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Ischemic stroke rates dropped as warfarin use increased among Medicare beneficiaries over a 19-year period -- even among groups that have not been well-represented in clinical trials, including the elderly, women, and blacks, researchers found.
Disparities remained, however, with higher rates of ischemic stroke and lower use of warfarin in blacks versus whites and in women versus men, despite higher levels of thromboembolic risk in those populations, according to Charles Herzog, MD, of the Minneapolis Medical Research Foundation, and colleagues.
Nevertheless, the authors wrote online in the Journal of the American Heart Association, "These trends, reflecting practice patterns in the United States over the past 2 decades, indicate gradually increasing comfort of clinicians in prescribing warfarin to all demographic subsets of Medicare patients with atrial fibrillation, and represent real-life extrapolation of data from randomized trials to patients with [the arrhythmia]."
The decline in ischemic stroke that has occurred at the same time as an increase in warfarin use is consistent with the results of the randomized trials evaluating the anticoagulant in patients with nonvalvular atrial fibrillation, but those trials under-represented certain patient groups, including the elderly, women, and racial and ethnic minorities. Thus, some questions have remained about the relative benefits of anticoagulation in these populations.
To explore the issue, Herzog and colleagues examined data from the Medicare 5% database to look at trends in ischemic stroke and warfarin use from 1992 to 2010, with a focus on these high-risk patient subsets. Atrial fibrillation and strokes were identified using diagnostic codes, and warfarin use was assessed by the presence of at least three prothrombin time claims in the year after an atrial fibrillation diagnosis.
Over the study period, the prevalence of atrial fibrillation increased from 3.2% to 7.6% and incidence saw little change, "likely indicating improved longevity of patients with [the condition]," the authors wrote.
Consistent with prior research, rates of ischemic stroke (per 1,000 patient-years) declined over time. For women, the rates dropped from 37.1 to 13.6 for those ages 65 to 74, from 55.2 to 16.5 for those ages 74 to 84, and from 66.9 to 22.9 for those 85 and older.
For men in those age groups, the rates fell from 33.8 to 11.7, from 49.2 to 13.8, and from 51.5 to 18.0, respectively, indicating slightly lower rates of stroke in men versus women.
In both men and women, warfarin use increased in all age groups over time, although the percentage of patients taking warfarin tended to be slightly higher in men.
Some differences by race were seen, with the ischemic stroke rate starting and ending higher among blacks compared with whites. However, the rate dropped in both whites (from 47.0 to 14.8) and blacks (from 73.0 to 29.3).
The percentage of atrial fibrillation patients taking warfarin increased in both whites (from 27% to 61%) and blacks (from 19% to 52%), although rates were persistently lower in blacks.
A possible explanation for the higher rates of stroke observed in women and blacks was seen in the CHADS2 score, which indicated higher average thromboembolic risk in those two groups compared with men and whites.
Regarding women, "it is reassuring ... that the proportional decline in ischemic stroke rates was similar for men and women, with the greatest reduction among patients aged 65 to 74 years," the authors wrote. "Nevertheless, this study raises concern about a 'gender gap' in prescription of warfarin among women, despite a paradoxically higher hazard of ischemic stroke."
And regarding the lower use of warfarin in blacks versus whites, despite the higher thromboembolic risk, the authors said, "Although no firm conclusions can be derived from these data, one possible theory based on existing literature could be that inadequate risk factor control, particularly untreated hypertension, could dissuade clinicians from using warfarin due to safety concerns."
But, they added, "Because we used a surrogate method to determine warfarin use, we cannot feasibly differentiate whether the lower warfarin use reflects clinical contraindications, lack of reliable international normalization ratio checks, or the perception among clinicians that stroke in this population is likely noncardioembolic."
Herzog and colleagues acknowledged some limitations of the study, including the use of administrative data, which precluded the separation of cardioembolic and noncardioembolic strokes, the lack of information on the effectiveness of anticoagulation, the use of surrogate measures of warfarin use, and the possibility that ischemic strokes were under-reported earlier in the study because of a less-intense focus on neuroimaging techniques at that time.
From the American Heart Association:
- Guidelines for the Early Management of Patients with Acute Ischemic Stroke
- Factors Influencing the Decline in Stroke Mortality
This study was supported by a research contract with Ortho-McNeil Janssen Scientific Affairs.
Herzog disclosed a relevant relationship with Johnson & Johnson.
Journal of the American Heart AssociationSource Reference: Shroff G, et al "Atrial fibrillation, stroke, and anticoagulation in Medicare beneficiaries: trends by age, sex, and race, 1992-2010" J Am Heart Assoc 2014; DOI: 10.1161/JAHA.113.000756.