INR Stability, Clinical Importance, and Predictors in Patients With Atrial Fibrillation and Venous Thromboembolism Receiving Vitamin K Antagonists

Objective: Compare and contrast systematic reviews/meta-analyses assessing the time in the therapeutic range (TTR) for vitamin K antagonists (VKAs), clinical impact, and predictors. Data Sources: OVID MEDLINE search (1980-June 1, 2016) using the terms “vitamin K antagonist or warfarin” and “systematic review or meta-analysis” with backwards citation tracking from procured articles. Study Selection and Data Extraction: Search results were limited to systematic reviews assessing TTR with VKAs in patients with atrial fibrillation (AF) or venous thromboembolism (VTE). Data Synthesis: Six systematic reviews assessed TTR (4 in AF, 2 in VTE), and 3 of those assessed control at the time of a thrombotic or bleeding event (2 in AF, 1 in VTE). In patients on VKAs, greater TTR is correlated with fewer thromboembolic events and bleeding complications. VKA naïve patients have a harder time maintaining TTR than those with a previous knowledge of the likely therapeutic dose. Patients in the United States spend less TTR than those in other countries. Randomized clinical trials and anticoagulation clinics achieve greater TTR than those treated outside of these settings. The overall TTR has not improved from the first systematic reviews to the newest ones even though they were conducted 10 years apart and contained many new studies. Also, TTR in AF and VTE is similar. Conclusions: TTR is an important metric of VKA efficacy and safety and needs to be optimized. Many factors such as being VKA naïve can compromise TTR, and the use of anticoagulation clinics to optimize therapy is an important approach.