Association between CHADS₂risk factors and anticoagulation-related bleeding: a systematic literature review

Abstract

Objective: To determine the strength of evidence supporting an accentuated bleeding risk when patients with CHADS(2) risk factors (chronic heart failure, hypertension, advanced age, diabetes, and prior stroke/transient ischemic attack) receive warfarin.

Methods: A systematic literature search of MEDLINE (January 1, 1950, through December 22, 2009) and Cochrane CENTRAL (through December 22, 2009) was conducted to identify studies that reported multivariate results on the association between CHADS(2) covariates and risk of bleeding in patients receiving warfarin. Each covariate was evaluated for its association with a specific type of bleeding. Individual evaluations were rated as good, fair, or poor using methods consistent with those recommended by the Agency for Healthcare Research and Quality. The strength of the associations between each CHADS(2) covariate and a specific type of bleeding was determined using Grading of Recommendations Assessment, Development and Evaluation criteria as insufficient, very low, low, moderate, or high for the entire body of evidence.

Results: Forty-one studies were identified, reporting 127 multivariate evaluations of the association between a CHADS(2) covariate and bleeding risk. No CHADS(2) covariate had a high strength of evidence for association with any bleeding type. For the vast majority of evaluations, the strength of evidence between covariates and bleeding was low. Advanced age was the only covariate that had a moderate strength of evidence for association; this was the strongest independent positive predictor for major bleeding. Similar findings were observed regardless of whether all included studies, or only those evaluating patients with atrial fibrillation, were assessed.

Conclusion: The associations between CHADS(2) covariates and increased bleeding risk were weak, with the exception of age. Given the known association of the CHADS(2) score and stroke risk, the decision to prescribe warfarin should be driven more by patients' risk of stroke than by the risk of bleeding.

FIGURE 1.

Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) flow diagram of study identification, inclusion, and exclusion of studies evaluating predictors of bleeding in patients treated with warfarin.

FIGURE 2.

Quality rating of multivariate associations between the covariates and major bleeding for (A) all included studies and (B) studies involving only patients with atrial fibrillation. The upright bars represent the evaluations that showed statistically significant independent associations between the covariate and major bleeding, whereas the inverted bars represent evaluations that did not show statistically significant independent associations between the covariate and major bleeding. The black, grey, and white shaded bars represent good, fair, and poor quality ratings of the evaluations, respectively. CHF = chronic heart failure; CVD = cerebrovascular disease; DM = diabetes mellitus; HTN = hypertension.