• The CHA₂DS₂-VASc is better at discriminating truly low-risk patients and finding those at high risk as well.
• In the first validation study from the EuroHeart survey, CHA₂DS₂-VASc had a similar C statistic to CHADS₂ but improved prediction in truly low-risk patients and classified only a small proportion into the intermediate-risk category.
• the more precise the risk tool is to assess future risk of stroke, the better the chance that low-risk patients can avoid anticoagulation and that those who will benefit from anticoagulation will be identified accurately.
• The major weakness of CHADS₂ is that a substantial proportion of patients (approximately 60%) are assigned a score of 1, indicating an intermediate risk of stroke, and the benefit of application of anticoagulation to this subset is uncertain.

Schemes to stratify stroke risk in atrial fibrillation (Figures 1, 2, and 3) have been used widely since the new millennium, but which scheme is best for assigning thromboembolic risk and predicting and predicting which patients may benefit from oral anticoagulation? The data demonstrate that the CHA₂DS₂-VASc is better at discriminating truly low-risk patients and finding those at high risk as well. 

CHADS₂

The CHADS₂ score was developed in 2001, and was used widely to assess the risk of stroke in patients with AF, thereby aiding clinicians in selecting AF patients who would derive benefit from anticoagulation. In 2010, a new risk score known as CHA₂DS₂-VASc was proposed to strengthen risk prediction by assigning points to additional risk factors not included in CHADS₂: female gender, age 65 to 74 years, and vascular disease. Patients with a CHADS₂ score of ≥2 are considered high risk, and are generally recommended to receive anticoagulation. The major weakness of CHADS₂ is that a substantial proportion of patients (approximately 60%) are assigned a score of 1, indicating an intermediate risk of stroke, and the benefit of application of anticoagulation to this subset is uncertain.

CHA₂DS₂-VASc

As with CHADS₂, the CHA₂DS₂-VASc (Table) assigns a score of 0 to indicate low risk, 1 as intermediate risk, and ≥2 as high risk. In the first validation study from the EuroHeart survey, CHA₂DS₂-VASc had a similar C statistic to CHADS₂ but improved prediction in truly low-risk patients and classified only a small proportion into the intermediate-risk category. 

A validation of the two risk tools was performed by Danish researchers who used data from a national hospital registry to identify 73,538 patients with nonvalvular AF. They found that CHA₂DS₂-VASc was more accurate at assessing stroke risk than CHADS₂.

Precision

About one third of patients were defined as intermediate risk by CHADS₂, but CHA₂DS₂-VASc had 92.7% of these patients classified as high risk. When assessing thromboembolic risk in those classified as intermediate risk via the 2 risk stratification schema, patients classified as intermediate risk by CHADS₂ were found to have 4.75 thromboembolic events per 100 person-years at 1 year, compared with 2.01 for those categorized as intermediate risk by CHA₂DS₂-VASc. At 5 years, intermediate-risk patients as defined by CHADS₂ also had more than twice the rate of thromboembolic events at 5 years compared with those classified as intermediate risk by CHA₂DS₂-VASc.

The proportion of patients classified as low risk of stroke was 22.3% by CHADS₂, but 39.5% of these patients were intermediate risk and 21.7% were high risk using CHA₂DS₂-VASc, and only 8.7% of patients were truly at low risk of stroke using CHA₂DS₂-VASc. These results suggest that some low-risk patients by CHADS₂ would actually benefit from anticoagulation.

Figure 3. Normal rhythm tracing (top), atrial fibrillation (bottom).
(Sources: Wikipedia/Creative Commons/By BruceBlaus.)

Systematic Review and Meta-Analysis

A systematic review and meta-analysis of 8 studies comparing the predictive abilities of CHADS₂ and CHA₂DS₂-VASc also determined that CHA₂DS₂-VASc assigned more AF patients to the high-risk group and significantly fewer (P=0.01) to the intermediate-risk group than CHADS₂.  “Therefore, the CHA₂DS₂-VASc score identifies more patients as high risk to avoid inadequate treatment,” the study authors wrote.

Further, “for the CHADS₂ low-risk patients, the rate of endpoint events in the anticoagulant subgroup was significantly lower than the non-anticoagulation subgroup (0.94% vs. 1.1%), which indicates that CHADS₂ stratifies some non-low-risk patients as low risk and that some CHADS₂ low-risk patients can still benefit from anticoagulation.” The diversion of intermediate-risk patients to a high-risk group through use of CHA₂DS₂-VASc avoids the concentration of patients in the intermediate-risk group and could facilitate the selection of treatment for these patients, according to this recent study. 

The value of CHA₂DS₂-VASc also lies in reclassification of about one fourth of intermediate-risk patients by CHADS₂ into a low-risk category, a risk that is “low enough to consider withholding anticoagulant treatment,” concluded investigators who examined data from patients with AF and a CHADS₂ risk score of 1 who participated in the AVERROES, ACTIVW, and ACTIVE-A trials.

This “very low-risk group” had a stroke risk of just 1% per year. “The very low-risk patients with a CHA₂DS₂-VASc score of 1 were men aged <65 years with either hypertension (87%), heart failure (8%), or diabetes mellitus (4%), the authors noted. “Given the risks of bleeding associated with VKA [vitamin K antagonist] treatment and the 1% per year stroke risk in patients with a CHA₂DS₂-VASc score of 1, we think it is unlikely that these patients will benefit from treatment with VKA therapy,” the authors noted.

Comparative Study

In a study of 2,179 AF patients who had undergone ablation, both risk scores performed exceptionally well in risk of AF recurrence, stroke, heart failure, and death at 5 years, but CHA₂DS₂-VASc was superior to CHADS₂ in predicting AF recurrence and AF-related morbidities. 

Both risk stratification schemes are easy to perform. The value of the CHA₂DS₂-VASc seems to lie in better discrimination of truly low-risk AF patients and in better risk stratification of those patients deemed intermediate risk by CHADS₂.