Oral anticoagulant therapy, such as vitamin K antagonists (VKAs), is prominent for the prevention of cerebral ischemic stroke or systemic embolism and all-cause mortality in patients with atrial fibrillation (AF) and one or more risk factors for stroke [
1‐
4]. Atrial fibrillation is the most common cardiac arrhythmia managed in clinical practice and the most common arrhythmia requiring hospitalization [
5‐
7]. Thromboembolism also occurs with similar incidence [
8,
9]. Anticoagulation with warfarin, at a target international normalized ratio (INR), has consistently been shown to reduce the risk of cerebral ischemic stroke, a major goal of therapy for AF [
10‐
12]. Oral anticoagulants are also frequently administrated for other indications, ranging from venous thromboembolism to mechanical prosthetic heart valves [
13]. In order to determine who should receive anticoagulation therapy, a risk-stratification model is used [
14]. The rationale behind risk stratification is that, although anticoagulation has clearly been shown to be more effective than antiplatelet agents or placebos in the prevention of thromboembolic stroke, their use should be restricted to patients whose risk for a thromboembolic event exceeds their risk of hemorrhage [
15‐
17]. Placebos are obsolete for the treatment of cerebral ischemic stroke [
18]. An initial score called CHADS
2 included the following risk factors for thromboembolic events in non-valvular AF: (i) a history of cerebral ischemic stroke, (ii) diabetes mellitus, (iii) hypertension, (iv) heart failure, and (v) age [
19‐
24]. A subsequent score, known as CHA
2DS
2-VASc, was developed to further determine the risk in the low-risk groups using the following risk factors: (i) age, (ii) sex, (iii) congestive heart failure, (iv) hypertension history, (v) stroke/TIA/thromboembolism history, (vi) vascular disease history, (vii) diabetes history [
25,
26]. The major bleeding risk was evaluated using the HAS-BLED score, consisting of the following risk factors: (i) hypertension, (ii) renal disease, (iii) liver disease, (iv) cerebral ischemic stroke history, (v) prior major bleeding or predisposition to bleeding, (vi) labile INR, (vii) age greater than 65 years, (viii) medication usage predisposing to bleeding, (ix) alcohol or drug usage history [
27]. Warfarin dosing is targeted to a therapeutic INR, which is usually 2–3 in AF, but may be higher, 2.5–3.5, for mechanical mitral valves [
27]. Numerous medications interact with warfarin and affect its metabolism. For these reason, VKA treatment requires monitoring of the INR in order to maintain it in a therapeutic range, avoiding some side effects, the major and most significant of which is bleeding [
27]. In fact, as already reported, an over-anticoagulation leads to significant risk of bleeding when the INR is greater than 3 [
28]. The aim of the present longitudinal follow-up study was to evaluate the event rates of several clinical composite outcomes, such as bleeding, thromboembolic events, and all-cause death, comparing three organizational models of the analytical patient management, on the basis of a centralized or a local control of the PT/INR [
29,
30]. In particular, in the first group the PT/INR test was performed and controlled by the surveillance center; in the second and third one the center did not have the possibility to perform the PT/INR test, but had only the ability to view the PT/INR results or all patients analyses, respectively. The present investigation was necessary to evaluate the best analytical organizational model for patients undergoing VKA therapy.