Findings from a Danish nationwide registry conducted among patients with Atrial Fibrillation (AF), initiated on Vitamin K Antagonists (VKA) for stroke prevention between 1997 and 2011, found that almost one-half of patients with prior good level of VKA control (TTR ≥70%) had TTR <70% during the following year. Additionally, those with a prior TTR of ≥70% had a limited long-term prognostic value for stroke, thromboembolism or major bleeding risk, according to the online publication in JACC.
Past literature has shown a 5 fold higher risk of stroke/thromboembolism (TE) in AF patients due to which the vast majority of them are recommended anticoagulation. While VKAs have long been the treatment of choice in this setting, many studies have demonstrated similar efficacy and safety of direct oral anticoagulants (DOACs). VKA therapy warrants frequent international normalized ratio (INR) monitoring in patients, with a close relationship between drug efficacy and safety to time in therapeutic range (TTR) with INR between 2.00 and 3.00. According to the guidelines, AF patients on VKA with time in therapeutic range (TTR) ≥70% are not recommended to switch to a direct oral anticoagulant, in contrast to patients with poor INR control. In the light of this, Bonde and his colleagues in Demark conducted this study to assess future VKA control (TTR) and risk of adverse outcomes such as stroke/thromboembolism and major bleeding, among AF patients on VKA with appropriate control (TTR ≥70%). Assessment for VKA control was performed using the time in therapeutic range (TTR) measure for the initial 6 months, then followed for a subsequent 12 months.
[perfectpullquote align=”full” bordertop=”false” cite=”” link=”” color=”” class=”” size=””]“Instability of anticoagulation intensity is common among patients with AF treated with VKA, even when anticoagulation control has been satisfactory in the past. Since previously good anticoagulation control does not reliably predict future outcomes, TTR ≥70% should not deter physicians from recommending substitution of a target-specific anticoagulant (DOAC).”- Dr. Anders Nissen Bonde, M.D.[/perfectpullquote]
Of the total AF patients remaining on VKA 6 months after initiation, 35.4% had a TTR ≥70%, and 65.6% had a TTR <70%. Among patients with prior TTR ≥70% still on treatment 12 months after inclusion, 55.7% still had a TTR ≥70%. Compared to those patients having a prior TTR ≥70% in the initial 6 month period, those with a prior TTR <70% in the 12 month follow up period did not have a higher risk of stroke/thromboembolism (HR: 1.14; 95% CI: 0.77 to 1.70) or major bleeding (HR: 1.12; 95% CI: 0.84 to 1.49). In the time-dependent estimation of TTR during follow-up, TTR <70% was associated with higher risk of stroke/thromboembolism (HR: 1.91; 95% CI: 1.30 to 2.82) and major bleeding (HR: 1.34; 95% CI: 1.02 to 1.76).
The authors professed that the main strength of the study was that the inclusion of a real-world cohort with no exclusion criteria and no loss to follow-up. Speaking about the relevance of the study findings, the primary investigator, Dr. Anders Nissen Bonde from the Copenhagen University Hospital Herlev and Gentofte, Hellerup, Denmark, stated, “Instability of anticoagulation intensity is common among patients with AF treated with VKA, even when anticoagulation control has been satisfactory in the past. Since previously good anticoagulation control does not reliably predict future outcomes, TTR ≥70% should not deter physicians from recommending substitution of a target-specific anticoagulant (DOAC).” The investigators concluded that only future research could serve as a guide for clinical decision making among patients with AF who happened to be successfully managed with VKA anticoagulants.
Source: http://www.onlinejacc.org/content/72/12/1357