Summary

• The CHADS₂ score classification is a validated scale used to estimate the risk of stroke for subjects who have atrial fibrillation.¹
• In ROCKET AF, the mean and median CHADS₂ scores were 3.5 and 3.0, respectively.²
• According to the ROCKET AF protocol, the proportion of patients who did not fit the criteria of having a previous thromboembolism or a CHADS₂ score ≥2 was limited to 10% of the cohort for each region. The remainder of patients were required to have had a previous thromboembolism or three or more risk factors for stroke.²

BACKGROUND

The CHADS₂ score classification is a validated scale used to estimate the risk of stroke for subjects who have atrial fibrillation. The CHADS₂ score ranges from 0 to 6 and is based upon assignment of points for each of the following: 1 point each for the presence of congestive heart failure, hypertension, age 75 years or older, and diabetes mellitus, and 2 points for history of stroke or transient ischemic attack (TIA), thus CHADS₂ is an acronym for the risk factors of stroke in this population.¹

CLINICAL STUDIES

ROCKET AF was a randomized, double-blind, double-dummy, active-controlled, parallel-group, multi-center, event-driven, non-inferiority study conducted to compare efficacy and safety between oral fixed-dose XARELTO 20 mg once daily (15 mg for patients with creatinine clearance [CrCl] 30-49 ml/min) and dose-adjusted warfarin (target international normalized ratio [INR] 2.0-3.0) for the prevention of stroke and non-central nervous system (CNS) systemic embolism in patients with non-valvular atrial fibrillation.²

Patients were included, but not limited to the following in this study:^2,3

• Age ≥18 years with documented paroxysmal, persistent, or permanent atrial fibrillation with moderate to high risk of stroke
• History of prior stroke, TIA, or systemic embolism, or had ≥2 of the following risk factors (CHADS₂ ≥2)
  • Heart failure or left ventricular ejection fraction ≤35%
  • Hypertension (use of antihypertensive medications within 6 months before the screening visit or persistent systolic blood pressure above 140 mmHg or diastolic blood pressure above 90 mmHg)
  • Age ≥75 years
  • Diabetes mellitus

According to the protocol, the proportion of patients who did not fit the criteria of having a previous thromboembolism or a CHADS₂ score ≥2 was limited to 10% of the cohort for each region. The remainder of patients were required to have had a previous thromboembolism or three or more risk factors for stroke.

Baseline characteristics of the 14,264 patients randomized in the study were similar between treatment groups. The mean and median CHADS₂ scores were 3.5 and 3.0, respectively. Please see Table: Characteristics of the Intention-to-Treat Population at Baseline.

Overall efficacy and major and non-major clinically relevant bleeding while on treatment by CHADS₂ score are presented in Table: Overall Efficacy by CHADS₂ Score and Table: Major and Non-Major Clinically Relevant Bleeding While on Treatment by CHADS₂ Score. The outcomes of patients with a CHADS₂ score of <2 were not noted in the publication.

Piccini et al (2013)⁴ performed an analysis to identify factors associated with stroke and systemic embolism in the ROCKET AF trial. After accounting for factors that constituted the CHADS₂ score, CrCl was strongly associated with stroke and systemic embolism, secondary only to prior stroke of TIA. The hazard ratio (HR) increased 12% per 10-mL/min decrease in renal function (HR, 1.12; 95% CI, 1.07-1.16; χ₂ score = 26.38) when CrCl was included as a continuous variable. The authors added renal function (CrCl <60 mL/min, 2 points) to the CHADS₂ score and designated it as the R₂CHADS₂ score. This model improved net reclassification index by 8.2% compared with CHADS₂ (C statistic=0.575). When this model was applied to an external population taking and not taking warfarin, net stroke reclassification improved 17.4% (95% CI, 12.1%-22.5%) compared with CHADS₂.

LITERATURE SEARCH

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 08 October 2024.