PARIS – Apixaban treatment produced better outcomes in atrial fibrillation patients compared with warfarin in the ARISTOTLE trial, regardless of the quality of warfarin treatment the comparator patients received, raising the possibility that all atrial fibrillation patients might benefit by switching from warfarin to apixaban.
"The benefits of apixaban over warfarin in preventing stroke, reducing bleeding, and improving survival appear consistent regardless of a center’s quality of INR [international normalized ratio] control. Therefore, in patients with atrial fibrillation, apixaban is a safer and more effective treatment than warfarin across a wide range of warfarin management," Dr. Lars Wallentin said at the annual congress of the European Society of Cardiology. Assessment of apixaban’s efficacy and safety relative to warfarin across the range of warfarin care that was delivered was one of the trial’s prespecified analyses.
Dr. Lars Wallentin
"It’s a very important question, [whether] a patient with very good INR control [could] benefit from switching to apixaban," commented Dr. Jean-Philippe Collet, a cardiologist at the Institute of Cardiology at Pitié Salpêtrière Hospital, Paris. "The local standards of care do not affect the benefits of apixaban over warfarin."
The time that patients spend in the INR therapeutic range of 2-3 is a marker of a patient’s risk, the quality of care that patients with atrial fibrillation (AF) receive, and patient outcomes, and probably can be used to compare different AF treatment studies, but "it is not a marker of the superiority of apixaban over warfarin," Dr. Collet said.
To assess the impact that the average quality of warfarin treatment had in the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) study, Dr. Wallentin and his associates calculated a median time in therapeutic range (TTR) for the more than 9,000 patients treated with warfarin in ARISTOTLE.
The researchers then calculated a median TTR for each of the 1,034 sites that participated in the trial. The median levels showed marked variability. When the medians were averaged for all sites in each of the 39 countries where they were located, the countrywide median TTRs ranged from a high of about 80% in Sweden to a low of about 45% in India.
The researchers then divided the centers into quartiles based on their median TTRs. The lowest quartile included centers with median TTRs of 58% or less, whereas the highest quartile had centers with median TTRs of 72% or greater, reported Dr. Wallentin, professor and head of cardiology research at Uppsala (Sweden) University. The analysis then examined the relative outcomes of the patients treated with apixaban and those treated with warfarin within each of the quartiles.
The hazard ratio between apixaban and warfarin treatment for the study’s primary outcome of the rate of strokes and systemic embolism showed consistency across all four quartiles. At the centers in the quartile with the best warfarin TTRs, apixaban treatment reduced the outcome by a relative 19% compared with patients treated with warfarin. At the centers with the poorest performance of keeping patients in their therapeutic range, apixaban improved the primary outcome by a relative 23%. The hazard ratio in the other two quartiles fell between these two, with relative risk reductions of 19% and 20%. The other study outcomes, such as the relative rates of major bleeds, and mortality showed a similarly consistent pattern across the four quartiles of median TTRs.
Dr. Wallentin said has received research grants from Bristol-Myers Squibb, Pfizer, Boehringer-Ingelheim, AstraZeneca, GlaxoSmithKline, Roche, and Merck-Schering Plough, and has been an advisor or consultant to Portola, CSL Behring, Evola, Athera, and Regado. Dr. Collet has received research grants, and lecture and consulting fees from Bristol-Myers Squibb, Sanofi-Aventis, and Eli Lilly. He has also reported receiving research grants from Guerbet Medical, Medtronic, Boston Scientific, Cordis, Stago, and Centocor.