By Michael H. Crawford, MD
Professor of Medicine, Chief of Clinical Cardiology, University of California, San Francisco
Dr. Crawford reports no financial relationships relevant to this field of study.
SYNOPSIS: An analysis of 34 randomized trials in atrial fibrillation patients not on anti-coagulation showed considerable variation in stroke rates corresponding to their predicted risk by the CHA2DS2-VASc scores. When these scores are 2 or less, stroke rates are low enough to question the benefit versus risk of anti-coagulation therapy.
SOURCES: Quinn GR, Severdija ON, Chang Y, Singer DE. Wide variation in reported rates of stroke across cohorts of patients with atrial fibrillation. Circulation 2017;135:208-219.
Nielsen PB, Lip GY. Adding rigor to stroke rate investigations in patients with atrial fibrillation. Circulation 2017;135:220-223.
Studies show that the adoption of oral anti-coagulant (OAC) use in atrial fibrillation (AF) patients is underutilized, largely because of concerns about bleeding risk. The stroke and bleeding risks vary in patients with AF, and popular clinical risk scores such as CHA2DS2-VASc do not define a fixed stroke risk for all. Investigators reviewed stroke rates in AF patient cohorts not on OACs from randomized trials worldwide to further refine the relationship between the CHA2DS2-VASc score and the actual stroke risk. Anti-platelet use was allowed but was not analyzed. To include the maximum number of patients, only one year follow-up data was used. Patients undergoing procedures or who exhibited high-risk comorbidities, such as hypertrophic cardiomyopathy, end-stage renal disease, myocardial infarction, or prior stroke, were excluded. Two groups of studies are reported: an overall stroke risk group, and a group in which CHA2DS2-VASc scores were used to stratify the data. There were 17 studies in the overall group, two in the CHA2DS2-VASc score-stratified group and 15 in both for 34 total studies. The total study population was > 500,000 AF patients not on OACs. Stroke rates for each study ranged from 0.45%/year to 9.28%/year. Stroke rates also varied by region, with the North American rate less than one-third the European rate. Also, stroke rates were lower in prospective vs. retrospective studies. In the 17 studies using the CHA2DS2-VASc score, with a score of 1, 76% of the studies showed stroke rates < 1%/year, and 18% exhibited rates > 2%/year. With a CHA2DS2-VASc score of 2, 27% of the studies demonstrated a stroke rate of < 1%/year, 49% showed a rate of 1-2%/year, and 33% exhibited rates > 2%/year. Notably, all North American studies showed stroke rates of < 1%/year for patients with CHA2DS2-VASc scores between 0 and 2. The authors concluded that considerable variation in stroke rates corresponding to the patients’ CHA2DS2-VASc scores is seen between studies of patients with AF who are not on OACs. Most studies did not show stroke rates that would justify anticoagulant therapy at CHA2DS2-VASc scores of 1 or 2.
COMMENTARY
One approach to OAC use in AF is finding the equipoise between stroke vs. bleeding risk. This is the point at which stroke risk equals bleeding risk, and the so-called net clinical benefit is zero. Scores above or below this point would inform OAC prescription decisions. However, the authors noted that the use of formal bleeding risk scores, such as HAS-BLED, doesn’t contribute much to this equation, and that the OAC decision is driven by the stroke risk in 90% of cases. Also, guidelines do not recommend the use of formal bleeding scores. Hence, Quinn et al focused on the variation in stroke risk across studies in patients with the same CHA2DS2-VASc scores. An editorial accompanying the article noted that this variation is not surprising given the international distribution of the studies. Also, it is known that the CHA2DS2-VASc score is only of modest predictive value (c index of about 0.60).
Quinn et al and the editorialists from Europe disagree on the stroke risk above which OAC is beneficial (1-2% and > 0.9%, respectively). This difference in opinion influences the interpretation of the study results, with the Europeans favoring OAC at CHA2DS2-VASc scores ≥ 1 for men and ≥ 2 for women. The study authors thought their findings only support OAC for scores > 2 in either sex. Basically, both approaches mean that once a clinician identifies one to three risk factors beyond female sex, OACs should be prescribed. So, there is no reason to calculate the score; one must remember what the risk factors are. Of course, not all the CHA2DS2-VASc risk factors are of equal weight. For example, having known vascular disease is not equal to being a woman, yet each is worth 1 point. Thus, some have recommended a more holistic approach considering the weighting of risk factors and other factors not in the CHA2DS2-VASc score, such as race. We know Asians are at a higher risk for stroke, for example. Also, risk is not static and can change over time, so the anticoagulant or not decision is not good forever.
Why stroke rates differ so widely in various studies probably is mainly due to study methodology. An analysis of the Swedish AF study showed that changing patient enrollment criteria could alter the stroke risk from 2.7% to 9.3% per year. However, the difference in stroke rates between North America and Europe is harder to explain and must color the editorialists’ opinion of who needs OACs. No clear trend related to time was found, and factors such as anti-platelet therapy and warfarin vs. new OACs were not investigated. At this point, one must acknowledge that stroke rates for specific CHA2DS2-VASc scores are uncertain, especially in the critical 1-2 range in which the tipping point for anti-coagulation therapy lies. Thus, other factors must be considered in this decision and well-documented in the medical record.
An analysis of 34 randomized trials in atrial fibrillation patients not on anti-coagulation showed considerable variation in stroke rates corresponding to their predicted risk by the CHA2DS2-VASc scores. When these scores are 2 or less, stroke rates are low enough to question the benefit versus risk of anti-coagulation therapy.
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