Benefit of anticoagulation in AF patients with a low risk of stroke questioned


The results from a retrospective study, based on a large dataset (over 140,000 patients), have cast doubt on the benefit of routine oral anticoagulants for patients with atrial fibrillation and low risk of stroke. The findings from this study contradict the recommendation of the current European guidelines from the European Society of Cardiology that advocate a low threshold for anticoagulant use.

A study published in the Journal of the American College of Cardiology has shown that the risk of ischaemic stroke in patients with atrial fibrillation and a CHA2DS2-VASc score of one seems to be lower than previously reported. While these findings have little practical implication for the management of high risk patients who will be considered for oral anticoagulant treatment, it does have bearing on the future treatment for patients who are at low stroke risk, as treatment will depend on the estimated stroke risk. The lower-than-previously-reported rates of ischaemic stroke risk in this patient population revealed by this study have led the authors to conclude that no benefit is anticipated for routine administration of oral anticoagulants to these patients.

Authors Leif Friberg, Karolinska Institute, Department of Clinical Sciences at Danderyd Hospital and Department of Cardiology at Danderyd Hospital, Stockholm, Sweden and colleagues, set out to assess atrial fibrillation-related stroke risk among patients with a score of one on the CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke/transient ischaemic attack, vascular disease, age 65–74 years, sex) score.

Friberg and colleagues write that patients with atrial fibrillation and ≥1 point on the stroke risk scheme CHA2DS2-VASc are considered at increased risk for future stroke, but state that the risk associated with a score of one differs markedly between studies. They conducted a retrospective study of 140,420 patients with atrial fibrillation in Swedish nationwide health registries using varying definitions of “stroke events.”

The study population consisted of all patients with a diagnosis of non-valvular atrial fibrillation in the Swedish National Patient Register between 1 July 2005 and 31 June 2010, who had not been exposed to warfarin at any time during follow-up. The researchers evaluated how the estimated event rates were affected by the various ways of counting these events that were used in previous studies.

The researchers found that using a wide “stroke” diagnosis (including hospital discharge diagnoses of ischaemic stroke as well as unspecified stroke, transient ischaemic attack, and pulmonary embolism) yielded a 44% higher annual risk than if only ischaemic strokes were counted.

As reported in the journal, “Including stroke events in conjunction with the index hospitalisation for atrial fibrillation doubled the long-term risk beyond the first four weeks. For women, annual stroke rates varied between 0.1% and 0.2% depending on which event definition was used and for men, the corresponding rates were 0.5% and 0.7%,” the authors write.

In the discussion of the paper, the authors note that the present study found that diverging estimates of stroke risks associated with atrial fibrillation are partly due to differences in study methods. “Although event rates in previous studies generally are thought of as describing stroke risk, the figures actually represent much more diverse endpoints. Several of the studies included pulmonary embolism in the “stroke” endpoint and some included transient ischaemic attack,” the authors point out.

Further, the researchers noted that with the rate of ischaemic stroke being found to be lower than previous studies indicate that there might have been unnecessary, and potentially harmful, oral anticoagulant treatment of low-risk patients based on the results of previous studies.

An extract from an accompanying editorial in the same journal by Daniel E Singer, Division of General Internal Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, USA, and Michael D Ezekowitz, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania states: “Guidelines recommend oral anticoagulant therapy for patients with atrial fibrillation on the basis of ischaemic stroke risk. Guidelines from both the USA (American College of Cardiology/American Heart Association/ Heart Rhythm Society [AHA/ACC/HRS]) and from Europe (European Society of Cardiology [ESC]) use the CHA2DS2-VASc risk score and recommend a low threshold for oral anticoagulant use. The ESC guideline proposes anticoagulation therapy for patients with a risk factor equal to one (≥1 point), whereas the AHA/ACC/HRS guideline uses a threshold of two points. Because ESC does not consider female sex as a stand-alone risk factor, the difference between the recommendations diminishes.”

Further, the editorial points out that Friberg et al conclude that the true stroke rate for patients with a CHA2DS2-VASc score of one is ≤0.7% per year, too low for oral anticoagulant therapy to benefit patients with atrial fibrillation. Singer and Ezekowitz comment that “different CHADS-VASc risk factors confer very different levels of stroke risk. In particular, age 65-74 confers much higher stroke risk than the other factors that confer a score of one point.” And they go on to make their own recommendation stating: “[…] given the current state of knowledge, atrial fibrillation patients who are below 65 years but with a CHA2DS2-VASc score of one are unlikely to benefit from anticoagulation.”

In an audio commentary on JACC, Valentin Fuster, director of Mount Sinai Heart, the Zena and Michael A Wiener Cardiovascular Institute and the Marie-Josée and Henry R Kravis Center for Cardiovascular Health, Mount Sinai hospital, New York, USA, said: “Both the European and US guidelines advocate the use of CHA2DS2-VASc scheme for risk stratification for patients with atrial fibrillation, but there is one difference, when we speak on a score of one. [For patients with this score] The European guidelines recommend the use of anticoagulants vs. asprin for a score of one, but the American guidelines recommend aspirin over the use of anticoagulants.”

Regarding aspirin use, Friberg tells Cardiac Rhythm News that patients have almost the same bleeding risk as with oral anticoagulants, but none of the benefits. “I would rather have CHA2DS2-VASc score one patients on no treatment, than on aspirin,” he says.

Fuster further illustrated the differences in guidelines and recommendations for patients who have a CHA2DS2-VASc score of one and age between 65 and 75 years but no other risk factors noting that Friberg et al and the American guidelines would recommend no anticoagulation whereas the European guidelines would recommend anticoagulation.