligible for standard anticoagulation were randomly assigned to aspirin 150 mg/day, low anticoagulation (international normalised ratio 1.1-1.6), or standard anticoagulation (international normalised ratio 2.5-3.5; randomisation stratum 1). Patients who were ineligible for standard anticoagulation were randomized between aspirin and low anticoagulation (randomization stratum 2), giving five subgroups in the two strata. General practitioners followed up participants at four month intervals and checked compliance. Patients were single blinded for the two intensities of anticoagulant, but end point ascertainments were blinded for treatment. Either phenprocoumon or acenocoumarol (nicoumalone) was prescribed by the thrombosis centres according to normal prescription practice and monitored at intervals of 2-6 weeks.
Principal Findings:
Within stratum 1, 131 patients received standard anticoagulation, 122 low-dose anticoagulation and 141 aspirin. Within stratum 2, 157 patients received low-dose anticoagulation and 178 received aspirin. Baseline characteristics were similar among treatment groups. The annual event rate was 5.5%. Compared with aspirin, the hazard ratio was 0.91 (95% confidence interval 0.61 to 1.4) for low anticoagulation (both strata) and 0.78 (0.34 to 1.8) for standard anticoagulation (stratum 1). For non-vascular death, the hazard ratio was 0.41 (0.20 to 0.82) comparing low anticoagulation with aspirin. In the per protocol analysis the risk of primary events was 0.77 (0.49 to 1.2) in the low anticoagulation group compared with aspirin; this fell to 0.66 (0.44 to 0.99) when non-vascular death was included. The hazards ratio for primary events with standard anticoagulation was 0.87 (0.34 to 2.2) and 0.62 (0.26 to 1.5) when non-vascular death was included. High systolic and low diastolic blood pressure, and age were independent prognostic factors. Risk was lower in non-smokers with intermittent atrial fibrillation receiving low anticoagulation. The annual bleeding rate was 3.9%, 1.2% for major or fatal bleeding (n=23) and 2.7% for minor bleeding (n=52). Seventeen of the major bleeds occurred in stratum 2, with 10 in the aspirin group. No significant difference in risk of bleeding was found between treatment groups.
Interpretation:
Among patients with non-rheumatic atrial fibrillation, standard or low anticoagulation was not shown to be more effective than aspirin. The authors recommendations based on these results were that the prophylactic choice in primary care is aspirin if there is no clear indication for full dose anticoagulation.
References:
Hellemons BSP, et al. Primary prevention of arterial thromboembolism in non-rheumatic atrial fibrillation in primary care: randomised controlled trial comparing two intensities of coumarin with aspirin. BMJ 1999;319:958-964.
Keywords: Thromboembolism, Platelet Aggregation Inhibitors, Phenprocoumon, Blood Pressure, Confidence Intervals, Electrocardiography
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