Direct oral anticoagulants associated with better outcomes than warfarin in older patients with stroke and AF (PROSPER)

Reference

Xian Y, Xu H, O'Brien EC, et al. Clinical effectiveness of direct oral anticoagulants vs warfarin in older patients with atrial fibrillation and ischemic stroke: findings from the Patient-Centered Research into Outcomes Stroke Patients Prefer and Effectiveness Research (PROSPER) study. JAMA Neurol 2019;76(10):1192-1202.(PROSPER) Study. JAMA Neurol. 2019;76(10):1192-1202.

Synopsis

The Patient-Centered Research into Outcomes Stroke Patients Prefer and Effectiveness Research (PROSPER) study investigators recruited nearly 12,000 patients 65 years or older with a history of atrial fibrillation or atrial flutter who were discharged from a hospital following an acute ischemic stroke and were newly taking either a DOAC (n = 4041) or warfarin (n = 7621). The researchers excluded terminally ill patients, patients with contraindications to anticoagulation, and patients with renal insufficiency or on dialysis. They collected standardized data, including demographics, medical history, medications, diagnostic testing, imaging, and in-hospital outcomes. They also used Medicare claims files to assess outcomes after discharge. Consistent with statistical approaches in observational studies, the researchers tried to take into account about skeighty-eight factors that might also be linked to the various outcomes they assessed. They did not, however, take into account the degree of control in the warfarin-treated patients. Recall from other studies, such as the Women's Health Initiative, that all the adjusting in the world is unable to take into account unmeasurable factors. Given the number of outcomes and the number of variables, the authors appropriately adjusted the P values and confidence intervals. After a median of 4 years of follow-up, the researchers found that DOAC treatment was associated with about 2 weeks more days alive and not in a hospital or skilled nursing facility during the first year after discharge (287 vs 263, respectively) compared with warfarin treatment. Nearly 2000 DOAC-treated patients (34%) had a major adverse cardiovascular event (a composite measure of all-cause mortality and cardiovascular or cerebrovascular readmission) compared with 40% of warfarin-treated patients (adjusted hazard ratio [HR] 0.89; 99% CI 0.83 - 0.96). They found no difference in subsequent admissions for ischemic stroke. After multiple adjustments, DOACs were associated with a lower all-cause mortality risk than warfarin (15.5% per year vs 19.6% per year, respectively).