Well-Monitored Warfarin Therapy Safe for AFib-Associated Stroke Prophylaxis

A retrospective analysis of Swedish cohort data indicates that warfarin is effective enough to remain a valid alternative to novel oral anticoagulants in patients with atrial fibrillation — if that warfarin therapy is as well managed as it was in Sweden.

The cohort provided up to 5 years of medical records from 40,449 patients with nonvalvular AFib who started on warfarin between January 1, 2006 and December 31, 2011. Cohort members, 60.0% of whom were men, started the study with a mean age of 72.5 years ± a standard deviation of 10.1 years and a mean CHA₂DS₂-VASc score of 3.3.

Over the course of the study period, the annual incidence of all-cause mortality was 2.19% (95% confidence interval [CI], 2.07% to 2.31%) and the annual incidence of intracranial bleeding was 0.44% (95% CI, 0.39% to 0.49%).

Patients who spent less than 70% of the study time in the therapeutic range (TTR) fared worse than average. Their annual rates of any major bleeding and any thromboembolism were 3.81% (95% CI, 3.51% to 4.11%) and 4.41% (95% CI, 4.09% to 4.73%), respectively.

Among patients whose international normalized ratio (INR) varied significantly, annual rates of any major bleeding and thromboembolism were 3.04% (95% CI, 2.85% to 3.24%) and 3.48% (95% CI, 3.27% to 3.69%), respectively. For patients with individual TTRs of 70% or more, however, the level of INR variability did not alter event rates.

Patients receiving concomitant aspirin also fared worse than average. They had annual rates of any major bleeding of 3.07% (95% CI, 2.70% to 3.44%) and thromboembolism of 4.90% (95% CI, 4.43% to 5.37%). Patients with renal failure were at higher risk of intracranial bleeding (hazard ratio, 2.25; 95% CI, 1.32 to 3.82).

“Well-managed warfarin therapy is associated with a low risk of complications and is still a valid alternative for prophylaxis of AFib-associated stroke,” the study authors wrote in JAMA Cardiology. “Therapy should be closely monitored for patients with renal failure, concomitant aspirin use, and poor INR control.”

The key, of course, is that the warfarin therapy be well-managed, as it is in Sweden, where studies have often found that collective patient TTRs exceed 75%. Such numbers, the authors of the new study noted, are unusual in most other countries.

“The NOACs have been compared with warfarin in large, global randomized trials, but the mean TTRs in these studies were 62.2% with apixaban, 64.4% with dabigatran, 64.9% with edoxaban and 55.2% with rivaroxaban,” they wrote. “With a mean individual TTR of 68.6% (compared with 55.2%-64.9% for the NOAC studies), it might be unsurprising that bleeding complication rates are lower in our cohort than in control groups in the randomized trials.”

The authors of the new study did not compare outcomes for warfarin and NOAC users directly, but they did note how outcomes for the warfarin users they studied compared to outcomes from NOAC trials. The 0.44% annual incidence of intracranial bleeding for the Swedish warfarin users was lower than those of warfarin users in the NOAC trials, which ranged from 0.70% to 0.85%, but it was still higher than the 0.30% rate reported for NOAC users. The 2.19% annual incidence of all-cause mortality in the Swedish study, however, was lower than all-cause mortality rates for any patient group in the NOAC trials.