Atrial fibrillation or flutter and stroke: effectiveness of oral anticoagulation in clinical practice

Dear Sir, In the interesting study of Frost et al. [1], clinical evolution of 5124 patients with nonvalvular atrial fibrillation or atrial flutter in Denmark to define the impact of oral anticoagulation on stroke of any nature was investigated (fatal or nonfatal, ischaemic or haemorrhagic). Diagnoses of atrial fibrillation, atrial flutter and stroke were obtained from the County Hospital Discharge Registry and data on prescriptions of anticoagulation from the National Health Service. The overall incidence of stroke was around 30 per 1000 persons-years of follow-up and the adjusted relative risks of stroke during anticoagulation were 0.6 [95% confidence interval (CI): 0.4–1.0] in men, and 1.0 (95% CI: 0.7–1.6) in women compared with nonuse periods. The authors concluded that the effectiveness of oral anticoagulation might be lesser than the efficacy reported from randomized trials. We think that some considerations must be performed facing the observed results. Current knowledge, supported by several randomized trials, is that adjusted-dose oral anticoagulation is more effective than no treatment or aspirin in the prevention of all stroke (both ischaemic or haemorrhagic) in nonvalvular atrial fibrillation [2, 3] (Table 1). However, it is also well-established that, in comparison with placebo, aspirin promotes a slight but significant reduction in the incidence of stroke in these patients. Consequently, the superiority of anticoagulation over aspirin is less evident than over no treatment (Table 1). In the Danish study, the use of aspirin was not evaluated. In the period out of anticoagulation, certainly many patients were taking this antiplatelet drug, and this may have hindered the demonstration of benefit with oral anticoagulation. Nonvalvular patients with previous stroke or transient ischaemic attack have a rate of subsequent stroke around 13% per year and benefit substantially with oral anticoagulation, whilst patients without previous embolic events have a rate of stroke of 5% per year [2]. In these cases, the decision for anticoagulation must consider other clinical and echocardiographic risk factors [3–6]. In the Danish study, patients with previous diagnosis of stroke or with a stroke occurring in the same month as a diagnosis of atrial fibrillation were excluded. Thus, this investigation was limited to primary prevention. In this setting, the superiority of anticoagulation therapy over no treatment or aspirin has been demonstrated, but with less importance than that for secondary prevention (Table 1). Dr L. Frost and colleagues hypothesized that in the ‘real world’, the advantage of anticoagulation may be less pronounced. Results of randomized trials may fail to achieve optimal results in clinical practice because the control of adjusted-dose of oral anticoagulation and patient follow-up are different. The most important evidence investigating the impact of oral anticoagulation in clinical practice with atrial fibrillation patients is the meta-analysis of Evans & Kalra [7]. In this study that included three series [8–10], patients in clinical practice were older and had more comorbid conditions compared with trial participants. However, the ischaemic stroke rate was similar between clinical practice and randomized studies [1.8% (95% CI: 0.9–2.7%) vs. 1.4% (95% CI: 0.9–2.0%)], as it was the occurrence of intracranial haemorrhage [0.1% (95% CI: 0–0.3%) vs. 0.3% (95% CI 0.06–0.5%)] and major bleeding [1.1% (95% CI: 0.4–1.8%) vs. 1.3% (95% CI: 0.8–1.8%)]. There was only a higher rate of minor bleeding in clinical practice than in trials [12.0% (95% CI: 9.7–14.3%) vs. 7.9% (95% CI: 6.6–9.2%)]. In conclusion, we do believe that the observation of a modest reduction of stroke with oral anticoagulation in the study of Frost et al. [1] should be restricted for the primary prevention setting. Furthermore, the use of aspirin out of anticoagulation period may have hindered a clear observation of an efficacy with oral anticoagulation. Received and accepted 14 November 2002. Henrique Horta Veloso, Clinical Electrophysiology Section, Federal University of São Paulo, Rua Napoleão de Barros 593, Vila Clementino, São Paulo – SP, Brazil, ZIP 04024-002 (fax: +55 11 55733572; e-mail: [email protected]).