More evidence suggesting that intermittent atrial fibrillation (AF) may be associated with a lower risk for stroke compared with permanent AF has come from a new systematic review of the literature.

The review, presented at the recent American Heart Association Scientific Sessions, was conducted by a Canadian group with lead author, Mandy N. Lauw, MD, McMaster University, Hamilton, Ontario, Canada.

The review included 18 studies with 134,847 patients with AF and found a lower risk for stroke in patients with paroxysmal AF than in those with permanent AF, whether or not patients were taking oral anticoagulants.

"The intuition that intermittent AF may carry less stroke risk than permanent AF is one that many people have," senior author, Stuart Connolly, MD, McMaster University, explained to Medscape Medical News. "It seems sensible that if you only have AF once very few months you would be at lower risk than someone who has AF all the time."

But he noted that an analysis from the SPAF (Stroke Prevention in Atrial Fibrillation) study published about 20 years ago suggested that the stroke rate did not appear to differ for intermittent vs permanent AF, and current guidelines do not take into account the pattern of AF. "They recommend that anticoagulation is based on stroke risk scores, which does not distinguish between paroxysmal and permanent AF."

Dr Connolly points out that few studies have looked at this issue, and the existing ones have mostly been observational. In addition, patients with permanent AF are more likely to be receiving oral anticoagulation, so it is difficult to interpret stroke risks.

More recent studies have suggested a lower stoke risk with paroxysmal AF vs permanent AF, including a large analysis of the ACTIVE A (Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events A) and AVERROES (Apixaban Versus Acetylsalicylic Acid [ASA] to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin K Antagonist Treatment) trials presented at the recent European Society of Cardiology meeting and published online in the European Heart Journal.

"It was this study that prompted us to look at the wider literature on the subject," Dr Connolly said.

For the current research, the Canadian group systematically searched PubMed (January 1966 to April 2014) for clinical, randomized controlled trials or cohort studies that reported different AF patterns in patients before occurrence of stroke events and that reported stroke rates as a function of paroxysmal or permanent AF pattern.

Of 411 identified citations, 18 papers were included and were analyzed according to use of oral anticoagulants. Results of a meta-analysis of all these studies found that the risk for stroke was lower for patients with paroxysmal AF than with permanent AF. This was true for all analyses, whether or not the patients were taking oral anticoagulants.

Table. Risk for Stroke From Paroxysmal vs Permanent AF

Oral Anticoagulant Use Odds Ratio for Stroke With Paroxysmal vs Permanent AF (95% Confidence Interval)
None 0.75 (0.61 - 0.93)
All 0.77 (0.68 - 0.88)
Mixed 0.70 (0.58 - 0.84)


But the researchers caution that whether AF pattern is an independent predictor of stroke or rather reflects patients' stroke risk profile cannot be concluded from this review because of heterogeneous study designs and AF populations.

"When we put all the literature together we see quite a strong signal that paroxysmal AF has a lower risk. The problem is allowing for confounders," Dr Connolly commented. "Paroxysmal patients are likely to be younger, with less advanced forms of heart disease. So this meta-analysis doesn't answer the question as to whether permanent AF is riskier in itself."

Their results show findings similar to those of the ACTIVE-A/AVERROES analysis, he added, "but these studies are still observational so need to be taken with a grain of salt. Even so, we believe the results are probably important."

Dr Connolly says it is still vitally important to identify AF. "But the big questions are 'How much AF does it take to increase stroke risk?' and 'Are relatively short intermittent episodes still a risk?' We don't know what to do with short runs of AF — from 30 seconds to 6 minutes. Do these patients need anticoagulation? We don't know that. More research needs to be done to answer this question."

The authors have disclosed no relevant financial relationships.

American Heart Association Scientific Sessions. Abstract #20413. Presented November 16, 2014.


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