乌鸦传媒

Stroke risk varied widely across populations of atrial fibrillation (AF) patients eligible for anticoagulation treatment under accepted guideline thresholds in a newly published study, suggesting the need, the researchers said, for a more individualized approach to risk assessment.

The most recent joint guidelines from the American Heart Association, the American College of Cardiology, and the Heart Rhythm Society conclude that the benefits of anticoagulation treatment outweigh the risks in AF patients with a CHA₂DS₂-VASc (congestive heart failure, hypertension, age, diabetes, stroke, and vascular disease) score of 2 or greater.

When the researchers assessed the outcomes of patients treated based on this threshold across four studies using analytic modeling, there was a nearly fourfold variation in the estimated benefit of warfarin anticoagulation in the different patient populations using current guidelines.

In one study, the modeling found that warfarin treatment of patients with a CHA₂DS₂-VASc score of 2 or more was associated with an expected median gain of seven quality-adjusted-life months, while in another, treatment was associated with a median expected gain of only five quality-adjusted life weeks.

"Our findings highlight the importance of accurate and precise estimates of ischemic stroke risk for patients with AF and the need to standardize methods for obtaining these estimates," said Sachin Shah, MD, of the University of California, San Francisco, and colleagues, writing online in .

Jennifer Wright, MD, of the University of Wisconsin School of Medicine and Public Health in Madison, told 乌鸦传媒 that the study highlights the limitations of assuming a net benefit or risk of anticoagulation based on a specific CHA₂DS₂-VASc score across populations: "We know that most people with a CHA₂DS₂VASc score or 2 or more benefit from anticoagulation, but there is a lot we still don't know." In addition, while the scoring system isn't perfect, it is the best stroke risk predictor available.

In an , Wright and Craig T. January, MD, PhD, also of the University of Wisconsin, wrote that the research suggests that the CHA₂DS₂-VASc score threshold for anticoagulation "may not be a 'one-size-fits-all' approach, but rather a starting point for a more tailored assessment.

"A risk calculator like the CHA₂DS₂-VASc algorithm, which uses fixed whole integers, may lack adequate sensitivity and flexibility for its components," the editorial stated. "For example, female sex now seems to be a risk modifier, and its intensity depends on other risk factors."

The study included 33,434 patients with incident AF participating in the AnTicoagulation and Risk Factors in Atrial Fibrillation-Cardiovascular Research Network (ATRIA-CVRN) study. A total of 27,179 patients had a CHA₂DS₂-VASc score of 2 or greater.

Shah and co-authors used Markov modeling to estimate the net clinical benefit of oral anticoagulation in quality of life years (QALYs), with warfarin using the base case and non-vitamin K antagonists modeled in the secondary analysis.

The team made four sequential measurements of the net clinical benefit of oral anticoagulation in this cohort and all model parameters were held constant except the stroke rate for a corresponding CHA₂DS₂-VASc score. In sequential measurements, the researchers used ischemic stroke rates corresponding to CHA₂DS₂-VASc score from the ATRIA CVRN cohort and three other cohorts: the Swedish AF cohort study, the Danish National Patient Registry, and the Stroke Prevention using ORal Thrombin Inhibitor in atrial Fibrillation (SPORTIF) study.

Among the main findings:

• The population benefit of warfarin anticoagulation for patients with a score of 2 or more was smallest using stroke rates from the ATRIA study and greatest using those from the Danish National Patient Registry (6,290 QALYs [95% CI, ± 2.3%] versus 24,110 QALYs [CI, ± 1.9%]; P<0.001)
• The optimal CHA₂DS₂-VASc score threshold for anticoagulation was 3 or more using stroke rates from ATRIA, 2 or more using those from the Swedish AF cohort study, 1 or more using those from the SPORTIF study, and 0 or more using those from the Danish National Patient Registry
• Accounting for lower rates of novel oral anticoagulant (NOAC)-associated intracranial hemorrhage decreased optimal CHA₂DS₂-VASc score thresholds, but these thresholds still varied widely

"The net clinical benefit of warfarin anticoagulation for patients with AF varies close to fourfold when variation in stroke rates published in different AF studies is accounted for," the researchers wrote. "Incorporating the lower risk for intracerebral hemorrhage associated with NOACs results in greater benefit and lower optimal CHA₂DS_2-VASc score thresholds for anticoagulation; nevertheless, these thresholds still vary widely depending on the choice of reported stroke rates.

"Standardized, rigorously applied methods are needed to obtain precise and reproducible stroke rates," and current guidelines based on the scoring system may need to be revised to better reflect individual risk," Shah et al wrote. "Until such time, guidelines should better reflect the uncertainty of the current approach in which a patient's CHA₂DS₂-VASc score is used as the primary basis for recommending oral anticoagulants."