Gene R. Quinn

Wide Variation in Reported Rates of Stroke Across Cohorts of Patients with Atrial Fibrillation

Background: Oral anticoagulants decrease ischemic stroke rates in patients with atrial fibrillation (AF) but increase the risk of bleeding. For the average patient with AF, the threshold of annual ischemic stroke rate where the benefit of anticoagulation outweighs the bleeding risk (net clinical benefit) has been shown to be ≈1% to 2%. Guideline recommendations for oral anticoagulants in AF are based on the CHA2DS2-VASc stroke risk point scores, assuming that those scores translate to fixed stroke rates. However, the relationship between stroke point scores and annual stroke rates may vary substantially across populations. We sought to comprehensively assess the reported rates of stroke in patients with AF and the relationship of stroke rates to stroke risk point scores. Methods: A systematic review of cohort studies and randomized controlled trials enrolled patients with nonvalvular AF not treated with oral anticoagulants. Results: Of the 3552 studies screened, we identified 34 studies eligible for analysis. Overall stroke rates in cohort studies were highly heterogeneous (Q=5706.54, P<0.001; I2 = 99.6%) and ranged from 0.45% to 9.28% per year, despite being of similar objective study quality. The mean North American stroke rate was less than one-third that of the mean European stroke rate (P<0.0001). However, a random effects regression indicated that between-study variability was not significantly accounted for by cohort region, prospective versus retrospective design, calendar year of study, or outcome event cluster. At a CHA2DS2-VASc score of 1, 76% of cohorts reported ischemic stroke rates <1% per year and only 18% of cohorts reported a stroke rate >2% per year. At a CHA2DS2-VASc score of 2, 27% of cohorts reported stroke rates below 1% per year, 40% reported stroke rates between 1 and 2% per year, and 33% reported stroke rates >2% per year. Conclusions: Substantial variation exists across cohorts in overall stroke rates and rates corresponding to CHA2DS2-VASc point scores. These variations can affect the point score threshold for recommending oral anticoagulants in AF. The majority of cohorts did not observe stroke rates that would indicate a clear expected net clinical benefit for anticoagulating AF patients with CHA2DS2-VASc scores of 1 or 2.

How Well Do Stroke Risk Scores Predict Hemorrhage in Patients With Atrial Fibrillation

The decision to use anticoagulants for atrial fibrillation depends on comparing a patients estimated risk of stroke to their bleeding risk. Several of the risk factors in the stroke risk schemes overlap with hemorrhage risk. We compared how well 2 stroke risk scores (CHADS2 and CHA2DS2-VASc) and 2 hemorrhage risk scores (the ATRIA bleeding score and the HAS-BLED score) predicted major hemorrhage on and off warfarin in a cohort of 13,559 community-dwelling adults with AF. Over a cumulative 64,741 person-years of follow-up, we identified a total of 777 incident major hemorrhage events. The ATRIA bleeding score had the highest predictive ability of all the scores in patients on warfarin (c-index of 0.74 [0.72 to 0.76] compared with 0.65 [0.62 to 0.67] for CHADS2, 0.65 [0.62 to 0.67] for CHA2DS2-VASc, and 0.64 [0.61 to 0.66] for HAS-BLED) and in those off warfarin (0.77 [0.74 to 0.79] compared with 0.67 [0.64 to 0.71] for CHADS2, 0.67 [0.64 to 0.70] for CHA2DS2-VASc, and 0.68 [0.65 to 0.71] for HAS-BLED). In conclusion, although CHADS2 and CHA2DS2-VASc stroke scores were better at predicting hemorrhage than chance alone, they were inferior to the ATRIA bleeding score. Our study supports the use of dedicated hemorrhage risk stratification tools to predict major hemorrhage in atrial fibrillation.

Atrial Fibrillation: Stroke Prevention in Older Adults

Atrial fibrillation (AF) is an increasingly prevalent disease in the elderly. Patients with AF are at increased risk of ischemic stroke, resulting in significant morbidity and mortality. Warfarin is highly effective at reducing stroke risk, with a net clinical benefit favoring treatment in older individuals. The advent of newer oral anticoagulants provides promising alternatives to warfarin. Appropriate risk stratification for stroke should be performed for all patients with AF to guide antithrombotic therapy. For patients at lower stroke risk, bleeding risk stratification tools can also be used when the benefit of anticoagulant therapy is unclear.

How can I predict bleeding in my elderly patient taking anticoagulants

We have tools, but their predictive value is modest. Clinical judgment is important.