title: Incidence of thromboembolic complications in patients with atrial fibrillation or mechanical heart valves with a subtherapeutic international normalized ratio: a prospective multicenter cohort study.
abstract: Subtherapeutic international normalized ratio (INR) is frequently encountered in clinical practice, and patients with high-risk atrial fibrillation (AF) and with mechanical heart valve (MHV) with inadequate anticoagulation may be exposed to an increased risk of thromboembolic events (TE). However, there are no prospective data evaluating this risk. Consecutive patients with a history of stable anticoagulation, but with a subtherapeutic INR, were prospectively included. Data on use and dose of low-molecular weight heparin (LMWH) bridging therapy were collected. The incidence of objectively confirmed TE and of major bleeding events within 90 days after the index INR was assessed. Five hundred and one patients with INR value 0.5-1 INR units below the lower limit of the patient-specific target INR were included in the study (280 with MHV and 221 with AF and CHADS2 score ≥3). LMWH was prescribed for 64 patients (12.8%). During follow-up, seven patients had a TE (1.40%; 95% confidence interval 0.68, 2.86%; 5.58 events for 100 patients year). All the events occurred within 14 days after the index INR. When we consider only patients who did not receive bridging therapy, the incidence of TE was 1.14% (5 of 437 patients; 95% confidence interval 0.49, 2.64%; 4.58 events for 100 patients year). There were no major bleeding events. The risk of TE in this population was not negligible. Given the frequent observation of subtherapeutic INR levels when monitoring vitamin K antagonists, this finding warrants additional investigation to improve the management of these patients.
authors.affiliation: Department of Clinical Medicine, Insubria University, Varese, Italy. fdentali@libero.it.
authors.forename: Francesco
authors.initials: F
authors.lastname: Dentali
authors.forename: Pasquale
authors.initials: P
authors.lastname: Pignatelli
authors.forename: Alessandra
authors.initials: A
authors.lastname: Malato
authors.forename: Daniela
authors.initials: D
authors.lastname: Poli
authors.forename: Matteo Nicola Dario
authors.initials: MN
authors.lastname: Di Minno
authors.forename: Leonardo
authors.initials: L
authors.lastname: Di Gennaro
authors.forename: Elena
authors.initials: E
authors.lastname: Rancan
authors.forename: Daniele
authors.initials: D
authors.lastname: Pastori
authors.forename: Elisa
authors.initials: E
authors.lastname: Grifoni
authors.forename: Elena
authors.initials: E
authors.lastname: Grifoni
authors.forename: Alessandro
authors.initials: A
authors.lastname: Squizzato
authors.forename: Sergio
authors.initials: S
authors.lastname: Siragusa
authors.forename: Giovanni
authors.initials: G
authors.lastname: Di Minno
authors.forename: Walter
authors.initials: W
authors.lastname: Ageno
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000097:blood / Q000150:complications*; D015897:Comorbidity; D005260:Female; D005500:Follow-Up Studies; D006350:Heart Valve Prosthesis / Q000009:adverse effects; D019918:Heart Valve Prosthesis Implantation; D006470:Hemorrhage / Q000139:chemically induced / Q000453:epidemiology; D006495:Heparin, Low-Molecular-Weight / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D015994:Incidence; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000097:blood / Q000453:epidemiology* / Q000209:etiology / Q000517:prevention & control; D011446:Prospective Studies; D012306:Risk; D013923:Thromboembolism / Q000097:blood / Q000453:epidemiology* / Q000209:etiology / Q000517:prevention & control; D019851:Thrombophilia / Q000188:drug therapy / Q000209:etiology; D014859:Warfarin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; D014859:Warfarin