Systemic Embolism in Atrial Fibrillation: Less Common Than Stroke but as Fatal

Marlene Busko

August 04, 2015

MINNEAPOLIS, MN — A new review based on data from four large contemporary trials of patients with atrial fibrillation (AF) has shed light on the incidence, risk factors, and morbidity of extracranial systemic embolic events (SEEs)—a less common but often lethal outcome[1].

In this analysis of more than 30,000 patients, nine in 10 thromboembolic events were stroke and only one in 10 were systemic embolic events. Within 30 days of an extracranial systemic embolic event, 25% of the patients had died (the same mortality rate as stroke) and only 54% of patients had fully recovered.

Thus, "clearly, these events are not benign and the adverse outcomes we observed suggest that SEEs should be managed as aggressively as stroke," Dr Wobo Bekwelem (University of Minnesota Medical School, Twin Cities) and colleagues report in their study, published July 29, 2015 in Circulation.

The real value is that this study used four randomized well-powered trials and provides the largest description of SEE to date, Dr Steven A Lubitz (Harvard Medical School, Boston, MA), coauthor with Dr Neal A Chatterjee (Harvard Medical School) of an accompanying editorial[2], told heartwire from Medscape.

The findings suggest that physicians should advise patients that "antithrombotic treatment of [AF] is key to their well-being and survival, due to the danger associated with all embolic events, whether to the brain or periphery," senior author Dr Alan T Hirsch (University of Minnesota Medical School) commented. When it comes to good cardiovascular health, "there is nothing 'peripheral' about peripheral ischemic events," he said.

How Does SEE Differ From Stroke?

Patients with AF are at risk of thromboembolic events, but relatively little is known about their risk of systemic embolism as opposed to stroke.

"We think that both stroke and systemic embolism have the same underlying mechanism, at least in AF—which is that a clot comes from the left atrium and goes to the brain or [another organ]," coauthor Dr Stuart J Connolly (McMaster University, Hamilton, ON) commented. Moreover, the brain only gets about 25% of the body's blood supply, but 90% to 95% of the emboli travel to the brain, "which has always been a bit of a mystery," he said.

To investigate this, Bekwelem and colleagues readjudicated all suspected cases of systemic embolic events reported among 37,973 participants of four large, randomized, contemporary trials of anticoagulation in AF: the Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events trials (ACTIVE-A and ACTIVE-W), the Apixaban Versus Acetylsalicylic Acid [ASA] to Prevent Stroke in Atrial Fibrillation in Patients Who Have Failed or Are Unsuitable for Vitamin K Antagonist Treatment Study (AVERROES), and the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial.

During a mean follow-up of 2.4 years, 1677 patients had a stroke, 174 patients had a confirmed clinical and objective evidence of sudden loss of perfusion of a limb or an organ (SEE), and 45 patients had both types of event.

The incidence of SEE was 0.24/100 patient years (roughly 0.2% per year), whereas the incidence of stroke was 1.92/100 patient-years (roughly 1.9% per year).

Patients with both types of events had a similar mean age (73.5) and CHADS2 score (2.5). However, compared with patients with stroke, those with a SEE were more likely to be female (56% vs 47%, P=0.01), white (77% vs 67.5%, P=0.01), and current or past smokers (54% vs 44%, P=0.01), with current or past peripheral artery disease (PAD) (9% vs 5%, P=0.02) and previous MI (26.5% vs 17.6%, P=0.005) or SEE (20% vs 3%, P=0.0001).

The systemic embolism occurred more frequently in patients' legs (58%) and less often in their visceral-mesenteric organs (32%) or arms (10%).

Most patients with an extracranial SEE were hospitalized and had a surgical or endovascular procedure (60%); about a third were hospitalized only (31%); 5% received outpatient care; and 4% had an amputation.

The 30-day mortality rate was similar for patients with systemic embolism alone (24%) or stroke alone (25%). However, compared with patients with stroke, the 30-day mortality was higher for patients with a mesenteric embolism (55%) and lower for patients with an embolism in the legs or arms (17% and 9%, respectively).

Within 30 days, only 54% of patients with SEE had fully recovered and 20% survived with deficits.

The relative risk of death during follow-up was 4.33 (95% CI 3.29–5.70) after a SEE vs 6.79 (95% CI 6.22–7.41) after a stroke.

Fragile Patients, Study Will Help Guide Future Research

According to Hirsch, the study's key message is: "Take each potential ischemic event with comparable seriousness. . . . These are fragile patients, and end-organ ischemia that causes recognizable dysfunction is a very poor prognostic signal."

The diagnosis can be tricky. "If there's a sudden loss of blood supply to a limb in a patient with AF, most clinicians will make a diagnosis [of SEE] fairly quickly and confirm it by doing . . . an angiogram, where you can see the blocked arteries easily," Connolly said. However, an embolism that travels to the small bowel can mimic other intestinal diseases, or an embolism that travels to the kidney might also be difficult to diagnose.

This study was not designed to describe what treatments are useful to prevent SEE, but for stroke, anticoagulants work the best, and antiplatelet therapies work to a lesser extent, and this appears to be the same for extracranial SEE, he continued.

"Given that several SEE risk factors (eg, female gender, peripheral vascular disease, prior myocardial infarction) are included in stroke-prediction algorithms, it is unlikely that the report by Bekwelem et al will significantly modify the decision to initiate anticoagulation," Lubitz and Chatterjee write.

However, "these data help us 'SEE' embolic risk more clearly, [and] ultimately such clarity will guide more effective application of therapies to stem the rising tide of AF and thromboembolic morbidity," they conclude.

The authors and editorialists have no relevant financial relationships.

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