Atrial fibrillation and stroke risk prevention in real-life clinical practice

Abstract

Thromb Haemost 2009; 101: 415–416 Patients with atrial fibrillation (AF) have a substantial risk of stroke and thromboembolism compared with age-matched people in sinus rhythm, which varies with associated comorbidities and risk factors (1, 2). When a stroke occurs in patients with AF, the severity of the stroke is much greater, as is mortality and disability compared to those in sinus rhythm (3). Unsurprisingly, the biggest challenge facing physicians caring for patients with AF is the prevention of stroke and thromboembolism, whether as primary or secondary prevention. Examination of stroke rates from the non-warfarin arms of trial cohorts and one epidemiological study have informed the development of stroke risk stratification schema for AF (4). More than a dozen stroke risk stratification schemes for AF patients have been proposed, but all have modest predictive value for stroke (1, 5). These risk stratification schemes are used in many guidelines, which generally recommend anti-thrombotic therapy with warfarin for AF patients at ‘high-risk’ of stroke and aspirin for those at ‘low-risk’. For those patients who fall into the ‘moderate-risk’ category (usually those with one single stroke risk factor), either aspirin or warfarin is recommended, due to the lack of evidence in favour of either drug, as well as the close margin between stroke reduction and bleeding risk of anticoagulation with warfarin. Thus, many guidelines recommend that anti-thrombotic therapy is decided on an individual basis. However, such an approach is confounded by new trial evidence from the Birmingham Atrial Fibrillation Treatment of the Aged Study (BAFTA) showing the substantial benefits – even in subjects aged >75 – of warfarin over aspirin for stroke prevention (1.8% vs. 3.8% events per year, respectively: relative risk [RR] 0.48, 95% confidence interval [CI] 0.28–0.80), with no difference in rates of major haemorrhage between warfarin or aspirin (6). The merits or otherwise of why warfarin should really be the drug of choice for stroke prevention in elderly patients with AF have recently been debated in this journal (7, 8). It is said that guidelines begat guidelines, and in real-life clinical practice, such guidelines on anti-thrombotic therapy for AF are often not adhered to (9). In the Euro Heart Survey, prescription of antithrombotic therapy was based on the type of AF and availability of warfarin monitoring clinic, rather than the stroke risk profile per se (9). The type of AF should not be a consideration, given that paroxysmal AF has a similar stroke risk to persistent or permanent AF, in the presence of risk factors, and such patients would derive much benefit from anticoagulation (10). In the current issue of Thrombosis and Haemostasis, Rietbrock et al. (11) evaluate the incidence of stroke in routine clinical practice among >51,000 chronic AF patients aged ≥40 years taking either aspirin or warfarin, by examining the United Kingdom General Practice Research Database from 1987 onwards. Virtually all the patients had been treated with warfarin or aspirin, with almost 10,000 patients who had received both (either concomitantly or separately). They compared non-use (never) with both ‘current use’ (defined as the time from the prescription date until three months after the expected duration of use) and ‘past use’ (defined as the period of time starting three months after the expected end of a prescription) and found that current use of warfarin was associated with a 38% (RR 0.62, 95% CI 0.54–0.71) reduction in stroke compared to past use after adjustment for age, sex, and stroke risk profile. Compared to no warfarin use, current and past use were both associated with a significant reduction in stroke rate, by 67% (RR 0.33, 95% CI 0.30–0.35) and 44% (RR 0.56, 95% CI 0.50–0.63), respectively. The benefits were more evident amongst the elderly, whereby the risk of stroke was reduced by 45% in elderly warfarin users (aged 75 years or older) and by 14% in younger users. As emphasised by the BAFTA trial (6), elderly patients with AF should not be denied warfarin thromboprophylaxis, given the impressive benefits of stroke prevention with anticoagulation in elderly AF patients. In contrast, there was no difference in the rate of stroke between current and past use of aspirin (RR 1.04, 95% CI 0.94 – 1.15). Thus, the stroke risk reduction with warfarin in routine clinical practice is similar to that achieved in clinical trials, in a UK general practice cohort involving >30,000 elderly AF patients, demonstrating that the evidence from clinical trials can translate into real-life clinical practice. Indeed, current or past use of aspirin did not seem to matter, and in fact, there were no significant changes in the rates of stroke were observed with dis© 2009 Schattauer GmbH, Stuttgart