Paroxysmal AF carries similar risk of stroke as sustained AF

November 19, 2007

Frankfurt, Germany - Patients with paroxysmal (intermittent) atrial fibrillation (AF) have similar risks of stroke and non-central nervous system (CNS) embolism as patients with sustained AF, a new analysis of the ACTIVE W trial shows[1]. The analysis also suggests that oral anticoagulation treatment is superior to a combination of aspirin plus clopidogrel in reducing stroke or non-CNS embolism in both types of AF.

These latest findings from the ACTIVE W study are published in the November 27, 2007 issue of the Journal of the American College of Cardiology.

The authors, led by Dr Stefan Hohnloser (JW Goethe University, Frankfurt, Germany), explain that guidelines on therapy of AF recommend the use of oral anticoagulants for patients with stroke risk factors irrespective of the type of AF they have, but they say the evidence for this in patients with paroxysmal AF is weak, with just one retrospective analysis specifically addressing the risk of stroke in patients with paroxysmal vs chronic AF. This analysis (of the SPAF trials) was conducted more than 15 years ago and was limited to patients treated with aspirin. Therefore, more contemporary data are needed on this issue.

They therefore conducted an analysis to look at this question using data from the ACTIVE W trial, which, with 6706 patients, is the largest AF trial ever completed. The trial, which was reported last year, showed clear superiority of warfarin over aspirin plus clopidogrel in reducing a composite of stroke, embolism, MI, and vascular death, with the biggest benefit on stroke prevention. Major bleeding events were similar between the two therapies. The current analysis focused on whether patients in the trial with paroxysmal AF were at a similar risk of stroke as those with sustained AF and whether there was a difference in efficacy and safety of warfarin or aspirin/clopidogrel depending on whether patients had paroxysmal or sustained AF.

The annualized risk of stroke or non-CNS systemic embolism in paroxysmal AF vs sustained AF

  Paroxysmal AF (n=1202) (%) Sustained AF (n=5495) (%) Adjusted relative risk (95% CI) p
Annualized risk of stroke/non-CNS embolism 2.0 2.2 0.94 (0.63-1.40) 0.755

Results also showed that the incidence of stroke and non-CNS embolism was lower for patients treated with oral anticoagulation irrespective of the type of AF they had.

The annualized risk of stroke or non-CNS systemic embolism in paroxysmal AF vs sustained AF by treatment

Treatment Paroxysmal AF (n=1202) (%) Sustained AF (n=5495) (%) Adjusted relative risk (95% CI) p
Clopidogrel/aspirin 2.4 3.0 0.84 (0.51-1.40) 0.509
Oral anticoagulation 1.5 1.5 1.14 (0.59-2.20) 0.696

Hohnloser commented to heartwire that many doctors believe paroxysmal AF may have a lesser risk of stroke compared with sustained AF, and in this trial the patients with paroxysmal AF did appear to be lower risk in that they were younger, had a shorter AF history, less valvular disease, less heart failure, and less diabetes mellitus than patients with sustained AF. They did, however, have more hypertension. At baseline, patients with paroxysmal AF had a CHADS2 risk score (which takes into account cardiac failure, hypertension, age, diabetes, and previous stroke or transient ischemic attack [TIA]) of 1.79 vs 2.04 for those with sustained AF. "Despite this, patients with paroxysmal AF had the same risk of thromboembolic complications, showing that it should be taken just as seriously as sustained AF," he added.

May explain high stroke rate in AFFIRM

In the paper, the researchers state that the present data represent the most up-to-date analysis of risk for stroke and non-CNS embolism in patients with paroxysmal AF vs patients with sustained AF. They also suggest that their findings may explain observations made in other contemporary trials, such as AFFIRM, in which the prevalence of ischemic stroke was 7.1% in patients in whom rhythm control was attempted compared with 5.5% in those who were randomized to rate control. "Based on the present data, it is possible that episodes of (asymptomatic) paroxysmal AF in the rhythm-control arm for which patients did not receive anticoagulation therapy may account for this finding," they say.

They also emphasize the finding that oral anticoagulation is effective in both patients with paroxysmal AF and with those with sustained AF. "Based on our data, 68 patients with sustained AF need to be treated with oral anticoagulation to prevent one thromboembolic event, compared with 135 patients with paroxysmal AF," they report.

But Hohnloser noted that patients recruited into the ACTIVE W study were already at medium risk. He commented to heart wire : "They had to have a CHADS2 score of at least 1, so they had to have at least one major risk factor for stroke as well as AF, and the average was 2, so there are still some AF patients who are relatively young, without heart failure, hypertension, diabetes, or a prior stroke/TIA who do not qualify for anticoagulation therapy. What we are saying is that if you have AF and at least one of these other risk factors, then you should take warfarin whether you have paroxysmal or sustained AF."

What degree of paroxysmal AF is harmful?

Noting that the results from the ACTIVE W study allow no firm conclusion as to what amount of paroxysmal AF increases risk for stroke and non-CNS embolism to that associated with sustained AF, Hohnloser el al point out that this issue is currently being evaluated in a prospective clinical trial (the Atrial Fibrillation Reduction Atrial Pacing Trial [ASSERT]), in which pacemaker memory is used to precisely determine the number of episodes and duration of paroxysmal AF. This arrhythmia burden will be linked to stroke risk during 2.5 years of follow-up.

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